State-Dependent Changes of Connectivity Patterns and Functional Brain Network Topology in Autism Spectrum Disorder

ERIC Educational Resources Information Center

Barttfeld, Pablo; Wicker, Bruno; Cukier, Sebastian; Navarta, Silvana; Lew, Sergio; Leiguarda, Ramon; Sigman, Mariano

2012-01-01

Anatomical and functional brain studies have converged to the hypothesis that autism spectrum disorders (ASD) are associated with atypical connectivity. Using a modified resting-state paradigm to drive subjects' attention, we provide evidence of a very marked interaction between ASD brain functional connectivity and cognitive state. We show that…

Modulation of Brain Resting-State Networks by Sad Mood Induction

PubMed Central

Harrison, Ben J.; Pujol, Jesus; Ortiz, Hector; Fornito, Alex; Pantelis, Christos; Yücel, Murat

2008-01-01

Background There is growing interest in the nature of slow variations of the blood oxygen level-dependent (BOLD) signal observed in functional MRI resting-state studies. In humans, these slow BOLD variations are thought to reflect an underlying or intrinsic form of brain functional connectivity in discrete neuroanatomical systems. While these ‘resting-state networks’ may be relatively enduring phenomena, other evidence suggest that dynamic changes in their functional connectivity may also emerge depending on the brain state of subjects during scanning. Methodology/Principal Findings In this study, we examined healthy subjects (n = 24) with a mood induction paradigm during two continuous fMRI recordings to assess the effects of a change in self-generated mood state (neutral to sad) on the functional connectivity of these resting-state networks (n = 24). Using independent component analysis, we identified five networks that were common to both experimental states, each showing dominant signal fluctuations in the very low frequency domain (∼0.04 Hz). Between the two states, we observed apparent increases and decreases in the overall functional connectivity of these networks. Primary findings included increased connectivity strength of a paralimbic network involving the dorsal anterior cingulate and anterior insula cortices with subjects' increasing sadness and decreased functional connectivity of the ‘default mode network’. Conclusions/Significance These findings support recent studies that suggest the functional connectivity of certain resting-state networks may, in part, reflect a dynamic image of the current brain state. In our study, this was linked to changes in subjective mood. PMID:18350136

Predicting efficacy of robot-aided rehabilitation in chronic stroke patients using an MRI-compatible robotic device.

PubMed

Sergi, Fabrizio; Krebs, Hermano Igo; Groissier, Benjamin; Rykman, Avrielle; Guglielmelli, Eugenio; Volpe, Bruce T; Schaechter, Judith D

2011-01-01

We are investigating the neural correlates of motor recovery promoted by robot-mediated therapy in chronic stroke. This pilot study asked whether efficacy of robot-aided motor rehabilitation in chronic stroke could be predicted by a change in functional connectivity within the sensorimotor network in response to a bout of motor rehabilitation. To address this question, two stroke patients participated in a functional connectivity MRI study pre and post a 12-week robot-aided motor rehabilitation program. Functional connectivity was evaluated during three consecutive scans before the rehabilitation program: resting-state; point-to-point reaching movements executed by the paretic upper extremity (UE) using a newly developed MRI-compatible sensorized passive manipulandum; resting-state. A single resting-state scan was conducted after the rehabilitation program. Before the program, UE movement reduced functional connectivity between the ipsilesional and contralesional primary motor cortex. Reduced interhemispheric functional connectivity persisted during the second resting-state scan relative to the first and during the resting-state scan after the rehabilitation program. Greater reduction in interhemispheric functional connectivity during the resting-state was associated with greater gains in UE motor function induced by the 12-week robotic therapy program. These findings suggest that greater reduction in interhemispheric functional connectivity in response to a bout of motor rehabilitation may predict greater efficacy of the full rehabilitation program.

A resting state functional magnetic resonance imaging study of concussion in collegiate athletes.

PubMed

Czerniak, Suzanne M; Sikoglu, Elif M; Liso Navarro, Ana A; McCafferty, Joseph; Eisenstock, Jordan; Stevenson, J Herbert; King, Jean A; Moore, Constance M

2015-06-01

Sports-related concussions are currently diagnosed through multi-domain assessment by a medical professional and may utilize neurocognitive testing as an aid. However, these tests have only been able to detect differences in the days to week post-concussion. Here, we investigate a measure of brain function, namely resting state functional connectivity, which may detect residual brain differences in the weeks to months after concussion. Twenty-one student athletes (9 concussed within 6 months of enrollment; 12 non-concussed; between ages 18 and 22 years) were recruited for this study. All participants completed the Wisconsin Card Sorting Task and the Color-Word Interference Test. Neuroimaging data, specifically resting state functional Magnetic Resonance Imaging data, were acquired to examine resting state functional connectivity. Two sample t-tests were used to compare the neurocognitive scores and resting state functional connectivity patterns among concussed and non-concussed participants. Correlations between neurocognitive scores and resting state functional connectivity measures were also determined across all subjects. There were no significant differences in neurocognitive performance between concussed and non-concussed groups. Concussed subjects had significantly increased connections between areas of the brain that underlie executive function. Across all subjects, better neurocognitive performance corresponded to stronger brain connectivity. Even at rest, brains of concussed athletes may have to 'work harder' than their healthy peers to achieve similar neurocognitive results. Resting state brain connectivity may be able to detect prolonged brain differences in concussed athletes in a more quantitative manner than neurocognitive test scores.

Disrupted functional brain connectivity in partial epilepsy: a resting-state fMRI study.

PubMed

Luo, Cheng; Qiu, Chuan; Guo, Zhiwei; Fang, Jiajia; Li, Qifu; Lei, Xu; Xia, Yang; Lai, Yongxiu; Gong, Qiyong; Zhou, Dong; Yao, Dezhong

2011-01-01

Examining the spontaneous activity to understand the neural mechanism of brain disorder is a focus in recent resting-state fMRI. In the current study, to investigate the alteration of brain functional connectivity in partial epilepsy in a systematical way, two levels of analyses (functional connectivity analysis within resting state networks (RSNs) and functional network connectivity (FNC) analysis) were carried out on resting-state fMRI data acquired from the 30 participants including 14 healthy controls(HC) and 16 partial epilepsy patients. According to the etiology, all patients are subdivided into temporal lobe epilepsy group (TLE, included 7 patients) and mixed partial epilepsy group (MPE, 9 patients). Using group independent component analysis, eight RSNs were identified, and selected to evaluate functional connectivity and FNC between groups. Compared with the controls, decreased functional connectivity within all RSNs was found in both TLE and MPE. However, dissociating patterns were observed within the 8 RSNs between two patient groups, i.e, compared with TLE, we found decreased functional connectivity in 5 RSNs increased functional connectivity in 1 RSN, and no difference in the other 2 RSNs in MPE. Furthermore, the hierarchical disconnections of FNC was found in two patient groups, in which the intra-system connections were preserved for all three subsystems while the lost connections were confined to intersystem connections in patients with partial epilepsy. These findings may suggest that decreased resting state functional connectivity and disconnection of FNC are two remarkable characteristics of partial epilepsy. The selective impairment of FNC implicated that it is unsuitable to understand the partial epilepsy only from global or local perspective. We presumed that studying epilepsy in the multi-perspective based on RSNs may be a valuable means to assess the functional changes corresponding to specific RSN and may contribute to the understanding of the neuro-pathophysiological mechanism of epilepsy.

Connectivity dynamics in typical development and its relationship to autistic traits and autism spectrum disorder.

PubMed

Rashid, Barnaly; Blanken, Laura M E; Muetzel, Ryan L; Miller, Robyn; Damaraju, Eswar; Arbabshirani, Mohammad R; Erhardt, Erik B; Verhulst, Frank C; van der Lugt, Aad; Jaddoe, Vincent W V; Tiemeier, Henning; White, Tonya; Calhoun, Vince

2018-03-30

Recent advances in neuroimaging techniques have provided significant insights into developmental trajectories of human brain function. Characterizations of typical neurodevelopment provide a framework for understanding altered neurodevelopment, including differences in brain function related to developmental disorders and psychopathology. Historically, most functional connectivity studies of typical and atypical development operate under the assumption that connectivity remains static over time. We hypothesized that relaxing stationarity assumptions would reveal novel features of both typical brain development related to children on the autism spectrum. We employed a "chronnectomic" (recurring, time-varying patterns of connectivity) approach to evaluate transient states of connectivity using resting-state functional MRI in a population-based sample of 774 6- to 10-year-old children. Dynamic connectivity was evaluated using a sliding-window approach, and revealed four transient states. Internetwork connectivity increased with age in modularized dynamic states, illustrating an important pattern of connectivity in the developing brain. Furthermore, we demonstrated that higher levels of autistic traits and ASD diagnosis were associated with longer dwell times in a globally disconnected state. These results provide a roadmap to the chronnectomic organization of the developing brain and suggest that characteristics of functional brain connectivity are related to children on the autism spectrum. © 2018 Wiley Periodicals, Inc.

Cerebro-cerebellar connectivity is increased in primary lateral sclerosis.

PubMed

Meoded, Avner; Morrissette, Arthur E; Katipally, Rohan; Schanz, Olivia; Gotts, Stephen J; Floeter, Mary Kay

2015-01-01

Increased functional connectivity in resting state networks was found in several studies of patients with motor neuron disorders, although diffusion tensor imaging studies consistently show loss of white matter integrity. To understand the relationship between structural connectivity and functional connectivity, we examined the structural connections between regions with altered functional connectivity in patients with primary lateral sclerosis (PLS), a long-lived motor neuron disease. Connectivity matrices were constructed from resting state fMRI in 16 PLS patients to identify areas of differing connectivity between patients and healthy controls. Probabilistic fiber tracking was used to examine structural connections between regions of differing connectivity. PLS patients had 12 regions with increased functional connectivity compared to controls, with a predominance of cerebro-cerebellar connections. Increased functional connectivity was strongest between the cerebellum and cortical motor areas and between the cerebellum and frontal and temporal cortex. Fiber tracking detected no difference in connections between regions with increased functional connectivity. We conclude that functional connectivity changes are not strongly based in structural connectivity. Increased functional connectivity may be caused by common inputs, or by reduced selectivity of cortical activation, which could result from loss of intracortical inhibition when cortical afferents are intact.

Resting state fMRI: A review on methods in resting state connectivity analysis and resting state networks.

PubMed

Smitha, K A; Akhil Raja, K; Arun, K M; Rajesh, P G; Thomas, Bejoy; Kapilamoorthy, T R; Kesavadas, Chandrasekharan

2017-08-01

The inquisitiveness about what happens in the brain has been there since the beginning of humankind. Functional magnetic resonance imaging is a prominent tool which helps in the non-invasive examination, localisation as well as lateralisation of brain functions such as language, memory, etc. In recent years, there is an apparent shift in the focus of neuroscience research to studies dealing with a brain at 'resting state'. Here the spotlight is on the intrinsic activity within the brain, in the absence of any sensory or cognitive stimulus. The analyses of functional brain connectivity in the state of rest have revealed different resting state networks, which depict specific functions and varied spatial topology. However, different statistical methods have been introduced to study resting state functional magnetic resonance imaging connectivity, yet producing consistent results. In this article, we introduce the concept of resting state functional magnetic resonance imaging in detail, then discuss three most widely used methods for analysis, describe a few of the resting state networks featuring the brain regions, associated cognitive functions and clinical applications of resting state functional magnetic resonance imaging. This review aims to highlight the utility and importance of studying resting state functional magnetic resonance imaging connectivity, underlining its complementary nature to the task-based functional magnetic resonance imaging.

Causal effect of disconnection lesions on interhemispheric functional connectivity in rhesus monkeys

PubMed Central

O’Reilly, Jill X.; Croxson, Paula L.; Jbabdi, Saad; Sallet, Jerome; Noonan, MaryAnn P.; Mars, Rogier B.; Browning, Philip G.F.; Wilson, Charles R. E.; Mitchell, Anna S.; Miller, Karla L.; Rushworth, Matthew F. S.; Baxter, Mark G.

2013-01-01

In the absence of external stimuli or task demands, correlations in spontaneous brain activity (functional connectivity) reflect patterns of anatomical connectivity. Hence, resting-state functional connectivity has been used as a proxy measure for structural connectivity and as a biomarker for brain changes in disease. To relate changes in functional connectivity to physiological changes in the brain, it is important to understand how correlations in functional connectivity depend on the physical integrity of brain tissue. The causal nature of this relationship has been called into question by patient data suggesting that decreased structural connectivity does not necessarily lead to decreased functional connectivity. Here we provide evidence for a causal but complex relationship between structural connectivity and functional connectivity: we tested interhemispheric functional connectivity before and after corpus callosum section in rhesus monkeys. We found that forebrain commissurotomy severely reduced interhemispheric functional connectivity, but surprisingly, this effect was greatly mitigated if the anterior commissure was left intact. Furthermore, intact structural connections increased their functional connectivity in line with the hypothesis that the inputs to each node are normalized. We conclude that functional connectivity is likely driven by corticocortical white matter connections but with complex network interactions such that a near-normal pattern of functional connectivity can be maintained by just a few indirect structural connections. These surprising results highlight the importance of network-level interactions in functional connectivity and may cast light on various paradoxical findings concerning changes in functional connectivity in disease states. PMID:23924609

Effects of Methylphenidate on Resting-State Functional Connectivity of the Mesocorticolimbic Dopamine Pathways in Cocaine Addiction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Konova, Anna B.; Moeller, Scott J.; Tomasi, Dardo

Cocaine addiction is associated with altered resting-state functional connectivity among regions of the mesocorticolimbic dopamine pathways. Methylphenidate hydrochloride, an indirect dopamine agonist, normalizes task-related regional brain activity and associated behavior in cocaine users; however, the neural systems–level effects of methylphenidate in this population have not yet been described. To use resting-state functional magnetic resonance imaging to examine changes in mesocorticolimbic connectivity with methylphenidate and how connectivity of affected pathways relates to severity of cocaine addiction.

Insulin Resistance-Associated Interhemispheric Functional Connectivity Alterations in T2DM: A Resting-State fMRI Study

PubMed Central

Xia, Wenqing; Wang, Shaohua; Spaeth, Andrea M.; Rao, Hengyi; Wang, Pin; Yang, Yue; Huang, Rong; Cai, Rongrong; Sun, Haixia

2015-01-01

We aim to investigate whether decreased interhemispheric functional connectivity exists in patients with type 2 diabetes mellitus (T2DM) by using resting-state functional magnetic resonance imaging (rs-fMRI). In addition, we sought to determine whether interhemispheric functional connectivity deficits associated with cognition and insulin resistance (IR) among T2DM patients. We compared the interhemispheric resting state functional connectivity of 32 T2DM patients and 30 healthy controls using rs-fMRI. Partial correlation coefficients were used to detect the relationship between rs-fMRI information and cognitive or clinical data. Compared with healthy controls, T2DM patients showed bidirectional alteration of functional connectivity in several brain regions. Functional connectivity values in the middle temporal gyrus (MTG) and in the superior frontal gyrus were inversely correlated with Trail Making Test-B score of patients. Notably, insulin resistance (log homeostasis model assessment-IR) negatively correlated with functional connectivity in the MTG of patients. In conclusion, T2DM patients exhibit abnormal interhemispheric functional connectivity in several default mode network regions, particularly in the MTG, and such alteration is associated with IR. Alterations in interhemispheric functional connectivity might contribute to cognitive dysfunction in T2DM patients. PMID:26064945

Test-retest reliability of functional connectivity networks during naturalistic fMRI paradigms.

PubMed

Wang, Jiahui; Ren, Yudan; Hu, Xintao; Nguyen, Vinh Thai; Guo, Lei; Han, Junwei; Guo, Christine Cong

2017-04-01

Functional connectivity analysis has become a powerful tool for probing the human brain function and its breakdown in neuropsychiatry disorders. So far, most studies adopted resting-state paradigm to examine functional connectivity networks in the brain, thanks to its low demand and high tolerance that are essential for clinical studies. However, the test-retest reliability of resting-state connectivity measures is moderate, potentially due to its low behavioral constraint. On the other hand, naturalistic neuroimaging paradigms, an emerging approach for cognitive neuroscience with high ecological validity, could potentially improve the reliability of functional connectivity measures. To test this hypothesis, we characterized the test-retest reliability of functional connectivity measures during a natural viewing condition, and benchmarked it against resting-state connectivity measures acquired within the same functional magnetic resonance imaging (fMRI) session. We found that the reliability of connectivity and graph theoretical measures of brain networks is significantly improved during natural viewing conditions over resting-state conditions, with an average increase of almost 50% across various connectivity measures. Not only sensory networks for audio-visual processing become more reliable, higher order brain networks, such as default mode and attention networks, but also appear to show higher reliability during natural viewing. Our results support the use of natural viewing paradigms in estimating functional connectivity of brain networks, and have important implications for clinical application of fMRI. Hum Brain Mapp 38:2226-2241, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Multiple Resting-State Networks Are Associated With Tremors and Cognitive Features in Essential Tremor.

PubMed

Fang, Weidong; Chen, Huiyue; Wang, Hansheng; Zhang, Han; Liu, Mengqi; Puneet, Munankami; Lv, Fajin; Cheng, Oumei; Wang, Xuefeng; Lu, Xiurong; Luo, Tianyou

2015-12-01

The heterogeneous clinical features of essential tremor indicate that the dysfunctions of this syndrome are not confined to motor networks, but extend to nonmotor networks. Currently, these neural network dysfunctions in essential tremor remain unclear. In this study, independent component analysis of resting-state functional MRI was used to study these neural network mechanisms. Thirty-five essential tremor patients and 35 matched healthy controls with clinical and neuropsychological tests were included, and eight resting-state networks were identified. After considering the structure and head-motion factors and testing the reliability of the selected resting-state networks, we assessed the functional connectivity changes within or between resting-state networks. Finally, image-behavior correlation analysis was performed. Compared to healthy controls, essential tremor patients displayed increased functional connectivity in the sensorimotor and salience networks and decreased functional connectivity in the cerebellum network. Additionally, increased functional network connectivity was observed between anterior and posterior default mode networks, and a decreased functional network connectivity was noted between the cerebellum network and the sensorimotor and posterior default mode networks. Importantly, the functional connectivity changes within and between these resting-state networks were correlated with the tremor severity and total cognitive scores of essential tremor patients. The findings of this study provide the first evidence that functional connectivity changes within and between multiple resting-state networks are associated with tremors and cognitive features of essential tremor, and this work demonstrates a potential approach for identifying the underlying neural network mechanisms of this syndrome. © 2015 International Parkinson and Movement Disorder Society.

Neonatal brain resting-state functional connectivity imaging modalities.

PubMed

Mohammadi-Nejad, Ali-Reza; Mahmoudzadeh, Mahdi; Hassanpour, Mahlegha S; Wallois, Fabrice; Muzik, Otto; Papadelis, Christos; Hansen, Anne; Soltanian-Zadeh, Hamid; Gelovani, Juri; Nasiriavanaki, Mohammadreza

2018-06-01

Infancy is the most critical period in human brain development. Studies demonstrate that subtle brain abnormalities during this state of life may greatly affect the developmental processes of the newborn infants. One of the rapidly developing methods for early characterization of abnormal brain development is functional connectivity of the brain at rest. While the majority of resting-state studies have been conducted using magnetic resonance imaging (MRI), there is clear evidence that resting-state functional connectivity (rs-FC) can also be evaluated using other imaging modalities. The aim of this review is to compare the advantages and limitations of different modalities used for the mapping of infants' brain functional connectivity at rest. In addition, we introduce photoacoustic tomography, a novel functional neuroimaging modality, as a complementary modality for functional mapping of infants' brain.

Altered Whole-Brain and Network-Based Functional Connectivity in Parkinson's Disease.

PubMed

de Schipper, Laura J; Hafkemeijer, Anne; van der Grond, Jeroen; Marinus, Johan; Henselmans, Johanna M L; van Hilten, Jacobus J

2018-01-01

Background: Functional imaging methods, such as resting-state functional magnetic resonance imaging, reflect changes in neural connectivity and may help to assess the widespread consequences of disease-specific network changes in Parkinson's disease. In this study we used a relatively new graph analysis approach in functional imaging: eigenvector centrality mapping. This model-free method, applied to all voxels in the brain, identifies prominent regions in the brain network hierarchy and detects localized differences between patient populations. In other neurological disorders, eigenvector centrality mapping has been linked to changes in functional connectivity in certain nodes of brain networks. Objectives: Examining changes in functional brain connectivity architecture on a whole brain and network level in patients with Parkinson's disease. Methods: Whole brain resting-state functional architecture was studied with a recently introduced graph analysis approach (eigenvector centrality mapping). Functional connectivity was further investigated in relation to eight known resting-state networks. Cross-sectional analyses included group comparison of functional connectivity measures of Parkinson's disease patients ( n = 107) with control subjects ( n = 58) and correlations with clinical data, including motor and cognitive impairment and a composite measure of predominantly non-dopaminergic symptoms. Results: Eigenvector centrality mapping revealed that frontoparietal regions were more prominent in the whole-brain network function in patients compared to control subjects, while frontal and occipital brain areas were less prominent in patients. Using standard resting-state networks, we found predominantly increased functional connectivity, namely within sensorimotor system and visual networks in patients. Regional group differences in functional connectivity of both techniques between patients and control subjects partly overlapped for highly connected posterior brain regions, in particular in the posterior cingulate cortex and precuneus. Clinico-functional imaging relations were not found. Conclusions: Changes on the level of functional brain connectivity architecture might provide a different perspective of pathological consequences of Parkinson's disease. The involvement of specific, highly connected (hub) brain regions may influence whole brain functional network architecture in Parkinson's disease.

Clinical symptoms and alpha band resting-state functional connectivity imaging in patients with schizophrenia: implications for novel approaches to treatment

PubMed Central

Hinkley, Leighton B.N.; Vinogradov, Sophia; Guggisberg, Adrian G.; Fisher, Melissa; Findlay, Anne M.; Nagarajan, Srikantan S.

2011-01-01

Background Schizophrenia is associated with functional decoupling between cortical regions, but we do not know whether and where this occurs in low-frequency electromagnetic oscillations. The goal of this study was to use magnetoencephalography (MEG) to identify brain regions that exhibit abnormal resting-state connectivity in the alpha frequency range in patients with schizophrenia and investigate associations between functional connectivity and clinical symptoms in stable outpatient participants. Method Thirty patients with schizophrenia and fifteen healthy comparison participants were scanned in resting-state MEG (eyes closed). Functional connectivity MEGI (fcMEGI) data were reconstructed globally in the alpha range, quantified by the mean imaginary coherence between a voxel and the rest of the brain. Results In patients, decreased connectivity was observed in left pre-frontal cortex (PFC) and right superior temporal cortex while increased connectivity was observed in left extrastriate cortex and the right inferior PFC. Functional connectivity of left inferior parietal cortex was negatively related to positive symptoms. Low left PFC connectivity was associated with negative symptoms. Functional connectivity of midline PFC was negatively correlated with depressed symptoms. Functional connectivity of right PFC was associated with other (cognitive) symptoms. Conclusions This study demonstrates direct functional disconnection in schizophrenia between specific cortical fields within low-frequency resting-state oscillations. Impaired alpha coupling in frontal, parietal, and temporal regions is associated with clinical symptoms in these stable outpatients. Our findings indicate that this level of functional disconnection between cortical regions is an important treatment target in schizophrenia. PMID:21861988

Modulation of steady state functional connectivity in the default mode and working memory networks by cognitive load.

PubMed

Newton, Allen T; Morgan, Victoria L; Rogers, Baxter P; Gore, John C

2011-10-01

Interregional correlations between blood oxygen level dependent (BOLD) magnetic resonance imaging (fMRI) signals in the resting state have been interpreted as measures of connectivity across the brain. Here we investigate whether such connectivity in the working memory and default mode networks is modulated by changes in cognitive load. Functional connectivity was measured in a steady-state verbal identity N-back task for three different conditions (N = 1, 2, and 3) as well as in the resting state. We found that as cognitive load increases, the functional connectivity within both the working memory the default mode network increases. To test whether functional connectivity between the working memory and the default mode networks changed, we constructed maps of functional connectivity to the working memory network as a whole and found that increasingly negative correlations emerged in a dorsal region of the posterior cingulate cortex. These results provide further evidence that low frequency fluctuations in BOLD signals reflect variations in neural activity and suggests interaction between the default mode network and other cognitive networks. Copyright © 2010 Wiley-Liss, Inc.

Functional Connectivity and Quantitative EEG in Women with Alcohol Use Disorders: A Resting-State Study.

PubMed

Herrera-Díaz, Adianes; Mendoza-Quiñones, Raúl; Melie-Garcia, Lester; Martínez-Montes, Eduardo; Sanabria-Diaz, Gretel; Romero-Quintana, Yuniel; Salazar-Guerra, Iraklys; Carballoso-Acosta, Mario; Caballero-Moreno, Antonio

2016-05-01

This study was aimed at exploring the electroencephalographic features associated with alcohol use disorders (AUD) during a resting-state condition, by using quantitative EEG and Functional Connectivity analyses. In addition, we explored whether EEG functional connectivity is associated with trait impulsivity. Absolute and relative powers and Synchronization Likelihood (SL) as a measure of functional connectivity were analyzed in 15 AUD women and fifteen controls matched in age, gender and education. Correlation analysis between self-report impulsivity as measured by the Barratt impulsiveness Scale (BIS-11) and SL values of AUD patients were performed. Our results showed increased absolute and relative beta power in AUD patients compared to matched controls, and reduced functional connectivity in AUD patients predominantly in the beta and alpha bands. Impaired connectivity was distributed at fronto-central and occipito-parietal regions in the alpha band, and over the entire scalp in the beta band. We also found that impaired functional connectivity particularly in alpha band at fronto-central areas was negative correlated with non-planning dimension of impulsivity. These findings suggest that functional brain abnormalities are present in AUD patients and a disruption of resting-state EEG functional connectivity is associated with psychopathological traits of addictive behavior.

Experimentally induced thyrotoxicosis leads to increased connectivity in temporal lobe structures: a resting state fMRI study.

PubMed

Göttlich, Martin; Heldmann, Marcus; Göbel, Anna; Dirk, Anna-Luise; Brabant, Georg; Münte, Thomas F

2015-06-01

Adult onset hyperthyroidism may impact on different cognitive domains, including attention and concentration, memory, perceptual function, language and executive function. Previous PET studies implicated changed functionality of limbic regions, the temporal and frontal lobes in hyperthyroidism, whereas it is unknown whether cognitive effects of hyperthyroidism may be due to changed brain connectivity. This study aimed to investigate the effect of experimentally induced short-term hyperthyroidism thyrotoxicosis on resting-state functional connectivity using functional magnetic resonance imaging. Twenty-nine healthy male right-handed subjects were examined twice, once prior and once after 8 weeks of oral administration of 250 μg levothyroxine per day. Resting-state fMRI was subjected to graph-theory based analysis methods to investigate whole-brain intrinsic functional connectivity. Despite a lack of subjective changes noticed by the subjects significant thyrotoxicosis was confirmed in all subjects. This induced a significant increase in resting-state functional connectivity specifically in the rostral temporal lobes (0.05 FDR corrected at the cluster level), which is caused by an increased connectivity to the cognitive control network. The increased connectivity between temporal poles and the cognitive control network shown here under experimental conditions supports an important function of thyroid hormones in the regulation of paralimbic structures. Copyright © 2015 Elsevier Ltd. All rights reserved.

Functional connectivity analysis of resting-state fMRI networks in nicotine dependent patients

NASA Astrophysics Data System (ADS)

Smith, Aria; Ehtemami, Anahid; Fratte, Daniel; Meyer-Baese, Anke; Zavala-Romero, Olmo; Goudriaan, Anna E.; Schmaal, Lianne; Schulte, Mieke H. J.

2016-03-01

Brain imaging studies identified brain networks that play a key role in nicotine dependence-related behavior. Functional connectivity of the brain is dynamic; it changes over time due to different causes such as learning, or quitting a habit. Functional connectivity analysis is useful in discovering and comparing patterns between functional magnetic resonance imaging (fMRI) scans of patients' brains. In the resting state, the patient is asked to remain calm and not do any task to minimize the contribution of external stimuli. The study of resting-state fMRI networks have shown functionally connected brain regions that have a high level of activity during this state. In this project, we are interested in the relationship between these functionally connected brain regions to identify nicotine dependent patients, who underwent a smoking cessation treatment. Our approach is on the comparison of the set of connections between the fMRI scans before and after treatment. We applied support vector machines, a machine learning technique, to classify patients based on receiving the treatment or the placebo. Using the functional connectivity (CONN) toolbox, we were able to form a correlation matrix based on the functional connectivity between different regions of the brain. The experimental results show that there is inadequate predictive information to classify nicotine dependent patients using the SVM classifier. We propose other classification methods be explored to better classify the nicotine dependent patients.

Anxiety Modulates Insula Recruitment in Resting-State Functional Magnetic Resonance Imaging in Youth and Adults

PubMed Central

Gotlib, Ian H.; Thompson, Paul M.; Thomason, Moriah E.

2011-01-01

Abstract Research on resting-state functional connectivity reveals intrinsically connected networks in the brain that are largely consistent across the general population. However, there are individual differences in these networks that have not been elucidated. Here, we measured the influence of naturally occurring mood on functional connectivity. In particular, we examined the association between self-reported levels of anxiety and connectivity in the default mode network (DMN). Healthy youth (n=43; ages 10–18) and adult participants (n=24, ages 19–59) completed a 6-min resting-state functional magnetic resonance imaging scan, then immediately completed questionnaires assessing their mood and thoughts during the scan. Regression analyses conducted separately for the youth and adult samples revealed brain regions in which increases in connectivity differentially corresponded to higher anxiety in each group. In one area, the left insular cortex, both groups showed similar increased connectivity to the DMN (youth: -30, 26, 14; adults: -33, 12, 14) with increased anxiety. State anxiety assessed during scanning was not correlated with trait anxiety, so our results likely reflect state levels of anxiety. To our knowledge, this is the first study to relate naturally occurring mood to resting state connectivity. PMID:22433052

Altered resting-state functional connectivity in women with chronic fatigue syndrome.

PubMed

Kim, Byung-Hoon; Namkoong, Kee; Kim, Jae-Jin; Lee, Seojung; Yoon, Kang Joon; Choi, Moonjong; Jung, Young-Chul

2015-12-30

The biological underpinnings of the psychological factors characterizing chronic fatigue syndrome (CFS) have not been extensively studied. Our aim was to evaluate alterations of resting-state functional connectivity in CFS patients. Participants comprised 18 women with CFS and 18 age-matched female healthy controls who were recruited from the local community. Structural and functional magnetic resonance images were acquired during a 6-min passive-viewing block scan. Posterior cingulate cortex seeded resting-state functional connectivity was evaluated, and correlation analyses of connectivity strength were performed. Graph theory analysis of 90 nodes of the brain was conducted to compare the global and local efficiency of connectivity networks in CFS patients with that in healthy controls. The posterior cingulate cortex in CFS patients showed increased resting-state functional connectivity with the dorsal and rostral anterior cingulate cortex. Connectivity strength of the posterior cingulate cortex to the dorsal anterior cingulate cortex significantly correlated with the Chalder Fatigue Scale score, while the Beck Depression Inventory (BDI) score was controlled. Connectivity strength to the rostral anterior cingulate cortex significantly correlated with the Chalder Fatigue Scale score. Global efficiency of the posterior cingulate cortex was significantly lower in CFS patients, while local efficiency showed no difference from findings in healthy controls. The findings suggest that CFS patients show inefficient increments in resting-state functional connectivity that are linked to the psychological factors observed in the syndrome. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

A method for functional network connectivity among spatially independent resting-state components in schizophrenia.

PubMed

Jafri, Madiha J; Pearlson, Godfrey D; Stevens, Michael; Calhoun, Vince D

2008-02-15

Functional connectivity of the brain has been studied by analyzing correlation differences in time courses among seed voxels or regions with other voxels of the brain in healthy individuals as well as in patients with brain disorders. The spatial extent of strongly temporally coherent brain regions co-activated during rest has also been examined using independent component analysis (ICA). However, the weaker temporal relationships among ICA component time courses, which we operationally define as a measure of functional network connectivity (FNC), have not yet been studied. In this study, we propose an approach for evaluating FNC and apply it to functional magnetic resonance imaging (fMRI) data collected from persons with schizophrenia and healthy controls. We examined the connectivity and latency among ICA component time courses to test the hypothesis that patients with schizophrenia would show increased functional connectivity and increased lag among resting state networks compared to controls. Resting state fMRI data were collected and the inter-relationships among seven selected resting state networks (identified using group ICA) were evaluated by correlating each subject's ICA time courses with one another. Patients showed higher correlation than controls among most of the dominant resting state networks. Patients also had slightly more variability in functional connectivity than controls. We present a novel approach for quantifying functional connectivity among brain networks identified with spatial ICA. Significant differences between patient and control connectivity in different networks were revealed possibly reflecting deficiencies in cortical processing in patients.

A Method for Functional Network Connectivity Among Spatially Independent Resting-State Components in Schizophrenia

PubMed Central

Jafri, Madiha J; Pearlson, Godfrey D; Stevens, Michael; Calhoun, Vince D

2011-01-01

Functional connectivity of the brain has been studied by analyzing correlation differences in time courses among seed voxels or regions with other voxels of the brain in patients versus controls. The spatial extent of strongly temporally coherent brain regions co-activated during rest has also been examined using independent component analysis (ICA). However, the weaker temporal relationships among ICA component time courses, which we operationally define as a measure of functional network connectivity (FNC), have not yet been studied. In this study, we propose an approach for evaluating FNC and apply it to functional magnetic resonance imaging (fMRI) data collected from persons with schizophrenia and healthy controls. We examined the connectivity and latency among ICA component time courses to test the hypothesis that patients with schizophrenia would show increased functional connectivity and increased lag among resting state networks compared to controls. Resting state fMRI data were collected and the inter-relationships among seven selected resting state networks (identified using group ICA) were evaluated by correlating each subject’s ICA time courses with one another. Patients showed higher correlation than controls among most of the dominant resting state networks. Patients also had slightly more variability in functional connectivity than controls. We present a novel approach for quantifying functional connectivity among brain networks identified with spatial ICA. Significant differences between patient and control connectivity in different networks were revealed possibly reflecting deficiencies in cortical processing in patients. PMID:18082428

The relation between resting state connectivity and creativity in adolescents before and after training.

PubMed

Cousijn, Janna; Zanolie, Kiki; Munsters, Robbert J M; Kleibeuker, Sietske W; Crone, Eveline A

2014-01-01

An important component of creativity is divergent thinking, which involves the ability to generate novel and useful problem solutions. In this study, we tested the relation between resting-state functional connectivity of brain areas activated during a divergent thinking task (i.e., supramarginal gyrus, middle temporal gyrus, medial frontal gyrus) and the effect of practice in 32 adolescents aged 15-16. Over a period of two weeks, an experimental group (n = 16) conducted an 8-session Alternative Uses Task (AUT) training and an active control group (n = 16) conducted an 8-session rule switching training. Resting-state functional connectivity was measured before (pre-test) and after (post-test) training. Across groups at pre-test, stronger connectivity between the middle temporal gyrus and bilateral postcentral gyrus was associated with better divergent thinking performance. The AUT-training, however, did not significantly change functional connectivity. Post hoc analyses showed that change in divergent thinking performance over time was predicted by connectivity between left supramarginal gyrus and right occipital cortex. These results provide evidence for a relation between divergent thinking and resting-state functional connectivity in a task-positive network, taking an important step towards understanding creative cognition and functional brain connectivity.

Whole brain resting-state analysis reveals decreased functional connectivity in major depression.

PubMed

Veer, Ilya M; Beckmann, Christian F; van Tol, Marie-José; Ferrarini, Luca; Milles, Julien; Veltman, Dick J; Aleman, André; van Buchem, Mark A; van der Wee, Nic J; Rombouts, Serge A R B

2010-01-01

Recently, both increases and decreases in resting-state functional connectivity have been found in major depression. However, these studies only assessed functional connectivity within a specific network or between a few regions of interest, while comorbidity and use of medication was not always controlled for. Therefore, the aim of the current study was to investigate whole-brain functional connectivity, unbiased by a priori definition of regions or networks of interest, in medication-free depressive patients without comorbidity. We analyzed resting-state fMRI data of 19 medication-free patients with a recent diagnosis of major depression (within 6 months before inclusion) and no comorbidity, and 19 age- and gender-matched controls. Independent component analysis was employed on the concatenated data sets of all participants. Thirteen functionally relevant networks were identified, describing the entire study sample. Next, individual representations of the networks were created using a dual regression method. Statistical inference was subsequently done on these spatial maps using voxel-wise permutation tests. Abnormal functional connectivity was found within three resting-state networks in depression: (1) decreased bilateral amygdala and left anterior insula connectivity in an affective network, (2) reduced connectivity of the left frontal pole in a network associated with attention and working memory, and (3) decreased bilateral lingual gyrus connectivity within ventromedial visual regions. None of these effects were associated with symptom severity or gray matter density. We found abnormal resting-state functional connectivity not previously associated with major depression, which might relate to abnormal affect regulation and mild cognitive deficits, both associated with the symptomatology of the disorder.

Whole Brain Resting-State Analysis Reveals Decreased Functional Connectivity in Major Depression

PubMed Central

Veer, Ilya M.; Beckmann, Christian F.; van Tol, Marie-José; Ferrarini, Luca; Milles, Julien; Veltman, Dick J.; Aleman, André; van Buchem, Mark A.; van der Wee, Nic J.; Rombouts, Serge A.R.B.

2010-01-01

Recently, both increases and decreases in resting-state functional connectivity have been found in major depression. However, these studies only assessed functional connectivity within a specific network or between a few regions of interest, while comorbidity and use of medication was not always controlled for. Therefore, the aim of the current study was to investigate whole-brain functional connectivity, unbiased by a priori definition of regions or networks of interest, in medication-free depressive patients without comorbidity. We analyzed resting-state fMRI data of 19 medication-free patients with a recent diagnosis of major depression (within 6 months before inclusion) and no comorbidity, and 19 age- and gender-matched controls. Independent component analysis was employed on the concatenated data sets of all participants. Thirteen functionally relevant networks were identified, describing the entire study sample. Next, individual representations of the networks were created using a dual regression method. Statistical inference was subsequently done on these spatial maps using voxel-wise permutation tests. Abnormal functional connectivity was found within three resting-state networks in depression: (1) decreased bilateral amygdala and left anterior insula connectivity in an affective network, (2) reduced connectivity of the left frontal pole in a network associated with attention and working memory, and (3) decreased bilateral lingual gyrus connectivity within ventromedial visual regions. None of these effects were associated with symptom severity or gray matter density. We found abnormal resting-state functional connectivity not previously associated with major depression, which might relate to abnormal affect regulation and mild cognitive deficits, both associated with the symptomatology of the disorder. PMID:20941370

Functional connectivity changes in adults with developmental stuttering: a preliminary study using quantitative electro-encephalography

PubMed Central

Joos, Kathleen; De Ridder, Dirk; Boey, Ronny A.; Vanneste, Sven

2014-01-01

Introduction: Stuttering is defined as speech characterized by verbal dysfluencies, but should not be seen as an isolated speech disorder, but as a generalized sensorimotor timing deficit due to impaired communication between speech related brain areas. Therefore we focused on resting state brain activity and functional connectivity. Method: We included 11 patients with developmental stuttering and 11 age matched controls. To objectify stuttering severity and the impact on quality of life (QoL), we used the Dutch validated Test for Stuttering Severity-Readers (TSS-R) and the Overall Assessment of the Speaker’s Experience of Stuttering (OASES), respectively. Furthermore, we used standardized low resolution brain electromagnetic tomography (sLORETA) analyses to look at resting state activity and functional connectivity differences and their correlations with the TSS-R and OASES. Results: No significant results could be obtained when looking at neural activity, however significant alterations in resting state functional connectivity could be demonstrated between persons who stutter (PWS) and fluently speaking controls, predominantly interhemispheric, i.e., a decreased functional connectivity for high frequency oscillations (beta and gamma) between motor speech areas (BA44 and 45) and the contralateral premotor (BA6) and motor (BA4) areas. Moreover, a positive correlation was found between functional connectivity at low frequency oscillations (theta and alpha) and stuttering severity, while a mixed increased and decreased functional connectivity at low and high frequency oscillations correlated with QoL. Discussion: PWS are characterized by decreased high frequency interhemispheric functional connectivity between motor speech, premotor and motor areas in the resting state, while higher functional connectivity in the low frequency bands indicates more severe speech disturbances, suggesting that increased interhemispheric and right sided functional connectivity is maladaptive. PMID:25352797

Distinctive Resting State Network Disruptions Among Alzheimer's Disease, Subcortical Vascular Dementia, and Mixed Dementia Patients.

PubMed

Kim, Hee Jin; Cha, Jungho; Lee, Jong-Min; Shin, Ji Soo; Jung, Na-Yeon; Kim, Yeo Jin; Choe, Yearn Seong; Lee, Kyung Han; Kim, Sung Tae; Kim, Jae Seung; Lee, Jae Hong; Na, Duk L; Seo, Sang Won

2016-01-01

Recent advances in resting-state functional MRI have revealed altered functional networks in Alzheimer's disease (AD), especially those of the default mode network (DMN) and central executive network (CEN). However, few studies have evaluated whether small vessel disease (SVD) or combined amyloid and SVD burdens affect the DMN or CEN. The aim of this study was to evaluate whether SVD or combined amyloid and SVD burdens affect the DMN or CEN. In this cross-sectional study, we investigated the resting-state functional connectivity within DMN and CEN in 37 Pittsburgh compound-B (PiB)(+) AD, 37 PiB(-) subcortical vascular dementia (SVaD), 13 mixed dementia patients, and 65 normal controls. When the resting-state DMN of PiB(+) AD and PiB(-) SVaD patients were compared, the PiB(+) AD patients displayed lower functional connectivity in the inferior parietal lobule while the PiB(-) SVaD patients displayed lower functional connectivity in the medial frontal and superior frontal gyri. Compared to the PiB(-) SVaD or PiB(+) AD, the mixed dementia patients displayed lower functional connectivity within the DMN in the posterior cingulate gyrus. When the resting-state CEN connectivity of PiB(+) AD and PiB(-) SVaD patients were compared, the PiB(-) SVaD patients displayed lower functional connectivity in the anterior insular region. Compared to the PiB(-) SVaD or PiB(+) AD, the mixed dementia patients displayed lower functional connectivity within the CEN in the inferior frontal gyrus. Our findings suggest that in PiB(+) AD and PiB(-) SVaD, there is divergent disruptions in resting-state DMN and CEN. Furthermore, patients with combined amyloid and SVD burdens exhibited more disrupted resting-state DMN and CEN than patients with only amyloid or SVD burden.

Functional Connectivity in Frontoparietal Network: Indicator of Preoperative Cognitive Function and Cognitive Outcome Following Surgery in Patients with Glioma.

PubMed

Lang, Stefan; Gaxiola-Valdez, Ismael; Opoku-Darko, Michael; Partlo, Lisa A; Goodyear, Bradley G; Kelly, John J P; Federico, Paolo

2017-09-01

Patients with diffuse glioma are known to have impaired cognitive functions preoperatively. However, the mechanism of these cognitive deficits remains unclear. Resting-state functional connectivity in the frontoparietal network (FPN) is associated with cognitive performance in healthy subjects. For this reason, it was hypothesized that functional connectivity of the FPN would be related to cognitive functioning in patients with glioma. To assess this relationship, preoperative cognitive status was correlated to patient-specific connectivity within the FPN. Further, we assessed whether connectivity could predict neuropsychologic outcome following surgery. Sixteen patients with diffuse glioma underwent neuropsychologic assessment and preoperative functional magnetic resonance imaging using task (n-back) and resting-state scans. Thirteen patients had postoperative cognitive assessment. An index of patient-specific functional connectivity in the FPN was derived by averaging connectivity values between 2 prefrontal and 2 parietal cortex regions defined by activation during the n-back task. The relationship of these indices with cognitive performance was assessed. Higher average connectivity within the FPN is associated with lower composite cognitive scores. Higher connectivity of the parietal region of the tumor-affected hemisphere is associated specifically with lower fluid cognition. Lower connectivity of the parietal region of the nontumor hemisphere is associated with worse neuropsychologic outcome 1 month after surgery. Resting-state functional connectivity between key regions of the FPN is associated with cognitive performance in patients with glioma and is related to cognitive outcome following surgery. Copyright © 2017 Elsevier Inc. All rights reserved.

Is Rest Really Rest? Resting State Functional Connectivity during Rest and Motor Task Paradigms.

PubMed

Jurkiewicz, Michael T; Crawley, Adrian P; Mikulis, David J

2018-04-18

Numerous studies have identified the default mode network (DMN) within the brain of healthy individuals, which has been attributed to the ongoing mental activity of the brain during the wakeful resting-state. While engaged during specific resting-state fMRI paradigms, it remains unclear as to whether traditional block-design simple movement fMRI experiments significantly influence the default mode network or other areas. Using blood-oxygen level dependent (BOLD) fMRI we characterized the pattern of functional connectivity in healthy subjects during a resting-state paradigm and compared this to the same resting-state analysis performed on motor task data residual time courses after regressing out the task paradigm. Using seed-voxel analysis to define the DMN, the executive control network (ECN), and sensorimotor, auditory and visual networks, the resting-state analysis of the residual time courses demonstrated reduced functional connectivity in the motor network and reduced connectivity between the insula and the ECN compared to the standard resting-state datasets. Overall, performance of simple self-directed motor tasks does little to change the resting-state functional connectivity across the brain, especially in non-motor areas. This would suggest that previously acquired fMRI studies incorporating simple block-design motor tasks could be mined retrospectively for assessment of the resting-state connectivity.

Intrinsic Resting-State Functional Connectivity in the Human Spinal Cord at 3.0 T.

PubMed

San Emeterio Nateras, Oscar; Yu, Fang; Muir, Eric R; Bazan, Carlos; Franklin, Crystal G; Li, Wei; Li, Jinqi; Lancaster, Jack L; Duong, Timothy Q

2016-04-01

To apply resting-state functional magnetic resonance (MR) imaging to map functional connectivity of the human spinal cord. Studies were performed in nine self-declared healthy volunteers with informed consent and institutional review board approval. Resting-state functional MR imaging was performed to map functional connectivity of the human cervical spinal cord from C1 to C4 at 1 × 1 × 3-mm resolution with a 3.0-T clinical MR imaging unit. Independent component analysis (ICA) was performed to derive resting-state functional MR imaging z-score maps rendered on two-dimensional and three-dimensional images. Seed-based analysis was performed for cross validation with ICA networks by using Pearson correlation. Reproducibility analysis of resting-state functional MR imaging maps from four repeated trials in a single participant yielded a mean z score of 6 ± 1 (P < .0001). The centroid coordinates across the four trials deviated by 2 in-plane voxels ± 2 mm (standard deviation) and up to one adjacent image section ± 3 mm. ICA of group resting-state functional MR imaging data revealed prominent functional connectivity patterns within the spinal cord gray matter. There were statistically significant (z score > 3, P < .001) bilateral, unilateral, and intersegmental correlations in the ventral horns, dorsal horns, and central spinal cord gray matter. Three-dimensional surface rendering provided visualization of these components along the length of the spinal cord. Seed-based analysis showed that many ICA components exhibited strong and significant (P < .05) correlations, corroborating the ICA results. Resting-state functional MR imaging connectivity networks are qualitatively consistent with known neuroanatomic and functional structures in the spinal cord. Resting-state functional MR imaging of the human cervical spinal cord with a 3.0-T clinical MR imaging unit and standard MR imaging protocols and hardware reveals prominent functional connectivity patterns within the spinal cord gray matter, consistent with known functional and anatomic layouts of the spinal cord.

A METHOD FOR USING BLOCKED AND EVENT-RELATED FMRI DATA TO STUDY “RESTING STATE” FUNCTIONAL CONNECTIVITY

PubMed Central

Fair, Damien A.; Schlaggar, Bradley L.; Cohen B.A., Alexander L.; Miezin, Francis M.; Dosenbach, Nico U.F.; Wenger, Kristin K.; Fox, Michael D.; Snyder, Abraham Z.; Raichle, Marcus E.; Petersen, Steven E.

2007-01-01

Resting state functional connectivity MRI (fcMRI) has become a particularly useful tool for studying regional relationships in typical and atypical populations. Because many investigators have already obtained large datasets of task related fMRI, the ability to use this existing task data for resting state fcMRI is of considerable interest. Two classes of datasets could potentially be modified to emulate resting state data. These datasets include: 1) “interleaved” resting blocks from blocked or mixed blocked/event-related sets, and 2) residual timecourses from event-related sets that lack rest blocks. Using correlation analysis, we compared the functional connectivity of resting epochs taken from a mixed blocked/event-related design fMRI data set and the residuals derived from event-related data with standard continuous resting state data to determine which class of data can best emulate resting state data. We show that despite some differences, the functional connectivity for the interleaved resting periods taken from blocked designs is both qualitatively and quantitatively very similar to that of “continuous” resting state data. In contrast, despite being qualitatively similar to “continuous” resting state data, residuals derived from event-related design data had several distinct quantitative differences. These results suggest that the interleaved resting state data such as those taken from blocked or mixed blocked/event-related fMRI designs are well-suited for resting state functional connectivity analyses. Although using event-related data residuals for resting state functional connectivity may still be useful, results should be interpreted with care. PMID:17239622

Differential Resting-State Functional Connectivity of Striatal Subregions in Bipolar Depression and Hypomania

PubMed Central

Altinay, Murat I.; Hulvershorn, Leslie A.; Karne, Harish; Beall, Erik B.

2016-01-01

Abstract Bipolar disorder (BP) is characterized by periods of depression (BPD) and (hypo)mania (BPM), but the underlying state-related brain circuit abnormalities are not fully understood. Striatal functional activation and connectivity abnormalities have been noted in BP, but consistent findings have not been reported. To further elucidate striatal abnormalities in different BP states, this study investigated differences in resting-state functional connectivity of six striatal subregions in BPD, BPM, and healthy control (HC) subjects. Ninety medication-free subjects (30 BPD, 30 BPM, and 30 HC), closely matched for age and gender, were scanned using 3T functional magnetic resonance imaging (fMRI) acquired at resting state. Correlations of low-frequency blood oxygen level dependent signal fluctuations for six previously described striatal subregions were used to obtain connectivity maps of each subregion. Using a factorial design, main effects for differences between groups were obtained and post hoc pairwise group comparisons performed. BPD showed increased connectivity of the dorsal caudal putamen with somatosensory areas such as the insula and temporal gyrus. BPM group showed unique increased connectivity between left dorsal caudate and midbrain regions, as well as increased connectivity between ventral striatum inferior and thalamus. In addition, both BPD and BPM exhibited widespread functional connectivity abnormalities between striatal subregions and frontal cortices, limbic regions, and midbrain structures. In summary, BPD exhibited connectivity abnormalities of associative and somatosensory subregions of the putamen, while BPM exhibited connectivity abnormalities of associative and limbic caudate. Most other striatal subregion connectivity abnormalities were common to both groups and may be trait related. PMID:26824737

Structural Brain Connectivity Constrains within-a-Day Variability of Direct Functional Connectivity

PubMed Central

Park, Bumhee; Eo, Jinseok; Park, Hae-Jeong

2017-01-01

The idea that structural white matter connectivity constrains functional connectivity (interactions among brain regions) has widely been explored in studies of brain networks; studies have mostly focused on the “average” strength of functional connectivity. The question of how structural connectivity constrains the “variability” of functional connectivity remains unresolved. In this study, we investigated the variability of resting state functional connectivity that was acquired every 3 h within a single day from 12 participants (eight time sessions within a 24-h period, 165 scans per session). Three different types of functional connectivity (functional connectivity based on Pearson correlation, direct functional connectivity based on partial correlation, and the pseudo functional connectivity produced by their difference) were estimated from resting state functional magnetic resonance imaging data along with structural connectivity defined using fiber tractography of diffusion tensor imaging. Those types of functional connectivity were evaluated with regard to properties of structural connectivity (fiber streamline counts and lengths) and types of structural connectivity such as intra-/inter-hemispheric edges and topological edge types in the rich club organization. We observed that the structural connectivity constrained the variability of direct functional connectivity more than pseudo-functional connectivity and that the constraints depended strongly on structural connectivity types. The structural constraints were greater for intra-hemispheric and heterologous inter-hemispheric edges than homologous inter-hemispheric edges, and feeder and local edges than rich club edges in the rich club architecture. While each edge was highly variable, the multivariate patterns of edge involvement, especially the direct functional connectivity patterns among the rich club brain regions, showed low variability over time. This study suggests that structural connectivity not only constrains the strength of functional connectivity, but also the within-a-day variability of functional connectivity and connectivity patterns, particularly the direct functional connectivity among brain regions. PMID:28848416

Association of Hippocampal Substructure Resting-State Functional Connectivity with Memory Performance in Older Adults.

PubMed

Smagula, Stephen F; Karim, Helmet T; Rangarajan, Anusha; Santos, Fernando Pasquini; Wood, Sossena C; Santini, Tales; Jakicic, John M; Reynolds, Charles F; Cameron, Judy L; Vallejo, Abbe N; Butters, Meryl A; Rosano, Caterina; Ibrahim, Tamer S; Erickson, Kirk I; Aizenstein, Howard J

2018-06-01

Hippocampal hyperactivation marks preclinical dementia pathophysiology, potentially due to differences in the connectivity of specific medial temporal lobe structures. Our aims were to characterize the resting-state functional connectivity of medial temporal lobe sub-structures in older adults, and evaluate whether specific substructural (rather than global) functional connectivity relates to memory function. In 15 adults (mean age: 69 years), we evaluated the resting state functional connectivity of medial temporal lobe substructures: dentate/Cornu Ammonis (CA) 4, CA1, CA2/3, subiculum, the molecular layer, entorhinal cortex, and parahippocampus. We used 7-Tesla susceptibility weighted imaging and magnetization-prepared rapid gradient echo sequences to segment substructures of the hippocampus, which were used as structural seeds for examining functional connectivity in a resting BOLD sequence. We then assessed correlations between functional connectivity with memory performance (short and long delay free recall on the California Verbal Learning Test [CVLT]). All the seed regions had significant connectivity within the temporal lobe (including the fusiform, temporal, and lingual gyri). The left CA1 was the only seed with significant functional connectivity to the amygdala. The left entorhinal cortex was the only seed to have significant functional connectivity with frontal cortex (anterior cingulate and superior frontal gyrus). Only higher left dentate-left lingual connectivity was associated with poorer CVLT performance (Spearman r = -0.81, p = 0.0003, Benjamini-Hochberg false discovery rate: 0.01) after multiple comparison correction. Rather than global hyper-connectivity of the medial temporal lobe, left dentate-lingual connectivity may provide a specific assay of medial temporal lobe hyper-connectivity relevant to memory in aging. Copyright © 2018 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Decreased functional connectivity in an executive control network is related to impaired executive function in Internet gaming disorder.

PubMed

Dong, Guangheng; Lin, Xiao; Potenza, Marc N

2015-03-03

Resting brain spontaneous neural activities across cortical regions have been correlated with specific functional properties in psychiatric groups. Individuals with Internet gaming disorder (IGD) demonstrate impaired executive control. Thus, it is important to examine executive control networks (ECNs) during resting states and their relationships to executive control during task performance. Thirty-five IGD and 36 healthy control participants underwent a resting-state fMRI scan and performed a Stroop task inside and outside of the MRI scanner. Correlations between Stroop effect and functional connectivity among ECN regions of interest (ROIs) were calculated within and between groups. IGD subjects show lower functional connectivity in ECNs than do HC participants during resting state; functional-connectivity measures in ECNs were negatively correlated with Stroop effect and positively correlated with brain activations in executive-control regions across groups. Within groups, negative trends were found between Stroop effect and functional connectivity in ECNs in IGD and HC groups, separately; positive trends were found between functional connectivity in ECNs and brain activations in Stroop task in IGD and HC groups, separately. Higher functional connectivity in ECNs may underlie better executive control and may provide resilience with respect to IGD. Lower functional connectivity in ECNs may represent an important feature in understanding and treating IGD. Copyright © 2013 Elsevier Inc. All rights reserved.

The Relation between Resting State Connectivity and Creativity in Adolescents before and after Training

PubMed Central

Cousijn, Janna; Zanolie, Kiki; Munsters, Robbert J. M.; Kleibeuker, Sietske W.; Crone, Eveline A.

2014-01-01

An important component of creativity is divergent thinking, which involves the ability to generate novel and useful problem solutions. In this study, we tested the relation between resting-state functional connectivity of brain areas activated during a divergent thinking task (i.e., supramarginal gyrus, middle temporal gyrus, medial frontal gyrus) and the effect of practice in 32 adolescents aged 15–16. Over a period of two weeks, an experimental group (n = 16) conducted an 8-session Alternative Uses Task (AUT) training and an active control group (n = 16) conducted an 8-session rule switching training. Resting-state functional connectivity was measured before (pre-test) and after (post-test) training. Across groups at pre-test, stronger connectivity between the middle temporal gyrus and bilateral postcentral gyrus was associated with better divergent thinking performance. The AUT-training, however, did not significantly change functional connectivity. Post hoc analyses showed that change in divergent thinking performance over time was predicted by connectivity between left supramarginal gyrus and right occipital cortex. These results provide evidence for a relation between divergent thinking and resting-state functional connectivity in a task-positive network, taking an important step towards understanding creative cognition and functional brain connectivity. PMID:25188416

Longitudinal Changes of Resting-State Functional Connectivity during Motor Recovery after Stroke

PubMed Central

Park, Chang-hyun; Chang, Won Hyuk; Ohn, Suk Hoon; Kim, Sung Tae; Bang, Oh Young; Pascual-Leone, Alvaro; Kim, Yun-Hee

2013-01-01

Background and Purpose Functional magnetic resonance imaging (fMRI) studies could provide crucial information on the neural mechanisms of motor recovery in stroke patients. Resting-state fMRI is applicable to stroke patients who are not capable of proper performance of the motor task. In this study, we explored neural correlates of motor recovery in stroke patients by investigating longitudinal changes in resting-state functional connectivity of the ipsilesional primary motor cortex (M1). Methods A longitudinal observational study using repeated fMRI experiments was conducted in 12 patients with stroke. Resting-state fMRI data were acquired four times over a period of 6 months. Patients participated in the first session of fMRI shortly after onset, and thereafter in subsequent sessions at 1, 3, and 6 months after onset. Resting-state functional connectivity of the ipsilesional M1 was assessed and compared with that of healthy subjects. Results Compared with healthy subjects, patients demonstrated higher functional connectivity with the ipsilesional frontal and parietal cortices, bilateral thalamus, and cerebellum. Instead, functional connectivity with the contralesional M1 and occipital cortex were decreased in stroke patients. Functional connectivity between the ipsilesional and contralesional M1 showed the most asymmetry at 1 month after onset to the ipsilesional side. Functional connectivity of the ipsilesional M1 with the contralesional thalamus, supplementary motor area, and middle frontal gyrus at onset was positively correlated with motor recovery at 6 months after stroke. Conclusions Resting-state fMRI elicited distinctive but comparable results with previous task-based fMRI, presenting complementary and practical values for use in the study of stroke patients. PMID:21441147

Evidence of a dissociation pattern in resting-state default mode network connectivity in first-episode, treatment-naive major depression patients.

PubMed

Zhu, Xueling; Wang, Xiang; Xiao, Jin; Liao, Jian; Zhong, Mingtian; Wang, Wei; Yao, Shuqiao

2012-04-01

Imaging studies have shown that major depressive disorder (MDD) is associated with altered activity patterns of the default mode network (DMN). However, the neural correlates of the resting-state DMN and MDD-related pathopsychological characteristics, such as depressive rumination and overgeneral autobiographical memory (OGM) phenomena, still remain unclear. Using independent component analysis, we analyzed resting-state functional magnetic resonance imaging data obtained from 35 first-episode, treatment-naive young adults with MDD and from 35 matched healthy control subjects. Patients with MDD exhibited higher levels of rumination and OGM than did the control subjects. We observed increased functional connectivity in the anterior medial cortex regions (especially the medial prefrontal cortex and anterior cingulate cortex) and decreased functional connectivity in the posterior medial cortex regions (especially the posterior cingulate cortex/precuneus) in MDD patients compared with control subjects. In the depressed group, the increased functional connectivity in the anterior medial cortex correlated positively with rumination score, while the decreased functional connectivity in the posterior medial cortex correlated negatively with OGM score. We report dissociation between anterior and posterior functional connectivity in resting-state DMNs of first-episode, treatment-naive young adults with MDD. Increased functional connectivity in anterior medial regions of the resting-state DMN was associated with rumination, whereas decreased functional connectivity in posterior medial regions was associated with OGM. These results provide new evidence for the importance of the DMN in the pathophysiology of MDD and suggest that abnormal DMN activity may be an MDD trait. Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Altered resting-state functional connectivity in post-traumatic stress disorder: a perfusion MRI study

NASA Astrophysics Data System (ADS)

Li, Baojuan; Liu, Jian; Liu, Yang; Lu, Hong-Bing; Yin, Hong

2013-03-01

The majority of studies on posttraumatic stress disorder (PTSD) so far have focused on delineating patterns of activations during cognitive processes. Recently, more and more researches have started to investigate functional connectivity in PTSD subjects using BOLD-fMRI. Functional connectivity analysis has been demonstrated as a powerful approach to identify biomarkers of different brain diseases. This study aimed to detect resting-state functional connectivity abnormities in patients with PTSD using arterial spin labeling (ASL) fMRI. As a completely non-invasive technique, ASL allows quantitative estimates of cerebral blood flow (CBF). Compared with BOLD-fMRI, ASL fMRI has many advantages, including less low-frequency signal drifts, superior functional localization, etc. In the current study, ASL images were collected from 10 survivors in mining disaster with recent onset PTSD and 10 survivors without PTSD. Decreased regional CBF in the right middle temporal gyrus, lingual gyrus, and postcentral gyrus was detected in the PTSD patients. Seed-based resting-state functional connectivity analysis was performed using an area in the right middle temporal gyrus as region of interest. Compared with the non-PTSD group, the PTSD subjects demonstrated increased functional connectivity between the right middle temporal gyrus and the right superior temporal gyrus, the left middle temporal gyrus. Meanwhile, decreased functional connectivity between the right middle temporal gyrus and the right postcentral gyrus, the right superior parietal lobule was also found in the PTSD patients. This is the first study which investigated resting-state functional connectivity in PTSD using ASL images. The results may provide new insight into the neural substrates of PTSD.

Functional Disconnectivity during Inter-Task Resting State in Dementia with Lewy Bodies.

PubMed

Chabran, Eléna; Roquet, Daniel; Gounot, Daniel; Sourty, Marion; Armspach, Jean-Paul; Blanc, Frédéric

2018-01-01

Limited research has been done on the functional connectivity in visuoperceptual regions in dementia with Lewy bodies (DLB) patients. This study aimed to investigate the functional connectivity differences between a task condition and an inter-task resting state condition within a visuoperceptual paradigm, in DLB patients compared with Alzheimer disease (AD) patients and healthy elderly control subjects. Twenty-six DLB, 29 AD, and 22 healthy subjects underwent a detailed clinical and neuropsychological examination along with a functional MRI during the different conditions of a visuoperceptual paradigm. Functional images were analyzed using group-level spatial independent component analysis and seed-based connectivity analyses. While the DLB patients scored well and did not differ from the control and AD groups in terms of functional activity and connectivity during the task conditions, they showed decreased functional connectivity in visuoperceptual regions during the resting state condition, along with a temporal impairment of the default-mode network activity. Functional connectivity disturbances were also found within two attentional-executive networks and between these networks and visuoperceptual regions. We found a specific functional profile in the switching between task and resting state conditions in DLB patients. This result could help better characterize functional impairments in DLB and their contribution to several core symptoms of this pathology such as visual hallucinations and cognitive fluctuations. © 2018 S. Karger AG, Basel.

A tensorial approach to access cognitive workload related to mental arithmetic from EEG functional connectivity estimates.

PubMed

Dimitriadis, S I; Sun, Yu; Kwok, K; Laskaris, N A; Bezerianos, A

2013-01-01

The association of functional connectivity patterns with particular cognitive tasks has long been a topic of interest in neuroscience, e.g., studies of functional connectivity have demonstrated its potential use for decoding various brain states. However, the high-dimensionality of the pairwise functional connectivity limits its usefulness in some real-time applications. In the present study, the methodology of tensor subspace analysis (TSA) is used to reduce the initial high-dimensionality of the pairwise coupling in the original functional connectivity network to a space of condensed descriptive power, which would significantly decrease the computational cost and facilitate the differentiation of brain states. We assess the feasibility of the proposed method on EEG recordings when the subject was performing mental arithmetic task which differ only in the difficulty level (easy: 1-digit addition v.s. 3-digit additions). Two different cortical connective networks were detected, and by comparing the functional connectivity networks in different work states, it was found that the task-difficulty is best reflected in the connectivity structure of sub-graphs extending over parietooccipital sites. Incorporating this data-driven information within original TSA methodology, we succeeded in predicting the difficulty level from connectivity patterns in an efficient way that can be implemented so as to work in real-time.

The CB1 Neutral Antagonist Tetrahydrocannabivarin Reduces Default Mode Network and Increases Executive Control Network Resting State Functional Connectivity in Healthy Volunteers.

PubMed

Rzepa, Ewelina; Tudge, Luke; McCabe, Ciara

2015-09-10

The cannabinoid cannabinoid type 1 (CB1) neutral antagonist tetrahydrocannabivarin (THCv) has been suggested as a possible treatment for obesity, but without the depressogenic side-effects of inverse antagonists such as Rimonabant. However, how THCv might affect the resting state functional connectivity of the human brain is as yet unknown. We examined the effects of a single 10mg oral dose of THCv and placebo in 20 healthy volunteers in a randomized, within-subject, double-blind design. Using resting state functional magnetic resonance imaging and seed-based connectivity analyses, we selected the amygdala, insula, orbitofrontal cortex, and dorsal medial prefrontal cortex (dmPFC) as regions of interest. Mood and subjective experience were also measured before and after drug administration using self-report scales. Our results revealed, as expected, no significant differences in the subjective experience with a single dose of THCv. However, we found reduced resting state functional connectivity between the amygdala seed region and the default mode network and increased resting state functional connectivity between the amygdala seed region and the dorsal anterior cingulate cortex and between the dmPFC seed region and the inferior frontal gyrus/medial frontal gyrus. We also found a positive correlation under placebo for the amygdala-precuneus connectivity with the body mass index, although this correlation was not apparent under THCv. Our findings are the first to show that treatment with the CB1 neutral antagonist THCv decreases resting state functional connectivity in the default mode network and increases connectivity in the cognitive control network and dorsal visual stream network. This effect profile suggests possible therapeutic activity of THCv for obesity, where functional connectivity has been found to be altered in these regions. © The Author 2015. Published by Oxford University Press on behalf of CINP.

Exploring connectivity with large-scale Granger causality on resting-state functional MRI.

PubMed

DSouza, Adora M; Abidin, Anas Z; Leistritz, Lutz; Wismüller, Axel

2017-08-01

Large-scale Granger causality (lsGC) is a recently developed, resting-state functional MRI (fMRI) connectivity analysis approach that estimates multivariate voxel-resolution connectivity. Unlike most commonly used multivariate approaches, which establish coarse-resolution connectivity by aggregating voxel time-series avoiding an underdetermined problem, lsGC estimates voxel-resolution, fine-grained connectivity by incorporating an embedded dimension reduction. We investigate application of lsGC on realistic fMRI simulations, modeling smoothing of neuronal activity by the hemodynamic response function and repetition time (TR), and empirical resting-state fMRI data. Subsequently, functional subnetworks are extracted from lsGC connectivity measures for both datasets and validated quantitatively. We also provide guidelines to select lsGC free parameters. Results indicate that lsGC reliably recovers underlying network structure with area under receiver operator characteristic curve (AUC) of 0.93 at TR=1.5s for a 10-min session of fMRI simulations. Furthermore, subnetworks of closely interacting modules are recovered from the aforementioned lsGC networks. Results on empirical resting-state fMRI data demonstrate recovery of visual and motor cortex in close agreement with spatial maps obtained from (i) visuo-motor fMRI stimulation task-sequence (Accuracy=0.76) and (ii) independent component analysis (ICA) of resting-state fMRI (Accuracy=0.86). Compared with conventional Granger causality approach (AUC=0.75), lsGC produces better network recovery on fMRI simulations. Furthermore, it cannot recover functional subnetworks from empirical fMRI data, since quantifying voxel-resolution connectivity is not possible as consequence of encountering an underdetermined problem. Functional network recovery from fMRI data suggests that lsGC gives useful insight into connectivity patterns from resting-state fMRI at a multivariate voxel-resolution. Copyright © 2017 Elsevier B.V. All rights reserved.

Spinal Cord Injury Disrupts Resting-State Networks in the Human Brain.

PubMed

Hawasli, Ammar H; Rutlin, Jerrel; Roland, Jarod L; Murphy, Rory K J; Song, Sheng-Kwei; Leuthardt, Eric C; Shimony, Joshua S; Ray, Wilson Z

2018-03-15

Despite 253,000 spinal cord injury (SCI) patients in the United States, little is known about how SCI affects brain networks. Spinal MRI provides only structural information with no insight into functional connectivity. Resting-state functional MRI (RS-fMRI) quantifies network connectivity through the identification of resting-state networks (RSNs) and allows detection of functionally relevant changes during disease. Given the robust network of spinal cord afferents to the brain, we hypothesized that SCI produces meaningful changes in brain RSNs. RS-fMRIs and functional assessments were performed on 10 SCI subjects. Blood oxygen-dependent RS-fMRI sequences were acquired. Seed-based correlation mapping was performed using five RSNs: default-mode (DMN), dorsal-attention (DAN), salience (SAL), control (CON), and somatomotor (SMN). RSNs were compared with normal control subjects using false-discovery rate-corrected two way t tests. SCI reduced brain network connectivity within the SAL, SMN, and DMN and disrupted anti-correlated connectivity between CON and SMN. When divided into separate cohorts, complete but not incomplete SCI disrupted connectivity within SAL, DAN, SMN and DMN and between CON and SMN. Finally, connectivity changed over time after SCI: the primary motor cortex decreased connectivity with the primary somatosensory cortex, the visual cortex decreased connectivity with the primary motor cortex, and the visual cortex decreased connectivity with the sensory parietal cortex. These unique findings demonstrate the functional network plasticity that occurs in the brain as a result of injury to the spinal cord. Connectivity changes after SCI may serve as biomarkers to predict functional recovery following an SCI and guide future therapy.

Reduced functional connectivity within and between ‘social’ resting state networks in autism spectrum conditions

PubMed Central

Stoyanova, Raliza S.; Baron-Cohen, Simon; Calder, Andrew J.

2013-01-01

Individuals with Autism Spectrum Conditions (ASC) have difficulties in social interaction and communication, which is reflected in hypoactivation of brain regions engaged in social processing, such as medial prefrontal cortex (mPFC), amygdala and insula. Resting state studies in ASC have identified reduced connectivity of the default mode network (DMN), which includes mPFC, suggesting that other resting state networks incorporating ‘social’ brain regions may also be abnormal. Using Seed-based Connectivity and Group Independent Component Analysis (ICA) approaches, we looked at resting functional connectivity in ASC between specific ‘social’ brain regions, as well as within and between whole networks incorporating these regions. We found reduced functional connectivity within the DMN in individuals with ASC, using both ICA and seed-based approaches. Two further networks identified by ICA, the salience network, incorporating the insula and a medial temporal lobe network, incorporating the amygdala, showed reduced inter-network connectivity. This was underlined by reduced seed-based connectivity between the insula and amygdala. The results demonstrate significantly reduced functional connectivity within and between resting state networks incorporating ‘social’ brain regions. This reduced connectivity may result in difficulties in communication and integration of information across these networks, which could contribute to the impaired processing of social signals in ASC. PMID:22563003

Errors on interrupter tasks presented during spatial and verbal working memory performance are linearly linked to large-scale functional network connectivity in high temporal resolution resting state fMRI.

PubMed

Magnuson, Matthew Evan; Thompson, Garth John; Schwarb, Hillary; Pan, Wen-Ju; McKinley, Andy; Schumacher, Eric H; Keilholz, Shella Dawn

2015-12-01

The brain is organized into networks composed of spatially separated anatomical regions exhibiting coherent functional activity over time. Two of these networks (the default mode network, DMN, and the task positive network, TPN) have been implicated in the performance of a number of cognitive tasks. To directly examine the stable relationship between network connectivity and behavioral performance, high temporal resolution functional magnetic resonance imaging (fMRI) data were collected during the resting state, and behavioral data were collected from 15 subjects on different days, exploring verbal working memory, spatial working memory, and fluid intelligence. Sustained attention performance was also evaluated in a task interleaved between resting state scans. Functional connectivity within and between the DMN and TPN was related to performance on these tasks. Decreased TPN resting state connectivity was found to significantly correlate with fewer errors on an interrupter task presented during a spatial working memory paradigm and decreased DMN/TPN anti-correlation was significantly correlated with fewer errors on an interrupter task presented during a verbal working memory paradigm. A trend for increased DMN resting state connectivity to correlate to measures of fluid intelligence was also observed. These results provide additional evidence of the relationship between resting state networks and behavioral performance, and show that such results can be observed with high temporal resolution fMRI. Because cognitive scores and functional connectivity were collected on nonconsecutive days, these results highlight the stability of functional connectivity/cognitive performance coupling.

Left-lateralization of resting state functional connectivity between the presupplementary motor area and primary language areas.

PubMed

Lou, William; Peck, Kyung K; Brennan, Nicole; Mallela, Arka; Holodny, Andrei

2017-07-05

An abundance of evidence points to the role of a presupplementary motor area (pre-SMA) in human language. This study explores the pre-SMA resting state connectivity network and the nature of its connections to known language areas. We tested the hypothesis that by seeding the pre-SMA, one would be able to establish language laterality to known cortical and subcortical language areas. We analyzed data from 30 right-handed healthy controls and performed the resting state functional MRI. A seed-based analysis using a manually drawn pre-SMA region of interest template was applied. Time-course signals in the pre-SMA region of interest were averaged and cross-correlated to every voxel in the brain. Results show that the pre-SMA has significant left-lateralized functional connectivity to the pars opercularis within Broca's area. Among cortical regions, pre-SMA functional connectivity is strongest to the pars opercularis In addition, pre-SMA connectivity was shown to exist to other cortical language-association regions, including Wernicke's Area, supramarginal gyri, angular gyri, and middle frontal gyri. Among subcortical areas, considerable left-lateralized functional connectivity occurs to the caudate and thalamus, whereas cerebellar subregions show right lateralization. The current study shows that the pre-SMA most strongly connects to the pars opercularis within Broca's area and that cortical connections to language areas are left lateralized among a sample of right-handed patients. We provide resting state functional MRI evidence that the functional connectivity of the pre-SMA is involved in semantic language processing and that this identification may be useful for establishing language laterality in preoperative neurosurgical planning.

Motor imagery learning modulates functional connectivity of multiple brain systems in resting state.

PubMed

Zhang, Hang; Long, Zhiying; Ge, Ruiyang; Xu, Lele; Jin, Zhen; Yao, Li; Liu, Yijun

2014-01-01

Learning motor skills involves subsequent modulation of resting-state functional connectivity in the sensory-motor system. This idea was mostly derived from the investigations on motor execution learning which mainly recruits the processing of sensory-motor information. Behavioral evidences demonstrated that motor skills in our daily lives could be learned through imagery procedures. However, it remains unclear whether the modulation of resting-state functional connectivity also exists in the sensory-motor system after motor imagery learning. We performed a fMRI investigation on motor imagery learning from resting state. Based on previous studies, we identified eight sensory and cognitive resting-state networks (RSNs) corresponding to the brain systems and further explored the functional connectivity of these RSNs through the assessments, connectivity and network strengths before and after the two-week consecutive learning. Two intriguing results were revealed: (1) The sensory RSNs, specifically sensory-motor and lateral visual networks exhibited greater connectivity strengths in precuneus and fusiform gyrus after learning; (2) Decreased network strength induced by learning was proved in the default mode network, a cognitive RSN. These results indicated that resting-state functional connectivity could be modulated by motor imagery learning in multiple brain systems, and such modulation displayed in the sensory-motor, visual and default brain systems may be associated with the establishment of motor schema and the regulation of introspective thought. These findings further revealed the neural substrates underlying motor skill learning and potentially provided new insights into the therapeutic benefits of motor imagery learning.

Resting-State Functional Connectivity Differentiates Anxious Apprehension and Anxious Arousal

PubMed Central

Burdwood, Erin N.; Infantolino, Zachary P.; Crocker, Laura D.; Spielberg, Jeffrey M.; Banich, Marie T.; Miller, Gregory A.; Heller, Wendy

2016-01-01

Brain regions in the default mode network (DMN) display greater functional connectivity at rest or during self-referential processing than during goal-directed tasks. The present study assessed resting-state connectivity as a function of anxious apprehension and anxious arousal, independent of depressive symptoms, in order to understand how these dimensions disrupt cognition. Whole-brain, seed-based analyses indicated differences between anxious apprehension and anxious arousal in DMN functional connectivity. Lower connectivity associated with higher anxious apprehension suggests decreased adaptive, inner-focused thought processes, whereas higher connectivity at higher levels of anxious arousal may reflect elevated monitoring of physiological responses to threat. These findings further the conceptualization of anxious apprehension and anxious arousal as distinct psychological dimensions with distinct neural instantiations. PMID:27406406

Partial covariance based functional connectivity computation using Ledoit-Wolf covariance regularization.

PubMed

Brier, Matthew R; Mitra, Anish; McCarthy, John E; Ances, Beau M; Snyder, Abraham Z

2015-11-01

Functional connectivity refers to shared signals among brain regions and is typically assessed in a task free state. Functional connectivity commonly is quantified between signal pairs using Pearson correlation. However, resting-state fMRI is a multivariate process exhibiting a complicated covariance structure. Partial covariance assesses the unique variance shared between two brain regions excluding any widely shared variance, hence is appropriate for the analysis of multivariate fMRI datasets. However, calculation of partial covariance requires inversion of the covariance matrix, which, in most functional connectivity studies, is not invertible owing to rank deficiency. Here we apply Ledoit-Wolf shrinkage (L2 regularization) to invert the high dimensional BOLD covariance matrix. We investigate the network organization and brain-state dependence of partial covariance-based functional connectivity. Although RSNs are conventionally defined in terms of shared variance, removal of widely shared variance, surprisingly, improved the separation of RSNs in a spring embedded graphical model. This result suggests that pair-wise unique shared variance plays a heretofore unrecognized role in RSN covariance organization. In addition, application of partial correlation to fMRI data acquired in the eyes open vs. eyes closed states revealed focal changes in uniquely shared variance between the thalamus and visual cortices. This result suggests that partial correlation of resting state BOLD time series reflect functional processes in addition to structural connectivity. Copyright © 2015 Elsevier Inc. All rights reserved.

Multimodal analysis of cortical chemoarchitecture and macroscale fMRI resting‐state functional connectivity

PubMed Central

Scholtens, Lianne H.; Turk, Elise; Mantini, Dante; Vanduffel, Wim; Feldman Barrett, Lisa

2016-01-01

Abstract The cerebral cortex is well known to display a large variation in excitatory and inhibitory chemoarchitecture, but the effect of this variation on global scale functional neural communication and synchronization patterns remains less well understood. Here, we provide evidence of the chemoarchitecture of cortical regions to be associated with large‐scale region‐to‐region resting‐state functional connectivity. We assessed the excitatory versus inhibitory chemoarchitecture of cortical areas as an ExIn ratio between receptor density mappings of excitatory (AMPA, M1) and inhibitory (GABAA, M2) receptors, computed on the basis of data collated from pioneering studies of autoradiography mappings as present in literature of the human (2 datasets) and macaque (1 dataset) cortex. Cortical variation in ExIn ratio significantly correlated with total level of functional connectivity as derived from resting‐state functional connectivity recordings of cortical areas across all three datasets (human I: P = 0.0004; human II: P = 0.0008; macaque: P = 0.0007), suggesting cortical areas with an overall more excitatory character to show higher levels of intrinsic functional connectivity during resting‐state. Our findings are indicative of the microscale chemoarchitecture of cortical regions to be related to resting‐state fMRI connectivity patterns at the global system's level of connectome organization. Hum Brain Mapp 37:3103–3113, 2016. © 2016 Wiley Periodicals, Inc. PMID:27207489

Partial covariance based functional connectivity computation using Ledoit-Wolf covariance regularization

PubMed Central

Brier, Matthew R.; Mitra, Anish; McCarthy, John E.; Ances, Beau M.; Snyder, Abraham Z.

2015-01-01

Functional connectivity refers to shared signals among brain regions and is typically assessed in a task free state. Functional connectivity commonly is quantified between signal pairs using Pearson correlation. However, resting-state fMRI is a multivariate process exhibiting a complicated covariance structure. Partial covariance assesses the unique variance shared between two brain regions excluding any widely shared variance, hence is appropriate for the analysis of multivariate fMRI datasets. However, calculation of partial covariance requires inversion of the covariance matrix, which, in most functional connectivity studies, is not invertible owing to rank deficiency. Here we apply Ledoit-Wolf shrinkage (L2 regularization) to invert the high dimensional BOLD covariance matrix. We investigate the network organization and brain-state dependence of partial covariance-based functional connectivity. Although RSNs are conventionally defined in terms of shared variance, removal of widely shared variance, surprisingly, improved the separation of RSNs in a spring embedded graphical model. This result suggests that pair-wise unique shared variance plays a heretofore unrecognized role in RSN covariance organization. In addition, application of partial correlation to fMRI data acquired in the eyes open vs. eyes closed states revealed focal changes in uniquely shared variance between the thalamus and visual cortices. This result suggests that partial correlation of resting state BOLD time series reflect functional processes in addition to structural connectivity. PMID:26208872

Working memory capacity and the functional connectome - insights from resting-state fMRI and voxelwise centrality mapping.

PubMed

Markett, Sebastian; Reuter, Martin; Heeren, Behrend; Lachmann, Bernd; Weber, Bernd; Montag, Christian

2018-02-01

The functional connectome represents a comprehensive network map of functional connectivity throughout the human brain. To date, the relationship between the organization of functional connectivity and cognitive performance measures is still poorly understood. In the present study we use resting-state functional magnetic resonance imaging (fMRI) data to explore the link between the functional connectome and working memory capacity in an individual differences design. Working memory capacity, which refers to the maximum amount of context information that an individual can retain in the absence of external stimulation, was assessed outside the MRI scanner and estimated based on behavioral data from a change detection task. Resting-state time series were analyzed by means of voxelwise degree and eigenvector centrality mapping, which are data-driven network analytic approaches for the characterization of functional connectivity. We found working memory capacity to be inversely correlated with both centrality in the right intraparietal sulcus. Exploratory analyses revealed that this relationship was putatively driven by an increase in negative connectivity strength of the structure. This resting-state connectivity finding fits previous task based activation studies that have shown that this area responds to manipulations of working memory load.

Replicability of time-varying connectivity patterns in large resting state fMRI samples.

PubMed

Abrol, Anees; Damaraju, Eswar; Miller, Robyn L; Stephen, Julia M; Claus, Eric D; Mayer, Andrew R; Calhoun, Vince D

2017-12-01

The past few years have seen an emergence of approaches that leverage temporal changes in whole-brain patterns of functional connectivity (the chronnectome). In this chronnectome study, we investigate the replicability of the human brain's inter-regional coupling dynamics during rest by evaluating two different dynamic functional network connectivity (dFNC) analysis frameworks using 7 500 functional magnetic resonance imaging (fMRI) datasets. To quantify the extent to which the emergent functional connectivity (FC) patterns are reproducible, we characterize the temporal dynamics by deriving several summary measures across multiple large, independent age-matched samples. Reproducibility was demonstrated through the existence of basic connectivity patterns (FC states) amidst an ensemble of inter-regional connections. Furthermore, application of the methods to conservatively configured (statistically stationary, linear and Gaussian) surrogate datasets revealed that some of the studied state summary measures were indeed statistically significant and also suggested that this class of null model did not explain the fMRI data fully. This extensive testing of reproducibility of similarity statistics also suggests that the estimated FC states are robust against variation in data quality, analysis, grouping, and decomposition methods. We conclude that future investigations probing the functional and neurophysiological relevance of time-varying connectivity assume critical importance. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Replicability of time-varying connectivity patterns in large resting state fMRI samples

PubMed Central

Abrol, Anees; Damaraju, Eswar; Miller, Robyn L.; Stephen, Julia M.; Claus, Eric D.; Mayer, Andrew R.; Calhoun, Vince D.

2018-01-01

The past few years have seen an emergence of approaches that leverage temporal changes in whole-brain patterns of functional connectivity (the chronnectome). In this chronnectome study, we investigate the replicability of the human brain’s inter-regional coupling dynamics during rest by evaluating two different dynamic functional network connectivity (dFNC) analysis frameworks using 7 500 functional magnetic resonance imaging (fMRI) datasets. To quantify the extent to which the emergent functional connectivity (FC) patterns are reproducible, we characterize the temporal dynamics by deriving several summary measures across multiple large, independent age-matched samples. Reproducibility was demonstrated through the existence of basic connectivity patterns (FC states) amidst an ensemble of inter-regional connections. Furthermore, application of the methods to conservatively configured (statistically stationary, linear and Gaussian) surrogate datasets revealed that some of the studied state summary measures were indeed statistically significant and also suggested that this class of null model did not explain the fMRI data fully. This extensive testing of reproducibility of similarity statistics also suggests that the estimated FC states are robust against variation in data quality, analysis, grouping, and decomposition methods. We conclude that future investigations probing the functional and neurophysiological relevance of time-varying connectivity assume critical importance. PMID:28916181

Joint Analysis of Band-Specific Functional Connectivity and Signal Complexity in Autism

ERIC Educational Resources Information Center

Ghanbari, Yasser; Bloy, Luke; Edgar, J. Christopher; Blaskey, Lisa; Verma, Ragini; Roberts, Timothy P. L.

2015-01-01

Examination of resting state brain activity using electrophysiological measures like complexity as well as functional connectivity is of growing interest in the study of autism spectrum disorders (ASD). The present paper jointly examined complexity and connectivity to obtain a more detailed characterization of resting state brain activity in ASD.…

Functional resting-state connectivity of the human motor network: differences between right- and left-handers.

PubMed

Pool, Eva-Maria; Rehme, Anne K; Eickhoff, Simon B; Fink, Gereon R; Grefkes, Christian

2015-04-01

Handedness is associated with differences in activation levels in various motor tasks performed with the dominant or non-dominant hand. Here we tested whether handedness is reflected in the functional architecture of the motor system even in the absence of an overt motor task. Using resting-state functional magnetic resonance imaging we investigated 18 right- and 18 left-handers. Whole-brain functional connectivity maps of the primary motor cortex (M1), supplementary motor area (SMA), dorsolateral premotor cortex (PMd), pre-SMA, inferior frontal junction and motor putamen were compared between right- and left-handers. We further used a multivariate linear support vector machine (SVM) classifier to reveal the specificity of brain regions for classifying handedness based on individual resting-state maps. Using left M1 as seed region, functional connectivity analysis revealed stronger interhemispheric functional connectivity between left M1 and right PMd in right-handers as compared to left-handers. This connectivity cluster contributed to the individual classification of right- and left-handers with 86.2% accuracy. Consistently, also seeding from right PMd yielded a similar handedness-dependent effect in left M1, albeit with lower classification accuracy (78.1%). Control analyses of the other resting-state networks including the speech and the visual network revealed no significant differences in functional connectivity related to handedness. In conclusion, our data revealed an intrinsically higher functional connectivity in right-handers. These results may help to explain that hand preference is more lateralized in right-handers than in left-handers. Furthermore, enhanced functional connectivity between left M1 and right PMd may serve as an individual marker of handedness. Copyright © 2015 Elsevier Inc. All rights reserved.

Functional resting-state connectivity of the human motor network: Differences between right- and left-handers

PubMed Central

Pool, Eva-Maria; Rehme, Anne K.; Eickhoff, Simon B.; Fink, Gereon R.; Grefkes, Christian

2016-01-01

Handedness is associated with differences in activation levels in various motor tasks performed with the dominant or non-dominant hand. Here we tested whether handedness is reflected in the functional architecture of the motor system even in the absence of an overt motor task. Using resting-state functional magnetic resonance imaging we investigated 18 right- and 18 left-handers. Whole-brain functional connectivity maps of the primary motor cortex (M1), supplementary motor area (SMA), dorsolateral premotor cortex (PMd), pre-SMA, inferior frontal junction and motor putamen were compared between right- and left-handers. We further used a multivariate linear support vector machine (SVM) classifier to reveal the specificity of brain regions for classifying handedness based on individual resting-state maps. Using left M1 as seed region, functional connectivity analysis revealed stronger interhemispheric functional connectivity between left M1 and right PMd in right-handers as compared to left-handers. This connectivity cluster contributed to the individual classification of right- and left-handers with 86.2% accuracy. Consistently, also seeding from right PMd yielded a similar handedness-dependent effect in left M1, albeit with lower classification accuracy (78.1%). Control analyses of the other resting-state networks including the speech and the visual network revealed no significant differences in functional connectivity related to handedness. In conclusion, our data revealed an intrinsically higher functional connectivity in right-handers. These results may help to explain that hand preference is more lateralized in right-handers than in left-handers. Furthermore, enhanced functional connectivity between left M1 and right PMd may serve as an individual marker of handedness. PMID:25613438

Sparse dictionary learning of resting state fMRI networks.

PubMed

Eavani, Harini; Filipovych, Roman; Davatzikos, Christos; Satterthwaite, Theodore D; Gur, Raquel E; Gur, Ruben C

2012-07-02

Research in resting state fMRI (rsfMRI) has revealed the presence of stable, anti-correlated functional subnetworks in the brain. Task-positive networks are active during a cognitive process and are anti-correlated with task-negative networks, which are active during rest. In this paper, based on the assumption that the structure of the resting state functional brain connectivity is sparse, we utilize sparse dictionary modeling to identify distinct functional sub-networks. We propose two ways of formulating the sparse functional network learning problem that characterize the underlying functional connectivity from different perspectives. Our results show that the whole-brain functional connectivity can be concisely represented with highly modular, overlapping task-positive/negative pairs of sub-networks.

Establishing the resting state default mode network derived from functional magnetic resonance imaging tasks as an endophenotype: A twins study.

PubMed

Korgaonkar, Mayuresh S; Ram, Kaushik; Williams, Leanne M; Gatt, Justine M; Grieve, Stuart M

2014-08-01

The resting state default mode network (DMN) has been shown to characterize a number of neurological and psychiatric disorders. Evidence suggests an underlying genetic basis for this network and hence could serve as potential endophenotype for these disorders. Heritability is a defining criterion for endophenotypes. The DMN is measured either using a resting-state functional magnetic resonance imaging (fMRI) scan or by extracting resting state activity from task-based fMRI. The current study is the first to evaluate heritability of this task-derived resting activity. 250 healthy adult twins (79 monozygotic and 46 dizygotic same sex twin pairs) completed five cognitive and emotion processing fMRI tasks. Resting state DMN functional connectivity was derived from these five fMRI tasks. We validated this approach by comparing connectivity estimates from task-derived resting activity for all five fMRI tasks, with those obtained using a dedicated task-free resting state scan in an independent cohort of 27 healthy individuals. Structural equation modeling using the classic twin design was used to estimate the genetic and environmental contributions to variance for the resting-state DMN functional connectivity. About 9-41% of the variance in functional connectivity between the DMN nodes was attributed to genetic contribution with the greatest heritability found for functional connectivity between the posterior cingulate and right inferior parietal nodes (P<0.001). Our data provide new evidence that functional connectivity measures from the intrinsic DMN derived from task-based fMRI datasets are under genetic control and have the potential to serve as endophenotypes for genetically predisposed psychiatric and neurological disorders. Copyright © 2014 Wiley Periodicals, Inc.

Amygdala subnuclei resting-state functional connectivity sex and estrogen differences.

PubMed

Engman, Jonas; Linnman, Clas; Van Dijk, Koene R A; Milad, Mohammed R

2016-01-01

The amygdala is a hub in emotional processing, including that of negative affect. Healthy men and women have distinct differences in amygdala responses, potentially setting the stage for the observed sex differences in the prevalence of fear, anxiety, and pain disorders. Here, we examined how amygdala subnuclei resting-state functional connectivity is affected by sex, as well as explored how the functional connectivity is related to estrogen levels. Resting-state functional connectivity was measured using functional magnetic resonance imaging (fMRI) with seeds placed in the left and right laterobasal (LB) and centromedial (CM) amygdala. Sex differences were studied in 48 healthy men and 48 healthy women, matched for age, while the association with estrogen was analyzed in a subsample of 24 women, for whom hormone levels had been assessed. For the hormone analyses, the subsample was further divided into a lower and higher estrogen levels group based on a median split. We found distinct sex differences in the LB and CM amygdala resting-state functional connectivity, as well as preliminary evidence for an association between estrogen levels and connectivity patterns. These results are potentially valuable in explaining why women are more afflicted by conditions of negative affect than are men, and could imply a mechanistic role for estrogen in modulating emotion. Copyright © 2015 Elsevier Ltd. All rights reserved.

Resting-state functional brain networks in first-episode psychosis: A 12-month follow-up study.

PubMed

Ganella, Eleni P; Seguin, Caio; Pantelis, Christos; Whittle, Sarah; Baune, Bernhard T; Olver, James; Amminger, G Paul; McGorry, Patrick D; Cropley, Vanessa; Zalesky, Andrew; Bartholomeusz, Cali F

2018-05-01

Schizophrenia is increasingly conceived as a disorder of brain network connectivity and organization. However, reports of network abnormalities during the early illness stage of psychosis are mixed. This study adopted a data-driven whole-brain approach to investigate functional connectivity and network architecture in a first-episode psychosis cohort relative to healthy controls and whether functional network properties changed abnormally over a 12-month period in first-episode psychosis. Resting-state functional connectivity was performed at two time points. At baseline, 29 first-episode psychosis individuals and 30 healthy controls were assessed, and at 12 months, 14 first-episode psychosis individuals and 20 healthy controls completed follow-up. Whole-brain resting-state functional connectivity networks were mapped for each individual and analyzed using graph theory to investigate whether network abnormalities associated with first-episode psychosis were evident and whether functional network properties changed abnormally over 12 months relative to controls. This study found no evidence of abnormal resting-state functional connectivity or topology in first-episode psychosis individuals relative to healthy controls at baseline or at 12-months follow-up. Furthermore, longitudinal changes in network properties over a 12-month period did not significantly differ between first-episode psychosis individuals and healthy control. Network measures did not significantly correlate with symptomatology, duration of illness or antipsychotic medication. This is the first study to show unaffected resting-state functional connectivity and topology in the early psychosis stage of illness. In light of previous literature, this suggests that a subgroup of first-episode psychosis individuals who have a neurotypical resting-state functional connectivity and topology may exist. Our preliminary longitudinal analyses indicate that there also does not appear to be deterioration in these network properties over a 12-month period. Future research in a larger sample is necessary to confirm our longitudinal findings.

Large-scale DCMs for resting-state fMRI.

PubMed

Razi, Adeel; Seghier, Mohamed L; Zhou, Yuan; McColgan, Peter; Zeidman, Peter; Park, Hae-Jeong; Sporns, Olaf; Rees, Geraint; Friston, Karl J

2017-01-01

This paper considers the identification of large directed graphs for resting-state brain networks based on biophysical models of distributed neuronal activity, that is, effective connectivity . This identification can be contrasted with functional connectivity methods based on symmetric correlations that are ubiquitous in resting-state functional MRI (fMRI). We use spectral dynamic causal modeling (DCM) to invert large graphs comprising dozens of nodes or regions. The ensuing graphs are directed and weighted, hence providing a neurobiologically plausible characterization of connectivity in terms of excitatory and inhibitory coupling. Furthermore, we show that the use of to discover the most likely sparse graph (or model) from a parent (e.g., fully connected) graph eschews the arbitrary thresholding often applied to large symmetric (functional connectivity) graphs. Using empirical fMRI data, we show that spectral DCM furnishes connectivity estimates on large graphs that correlate strongly with the estimates provided by stochastic DCM. Furthermore, we increase the efficiency of model inversion using functional connectivity modes to place prior constraints on effective connectivity. In other words, we use a small number of modes to finesse the potentially redundant parameterization of large DCMs. We show that spectral DCM-with functional connectivity priors-is ideally suited for directed graph theoretic analyses of resting-state fMRI. We envision that directed graphs will prove useful in understanding the psychopathology and pathophysiology of neurodegenerative and neurodevelopmental disorders. We will demonstrate the utility of large directed graphs in clinical populations in subsequent reports, using the procedures described in this paper.

Resting State Network Topology of the Ferret Brain

PubMed Central

Zhou, Zhe Charles; Salzwedel, Andrew P.; Radtke-Schuller, Susanne; Li, Yuhui; Sellers, Kristin K.; Gilmore, John H.; Shih, Yen-Yu Ian; Fröhlich, Flavio; Gao, Wei

2016-01-01

Resting state functional magnetic resonance imaging (rsfMRI) has emerged as a versatile tool for non-invasive measurement of functional connectivity patterns in the brain. RsfMRI brain dynamics in rodents, non-human primates, and humans share similar properties; however, little is known about the resting state functional connectivity patterns in the ferret, an animal model with high potential for developmental and cognitive translational study. To address this knowledge-gap, we performed rsfMRI on anesthetized ferrets using a 9.4 tesla MRI scanner, and subsequently performed group-level independent component analysis (gICA) to identify functionally connected brain networks. Group-level ICA analysis revealed distributed sensory, motor, and higher-order networks in the ferret brain. Subsequent connectivity analysis showed interconnected higher-order networks that constituted a putative default mode network (DMN), a network that exhibits altered connectivity in neuropsychiatric disorders. Finally, we assessed ferret brain topological efficiency using graph theory analysis and found that the ferret brain exhibits small-world properties. Overall, these results provide additional evidence for pan-species resting-state networks, further supporting ferret-based studies of sensory and cognitive function. PMID:27596024

Associations of resting-state fMRI functional connectivity with flow-BOLD coupling and regional vasculature.

PubMed

Tak, Sungho; Polimeni, Jonathan R; Wang, Danny J J; Yan, Lirong; Chen, J Jean

2015-04-01

There has been tremendous interest in applying functional magnetic resonance imaging-based resting-state functional connectivity (rs-fcMRI) measurements to the study of brain function. However, a lack of understanding of the physiological mechanisms of rs-fcMRI limits their ability to interpret rs-fcMRI findings. In this work, the authors examine the regional associations between rs-fcMRI estimates and dynamic coupling between the blood oxygenation level-dependent (BOLD) and cerebral blood flow (CBF), as well as resting macrovascular volume. Resting-state BOLD and CBF data were simultaneously acquired using a dual-echo pseudocontinuous arterial spin labeling (pCASL) technique, whereas macrovascular volume fraction was estimated using time-of-flight MR angiography. Functional connectivity within well-known functional networks—including the default mode, frontoparietal, and primary sensory-motor networks—was calculated using a conventional seed-based correlation approach. They found the functional connectivity strength to be significantly correlated with the regional increase in CBF-BOLD coupling strength and inversely proportional to macrovascular volume fraction. These relationships were consistently observed within all functional networks considered. Their findings suggest that highly connected networks observed using rs-fcMRI are not likely to be mediated by common vascular drainage linking distal cortical areas. Instead, high BOLD functional connectivity is more likely to reflect tighter neurovascular connections, attributable to neuronal pathways.

Temporal and spectral characteristics of dynamic functional connectivity between resting-state networks reveal information beyond static connectivity

PubMed Central

Yeh, Hsiang J.; Guindani, Michele; Vannucci, Marina; Haneef, Zulfi; Stern, John M.

2018-01-01

Estimation of functional connectivity (FC) has become an increasingly powerful tool for investigating healthy and abnormal brain function. Static connectivity, in particular, has played a large part in guiding conclusions from the majority of resting-state functional MRI studies. However, accumulating evidence points to the presence of temporal fluctuations in FC, leading to increasing interest in estimating FC as a dynamic quantity. One central issue that has arisen in this new view of connectivity is the dramatic increase in complexity caused by dynamic functional connectivity (dFC) estimation. To computationally handle this increased complexity, a limited set of dFC properties, primarily the mean and variance, have generally been considered. Additionally, it remains unclear how to integrate the increased information from dFC into pattern recognition techniques for subject-level prediction. In this study, we propose an approach to address these two issues based on a large number of previously unexplored temporal and spectral features of dynamic functional connectivity. A Generalized Autoregressive Conditional Heteroskedasticity (GARCH) model is used to estimate time-varying patterns of functional connectivity between resting-state networks. Time-frequency analysis is then performed on dFC estimates, and a large number of previously unexplored temporal and spectral features drawn from signal processing literature are extracted for dFC estimates. We apply the investigated features to two neurologic populations of interest, healthy controls and patients with temporal lobe epilepsy, and show that the proposed approach leads to substantial increases in predictive performance compared to both traditional estimates of static connectivity as well as current approaches to dFC. Variable importance is assessed and shows that there are several quantities that can be extracted from dFC signal which are more informative than the traditional mean or variance of dFC. This work illuminates many previously unexplored facets of the dynamic properties of functional connectivity between resting-state networks, and provides a platform for dynamic functional connectivity analysis that facilitates its usage as an investigative measure for healthy as well as abnormal brain function. PMID:29320526

Decreased functional connectivity between ventral tegmental area and nucleus accumbens in Internet gaming disorder: evidence from resting state functional magnetic resonance imaging.

PubMed

Zhang, Jin-Tao; Ma, Shan-Shan; Yip, Sarah W; Wang, Ling-Jiao; Chen, Chao; Yan, Chao-Gan; Liu, Lu; Liu, Ben; Deng, Lin-Yuan; Liu, Qin-Xue; Fang, Xiao-Yi

2015-11-18

Internet gaming disorder (IGD) has become an increasing mental health problem worldwide. Decreased resting-state functional connectivity (rsFC) between the ventral tegmental area (VTA) and the nucleus accumbens (NAcc) has been found in substance use and is thought to play an important role in the development of substance addiction. However, rsFC between the VTA and NAcc in a non-substance addiction, such as IGD, has not been assessed previously. The current study aimed to investigate: (1) if individuals with IGD exhibit alterations in VTA-NAcc functional connectivity; and (2) whether VTA-NAcc functional connectivity is associated with subjective Internet craving. Thirty-five male participants with IGD and 24 healthy control (HC) individuals participated in resting-state functional magnetic resonance imaging. Regions of interest (left NAcc, right NAcc and VTA) were selected based on the literature and were defined by placing spheres centered on Talairach Daemon coordinates. In comparison with HCs, individuals with IGD had significantly decreased rsFC between the VTA and right NAcc. Resting-state functional connectivity strength between the VTA and right NAcc was negatively correlated with self-reported subjective craving for the Internet. These results suggest possible neural functional similarities between individuals with IGD and individuals with substance addictions.

Resting-state functional connectivity differentiates anxious apprehension and anxious arousal.

PubMed

Burdwood, Erin N; Infantolino, Zachary P; Crocker, Laura D; Spielberg, Jeffrey M; Banich, Marie T; Miller, Gregory A; Heller, Wendy

2016-10-01

Brain regions in the default mode network (DMN) display greater functional connectivity at rest or during self-referential processing than during goal-directed tasks. The present study assessed resting-state connectivity as a function of anxious apprehension and anxious arousal, independent of depressive symptoms, in order to understand how these dimensions disrupt cognition. Whole-brain, seed-based analyses indicated differences between anxious apprehension and anxious arousal in DMN functional connectivity. Lower connectivity associated with higher anxious apprehension suggests decreased adaptive, inner-focused thought processes, whereas higher connectivity at higher levels of anxious arousal may reflect elevated monitoring of physiological responses to threat. These findings further the conceptualization of anxious apprehension and anxious arousal as distinct psychological dimensions with distinct neural instantiations. © 2016 Society for Psychophysiological Research.

Glutamatergic and Resting-State Functional Connectivity Correlates of Severity in Major Depression – The Role of Pregenual Anterior Cingulate Cortex and Anterior Insula

PubMed Central

Horn, Dorothea I.; Yu, Chunshui; Steiner, Johann; Buchmann, Julia; Kaufmann, Joern; Osoba, Annemarie; Eckert, Ulf; Zierhut, Kathrin C.; Schiltz, Kolja; He, Huiguang; Biswal, Bharat; Bogerts, Bernhard; Walter, Martin

2010-01-01

Glutamatergic mechanisms and resting-state functional connectivity alterations have been recently described as factors contributing to major depressive disorder (MDD). Furthermore, the pregenual anterior cingulate cortex (pgACC) seems to play an important role for major depressive symptoms such as anhedonia and impaired emotion processing. We investigated 22 MDD patients and 22 healthy subjects using a combined magnetic resonance spectroscopy (MRS) and resting-state functional magnetic resonance imaging (fMRI) approach. Severity of depression was rated using the 21-item Hamilton depression scale (HAMD) and patients were divided into severely and mildly depressed subgroups according to HAMD scores. Because of their hypothesized role in depression we investigated the functional connectivity between pgACC and left anterior insular cortex (AI). The sum of Glutamate and Glutamine (Glx) in the pgACC, but not in left AI, predicted the resting-state functional connectivity between the two regions exclusively in depressed patients. Furthermore, functional connectivity between these regions was significantly altered in the subgroup of severely depressed patients (HAMD > 15) compared to healthy subjects and mildly depressed patients. Similarly the Glx ratios, relative to Creatine, in the pgACC were lowest in severely depressed patients. These findings support the involvement of glutamatergic mechanisms in severe MDD which are related to the functional connectivity between pgACC and AI and depression severity. PMID:20700385

Motor Imagery Learning Modulates Functional Connectivity of Multiple Brain Systems in Resting State

PubMed Central

Zhang, Hang; Long, Zhiying; Ge, Ruiyang; Xu, Lele; Jin, Zhen; Yao, Li; Liu, Yijun

2014-01-01

Background Learning motor skills involves subsequent modulation of resting-state functional connectivity in the sensory-motor system. This idea was mostly derived from the investigations on motor execution learning which mainly recruits the processing of sensory-motor information. Behavioral evidences demonstrated that motor skills in our daily lives could be learned through imagery procedures. However, it remains unclear whether the modulation of resting-state functional connectivity also exists in the sensory-motor system after motor imagery learning. Methodology/Principal Findings We performed a fMRI investigation on motor imagery learning from resting state. Based on previous studies, we identified eight sensory and cognitive resting-state networks (RSNs) corresponding to the brain systems and further explored the functional connectivity of these RSNs through the assessments, connectivity and network strengths before and after the two-week consecutive learning. Two intriguing results were revealed: (1) The sensory RSNs, specifically sensory-motor and lateral visual networks exhibited greater connectivity strengths in precuneus and fusiform gyrus after learning; (2) Decreased network strength induced by learning was proved in the default mode network, a cognitive RSN. Conclusions/Significance These results indicated that resting-state functional connectivity could be modulated by motor imagery learning in multiple brain systems, and such modulation displayed in the sensory-motor, visual and default brain systems may be associated with the establishment of motor schema and the regulation of introspective thought. These findings further revealed the neural substrates underlying motor skill learning and potentially provided new insights into the therapeutic benefits of motor imagery learning. PMID:24465577

Defining functional SMA and pre-SMA subregions in human MFC using resting state fMRI: functional connectivity-based parcellation method.

PubMed

Kim, Jae-Hun; Lee, Jong-Min; Jo, Hang Joon; Kim, Sook Hui; Lee, Jung Hee; Kim, Sung Tae; Seo, Sang Won; Cox, Robert W; Na, Duk L; Kim, Sun I; Saad, Ziad S

2010-02-01

Noninvasive parcellation of the human cerebral cortex is an important goal for understanding and examining brain functions. Recently, the patterns of anatomical connections using diffusion tensor imaging (DTI) have been used to parcellate brain regions. Here, we present a noninvasive parcellation approach that uses "functional fingerprints" obtained by correlation measures on resting state functional magnetic resonance imaging (fMRI) data to parcellate brain regions. In other terms, brain regions are parcellated based on the similarity of their connection--as reflected by correlation during resting state--to the whole brain. The proposed method was used to parcellate the medial frontal cortex (MFC) into supplementary motor areas (SMA) and pre-SMA subregions. In agreement with anatomical landmark-based parcellation, we find that functional fingerprint clustering of the MFC results in anterior and posterior clusters. The probabilistic maps from 12 subjects showed that the anterior cluster is mainly located rostral to the vertical commissure anterior (VCA) line, whereas the posterior cluster is mainly located caudal to VCA line, suggesting the homologues of pre-SMA and SMA. The functional connections from the putative pre-SMA cluster were connected to brain regions which are responsible for complex/cognitive motor control, whereas those from the putative SMA cluster were connected to brain regions which are related to the simple motor control. These findings demonstrate the feasibility of the functional connectivity-based parcellation of the human cerebral cortex using resting state fMRI. Copyright (c) 2009 Elsevier Inc. All rights reserved.

Testing a dual-systems model of adolescent brain development using resting-state connectivity analyses.

PubMed

van Duijvenvoorde, A C K; Achterberg, M; Braams, B R; Peters, S; Crone, E A

2016-01-01

The current study aimed to test a dual-systems model of adolescent brain development by studying changes in intrinsic functional connectivity within and across networks typically associated with cognitive-control and affective-motivational processes. To this end, resting-state and task-related fMRI data were collected of 269 participants (ages 8-25). Resting-state analyses focused on seeds derived from task-related neural activation in the same participants: the dorsal lateral prefrontal cortex (dlPFC) from a cognitive rule-learning paradigm and the nucleus accumbens (NAcc) from a reward-paradigm. Whole-brain seed-based resting-state analyses showed an age-related increase in dlPFC connectivity with the caudate and thalamus, and an age-related decrease in connectivity with the (pre)motor cortex. nAcc connectivity showed a strengthening of connectivity with the dorsal anterior cingulate cortex (ACC) and subcortical structures such as the hippocampus, and a specific age-related decrease in connectivity with the ventral medial PFC (vmPFC). Behavioral measures from both functional paradigms correlated with resting-state connectivity strength with their respective seed. That is, age-related change in learning performance was mediated by connectivity between the dlPFC and thalamus, and age-related change in winning pleasure was mediated by connectivity between the nAcc and vmPFC. These patterns indicate (i) strengthening of connectivity between regions that support control and learning, (ii) more independent functioning of regions that support motor and control networks, and (iii) more independent functioning of regions that support motivation and valuation networks with age. These results are interpreted vis-à-vis a dual-systems model of adolescent brain development. Copyright © 2015. Published by Elsevier Inc.

Dynamic connectivity states estimated from resting fMRI Identify differences among Schizophrenia, bipolar disorder, and healthy control subjects.

PubMed

Rashid, Barnaly; Damaraju, Eswar; Pearlson, Godfrey D; Calhoun, Vince D

2014-01-01

Schizophrenia (SZ) and bipolar disorder (BP) share significant overlap in clinical symptoms, brain characteristics, and risk genes, and both are associated with dysconnectivity among large-scale brain networks. Resting state functional magnetic resonance imaging (rsfMRI) data facilitates studying macroscopic connectivity among distant brain regions. Standard approaches to identifying such connectivity include seed-based correlation and data-driven clustering methods such as independent component analysis (ICA) but typically focus on average connectivity. In this study, we utilize ICA on rsfMRI data to obtain intrinsic connectivity networks (ICNs) in cohorts of healthy controls (HCs) and age matched SZ and BP patients. Subsequently, we investigated difference in functional network connectivity, defined as pairwise correlations among the timecourses of ICNs, between HCs and patients. We quantified differences in both static (average) and dynamic (windowed) connectivity during the entire scan duration. Disease-specific differences were identified in connectivity within different dynamic states. Notably, results suggest that patients make fewer transitions to some states (states 1, 2, and 4) compared to HCs, with most such differences confined to a single state. SZ patients showed more differences from healthy subjects than did bipolars, including both hyper and hypo connectivity in one common connectivity state (dynamic state 3). Also group differences between SZ and bipolar patients were identified in patterns (states) of connectivity involving the frontal (dynamic state 1) and frontal-parietal regions (dynamic state 3). Our results provide new information about these illnesses and strongly suggest that state-based analyses are critical to avoid averaging together important factors that can help distinguish these clinical groups.

Sources of Disconnection in Neurocognitive Aging: Cerebral White Matter Integrity, Resting-state Functional Connectivity, and White Matter Hyperintensity Volume

PubMed Central

Madden, David J.; Parks, Emily L.; Tallman, Catherine W.; Boylan, Maria A.; Hoagey, David A.; Cocjin, Sally B.; Packard, Lauren E.; Johnson, Micah A.; Chou, Ying-hui; Potter, Guy G.; Chen, Nan-kuei; Siciliano, Rachel E.; Monge, Zachary A.; Honig, Jesse A.; Diaz, Michele T.

2017-01-01

Age-related decline in fluid cognition can be characterized as a disconnection among specific brain structures, leading to a decline in functional efficiency. The potential sources of disconnection, however, are unclear. We investigated imaging measures of cerebral white matter integrity, resting-state functional connectivity, and white matter hyperintensity (WMH) volume as mediators of the relation between age and fluid cognition, in 145 healthy, community-dwelling adults 19–79 years of age. At a general level of analysis, with a single composite measure of fluid cognition and single measures of each of the three imaging modalities, age exhibited an independent influence on the cognitive and imaging measures, and the imaging variables did not mediate the age-cognition relation. At a more specific level of analysis, resting-state functional connectivity of sensorimotor networks was a significant mediator of the age-related decline in executive function. These findings suggest that different levels of analysis lead to different models of neurocognitive disconnection, and that resting-state functional connectivity, in particular, may contribute to age-related decline in executive function. PMID:28389085

Increased resting state functional connectivity in the fronto-parietal and default mode network in anorexia nervosa

PubMed Central

Boehm, Ilka; Geisler, Daniel; King, Joseph A.; Ritschel, Franziska; Seidel, Maria; Deza Araujo, Yacila; Petermann, Juliane; Lohmeier, Heidi; Weiss, Jessika; Walter, Martin; Roessner, Veit; Ehrlich, Stefan

2014-01-01

The etiology of anorexia nervosa (AN) is poorly understood. Results from functional brain imaging studies investigating the neural profile of AN using cognitive and emotional task paradigms are difficult to reconcile. Task-related imaging studies often require a high level of compliance and can only partially explore the distributed nature and complexity of brain function. In this study, resting state functional connectivity imaging was used to investigate well-characterized brain networks potentially relevant to understand the neural mechanisms underlying the symptomatology and etiology of AN. Resting state functional magnetic resonance imaging data was obtained from 35 unmedicated female acute AN patients and 35 closely matched healthy controls female participants (HC) and decomposed using spatial group independent component analyses (ICA). Using validated templates, we identified components covering the fronto-parietal “control” network, the default mode network (DMN), the salience network, the visual and the sensory-motor network. Group comparison revealed an increased functional connectivity between the angular gyrus and the other parts of the fronto-parietal network in patients with AN in comparison to HC. Connectivity of the angular gyrus was positively associated with self-reported persistence in HC. In the DMN, AN patients also showed an increased functional connectivity strength in the anterior insula in comparison to HC. Anterior insula connectivity was associated with self-reported problems with interoceptive awareness. This study, with one of the largest sample to date, shows that acute AN is associated with abnormal brain connectivity in two major resting state networks (RSN). The finding of an increased functional connectivity in the fronto-parietal network adds novel support for the notion of AN as a disorder of excessive cognitive control, whereas the elevated functional connectivity of the anterior insula with the DMN may reflect the high levels of self- and body-focused ruminations when AN patients are at rest. PMID:25324749

Resting-State fMRI Functional Connectivity Is Associated with Sleepiness, Imagery, and Discontinuity of Mind

PubMed Central

Chen, Gang; den Braber, Anouk; van ‘t Ent, Dennis; Boomsma, Dorret I.; Mansvelder, Huibert D.; de Geus, Eco; Van Someren, Eus J. W.; Linkenkaer-Hansen, Klaus

2015-01-01

Resting-state functional magnetic resonance imaging (rs-fMRI) is widely used to investigate the functional architecture of the healthy human brain and how it is affected by learning, lifelong development, brain disorders or pharmacological intervention. Non-sensory experiences are prevalent during rest and must arise from ongoing brain activity, yet little is known about this relationship. Here, we used two runs of rs-fMRI both immediately followed by the Amsterdam Resting-State Questionnaire (ARSQ) to investigate the relationship between functional connectivity within ten large-scale functional brain networks and ten dimensions of thoughts and feelings experienced during the scan in 106 healthy participants. We identified 11 positive associations between brain-network functional connectivity and ARSQ dimensions. ‘Sleepiness’ exhibited significant associations with functional connectivity within Visual, Sensorimotor and Default Mode networks. Similar associations were observed for ‘Visual Thought’ and ‘Discontinuity of Mind’, which may relate to variation in imagery and thought control mediated by arousal fluctuations. Our findings show that self-reports of thoughts and feelings experienced during a rs-fMRI scan help understand the functional significance of variations in functional connectivity, which should be of special relevance to clinical studies. PMID:26540239

White Matter Connectivity of the Thalamus Delineates the Functional Architecture of Competing Thalamocortical Systems

PubMed Central

O'Muircheartaigh, Jonathan; Keller, Simon S.; Barker, Gareth J.; Richardson, Mark P.

2015-01-01

There is an increasing awareness of the involvement of thalamic connectivity on higher level cortical functioning in the human brain. This is reflected by the influence of thalamic stimulation on cortical activity and behavior as well as apparently cortical lesion syndromes occurring as a function of small thalamic insults. Here, we attempt to noninvasively test the correspondence of structural and functional connectivity of the human thalamus using diffusion-weighted and resting-state functional MRI. Using a large sample of 102 adults, we apply tensor independent component analysis to diffusion MRI tractography data to blindly parcellate bilateral thalamus according to diffusion tractography-defined structural connectivity. Using resting-state functional MRI collected in the same subjects, we show that the resulting structurally defined thalamic regions map to spatially distinct, and anatomically predictable, whole-brain functional networks in the same subjects. Although there was significant variability in the functional connectivity patterns, the resulting 51 structural and functional patterns could broadly be reduced to a subset of 7 similar core network types. These networks were distinct from typical cortical resting-state networks. Importantly, these networks were distributed across the brain and, in a subset, map extremely well to known thalamocortico-basal-ganglial loops. PMID:25899706

Fine-Grained Parcellation of Brain Connectivity Improves Differentiation of States of Consciousness During Graded Propofol Sedation.

PubMed

Liu, Xiaolin; Lauer, Kathryn K; Ward, B Douglas; Roberts, Christopher J; Liu, Suyan; Gollapudy, Suneeta; Rohloff, Robert; Gross, William; Xu, Zhan; Chen, Guangyu; Binder, Jeffrey R; Li, Shi-Jiang; Hudetz, Anthony G

2017-08-01

Conscious perception relies on interactions between spatially and functionally distinct modules of the brain at various spatiotemporal scales. These interactions are altered by anesthesia, an intervention that leads to fading consciousness. Relatively little is known about brain functional connectivity and its anesthetic modulation at a fine spatial scale. Here, we used functional imaging to examine propofol-induced changes in functional connectivity in brain networks defined at a fine-grained parcellation based on a combination of anatomical and functional features. Fifteen healthy volunteers underwent resting-state functional imaging in wakeful baseline, mild sedation, deep sedation, and recovery of consciousness. Compared with wakeful baseline, propofol produced widespread, dose-dependent functional connectivity changes that scaled with the extent to which consciousness was altered. The dominant changes in connectivity were associated with the frontal lobes. By examining node pairs that demonstrated a trend of functional connectivity change between wakefulness and deep sedation, quadratic discriminant analysis differentiated the states of consciousness in individual participants more accurately at a fine-grained parcellation (e.g., 2000 nodes) than at a coarse-grained parcellation (e.g., 116 anatomical nodes). Our study suggests that defining brain networks at a high granularity may provide a superior imaging-based distinction of the graded effect of anesthesia on consciousness.

Dynamic Functional Connectivity States Reflecting Psychotic-like Experiences.

PubMed

Barber, Anita D; Lindquist, Martin A; DeRosse, Pamela; Karlsgodt, Katherine H

2018-05-01

Psychotic-like experiences (PLEs) are associated with lower social and occupational functioning, and lower executive function. Emerging evidence also suggests that PLEs reflect neural dysfunction resembling that of psychotic disorders. The present study examined dynamic connectivity related to a measure of PLEs derived from the Achenbach Adult Self-Report, in an otherwise-healthy sample of adults from the Human Connectome Project. A total of 76 PLE-endorsing and 153 control participants were included in the final sample. To characterize network dysfunction, dynamic connectivity states were examined across large-scale resting-state networks using dynamic conditional correlation and k-means clustering. Three dynamic states were identified. The PLE-endorsing group spent more time than the control group in state 1, a state reflecting hyperconnectivity within visual regions and hypoconnectivity within the default mode network, and less time in state 2, a state characterized by robust within-network connectivity for all networks and strong default mode network anticorrelations. Within the PLE-endorsing group, worse executive function was associated with more time spent in and more transitions into state 1 and less time spent in and fewer transitions into state 3. PLEs are associated with altered large-scale brain dynamics, which tip the system away from spending more time in states reflecting more "typical" connectivity patterns toward more time in states reflecting visual hyperconnectivity and default mode hypoconnectivity. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Disrupted resting-state functional connectivity in minimally treated chronic schizophrenia.

PubMed

Wang, Xijin; Xia, Mingrui; Lai, Yunyao; Dai, Zhengjia; Cao, Qingjiu; Cheng, Zhang; Han, Xue; Yang, Lei; Yuan, Yanbo; Zhang, Yong; Li, Keqing; Ma, Hong; Shi, Chuan; Hong, Nan; Szeszko, Philip; Yu, Xin; He, Yong

2014-07-01

The pathophysiology of chronic schizophrenia may reflect long term brain changes related to the disorder. The effect of chronicity on intrinsic functional connectivity patterns in schizophrenia without the potentially confounding effect of antipsychotic medications, however, remains largely unknown. We collected resting-state fMRI data in 21 minimally treated chronic schizophrenia patients and 20 healthy controls. We computed regional functional connectivity strength for each voxel in the brain, and further divided regional functional connectivity strength into short-range regional functional connectivity strength and long-range regional functional connectivity strength. General linear models were used to detect between-group differences in these regional functional connectivity strength metrics and to further systematically investigate the relationship between these differences and clinical/behavioral variables in the patients. Compared to healthy controls, the minimally treated chronic schizophrenia patients showed an overall reduced regional functional connectivity strength especially in bilateral sensorimotor cortex, right lateral prefrontal cortex, left insula and right lingual gyrus, and these regional functional connectivity strength decreases mainly resulted from disruption of short-range regional functional connectivity strength. The minimally treated chronic schizophrenia patients also showed reduced long-range regional functional connectivity strength in the bilateral posterior cingulate cortex/precuneus, and increased long-range regional functional connectivity strength in the right lateral prefrontal cortex and lingual gyrus. Notably, disrupted short-range regional functional connectivity strength mainly correlated with duration of illness and negative symptoms, whereas disrupted long-range regional functional connectivity strength correlated with neurocognitive performance. All of the results were corrected using Monte-Carlo simulation. This exploratory study demonstrates a disruption of intrinsic functional connectivity without long-term exposure to antipsychotic medications in chronic schizophrenia. Furthermore, this disruption was connection-distance dependent, thus raising the possibility for differential neural pathways in neurocognitive impairment and psychiatric symptoms in schizophrenia. Copyright © 2014 Elsevier B.V. All rights reserved.

Altered resting-state functional connectivity in patients with chronic bilateral vestibular failure.

PubMed

Göttlich, Martin; Jandl, Nico M; Wojak, Jann F; Sprenger, Andreas; von der Gablentz, Janina; Münte, Thomas F; Krämer, Ulrike M; Helmchen, Christoph

2014-01-01

Patients with bilateral vestibular failure (BVF) suffer from gait unsteadiness, oscillopsia and impaired spatial orientation. Brain imaging studies applying caloric irrigation to patients with BVF have shown altered neural activity of cortical visual-vestibular interaction: decreased bilateral neural activity in the posterior insula and parietal operculum and decreased deactivations in the visual cortex. It is unknown how this affects functional connectivity in the resting brain and how changes in connectivity are related to vestibular impairment. We applied a novel data driven approach based on graph theory to investigate altered whole-brain resting-state functional connectivity in BVF patients (n= 22) compared to age- and gender-matched healthy controls (n= 25) using resting-state fMRI. Changes in functional connectivity were related to subjective (vestibular scores) and objective functional parameters of vestibular impairment, specifically, the adaptive changes during active (self-guided) and passive (investigator driven) head impulse test (HIT) which reflects the integrity of the vestibulo-ocular reflex (VOR). BVF patients showed lower bilateral connectivity in the posterior insula and parietal operculum but higher connectivity in the posterior cerebellum compared to controls. Seed-based analysis revealed stronger connectivity from the right posterior insula to the precuneus, anterior insula, anterior cingulate cortex and the middle frontal gyrus. Excitingly, functional connectivity in the supramarginal gyrus (SMG) of the inferior parietal lobe and posterior cerebellum correlated with the increase of VOR gain during active as compared to passive HIT, i.e., the larger the adaptive VOR changes the larger was the increase in regional functional connectivity. Using whole brain resting-state connectivity analysis in BVF patients we show that enduring bilateral deficient or missing vestibular input leads to changes in resting-state connectivity of the brain. These changes in the resting brain are robust and task-independent as they were found in the absence of sensory stimulation and without a region-related a priori hypothesis. Therefore they may indicate a fundamental disease-related change in the resting brain. They may account for the patients' persistent deficits in visuo-spatial attention, spatial orientation and unsteadiness. The relation of increasing connectivity in the inferior parietal lobe, specifically SMG, to improvement of VOR during active head movements reflects cortical plasticity in BVF and may play a clinical role in vestibular rehabilitation.

Localized reductions in resting-state functional connectivity in children with prenatal alcohol exposure.

PubMed

Fan, Jia; Taylor, Paul A; Jacobson, Sandra W; Molteno, Christopher D; Gohel, Suril; Biswal, Bharat B; Jacobson, Joseph L; Meintjes, Ernesta M

2017-10-01

Fetal alcohol spectrum disorders (FASD) are characterized by impairment in cognitive function that may or may not be accompanied by craniofacial anomalies, microcephaly, and/or growth retardation. Resting-state functional MRI (rs-fMRI), which examines the low-frequency component of the blood oxygen level dependent (BOLD) signal in the absence of an explicit task, provides an efficient and powerful mechanism for studying functional brain networks even in low-functioning and young subjects. Studies using independent component analysis (ICA) have identified a set of resting-state networks (RSNs) that have been linked to distinct domains of cognitive and perceptual function, which are believed to reflect the intrinsic functional architecture of the brain. This study is the first to examine resting-state functional connectivity within these RSNs in FASD. Rs-fMRI scans were performed on 38 children with FASD (19 with either full fetal alcohol syndrome (FAS) or partial FAS (PFAS), 19 nonsyndromal heavily exposed (HE)), and 19 controls, mean age 11.3 ± 0.9 years, from the Cape Town Longitudinal Cohort. Nine resting-state networks were generated by ICA. Voxelwise group comparison between a combined FAS/PFAS group and controls revealed localized dose-dependent functional connectivity reductions in five regions in separate networks: anterior default mode, salience, ventral and dorsal attention, and R executive control. The former three also showed lower connectivity in the HE group. Gray matter connectivity deficits in four of the five networks appear to be related to deficits in white matter tracts that provide intra-RSN connections. Hum Brain Mapp 38:5217-5233, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Spontaneous eyelid closures link vigilance fluctuation with fMRI dynamic connectivity states

PubMed Central

Wang, Chenhao; Ong, Ju Lynn; Patanaik, Amiya; Chee, Michael W. L.

2016-01-01

Fluctuations in resting-state functional connectivity occur but their behavioral significance remains unclear, largely because correlating behavioral state with dynamic functional connectivity states (DCS) engages probes that disrupt the very behavioral state we seek to observe. Observing spontaneous eyelid closures following sleep deprivation permits nonintrusive arousal monitoring. During periods of low arousal dominated by eyelid closures, sliding-window correlation analysis uncovered a DCS associated with reduced within-network functional connectivity of default mode and dorsal/ventral attention networks, as well as reduced anticorrelation between these networks. Conversely, during periods when participants’ eyelids were wide open, a second DCS was associated with less decoupling between the visual network and higher-order cognitive networks that included dorsal/ventral attention and default mode networks. In subcortical structures, eyelid closures were associated with increased connectivity between the striatum and thalamus with the ventral attention network, and greater anticorrelation with the dorsal attention network. When applied to task-based fMRI data, these two DCS predicted interindividual differences in frequency of behavioral lapsing and intraindividual temporal fluctuations in response speed. These findings with participants who underwent a night of total sleep deprivation were replicated in an independent dataset involving partially sleep-deprived participants. Fluctuations in functional connectivity thus appear to be clearly associated with changes in arousal. PMID:27512040

Comparison of continuously acquired resting state and extracted analogues from active tasks.

PubMed

Ganger, Sebastian; Hahn, Andreas; Küblböck, Martin; Kranz, Georg S; Spies, Marie; Vanicek, Thomas; Seiger, René; Sladky, Ronald; Windischberger, Christian; Kasper, Siegfried; Lanzenberger, Rupert

2015-10-01

Functional connectivity analysis of brain networks has become an important tool for investigation of human brain function. Although functional connectivity computations are usually based on resting-state data, the application to task-specific fMRI has received growing attention. Three major methods for extraction of resting-state data from task-related signal have been proposed (1) usage of unmanipulated task data for functional connectivity; (2) regression against task effects, subsequently using the residuals; and (3) concatenation of baseline blocks located in-between task blocks. Despite widespread application in current research, consensus on which method best resembles resting-state seems to be missing. We, therefore, evaluated these techniques in a sample of 26 healthy controls measured at 7 Tesla. In addition to continuous resting-state, two different task paradigms were assessed (emotion discrimination and right finger-tapping) and five well-described networks were analyzed (default mode, thalamus, cuneus, sensorimotor, and auditory). Investigating the similarity to continuous resting-state (Dice, Intraclass correlation coefficient (ICC), R(2) ) showed that regression against task effects yields functional connectivity networks most alike to resting-state. However, all methods exhibited significant differences when compared to continuous resting-state and similarity metrics were lower than test-retest of two resting-state scans. Omitting global signal regression did not change these findings. Visually, the networks are highly similar, but through further investigation marked differences can be found. Therefore, our data does not support referring to resting-state when extracting signals from task designs, although functional connectivity computed from task-specific data may indeed yield interesting information. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

Comparison of continuously acquired resting state and extracted analogues from active tasks

PubMed Central

Ganger, Sebastian; Hahn, Andreas; Küblböck, Martin; Kranz, Georg S.; Spies, Marie; Vanicek, Thomas; Seiger, René; Sladky, Ronald; Windischberger, Christian; Kasper, Siegfried

2015-01-01

Abstract Functional connectivity analysis of brain networks has become an important tool for investigation of human brain function. Although functional connectivity computations are usually based on resting‐state data, the application to task‐specific fMRI has received growing attention. Three major methods for extraction of resting‐state data from task‐related signal have been proposed (1) usage of unmanipulated task data for functional connectivity; (2) regression against task effects, subsequently using the residuals; and (3) concatenation of baseline blocks located in‐between task blocks. Despite widespread application in current research, consensus on which method best resembles resting‐state seems to be missing. We, therefore, evaluated these techniques in a sample of 26 healthy controls measured at 7 Tesla. In addition to continuous resting‐state, two different task paradigms were assessed (emotion discrimination and right finger‐tapping) and five well‐described networks were analyzed (default mode, thalamus, cuneus, sensorimotor, and auditory). Investigating the similarity to continuous resting‐state (Dice, Intraclass correlation coefficient (ICC), R 2) showed that regression against task effects yields functional connectivity networks most alike to resting‐state. However, all methods exhibited significant differences when compared to continuous resting‐state and similarity metrics were lower than test‐retest of two resting‐state scans. Omitting global signal regression did not change these findings. Visually, the networks are highly similar, but through further investigation marked differences can be found. Therefore, our data does not support referring to resting‐state when extracting signals from task designs, although functional connectivity computed from task‐specific data may indeed yield interesting information. Hum Brain Mapp 36:4053–4063, 2015. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. PMID:26178250

Differences in Resting State Functional Connectivity between Young Adult Endurance Athletes and Healthy Controls

PubMed Central

Raichlen, David A.; Bharadwaj, Pradyumna K.; Fitzhugh, Megan C.; Haws, Kari A.; Torre, Gabrielle-Ann; Trouard, Theodore P.; Alexander, Gene E.

2016-01-01

Expertise and training in fine motor skills has been associated with changes in brain structure, function, and connectivity. Fewer studies have explored the neural effects of athletic activities that do not seem to rely on precise fine motor control (e.g., distance running). Here, we compared resting-state functional connectivity in a sample of adult male collegiate distance runners (n = 11; age = 21.3 ± 2.5) and a group of healthy age-matched non-athlete male controls (n = 11; age = 20.6 ± 1.1), to test the hypothesis that expertise in sustained aerobic motor behaviors affects resting state functional connectivity in young adults. Although generally considered an automated repetitive task, locomotion, especially at an elite level, likely engages multiple cognitive actions including planning, inhibition, monitoring, attentional switching and multi-tasking, and motor control. Here, we examined connectivity in three resting-state networks that link such executive functions with motor control: the default mode network (DMN), the frontoparietal network (FPN), and the motor network (MN). We found two key patterns of significant between-group differences in connectivity that are consistent with the hypothesized cognitive demands of elite endurance running. First, enhanced connectivity between the FPN and brain regions often associated with aspects of working memory and other executive functions (frontal cortex), suggest endurance running may stress executive cognitive functions in ways that increase connectivity in associated networks. Second, we found significant anti-correlations between the DMN and regions associated with motor control (paracentral area), somatosensory functions (post-central region), and visual association abilities (occipital cortex). DMN deactivation with task-positive regions has been shown to be generally beneficial for cognitive performance, suggesting anti-correlated regions observed here are engaged during running. For all between-group differences, there were significant associations between connectivity, self-reported physical activity, and estimates of maximum aerobic capacity, suggesting a dose-response relationship between engagement in endurance running and connectivity strength. Together these results suggest that differences in experience with endurance running are associated with differences in functional brain connectivity. High intensity aerobic activity that requires sustained, repetitive locomotor and navigational skills may stress cognitive domains in ways that lead to altered brain connectivity, which in turn has implications for understanding the beneficial role of exercise for brain and cognitive function over the lifespan. PMID:28018192

Altered interhemispheric functional connectivity in patients with anisometropic and strabismic amblyopia: a resting-state fMRI study.

PubMed

Liang, Minglong; Xie, Bing; Yang, Hong; Yin, Xuntao; Wang, Hao; Yu, Longhua; He, Sheng; Wang, Jian

2017-05-01

Altered brain functional connectivity has been reported in patients with amblyopia by recent neuroimaging studies. However, relatively little is known about the alterations in interhemispheric functional connectivity in amblyopia. The present study aimed to investigate the functional connectivity patterns between homotopic regions across hemispheres in patients with anisometropic and strabismic amblyopia under resting state. Nineteen monocular anisometropic amblyopia (AA), 18 strabismic amblyopia (SA), and 20 normal-sight controls (NC) were enrolled in this study. After a comprehensive ophthalmologic examination, resting-state fMRI scanning was performed in all participants. The pattern of the interhemispheric functional connectivity was measured with the voxel-mirrored homotopic connectivity (VMHC) approach. VMHC values differences within and between three groups were compared, and correlations between VMHC values and each the clinical variable were also analyzed. Altered VMHC was observed in AA and SA patients in lingual gyrus and fusiform gyrus compared with NC subjects. The altered VMHC of lingual gyrus showed a pattern of AA > SA > NC, while the altered VMHC of fusiform gyrus showed a pattern of AA > NC > SA. Moreover, the VMHC values of lingual gyrus were positively correlated with the stereoacuity both in AA and SA patients, and the VMHC values of fusiform gyrus were positively correlated with the amount of anisometropia just in AA patients. These findings suggest that interhemispheric functional coordination between several homotopic visual-related brain regions is impaired both in AA and SA patients under resting state and revealed the similarities and differences in interhemispheric functional connectivity between the anisometropic and strabismic amblyopia.

Impact of 36 h of total sleep deprivation on resting-state dynamic functional connectivity.

PubMed

Xu, Huaze; Shen, Hui; Wang, Lubin; Zhong, Qi; Lei, Yu; Yang, Liu; Zeng, Ling-Li; Zhou, Zongtan; Hu, Dewen; Yang, Zheng

2018-06-01

Resting-state functional magnetic resonance imaging (fMRI) studies using static functional connectivity (sFC) measures have shown that the brain function is severely disrupted after long-term sleep deprivation (SD). However, increasing evidence has suggested that resting-state functional connectivity (FC) is dynamic and exhibits spontaneous fluctuation on a smaller timescale. The process by which long-term SD can influence dynamic functional connectivity (dFC) remains unclear. In this study, 37 healthy subjects participated in the SD experiment, and they were scanned both during rested wakefulness (RW) and after 36 h of SD. A sliding-window based approach and a spectral clustering algorithm were used to evaluate the effects of SD on dFC based on the 26 qualified subjects' data. The outcomes showed that time-averaging FC across specific regions as well as temporal properties of the FC states, such as the dwell time and transition probability, was strongly influenced after SD in contrast to the RW condition. Based on the occurrences of FC states, we further identified some RW-dominant states characterized by anti-correlation between the default mode network (DMN) and other cortices, and some SD-dominant states marked by significantly decreased thalamocortical connectivity. In particular, the temporal features of these FC states were negatively correlated with the correlation coefficients between the DMN and dorsal attention network (dATN) and demonstrated high potential in classification of sleep state (with 10-fold cross-validation accuracy of 88.6% for dwell time and 88.1% for transition probability). Collectively, our results suggested that the temporal properties of the FC states greatly account for changes in the resting-state brain networks following SD, which provides new insights into the impact of SD on the resting-state functional organization in the human brain. Copyright © 2017. Published by Elsevier B.V.

Measuring Brain Connectivity: Diffusion Tensor Imaging Validates Resting State Temporal Correlations

PubMed Central

Skudlarski, Pawel; Jagannathan, Kanchana; Calhoun, Vince D.; Hampson, Michelle; Skudlarska, Beata A.; Pearlson, Godfrey

2015-01-01

Diffusion tensor imaging (DTI) and resting state temporal correlations (RSTC) are two leading techniques for investigating the connectivity of the human brain. They have been widely used to investigate the strength of anatomical and functional connections between distant brain regions in healthy subjects, and in clinical populations. Though they are both based on magnetic resonance imaging (MRI) they have not yet been compared directly. In this work both techniques were employed to create global connectivity matrices covering the whole brain gray matter. This allowed for direct comparisons between functional connectivity measured by RSTC with anatomical connectivity quantified using DTI tractography. We found that connectivity matrices obtained using both techniques showed significant agreement. Connectivity maps created for a priori defined anatomical regions showed significant correlation, and furthermore agreement was especially high in regions showing strong overall connectivity, such as those belonging to the default mode network. Direct comparison between functional RSTC and anatomical DTI connectivity, presented here for the first time, links two powerful approaches for investigating brain connectivity and shows their strong agreement. It provides a crucial multi-modal validation for resting state correlations as representing neuronal connectivity. The combination of both techniques presented here allows for further combining them to provide richer representation of brain connectivity both in the healthy brain and in clinical conditions. PMID:18771736

Measuring brain connectivity: diffusion tensor imaging validates resting state temporal correlations.

PubMed

Skudlarski, Pawel; Jagannathan, Kanchana; Calhoun, Vince D; Hampson, Michelle; Skudlarska, Beata A; Pearlson, Godfrey

2008-11-15

Diffusion tensor imaging (DTI) and resting state temporal correlations (RSTC) are two leading techniques for investigating the connectivity of the human brain. They have been widely used to investigate the strength of anatomical and functional connections between distant brain regions in healthy subjects, and in clinical populations. Though they are both based on magnetic resonance imaging (MRI) they have not yet been compared directly. In this work both techniques were employed to create global connectivity matrices covering the whole brain gray matter. This allowed for direct comparisons between functional connectivity measured by RSTC with anatomical connectivity quantified using DTI tractography. We found that connectivity matrices obtained using both techniques showed significant agreement. Connectivity maps created for a priori defined anatomical regions showed significant correlation, and furthermore agreement was especially high in regions showing strong overall connectivity, such as those belonging to the default mode network. Direct comparison between functional RSTC and anatomical DTI connectivity, presented here for the first time, links two powerful approaches for investigating brain connectivity and shows their strong agreement. It provides a crucial multi-modal validation for resting state correlations as representing neuronal connectivity. The combination of both techniques presented here allows for further combining them to provide richer representation of brain connectivity both in the healthy brain and in clinical conditions.

Correlated gene expression and anatomical communication support synchronized brain activity in the mouse functional connectome.

PubMed

Mills, Brian D; Grayson, David S; Shunmugavel, Anandakumar; Miranda-Dominguez, Oscar; Feczko, Eric; Earl, Eric; Neve, Kim; Fair, Damien A

2018-05-22

Cognition and behavior depend on synchronized intrinsic brain activity that is organized into functional networks across the brain. Research has investigated how anatomical connectivity both shapes and is shaped by these networks, but not how anatomical connectivity interacts with intra-areal molecular properties to drive functional connectivity. Here, we present a novel linear model to explain functional connectivity by integrating systematically obtained measurements of axonal connectivity, gene expression, and resting state functional connectivity MRI in the mouse brain. The model suggests that functional connectivity arises from both anatomical links and inter-areal similarities in gene expression. By estimating these effects, we identify anatomical modules in which correlated gene expression and anatomical connectivity support functional connectivity. Along with providing evidence that not all genes equally contribute to functional connectivity, this research establishes new insights regarding the biological underpinnings of coordinated brain activity measured by BOLD fMRI. SIGNIFICANCE STATEMENT Efforts at characterizing the functional connectome with fMRI have risen exponentially over the last decade. Yet despite this rise, the biological underpinnings of these functional measurements are still largely unknown. The current report begins to fill this void by investigating the molecular underpinnings of the functional connectome through an integration of systematically obtained structural information and gene expression data throughout the rodent brain. We find that both white matter connectivity and similarity in regional gene expression relate to resting state functional connectivity. The current report furthers our understanding of the biological underpinnings of the functional connectome and provides a linear model that can be utilized to streamline preclinical animal studies of disease. Copyright © 2018 the authors.

How Visual Is the Visual Cortex? Comparing Connectional and Functional Fingerprints between Congenitally Blind and Sighted Individuals.

PubMed

Wang, Xiaoying; Peelen, Marius V; Han, Zaizhu; He, Chenxi; Caramazza, Alfonso; Bi, Yanchao

2015-09-09

Classical animal visual deprivation studies and human neuroimaging studies have shown that visual experience plays a critical role in shaping the functionality and connectivity of the visual cortex. Interestingly, recent studies have additionally reported circumscribed regions in the visual cortex in which functional selectivity was remarkably similar in individuals with and without visual experience. Here, by directly comparing resting-state and task-based fMRI data in congenitally blind and sighted human subjects, we obtained large-scale continuous maps of the degree to which connectional and functional "fingerprints" of ventral visual cortex depend on visual experience. We found a close agreement between connectional and functional maps, pointing to a strong interdependence of connectivity and function. Visual experience (or the absence thereof) had a pronounced effect on the resting-state connectivity and functional response profile of occipital cortex and the posterior lateral fusiform gyrus. By contrast, connectional and functional fingerprints in the anterior medial and posterior lateral parts of the ventral visual cortex were statistically indistinguishable between blind and sighted individuals. These results provide a large-scale mapping of the influence of visual experience on the development of both functional and connectivity properties of visual cortex, which serves as a basis for the formulation of new hypotheses regarding the functionality and plasticity of specific subregions. Significance statement: How is the functionality and connectivity of the visual cortex shaped by visual experience? By directly comparing resting-state and task-based fMRI data in congenitally blind and sighted subjects, we obtained large-scale continuous maps of the degree to which connectional and functional "fingerprints" of ventral visual cortex depend on visual experience. In addition to revealing regions that are strongly dependent on visual experience (early visual cortex and posterior fusiform gyrus), our results showed regions in which connectional and functional patterns are highly similar in blind and sighted individuals (anterior medial and posterior lateral ventral occipital temporal cortex). These results serve as a basis for the formulation of new hypotheses regarding the functionality and plasticity of specific subregions of the visual cortex. Copyright © 2015 the authors 0270-6474/15/3512545-15$15.00/0.

Opportunities and methodological challenges in EEG and MEG resting state functional brain network research.

PubMed

van Diessen, E; Numan, T; van Dellen, E; van der Kooi, A W; Boersma, M; Hofman, D; van Lutterveld, R; van Dijk, B W; van Straaten, E C W; Hillebrand, A; Stam, C J

2015-08-01

Electroencephalogram (EEG) and magnetoencephalogram (MEG) recordings during resting state are increasingly used to study functional connectivity and network topology. Moreover, the number of different analysis approaches is expanding along with the rising interest in this research area. The comparison between studies can therefore be challenging and discussion is needed to underscore methodological opportunities and pitfalls in functional connectivity and network studies. In this overview we discuss methodological considerations throughout the analysis pipeline of recording and analyzing resting state EEG and MEG data, with a focus on functional connectivity and network analysis. We summarize current common practices with their advantages and disadvantages; provide practical tips, and suggestions for future research. Finally, we discuss how methodological choices in resting state research can affect the construction of functional networks. When taking advantage of current best practices and avoid the most obvious pitfalls, functional connectivity and network studies can be improved and enable a more accurate interpretation and comparison between studies. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Structural and functional cerebral correlates of hypnotic suggestibility.

PubMed

Huber, Alexa; Lui, Fausta; Duzzi, Davide; Pagnoni, Giuseppe; Porro, Carlo Adolfo

2014-01-01

Little is known about the neural bases of hypnotic suggestibility, a cognitive trait referring to the tendency to respond to hypnotic suggestions. In the present magnetic resonance imaging study, we performed regression analyses to assess hypnotic suggestibility-related differences in local gray matter volume, using voxel-based morphometry, and in waking resting state functional connectivity of 10 resting state networks, in 37 healthy women. Hypnotic suggestibility was positively correlated with gray matter volume in portions of the left superior and medial frontal gyri, roughly overlapping with the supplementary and pre-supplementary motor area, and negatively correlated with gray matter volume in the left superior temporal gyrus and insula. In the functional connectivity analysis, hypnotic suggestibility was positively correlated with functional connectivity between medial posterior areas, including bilateral posterior cingulate cortex and precuneus, and both the lateral visual network and the left fronto-parietal network; a positive correlation was also found with functional connectivity between the executive-control network and a right postcentral/parietal area. In contrast, hypnotic suggestibility was negatively correlated with functional connectivity between the right fronto-parietal network and the right lateral thalamus. These findings demonstrate for the first time a correlation between hypnotic suggestibility, the structural features of specific cortical regions, and the functional connectivity during the normal resting state of brain structures involved in imagery and self-monitoring activity.

Resting-state functional connectivity in combat veterans suffering from impulsive aggression

PubMed Central

Heesink, Lieke; van Honk, Jack; Geuze, Elbert

2017-01-01

Abstract Impulsive aggression is common among military personnel after deployment and may arise because of impaired top-down regulation of the amygdala by prefrontal regions. This study sought to further explore this hypothesis via resting-state functional connectivity analyses in impulsively aggressive combat veterans. Male combat veterans with (n = 28) and without (n = 30) impulsive aggression problems underwent resting-state functional magnetic resonance imaging. Functional connectivity analyses were conducted with the following seed-regions: basolateral amygdala (BLA), centromedial amygdala, anterior cingulate cortex (ACC), and anterior insular cortex (AIC). Regions-of-interest analyses focused on the orbitofrontal cortex and periaqueductal gray, and yielded no significant results. In exploratory cluster analyses, we observed reduced functional connectivity between the (bilateral) BLA and left dorsolateral prefrontal cortex in the impulsive aggression group, relative to combat controls. This finding indicates that combat-related impulsive aggression may be marked by weakened functional connectivity between the amygdala and prefrontal regions, already in the absence of explicit emotional stimuli. Group differences in functional connectivity were also observed between the (bilateral) ACC and left cuneus, which may be related to heightened vigilance to potentially threatening visual cues, as well as between the left AIC and right temporal pole, possibly related to negative memory association in impulsive aggression. PMID:29040723

Resting state network topology of the ferret brain.

PubMed

Zhou, Zhe Charles; Salzwedel, Andrew P; Radtke-Schuller, Susanne; Li, Yuhui; Sellers, Kristin K; Gilmore, John H; Shih, Yen-Yu Ian; Fröhlich, Flavio; Gao, Wei

2016-12-01

Resting state functional magnetic resonance imaging (rsfMRI) has emerged as a versatile tool for non-invasive measurement of functional connectivity patterns in the brain. RsfMRI brain dynamics in rodents, non-human primates, and humans share similar properties; however, little is known about the resting state functional connectivity patterns in the ferret, an animal model with high potential for developmental and cognitive translational study. To address this knowledge-gap, we performed rsfMRI on anesthetized ferrets using a 9.4T MRI scanner, and subsequently performed group-level independent component analysis (gICA) to identify functionally connected brain networks. Group-level ICA analysis revealed distributed sensory, motor, and higher-order networks in the ferret brain. Subsequent connectivity analysis showed interconnected higher-order networks that constituted a putative default mode network (DMN), a network that exhibits altered connectivity in neuropsychiatric disorders. Finally, we assessed ferret brain topological efficiency using graph theory analysis and found that the ferret brain exhibits small-world properties. Overall, these results provide additional evidence for pan-species resting-state networks, further supporting ferret-based studies of sensory and cognitive function. Copyright © 2016 Elsevier Inc. All rights reserved.

Mutual connectivity analysis (MCA) using generalized radial basis function neural networks for nonlinear functional connectivity network recovery in resting-state functional MRI

NASA Astrophysics Data System (ADS)

D'Souza, Adora M.; Abidin, Anas Zainul; Nagarajan, Mahesh B.; Wismüller, Axel

2016-03-01

We investigate the applicability of a computational framework, called mutual connectivity analysis (MCA), for directed functional connectivity analysis in both synthetic and resting-state functional MRI data. This framework comprises of first evaluating non-linear cross-predictability between every pair of time series prior to recovering the underlying network structure using community detection algorithms. We obtain the non-linear cross-prediction score between time series using Generalized Radial Basis Functions (GRBF) neural networks. These cross-prediction scores characterize the underlying functionally connected networks within the resting brain, which can be extracted using non-metric clustering approaches, such as the Louvain method. We first test our approach on synthetic models with known directional influence and network structure. Our method is able to capture the directional relationships between time series (with an area under the ROC curve = 0.92 +/- 0.037) as well as the underlying network structure (Rand index = 0.87 +/- 0.063) with high accuracy. Furthermore, we test this method for network recovery on resting-state fMRI data, where results are compared to the motor cortex network recovered from a motor stimulation sequence, resulting in a strong agreement between the two (Dice coefficient = 0.45). We conclude that our MCA approach is effective in analyzing non-linear directed functional connectivity and in revealing underlying functional network structure in complex systems.

Mutual Connectivity Analysis (MCA) Using Generalized Radial Basis Function Neural Networks for Nonlinear Functional Connectivity Network Recovery in Resting-State Functional MRI.

PubMed

DSouza, Adora M; Abidin, Anas Zainul; Nagarajan, Mahesh B; Wismüller, Axel

2016-03-29

We investigate the applicability of a computational framework, called mutual connectivity analysis (MCA), for directed functional connectivity analysis in both synthetic and resting-state functional MRI data. This framework comprises of first evaluating non-linear cross-predictability between every pair of time series prior to recovering the underlying network structure using community detection algorithms. We obtain the non-linear cross-prediction score between time series using Generalized Radial Basis Functions (GRBF) neural networks. These cross-prediction scores characterize the underlying functionally connected networks within the resting brain, which can be extracted using non-metric clustering approaches, such as the Louvain method. We first test our approach on synthetic models with known directional influence and network structure. Our method is able to capture the directional relationships between time series (with an area under the ROC curve = 0.92 ± 0.037) as well as the underlying network structure (Rand index = 0.87 ± 0.063) with high accuracy. Furthermore, we test this method for network recovery on resting-state fMRI data, where results are compared to the motor cortex network recovered from a motor stimulation sequence, resulting in a strong agreement between the two (Dice coefficient = 0.45). We conclude that our MCA approach is effective in analyzing non-linear directed functional connectivity and in revealing underlying functional network structure in complex systems.

Brain dynamics of post-task resting state are influenced by expertise: Insights from baseball players.

PubMed

Muraskin, Jordan; Dodhia, Sonam; Lieberman, Gregory; Garcia, Javier O; Verstynen, Timothy; Vettel, Jean M; Sherwin, Jason; Sajda, Paul

2016-12-01

Post-task resting state dynamics can be viewed as a task-driven state where behavioral performance is improved through endogenous, non-explicit learning. Tasks that have intrinsic value for individuals are hypothesized to produce post-task resting state dynamics that promote learning. We measured simultaneous fMRI/EEG and DTI in Division-1 collegiate baseball players and compared to a group of controls, examining differences in both functional and structural connectivity. Participants performed a surrogate baseball pitch Go/No-Go task before a resting state scan, and we compared post-task resting state connectivity using a seed-based analysis from the supplementary motor area (SMA), an area whose activity discriminated players and controls in our previous results using this task. Although both groups were equally trained on the task, the experts showed differential activity in their post-task resting state consistent with motor learning. Specifically, we found (1) differences in bilateral SMA-L Insula functional connectivity between experts and controls that may reflect group differences in motor learning, (2) differences in BOLD-alpha oscillation correlations between groups suggests variability in modulatory attention in the post-task state, and (3) group differences between BOLD-beta oscillations that may indicate cognitive processing of motor inhibition. Structural connectivity analysis identified group differences in portions of the functionally derived network, suggesting that functional differences may also partially arise from variability in the underlying white matter pathways. Generally, we find that brain dynamics in the post-task resting state differ as a function of subject expertise and potentially result from differences in both functional and structural connectivity. Hum Brain Mapp 37:4454-4471, 2016. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

Resting State Functional Connectivity in Mild Traumatic Brain Injury at the Acute Stage: Independent Component and Seed-Based Analyses

PubMed Central

Iraji, Armin; Benson, Randall R.; Welch, Robert D.; O'Neil, Brian J.; Woodard, John L.; Imran Ayaz, Syed; Kulek, Andrew; Mika, Valerie; Medado, Patrick; Soltanian-Zadeh, Hamid; Liu, Tianming; Haacke, E. Mark

2015-01-01

Abstract Mild traumatic brain injury (mTBI) accounts for more than 1 million emergency visits each year. Most of the injured stay in the emergency department for a few hours and are discharged home without a specific follow-up plan because of their negative clinical structural imaging. Advanced magnetic resonance imaging (MRI), particularly functional MRI (fMRI), has been reported as being sensitive to functional disturbances after brain injury. In this study, a cohort of 12 patients with mTBI were prospectively recruited from the emergency department of our local Level-1 trauma center for an advanced MRI scan at the acute stage. Sixteen age- and sex-matched controls were also recruited for comparison. Both group-based and individual-based independent component analysis of resting-state fMRI (rsfMRI) demonstrated reduced functional connectivity in both posterior cingulate cortex (PCC) and precuneus regions in comparison with controls, which is part of the default mode network (DMN). Further seed-based analysis confirmed reduced functional connectivity in these two regions and also demonstrated increased connectivity between these regions and other regions of the brain in mTBI. Seed-based analysis using the thalamus, hippocampus, and amygdala regions further demonstrated increased functional connectivity between these regions and other regions of the brain, particularly in the frontal lobe, in mTBI. Our data demonstrate alterations of multiple brain networks at the resting state, particularly increased functional connectivity in the frontal lobe, in response to brain concussion at the acute stage. Resting-state functional connectivity of the DMN could serve as a potential biomarker for improved detection of mTBI in the acute setting. PMID:25285363

Multimodal connectivity of motor learning-related dorsal premotor cortex.

PubMed

Hardwick, Robert M; Lesage, Elise; Eickhoff, Claudia R; Clos, Mareike; Fox, Peter; Eickhoff, Simon B

2015-12-01

The dorsal premotor cortex (dPMC) is a key region for motor learning and sensorimotor integration, yet we have limited understanding of its functional interactions with other regions. Previous work has started to examine functional connectivity in several brain areas using resting state functional connectivity (RSFC) and meta-analytical connectivity modelling (MACM). More recently, structural covariance (SC) has been proposed as a technique that may also allow delineation of functional connectivity. Here, we applied these three approaches to provide a comprehensive characterization of functional connectivity with a seed in the left dPMC that a previous meta-analysis of functional neuroimaging studies has identified as playing a key role in motor learning. Using data from two sources (the Rockland sample, containing resting state data and anatomical scans from 132 participants, and the BrainMap database, which contains peak activation foci from over 10,000 experiments), we conducted independent whole-brain functional connectivity mapping analyses of a dPMC seed. RSFC and MACM revealed similar connectivity maps spanning prefrontal, premotor, and parietal regions, while the SC map identified more widespread frontal regions. Analyses indicated a relatively consistent pattern of functional connectivity between RSFC and MACM that was distinct from that identified by SC. Notably, results indicate that the seed is functionally connected to areas involved in visuomotor control and executive functions, suggesting that the dPMC acts as an interface between motor control and cognition. Copyright © 2015 Elsevier Inc. All rights reserved.

The Role of Corpus Callosum Development in Functional Connectivity and Cognitive Processing

PubMed Central

Findlay, Anne M.; Honma, Susanne; Jeremy, Rita J.; Strominger, Zoe; Bukshpun, Polina; Wakahiro, Mari; Brown, Warren S.; Paul, Lynn K.; Barkovich, A. James; Mukherjee, Pratik; Nagarajan, Srikantan S.; Sherr, Elliott H.

2012-01-01

The corpus callosum is hypothesized to play a fundamental role in integrating information and mediating complex behaviors. Here, we demonstrate that lack of normal callosal development can lead to deficits in functional connectivity that are related to impairments in specific cognitive domains. We examined resting-state functional connectivity in individuals with agenesis of the corpus callosum (AgCC) and matched controls using magnetoencephalographic imaging (MEG-I) of coherence in the alpha (8–12 Hz), beta (12–30 Hz) and gamma (30–55 Hz) bands. Global connectivity (GC) was defined as synchronization between a region and the rest of the brain. In AgCC individuals, alpha band GC was significantly reduced in the dorsolateral pre-frontal (DLPFC), posterior parietal (PPC) and parieto-occipital cortices (PO). No significant differences in GC were seen in either the beta or gamma bands. We also explored the hypothesis that, in AgCC, this regional reduction in functional connectivity is explained primarily by a specific reduction in interhemispheric connectivity. However, our data suggest that reduced connectivity in these regions is driven by faulty coupling in both inter- and intrahemispheric connectivity. We also assessed whether the degree of connectivity correlated with behavioral performance, focusing on cognitive measures known to be impaired in AgCC individuals. Neuropsychological measures of verbal processing speed were significantly correlated with resting-state functional connectivity of the left medial and superior temporal lobe in AgCC participants. Connectivity of DLPFC correlated strongly with performance on the Tower of London in the AgCC cohort. These findings indicate that the abnormal callosal development produces salient but selective (alpha band only) resting-state functional connectivity disruptions that correlate with cognitive impairment. Understanding the relationship between impoverished functional connectivity and cognition is a key step in identifying the neural mechanisms of language and executive dysfunction in common neurodevelopmental and psychiatric disorders where disruptions of callosal development are consistently identified. PMID:22870191

Intrinsic and task-evoked network architectures of the human brain

PubMed Central

Cole, Michael W.; Bassett, Danielle S.; Power, Jonathan D.; Braver, Todd S.; Petersen, Steven E.

2014-01-01

Summary Many functional network properties of the human brain have been identified during rest and task states, yet it remains unclear how the two relate. We identified a whole-brain network architecture present across dozens of task states that was highly similar to the resting-state network architecture. The most frequent functional connectivity strengths across tasks closely matched the strengths observed at rest, suggesting this is an “intrinsic”, standard architecture of functional brain organization. Further, a set of small but consistent changes common across tasks suggests the existence of a task-general network architecture distinguishing task states from rest. These results indicate the brain’s functional network architecture during task performance is shaped primarily by an intrinsic network architecture that is also present during rest, and secondarily by evoked task-general and task-specific network changes. This establishes a strong relationship between resting-state functional connectivity and task-evoked functional connectivity – areas of neuroscientific inquiry typically considered separately. PMID:24991964

Resting-State Functional Connectivity in Autism Spectrum Disorders: A Review

PubMed Central

Hull, Jocelyn V.; Jacokes, Zachary J.; Torgerson, Carinna M.; Irimia, Andrei; Van Horn, John Darrell

2017-01-01

Ongoing debate exists within the resting-state functional MRI (fMRI) literature over how intrinsic connectivity is altered in the autistic brain, with reports of general over-connectivity, under-connectivity, and/or a combination of both. Classifying autism using brain connectivity is complicated by the heterogeneous nature of the condition, allowing for the possibility of widely variable connectivity patterns among individuals with the disorder. Further differences in reported results may be attributable to the age and sex of participants included, designs of the resting-state scan, and to the analysis technique used to evaluate the data. This review systematically examines the resting-state fMRI autism literature to date and compares studies in an attempt to draw overall conclusions that are presently challenging. We also propose future direction for rs-fMRI use to categorize individuals with autism spectrum disorder, serve as a possible diagnostic tool, and best utilize data-sharing initiatives. PMID:28101064

Superior colliculus resting state networks in post-traumatic stress disorder and its dissociative subtype.

PubMed

Olivé, Isadora; Densmore, Maria; Harricharan, Sherain; Théberge, Jean; McKinnon, Margaret C; Lanius, Ruth

2018-01-01

The innate alarm system (IAS) models the neurocircuitry involved in threat processing in posttraumatic stress disorder (PTSD). Here, we investigate a primary subcortical structure of the IAS model, the superior colliculus (SC), where the SC is thought to contribute to the mechanisms underlying threat-detection in PTSD. Critically, the functional connectivity between the SC and other nodes of the IAS remains unexplored. We conducted a resting-state fMRI study to investigate the functional architecture of the IAS, focusing on connectivity of the SC in PTSD (n = 67), its dissociative subtype (n = 41), and healthy controls (n = 50) using region-of-interest seed-based analysis. We observed group-specific resting state functional connectivity between the SC for both PTSD and its dissociative subtype, indicative of dedicated IAS collicular pathways in each group of patients. When comparing PTSD to its dissociative subtype, we observed increased resting state functional connectivity between the left SC and the right dorsolateral prefrontal cortex (DLPFC) in PTSD. The DLPFC is involved in modulation of emotional processes associated with active defensive responses characterising PTSD. Moreover, when comparing PTSD to its dissociative subtype, increased resting state functional connectivity was observed between the right SC and the right temporoparietal junction in the dissociative subtype. The temporoparietal junction is involved in depersonalization responses associated with passive defensive responses typical of the dissociative subtype. Our findings suggest that unique resting state functional connectivity of the SC parallels the unique symptom profile and defensive responses observed in PTSD and its dissociative subtype. Hum Brain Mapp 39:563-574, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Extraversion modulates functional connectivity hubs of resting-state brain networks.

PubMed

Pang, Yajing; Cui, Qian; Duan, Xujun; Chen, Heng; Zeng, Ling; Zhang, Zhiqiang; Lu, Guangming; Chen, Huafu

2017-09-01

Personality dimension extraversion describes individual differences in social behaviour and socio-emotional functioning. The intrinsic functional connectivity patterns of the brain are reportedly associated with extraversion. However, whether or not extraversion is associated with functional hubs warrants clarification. Functional hubs are involved in the rapid integration of neural processing, and their dysfunction contributes to the development of neuropsychiatric disorders. In this study, we employed the functional connectivity density (FCD) method for the first time to distinguish the energy-efficient hubs associated with extraversion. The resting-state functional magnetic resonance imaging data of 71 healthy subjects were used in the analysis. Short-range FCD was positively correlated with extraversion in the left cuneus, revealing a link between the local functional activity of this region and extraversion in risk-taking. Long-range FCD was negatively correlated with extraversion in the right superior frontal gyrus and the inferior frontal gyrus. Seed-based resting-state functional connectivity (RSFC) analyses revealed that a decreased long-range FCD in individuals with high extraversion scores showed a low long-range functional connectivity pattern between the medial and dorsolateral prefrontal cortex, middle temporal gyrus, and anterior cingulate cortex. This result suggests that decreased RSFC patterns are responsible for self-esteem, self-evaluation, and inhibitory behaviour system that account for the modulation and shaping of extraversion. Overall, our results emphasize specific brain hubs, and reveal long-range functional connections in relation to extraversion, thereby providing a neurobiological basis of extraversion. © 2015 The British Psychological Society.

[Functional connectivity of temporal parietal junction in online game addicts:a resting-state functional magnetic resonance imaging study].

PubMed

Yuan, Ji; Qian, Ruobing; Lin, Bin; Fu, Xianming; Wei, Xiangpin; Weng, Chuanbo; Niu, Chaoshi; Wang, Yehan

2014-02-11

To explore the functions of temporal parietal junction (TPJ) as parts of attention networks in the pathogenesis of online game addiction using resting-state functional magnetic resonance imaging (fMRI). A total of 17 online game addicts (OGA) were recruited as OGA group and 17 healthy controls during the same period were recruited as CON group. The neuropsychological tests were performed for all of them to compare the inter-group differences in the results of Internet Addiction Test (IAT) and attention functions. All fMRI data were preprocessed after resting-state fMRI scanning. Then left and right TPJ were selected as regions of interest (ROIs) to calculate the linear correlation between TPJ and entire brain to compare the inter-group differences. Obvious differences existed between OGA group (71 ± 5 scores) and CON group (19 ± 7 scores) in the IAT results and attention function (P < 0.05). Compared with the controls, right TPJ in online game addicts showed decreased functional connectivity with bilateral ventromedial prefrontal cortex (VMPFC), bilateral hippocampal gyrus and bilateral amygdaloid nucleus, but increased functional connectivity with right cuneus.However, left TPJ demonstrated decreased functional connectivity with bilateral superior frontal gyrus and bilateral middle frontal gyrus, but increased functional connectivity with bilateral cuneus (P < 0.05). Altered functional connectivity of TPJ reflected its dysfunction in online game addicts.It suggests that TPJ is an important component of attention networks participating in the generation of online game addiction.

Reduced brain resting-state network specificity in infants compared with adults.

PubMed

Wylie, Korey P; Rojas, Donald C; Ross, Randal G; Hunter, Sharon K; Maharajh, Keeran; Cornier, Marc-Andre; Tregellas, Jason R

2014-01-01

Infant resting-state networks do not exhibit the same connectivity patterns as those of young children and adults. Current theories of brain development emphasize developmental progression in regional and network specialization. We compared infant and adult functional connectivity, predicting that infants would exhibit less regional specificity and greater internetwork communication compared with adults. Functional magnetic resonance imaging at rest was acquired in 12 healthy, term infants and 17 adults. Resting-state networks were extracted, using independent components analysis, and the resulting components were then compared between the adult and infant groups. Adults exhibited stronger connectivity in the posterior cingulate cortex node of the default mode network, but infants had higher connectivity in medial prefrontal cortex/anterior cingulate cortex than adults. Adult connectivity was typically higher than infant connectivity within structures previously associated with the various networks, whereas infant connectivity was frequently higher outside of these structures. Internetwork communication was significantly higher in infants than in adults. We interpret these findings as consistent with evidence suggesting that resting-state network development is associated with increasing spatial specificity, possibly reflecting the corresponding functional specialization of regions and their interconnections through experience.

Cannabis, cigarettes, and their co-occurring use: disentangling differences in default mode network functional connectivity

PubMed Central

Wetherill, Reagan R.; Fang, Zhuo; Jagannathan, Kanchana; Childress, Anna Rose; Rao, Hengyi; Franklin, Teresa R.

2015-01-01

Background Resting-state functional connectivity is a noninvasive, neuroimaging method for assessing neural network function. Altered functional connectivity among regions of the default-mode network have been associated with both nicotine and cannabis use; however, less is known about co-occurring cannabis and tobacco use. Methods We used posterior cingulate cortex (PCC) seed-based resting-state functional connectivity analyses to examine default mode network (DMN) connectivity strength differences between four groups: 1) individuals diagnosed with cannabis dependence who do not smoke tobacco (n=19; ages 20–50), 2) cannabis-dependent individuals who smoke tobacco (n=23, ages 21–52), 3) cannabis-naïve, nicotine-dependent individuals who smoke tobacco (n=24, ages 21–57), and 4) cannabis- and tobacco-naïve healthy controls (n=21, ages 21–50), controlling for age, sex, and alcohol use. We also explored associations between connectivity strength and measures of cannabis and tobacco use. Results PCC seed-based analyses identified the core nodes of the DMN (i.e., PCC, medial prefrontal cortex, inferior parietal cortex, and temporal cortex). In general, the cannabis-dependent, nicotine-dependent, and co-occurring use groups showed lower DMN connectivity strengths than controls, with unique group differences in connectivity strength between the PCC and the cerebellum, medial prefrontal cortex, parahippocampus, and anterior insula. In cannabis-dependent individuals, PCC-right anterior insula connectivity strength correlated with duration of cannabis use. Conclusions This study extends previous research that independently examined the differences in resting-state functional connectivity among individuals who smoke cannabis and tobacco by including an examination of co-occurring cannabis and tobacco use and provides further evidence that cannabis and tobacco exposure is associated with alterations in DMN connectivity. PMID:26094186

Functional brain imaging across development.

PubMed

Rubia, Katya

2013-12-01

The developmental cognitive neuroscience literature has grown exponentially over the last decade. This paper reviews the functional magnetic resonance imaging (fMRI) literature on brain function development of typically late developing functions of cognitive and motivation control, timing and attention as well as of resting state neural networks. Evidence shows that between childhood and adulthood, concomitant with cognitive maturation, there is progressively increased functional activation in task-relevant lateral and medial frontal, striatal and parieto-temporal brain regions that mediate these higher level control functions. This is accompanied by progressively stronger functional inter-regional connectivity within task-relevant fronto-striatal and fronto-parieto-temporal networks. Negative age associations are observed in earlier developing posterior and limbic regions, suggesting a shift with age from the recruitment of "bottom-up" processing regions towards "top-down" fronto-cortical and fronto-subcortical connections, leading to a more mature, supervised cognition. The resting state fMRI literature further complements this evidence by showing progressively stronger deactivation with age in anti-correlated task-negative resting state networks, which is associated with better task performance. Furthermore, connectivity analyses during the resting state show that with development increasingly stronger long-range connections are being formed, for example, between fronto-parietal and fronto-cerebellar connections, in both task-positive networks and in task-negative default mode networks, together with progressively lesser short-range connections, suggesting progressive functional integration and segregation with age. Overall, evidence suggests that throughout development between childhood and adulthood, there is progressive refinement and integration of both task-positive fronto-cortical and fronto-subcortical activation and task-negative deactivation, leading to a more mature and controlled cognition.

Brain Structure and Resting-State Functional Connectivity in University Professors with High Academic Achievement

ERIC Educational Resources Information Center

Li, Weiwei; Yang, Wenjing; Li, Wenfu; Li, Yadan; Wei, Dongtao; Li, Huimin; Qiu, Jiang; Zhang, Qinglin

2015-01-01

Creative persons play an important role in technical innovation and social progress. There is little research on the neural correlates with researchers with high academic achievement. We used a combined structural (regional gray matter volume, rGMV) and functional (resting-state functional connectivity analysis, rsFC) approach to examine the…

Reactivity of hemodynamic responses and functional connectivity to different states of alpha synchrony: a concurrent EEG-fMRI study.

PubMed

Wu, Lei; Eichele, Tom; Calhoun, Vince D

2010-10-01

Concurrent EEG-fMRI studies have provided increasing details of the dynamics of intrinsic brain activity during the resting state. Here, we investigate a prominent effect in EEG during relaxed resting, i.e. the increase of the alpha power when the eyes are closed compared to when the eyes are open. This phenomenon is related to changes in thalamo-cortical and cortico-cortical synchronization. In order to investigate possible changes to EEG-fMRI coupling and fMRI functional connectivity during the two states we adopted a data-driven approach that fuses the multimodal data on the basis of parallel ICA decompositions of the fMRI data in the spatial domain and of the EEG data in the spectral domain. The power variation of a posterior alpha component was used as a reference function to deconvolve the hemodynamic responses from occipital, frontal, temporal, and subcortical fMRI components. Additionally, we computed the functional connectivity between these components. The results showed widespread alpha hemodynamic responses and high functional connectivity during eyes-closed (EC) rest, while eyes open (EO) resting abolished many of the hemodynamic responses and markedly decreased functional connectivity. These data suggest that generation of local hemodynamic responses is highly sensitive to state changes that do not involve changes of mental effort or awareness. They also indicate the localized power differences in posterior alpha between EO and EC in resting state data are accompanied by spatially widespread amplitude changes in hemodynamic responses and inter-regional functional connectivity, i.e. low frequency hemodynamic signals display an equivalent of alpha reactivity. Copyright 2010 Elsevier Inc. All rights reserved.

Amygdala-prefrontal cortex resting-state functional connectivity varies with first depressive or manic episode in bipolar disorder.

PubMed

Wei, Shengnan; Geng, Haiyang; Jiang, Xiaowei; Zhou, Qian; Chang, Miao; Zhou, Yifang; Xu, Ke; Tang, Yanqing; Wang, Fei

2017-02-22

Bipolar disorder (BD) is one of the most complex mental illnesses, characterized by interactive depressive and manic states that are 2 contrary symptoms of disease states. The bilateral amygdala and prefrontal cortex (PFC) appear to play critical roles in BD; however, abnormalities seem to manifest differently in the 2 states and may provide further insight into underlying mechanisms. Sixteen participants with first-episode depressive and 13 participants with first-episode manic states of bipolar disorder as well as 30 healthy control (HC) participants underwent resting-state functional magnetic resonance imaging (fMRI). Resting-state functional connectivity (rsFC) between the bilateral amygdala and PFC was compared among the 3 groups. Compared with depressive state participants of the BD group, manic state participants of the BD group showed a significant decrease in rsFC between the amygdala and right orbital frontal cortex (p<0.05, corrected). In addition, rsFC between the amygdala and left middle frontal cortex was significantly decreased in depressive and manic state participants of the BD group when compared with the HC group (p<0.05, corrected). Our findings suggest that mood state during the first episodes of BD may be related to abnormality in hemispheric lateralization. The abnormalities in amygdala- left PFC functional connectivity might present the trait feature for BD, while deficits in amygdala- right PFC functional connectivity might be specific to manic episode, compared to depressive episode. Copyright © 2017 Elsevier B.V. All rights reserved.

Altered functional connectivity in early Alzheimer's disease: a resting-state fMRI study.

PubMed

Wang, Kun; Liang, Meng; Wang, Liang; Tian, Lixia; Zhang, Xinqing; Li, Kuncheng; Jiang, Tianzi

2007-10-01

Previous studies have led to the proposal that patients with Alzheimer's disease (AD) may have disturbed functional connectivity between different brain regions. Furthermore, recent resting-state functional magnetic resonance imaging (fMRI) studies have also shown that low-frequency (<0.08 Hz) fluctuations (LFF) of the blood oxygenation level-dependent signals were abnormal in several brain areas of AD patients. However, few studies have investigated disturbed LFF connectivity in AD patients. By using resting-state fMRI, this study sought to investigate the abnormal functional connectivities throughout the entire brain of early AD patients, and analyze the global distribution of these abnormalities. For this purpose, the authors divided the whole brain into 116 regions and identified abnormal connectivities by comparing the correlation coefficients of each pair. Compared with healthy controls, AD patients had decreased positive correlations between the prefrontal and parietal lobes, but increased positive correlations within the prefrontal lobe, parietal lobe, and occipital lobe. The AD patients also had decreased negative correlations (closer to zero) between two intrinsically anti-correlated networks that had previously been found in the resting brain. By using resting-state fMRI, our results supported previous studies that have reported an anterior-posterior disconnection phenomenon and increased within-lobe functional connectivity in AD patients. In addition, the results also suggest that AD may disturb the correlation/anti-correlation effect in the two intrinsically anti-correlated networks. Wiley-Liss, Inc.

A posteriori model validation for the temporal order of directed functional connectivity maps.

PubMed

Beltz, Adriene M; Molenaar, Peter C M

2015-01-01

A posteriori model validation for the temporal order of neural directed functional connectivity maps is rare. This is striking because models that require sequential independence among residuals are regularly implemented. The aim of the current study was (a) to apply to directed functional connectivity maps of functional magnetic resonance imaging data an a posteriori model validation procedure (i.e., white noise tests of one-step-ahead prediction errors combined with decision criteria for revising the maps based upon Lagrange Multiplier tests), and (b) to demonstrate how the procedure applies to single-subject simulated, single-subject task-related, and multi-subject resting state data. Directed functional connectivity was determined by the unified structural equation model family of approaches in order to map contemporaneous and first order lagged connections among brain regions at the group- and individual-levels while incorporating external input, then white noise tests were run. Findings revealed that the validation procedure successfully detected unmodeled sequential dependencies among residuals and recovered higher order (greater than one) simulated connections, and that the procedure can accommodate task-related input. Findings also revealed that lags greater than one were present in resting state data: With a group-level network that contained only contemporaneous and first order connections, 44% of subjects required second order, individual-level connections in order to obtain maps with white noise residuals. Results have broad methodological relevance (e.g., temporal validation is necessary after directed functional connectivity analyses because the presence of unmodeled higher order sequential dependencies may bias parameter estimates) and substantive implications (e.g., higher order lags may be common in resting state data).

Resting-state activity in development and maintenance of normal brain function.

PubMed

Pizoli, Carolyn E; Shah, Manish N; Snyder, Abraham Z; Shimony, Joshua S; Limbrick, David D; Raichle, Marcus E; Schlaggar, Bradley L; Smyth, Matthew D

2011-07-12

One of the most intriguing recent discoveries concerning brain function is that intrinsic neuronal activity manifests as spontaneous fluctuations of the blood oxygen level-dependent (BOLD) functional MRI signal. These BOLD fluctuations exhibit temporal synchrony within widely distributed brain regions known as resting-state networks. Resting-state networks are present in the waking state, during sleep, and under general anesthesia, suggesting that spontaneous neuronal activity plays a fundamental role in brain function. Despite its ubiquitous presence, the physiological role of correlated, spontaneous neuronal activity remains poorly understood. One hypothesis is that this activity is critical for the development of synaptic connections and maintenance of synaptic homeostasis. We had a unique opportunity to test this hypothesis in a 5-y-old boy with severe epileptic encephalopathy. The child developed marked neurologic dysfunction in association with a seizure disorder, resulting in a 1-y period of behavioral regression and progressive loss of developmental milestones. His EEG showed a markedly abnormal pattern of high-amplitude, disorganized slow activity with frequent generalized and multifocal epileptiform discharges. Resting-state functional connectivity MRI showed reduced BOLD fluctuations and a pervasive lack of normal connectivity. The child underwent successful corpus callosotomy surgery for treatment of drop seizures. Postoperatively, the patient's behavior returned to baseline, and he resumed development of new skills. The waking EEG revealed a normal background, and functional connectivity MRI demonstrated restoration of functional connectivity architecture. These results provide evidence that intrinsic, coherent neuronal signaling may be essential to the development and maintenance of the brain's functional organization.

Caffeine reduces resting-state BOLD functional connectivity in the motor cortex.

PubMed

Rack-Gomer, Anna Leigh; Liau, Joy; Liu, Thomas T

2009-05-15

In resting-state functional magnetic resonance imaging (fMRI), correlations between spontaneous low-frequency fluctuations in the blood oxygenation level dependent (BOLD) signal are used to assess functional connectivity between different brain regions. Changes in resting-state BOLD connectivity measures are typically interpreted as changes in coherent neural activity across spatially distinct brain regions. However, this interpretation can be complicated by the complex dependence of the BOLD signal on both neural and vascular factors. For example, prior studies have shown that vasoactive agents that alter baseline cerebral blood flow, such as caffeine and carbon dioxide, can significantly alter the amplitude and dynamics of the task-related BOLD response. In this study, we examined the effect of caffeine (200 mg dose) on resting-state BOLD connectivity in the motor cortex across a sample of healthy young subjects (N=9). We found that caffeine significantly (p<0.05) reduced measures of resting-state BOLD connectivity in the motor cortex. Baseline cerebral blood flow and spectral energy in the low-frequency BOLD fluctuations were also significantly decreased by caffeine. These results suggest that caffeine usage should be carefully considered in the design and interpretation of resting-state BOLD fMRI studies.

State and Training Effects of Mindfulness Meditation on Brain Networks Reflect Neuronal Mechanisms of Its Antidepressant Effect.

PubMed

Yang, Chuan-Chih; Barrós-Loscertales, Alfonso; Pinazo, Daniel; Ventura-Campos, Noelia; Borchardt, Viola; Bustamante, Juan-Carlos; Rodríguez-Pujadas, Aina; Fuentes-Claramonte, Paola; Balaguer, Raúl; Ávila, César; Walter, Martin

2016-01-01

The topic of investigating how mindfulness meditation training can have antidepressant effects via plastic changes in both resting state and meditation state brain activity is important in the rapidly emerging field of neuroplasticity. In the present study, we used a longitudinal design investigating resting state fMRI both before and after 40 days of meditation training in 13 novices. After training, we compared differences in network connectivity between rest and meditation using common resting state functional connectivity methods. Interregional methods were paired with local measures such as Regional Homogeneity. As expected, significant differences in functional connectivity both between states (rest versus meditation) and between time points (before versus after training) were observed. During meditation, the internal consistency in the precuneus and the temporoparietal junction increased, while the internal consistency of frontal brain regions decreased. A follow-up analysis of regional connectivity of the dorsal anterior cingulate cortex further revealed reduced connectivity with anterior insula during meditation. After meditation training, reduced resting state functional connectivity between the pregenual anterior cingulate and dorsal medical prefrontal cortex was observed. Most importantly, significantly reduced depression/anxiety scores were observed after training. Hence, these findings suggest that mindfulness meditation might be of therapeutic use by inducing plasticity related network changes altering the neuronal basis of affective disorders such as depression.

State and Training Effects of Mindfulness Meditation on Brain Networks Reflect Neuronal Mechanisms of Its Antidepressant Effect

PubMed Central

Yang, Chuan-Chih; Barrós-Loscertales, Alfonso; Pinazo, Daniel; Ventura-Campos, Noelia; Borchardt, Viola; Bustamante, Juan-Carlos; Rodríguez-Pujadas, Aina; Fuentes-Claramonte, Paola; Balaguer, Raúl; Ávila, César; Walter, Martin

2016-01-01

The topic of investigating how mindfulness meditation training can have antidepressant effects via plastic changes in both resting state and meditation state brain activity is important in the rapidly emerging field of neuroplasticity. In the present study, we used a longitudinal design investigating resting state fMRI both before and after 40 days of meditation training in 13 novices. After training, we compared differences in network connectivity between rest and meditation using common resting state functional connectivity methods. Interregional methods were paired with local measures such as Regional Homogeneity. As expected, significant differences in functional connectivity both between states (rest versus meditation) and between time points (before versus after training) were observed. During meditation, the internal consistency in the precuneus and the temporoparietal junction increased, while the internal consistency of frontal brain regions decreased. A follow-up analysis of regional connectivity of the dorsal anterior cingulate cortex further revealed reduced connectivity with anterior insula during meditation. After meditation training, reduced resting state functional connectivity between the pregenual anterior cingulate and dorsal medical prefrontal cortex was observed. Most importantly, significantly reduced depression/anxiety scores were observed after training. Hence, these findings suggest that mindfulness meditation might be of therapeutic use by inducing plasticity related network changes altering the neuronal basis of affective disorders such as depression. PMID:26998365

DIFFUSION-WEIGHTED IMAGING TRACTOGRAPHY-BASED PARCELLATION OF THE HUMAN PARIETAL CORTEX AND COMPARISON WITH HUMAN AND MACAQUE RESTING STATE FUNCTIONAL CONNECTIVITY

PubMed Central

Mars, Rogier B.; Jbabdi, Saad; Sallet, Jérôme; O’Reilly, Jill X.; Croxson, Paula L.; Olivier, Etienne; Noonan, MaryAnn P.; Bergmann, Caroline; Mitchell, Anna S.; Baxter, Mark G.; Behrens, Timothy E.J.; Johansen-Berg, Heidi; Tomassini, Valentina; Miller, Karla L.; Rushworth, Matthew F.S.

2011-01-01

Despite the prominence of parietal activity in human neuromaging investigations of sensorimotor and cognitive processes there remains uncertainty about basic aspects of parietal cortical anatomical organization. Descriptions of human parietal cortex draw heavily on anatomical schemes developed in other primate species but the validity of such comparisons has been questioned by claims that there are fundamental differences between the parietal cortex in humans and other primates. A scheme is presented for parcellation of human lateral parietal cortex into component regions on the basis of anatomical connectivity and the functional interactions of the resulting clusters with other brain regions. Anatomical connectivity was estimated using diffusion-weighted magnetic resonance image (MRI) based tractography and functional interactions were assessed by correlations in activity measured with functional MRI (fMRI) at rest. Resting state functional connectivity was also assessed directly in the rhesus macaque lateral parietal cortex in an additional experiment and the patterns found reflected known neuroanatomical connections. Cross-correlation in the tractography-based connectivity patterns of parietal voxels reliably parcellated human lateral parietal cortex into ten component clusters. The resting state functional connectivity of human superior parietal and intraparietal clusters with frontal and extrastriate cortex suggested correspondences with areas in macaque superior and intraparietal sulcus. Functional connectivity patterns with parahippocampal cortex and premotor cortex again suggested fundamental correspondences between inferior parietal cortex in humans and macaques. In contrast, the human parietal cortex differs in the strength of its interactions between the central inferior parietal lobule region and the anterior prefrontal cortex. PMID:21411650

Different Resting-State Functional Connectivity Alterations in Smokers and Nonsmokers with Internet Gaming Addiction

PubMed Central

Chen, Xue; Wang, Yao; Zhou, Yan; Sun, Yawen; Ding, Weina; Zhuang, Zhiguo; Xu, Jianrong; Du, Yasong

2014-01-01

This study investigated changes in resting-state functional connectivity (rsFC) of posterior cingulate cortex (PCC) in smokers and nonsmokers with Internet gaming addiction (IGA). Twenty-nine smokers with IGA, 22 nonsmokers with IGA, and 30 healthy controls (HC group) underwent a resting-state fMRI scan. PCC connectivity was determined in all subjects by investigating synchronized low-frequency fMRI signal fluctuations using a temporal correlation method. Compared with the nonsmokers with IGA, the smokers with IGA exhibited decreased rsFC with PCC in the right rectus gyrus. Left middle frontal gyrus exhibited increased rsFC. The PCC connectivity with the right rectus gyrus was found to be negatively correlated with the CIAS scores in the smokers with IGA before correction. Our results suggested that smokers with IGA had functional changes in brain areas related to motivation and executive function compared with the nonsmokers with IGA. PMID:25506057

Behavioral Interpretations of Intrinsic Connectivity Networks

ERIC Educational Resources Information Center

Laird, Angela R.; Fox, P. Mickle; Eickhoff, Simon B.; Turner, Jessica A.; Ray, Kimberly L.; McKay, D. Reese; Glahn, David C.; Beckmann, Christian F.; Smith, Stephen M.; Fox, Peter T.

2011-01-01

An increasingly large number of neuroimaging studies have investigated functionally connected networks during rest, providing insight into human brain architecture. Assessment of the functional qualities of resting state networks has been limited by the task-independent state, which results in an inability to relate these networks to specific…

Cerebro-cerebellar resting state functional connectivity in children and adolescents with autism spectrum disorder

PubMed Central

Khan, Amanda J.; Nair, Aarti; Keown, Christopher L.; Datko, Michael C.; Lincoln, Alan J.; Müller, Ralph-Axel

2017-01-01

Background The cerebellum plays important roles in both sensorimotor and supramodal cognitive functions. Cellular, volumetric, and functional abnormalities of the cerebellum have been found in autism spectrum disorders (ASD), but no comprehensive investigation of cerebro-cerebellar connectivity in ASD is available. Methods We used resting-state functional connectivity MRI in 56 children and adolescents (28 ASD, 28 typically developing [TD]) aged 8–17 years. Partial and total correlation analyses were performed for unilateral regions of interest (ROIs), distinguished in two broad domains as sensorimotor (premotor/primary motor, somatosensory, superior temporal, occipital) and supramodal (prefrontal, posterior parietal, and inferior and middle temporal). Results There were three main findings: (i) Total correlation analyses showed predominant cerebro-cerebellar functional overconnectivity in the ASD group; (ii) partial correlation analyses that emphasized domain-specificity (sensorimotor vs. supramodal) indicated a pattern of robustly increased connectivity in the ASD group (compared to the TD group) for sensorimotor ROIs, but predominantly reduced connectivity for supramodal ROIs; (iii) this atypical pattern of connectivity was supported by significantly increased non-canonical connections (between sensorimotor cerebral and supramodal cerebellar ROIs, and vice versa) in the ASD group. Conclusions Our findings indicate that sensorimotor intrinsic functional connectivity is atypically increased in ASD, at the expense of connectivity supporting cerebellar participation in supramodal cognition. PMID:25959247

The intrinsic resting state voice network in Parkinson's disease

PubMed Central

New, Anneliese B.; Parkinson, Amy L.; Eickhoff, Claudia R.; Reetz, Kathrin; Hoffstaedter, Felix; Mathys, Christian; Sudmeyer, Martin; Michely, Jochen; Caspers, Julian; Grefkes, Christian; Larson, Charles R.; Ramig, Loraine O.; Fox, Peter T.; Eickhoff, Simon B.

2015-01-01

Abstract Over 90 percent of patients with Parkinson's disease experience speech‐motor impairment, namely, hypokinetic dysarthria characterized by reduced pitch and loudness. Resting‐state functional connectivity analysis of blood oxygen level‐dependent functional magnetic resonance imaging is a useful measure of intrinsic neural functioning. We utilized resting‐state functional connectivity modeling to analyze the intrinsic connectivity in patients with Parkinson's disease within a vocalization network defined by a previous meta‐analysis of speech (Brown et al., 2009). Functional connectivity of this network was assessed in 56 patients with Parkinson's disease and 56 gender‐, age‐, and movement‐matched healthy controls. We also had item 5 and 18 of the UPDRS, and the PDQ‐39 Communication subscale available for correlation with the voice network connectivity strength in patients. The within‐group analyses of connectivity patterns demonstrated a lack of subcortical–cortical connectivity in patients with Parkinson's disease. At the cortical level, we found robust (homotopic) interhemispheric connectivity but only inconsistent evidence for many intrahemispheric connections. When directly contrasted to the control group, we found a significant reduction of connections between the left thalamus and putamen, and cortical motor areas, as well as reduced right superior temporal gyrus connectivity. Furthermore, most symptom measures correlated with right putamen, left cerebellum, left superior temporal gyrus, right premotor, and left Rolandic operculum connectivity in the voice network. The results reflect the importance of (right) subcortical nodes and the superior temporal gyrus in Parkinson's disease, enhancing our understanding of the neurobiological underpinnings of vocalization impairment in Parkinson's disease. Hum Brain Mapp 36:1951–1962, 2015. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.. PMID:25627959

Changes in Thalamic Connectivity in the Early and Late Stages of Amnestic Mild Cognitive Impairment: A Resting-State Functional Magnetic Resonance Study from ADNI

PubMed Central

Cai, Suping; Huang, Liyu; Zou, Jia; Jing, Longlong; Zhai, Buzhong; Ji, Gongjun; von Deneen, Karen M.; Ren, Junchan; Ren, Aifeng

2015-01-01

We used resting-state functional magnetic resonance imaging (fMRI) to investigate changes in the thalamus functional connectivity in early and late stages of amnestic mild cognitive impairment. Data of 25 late stages of amnestic mild cognitive impairment (LMCI) patients, 30 early stages of amnestic mild cognitive impairment (EMCI) patients and 30 well-matched healthy controls (HC) were analyzed from the Alzheimer’s disease Neuroimaging Initiative (ADNI). We focused on the correlation between low frequency fMRI signal fluctuations in the thalamus and those in all other brain regions. Compared to healthy controls, we found functional connectivity between the left/right thalamus and a set of brain areas was decreased in LMCI and/or EMCI including right fusiform gyrus (FG), left and right superior temporal gyrus, left medial frontal gyrus extending into supplementary motor area, right insula, left middle temporal gyrus (MTG) extending into middle occipital gyrus (MOG). We also observed increased functional connectivity between the left/right thalamus and several regions in LMCI and/or EMCI including left FG, right MOG, left and right precuneus, right MTG and left inferior temporal gyrus. In the direct comparison between the LMCI and EMCI groups, we obtained several brain regions showed thalamus-seeded functional connectivity differences such as the precentral gyrus, hippocampus, FG and MTG. Briefly, these brain regions mentioned above were mainly located in the thalamo-related networks including thalamo-hippocampus, thalamo-temporal, thalamo-visual, and thalamo-default mode network. The decreased functional connectivity of the thalamus might suggest reduced functional integrity of thalamo-related networks and increased functional connectivity indicated that aMCI patients could use additional brain resources to compensate for the loss of cognitive function. Our study provided a new sight to understand the two important states of aMCI and revealed resting-state fMRI is an appropriate method for exploring pathophysiological changes in aMCI. PMID:25679386

Changes in thalamic connectivity in the early and late stages of amnestic mild cognitive impairment: a resting-state functional magnetic resonance study from ADNI.

PubMed

Cai, Suping; Huang, Liyu; Zou, Jia; Jing, Longlong; Zhai, Buzhong; Ji, Gongjun; von Deneen, Karen M; Ren, Junchan; Ren, Aifeng

2015-01-01

We used resting-state functional magnetic resonance imaging (fMRI) to investigate changes in the thalamus functional connectivity in early and late stages of amnestic mild cognitive impairment. Data of 25 late stages of amnestic mild cognitive impairment (LMCI) patients, 30 early stages of amnestic mild cognitive impairment (EMCI) patients and 30 well-matched healthy controls (HC) were analyzed from the Alzheimer's disease Neuroimaging Initiative (ADNI). We focused on the correlation between low frequency fMRI signal fluctuations in the thalamus and those in all other brain regions. Compared to healthy controls, we found functional connectivity between the left/right thalamus and a set of brain areas was decreased in LMCI and/or EMCI including right fusiform gyrus (FG), left and right superior temporal gyrus, left medial frontal gyrus extending into supplementary motor area, right insula, left middle temporal gyrus (MTG) extending into middle occipital gyrus (MOG). We also observed increased functional connectivity between the left/right thalamus and several regions in LMCI and/or EMCI including left FG, right MOG, left and right precuneus, right MTG and left inferior temporal gyrus. In the direct comparison between the LMCI and EMCI groups, we obtained several brain regions showed thalamus-seeded functional connectivity differences such as the precentral gyrus, hippocampus, FG and MTG. Briefly, these brain regions mentioned above were mainly located in the thalamo-related networks including thalamo-hippocampus, thalamo-temporal, thalamo-visual, and thalamo-default mode network. The decreased functional connectivity of the thalamus might suggest reduced functional integrity of thalamo-related networks and increased functional connectivity indicated that aMCI patients could use additional brain resources to compensate for the loss of cognitive function. Our study provided a new sight to understand the two important states of aMCI and revealed resting-state fMRI is an appropriate method for exploring pathophysiological changes in aMCI.

Hierarchical functional modularity in the resting-state human brain.

PubMed

Ferrarini, Luca; Veer, Ilya M; Baerends, Evelinda; van Tol, Marie-José; Renken, Remco J; van der Wee, Nic J A; Veltman, Dirk J; Aleman, André; Zitman, Frans G; Penninx, Brenda W J H; van Buchem, Mark A; Reiber, Johan H C; Rombouts, Serge A R B; Milles, Julien

2009-07-01

Functional magnetic resonance imaging (fMRI) studies have shown that anatomically distinct brain regions are functionally connected during the resting state. Basic topological properties in the brain functional connectivity (BFC) map have highlighted the BFC's small-world topology. Modularity, a more advanced topological property, has been hypothesized to be evolutionary advantageous, contributing to adaptive aspects of anatomical and functional brain connectivity. However, current definitions of modularity for complex networks focus on nonoverlapping clusters, and are seriously limited by disregarding inclusive relationships. Therefore, BFC's modularity has been mainly qualitatively investigated. Here, we introduce a new definition of modularity, based on a recently improved clustering measurement, which overcomes limitations of previous definitions, and apply it to the study of BFC in resting state fMRI of 53 healthy subjects. Results show hierarchical functional modularity in the brain. Copyright 2009 Wiley-Liss, Inc

Structural and Functional Cerebral Correlates of Hypnotic Suggestibility

PubMed Central

Huber, Alexa; Lui, Fausta; Duzzi, Davide; Pagnoni, Giuseppe; Porro, Carlo Adolfo

2014-01-01

Little is known about the neural bases of hypnotic suggestibility, a cognitive trait referring to the tendency to respond to hypnotic suggestions. In the present magnetic resonance imaging study, we performed regression analyses to assess hypnotic suggestibility-related differences in local gray matter volume, using voxel-based morphometry, and in waking resting state functional connectivity of 10 resting state networks, in 37 healthy women. Hypnotic suggestibility was positively correlated with gray matter volume in portions of the left superior and medial frontal gyri, roughly overlapping with the supplementary and pre-supplementary motor area, and negatively correlated with gray matter volume in the left superior temporal gyrus and insula. In the functional connectivity analysis, hypnotic suggestibility was positively correlated with functional connectivity between medial posterior areas, including bilateral posterior cingulate cortex and precuneus, and both the lateral visual network and the left fronto-parietal network; a positive correlation was also found with functional connectivity between the executive-control network and a right postcentral/parietal area. In contrast, hypnotic suggestibility was negatively correlated with functional connectivity between the right fronto-parietal network and the right lateral thalamus. These findings demonstrate for the first time a correlation between hypnotic suggestibility, the structural features of specific cortical regions, and the functional connectivity during the normal resting state of brain structures involved in imagery and self-monitoring activity. PMID:24671130

Cognitive Enhancement Therapy Improves Resting-State Functional Connectivity in Early Course Schizophrenia

PubMed Central

Eack, Shaun M.; Newhill, Christina E.; Keshavan, Matcheri S.

2016-01-01

Objective Cognitive remediation is emerging as an effective psychosocial intervention for addressing untreated cognitive and functional impairments in persons with schizophrenia, and might achieve its benefits through neuroplastic changes in brain connectivity. This study seeks to examine the effects of cognitive enhancement therapy (CET) on fronto-temporal brain connectivity in a randomized controlled trial with individuals in the early course of schizophrenia. Method Stabilized, early course outpatients with schizophrenia or schizoaffective disorder (N = 41) were randomly assigned to CET (n = 25) or an active enriched supportive therapy (EST) control (n = 16) and treated for 2 years. Functional MRI data were collected annually, and pseudo resting-state functional connectivity analysis was used to examine differential changes in fronto-temporal connectivity between those treated with CET compared with EST. Results Individuals receiving CET evidenced significantly less functional connectivity loss between the resting-state network and the left dorsolateral prefrontal cortex as well as significantly increased connectivity with the right insular cortex compared to EST (all corrected p < .01). These neural networks are involved in emotion processing and problem-solving. Increased connectivity with the right insula significantly mediated CET effects on improved emotion perception (z′ = −1.96, p = .021), and increased connectivity with the left dorsolateral prefrontal cortex mediated CET-related improvements in emotion regulation (z′ = −1.71, p = .052). Conclusions These findings provide preliminary evidence that CET, a psychosocial cognitive remediation intervention, may enhance connectivity between frontal and temporal brain regions implicated in problem-solving and emotion processing in service of cognitive enhancement in schizophrenia. PMID:27713804

Bupropion Administration Increases Resting-State Functional Connectivity in Dorso-Medial Prefrontal Cortex.

PubMed

Rzepa, Ewelina; Dean, Zola; McCabe, Ciara

2017-06-01

Patients on the selective serotonergic reuptake inhibitors like citalopram report emotional blunting. We showed previously that citalopram reduces resting-state functional connectivity in healthy volunteers in a number of brain regions, including the dorso-medial prefrontal cortex, which may be related to its clinical effects. Bupropion is a dopaminergic and noradrenergic reuptake inhibitor and is not reported to cause emotional blunting. However, how bupropion affects resting-state functional connectivity in healthy controls remains unknown. Using a within-subjects, repeated-measures, double-blind, crossover design, we examined 17 healthy volunteers (9 female, 8 male). Volunteers received 7 days of bupropion (150 mg/d) and 7 days of placebo treatment and underwent resting-state functional Magnetic Resonance Imaging. We selected seed regions in the salience network (amygdala and pregenual anterior cingulate cortex) and the central executive network (dorsal medial prefrontal cortex). Mood and anhedonia measures were also recorded and examined in relation to resting-state functional connectivity. Relative to placebo, bupropion increased resting-state functional connectivity in healthy volunteers between the dorsal medial prefrontal cortex seed region and the posterior cingulate cortex and the precuneus cortex, key parts of the default mode network. These results are opposite to that which we found with 7 days treatment of citalopram in healthy volunteers. These results reflect a different mechanism of action of bupropion compared with selective serotonergic reuptake inhibitors. These results help explain the apparent lack of emotional blunting caused by bupropion in depressed patients. © The Author 2017. Published by Oxford University Press on behalf of CINP.

Regional homogeneity, resting-state functional connectivity and amplitude of low frequency fluctuation associated with creativity measured by divergent thinking in a sex-specific manner.

PubMed

Takeuchi, Hikaru; Taki, Yasuyuki; Nouchi, Rui; Yokoyama, Ryoichi; Kotozaki, Yuka; Nakagawa, Seishu; Sekiguchi, Atsushi; Iizuka, Kunio; Yamamoto, Yuki; Hanawa, Sugiko; Araki, Tsuyoshi; Makoto Miyauchi, Carlos; Shinada, Takamitsu; Sakaki, Kohei; Nozawa, Takayuki; Ikeda, Shigeyuki; Yokota, Susumu; Daniele, Magistro; Sassa, Yuko; Kawashima, Ryuta

2017-05-15

Brain connectivity is traditionally thought to be important for creativity. Here we investigated the associations of creativity measured by divergent thinking (CMDT) with resting-state functional magnetic imaging (fMRI) measures and their sex differences. We examined these relationships in the brains of 1277 healthy young adults. Whole-brain analyses revealed a significant interaction between verbal CMDT and sex on (a) regional homogeneity within an area from the left anterior temporal lobe (b) on the resting state functional connectivity (RSFC) between the mPFC and the left inferior frontal gyrus and (c) on fractional amplitude of low frequency fluctuations (fALFF) in several distinct areas, including the precuneus and middle cingulate gyrus, left middle temporal gyrus, right middle frontal gyrus, and cerebellum. These interactions were mediated by positive correlations in females and negative correlations in males. These findings suggest that greater CMDT in females is reflected by (a) regional coherence (regional homogeneity) of brain areas responsible for representing and combining concepts as well as (b) the efficient functional connection (RSFC) between the key areas for the default state of cognitive activity and speech production, and (c) greater spontaneous neural activity (fALFF) during the resting of brain areas involved in frontal lobe functions, default cognitive activities, and language functions. Furthermore, these findings suggest that the associations between creativity and resting state brain connectivity patterns are different between males and females. Copyright © 2017 Elsevier Inc. All rights reserved.

Two Days' Sleep Debt Causes Mood Decline During Resting State Via Diminished Amygdala-Prefrontal Connectivity.

PubMed

Motomura, Yuki; Katsunuma, Ruri; Yoshimura, Michitaka; Mishima, Kazuo

2017-10-01

Sleep debt (SD) has been suggested to evoke emotional instability by diminishing the suppression of the amygdala by the medial prefrontal cortex (MPFC). Here, we investigated how short-term SD affects resting-state functional connectivity between the amygdala and MPFC, self-reported mood, and sleep parameters. Eighteen healthy adult men aged 29 ± 8.24 years participated in a 2-day sleep control session (SC; time in bed [TIB], 9 hours) and 2-day SD session (TIB, 3 hours). On day 2 of each session, resting-state functional magnetic resonance imaging was performed, followed immediately by measuring self-reported mood on the State-Trait Anxiety Inventory-State subscale (STAI-S). STAI-S score was significantly increased, and functional connectivity between the amygdala and MPFC was significantly decreased in SD compared with SC. Significant correlations were observed between reduced rapid eye movement (REM) sleep and reduced left amygdala-MPFC functional connectivity (FCL_amg-MPFC) and between reduced FCL_amg-MPFC and increased STAI-S score in SD compared with SC. These findings suggest that reduced MPFC functional connectivity of amygdala activity is involved in mood deterioration under SD, and that REM sleep reduction is involved in functional changes in the corresponding brain regions. Having adequate REM sleep may be important for mental health maintenance. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

BRAIN NETWORKS. Correlated gene expression supports synchronous activity in brain networks.

PubMed

Richiardi, Jonas; Altmann, Andre; Milazzo, Anna-Clare; Chang, Catie; Chakravarty, M Mallar; Banaschewski, Tobias; Barker, Gareth J; Bokde, Arun L W; Bromberg, Uli; Büchel, Christian; Conrod, Patricia; Fauth-Bühler, Mira; Flor, Herta; Frouin, Vincent; Gallinat, Jürgen; Garavan, Hugh; Gowland, Penny; Heinz, Andreas; Lemaître, Hervé; Mann, Karl F; Martinot, Jean-Luc; Nees, Frauke; Paus, Tomáš; Pausova, Zdenka; Rietschel, Marcella; Robbins, Trevor W; Smolka, Michael N; Spanagel, Rainer; Ströhle, Andreas; Schumann, Gunter; Hawrylycz, Mike; Poline, Jean-Baptiste; Greicius, Michael D

2015-06-12

During rest, brain activity is synchronized between different regions widely distributed throughout the brain, forming functional networks. However, the molecular mechanisms supporting functional connectivity remain undefined. We show that functional brain networks defined with resting-state functional magnetic resonance imaging can be recapitulated by using measures of correlated gene expression in a post mortem brain tissue data set. The set of 136 genes we identify is significantly enriched for ion channels. Polymorphisms in this set of genes significantly affect resting-state functional connectivity in a large sample of healthy adolescents. Expression levels of these genes are also significantly associated with axonal connectivity in the mouse. The results provide convergent, multimodal evidence that resting-state functional networks correlate with the orchestrated activity of dozens of genes linked to ion channel activity and synaptic function. Copyright © 2015, American Association for the Advancement of Science.

ZNF804A Variation May Affect Hippocampal-Prefrontal Resting-State Functional Connectivity in Schizophrenic and Healthy Individuals.

PubMed

Zhang, Yuyanan; Yan, Hao; Liao, Jinmin; Yu, Hao; Jiang, Sisi; Liu, Qi; Zhang, Dai; Yue, Weihua

2018-06-01

The ZNF804A variant rs1344706 has consistently been associated with schizophrenia and plays a role in hippocampal-prefrontal functional connectivity during working memory. Whether the effect exists in the resting state and in patients with schizophrenia remains unclear. In this study, we investigated the ZNF804A polymorphism at rs1344706 in 92 schizophrenic patients and 99 healthy controls of Han Chinese descent, and used resting-state functional magnetic resonance imaging to explore the functional connectivity in the participants. We found a significant main effect of genotype on the resting-state functional connectivity (RSFC) between the hippocampus and the dorsolateral prefrontal cortex (DLPFC) in both schizophrenic patients and healthy controls. The homozygous ZNF804A rs1344706 genotype (AA) conferred a high risk of schizophrenia, and also exhibited significantly decreased resting functional coupling between the left hippocampus and right DLPFC (F(2,165) = 13.43, P < 0.001). The RSFC strength was also correlated with cognitive performance and the severity of psychosis in schizophrenia. The current findings identified the neural impact of the ZNF804A rs1344706 on hippocampal-prefrontal RSFC associated with schizophrenia.

Abnormal amygdala connectivity in patients with primary insomnia: evidence from resting state fMRI.

PubMed

Huang, Zhaoyang; Liang, Peipeng; Jia, Xiuqin; Zhan, Shuqin; Li, Ning; Ding, Yan; Lu, Jie; Wang, Yuping; Li, Kuncheng

2012-06-01

Neurobiological mechanisms underlying insomnia are poorly understood. Previous findings indicated that dysfunction of the emotional circuit might contribute to the neurobiological mechanisms underlying insomnia. The present study will test this hypothesis by examining alterations in functional connectivity of the amygdala in patients with primary insomnia (PI). Resting-state functional connectivity analysis was used to examine the temporal correlation between the amygdala and whole-brain regions in 10 medication-naive PI patients and 10 age- and sex-matched healthy controls. Additionally, the relationship between the abnormal functional connectivity and insomnia severity was investigated. We found decreased functional connectivity mainly between the amygdala and insula, striatum and thalamus, and increased functional connectivity mainly between the amygdala and premotor cortex, sensorimotor cortex in PI patients as compared to healthy controls. The connectivity of the amygdala with the premotor cortex in PI patients showed significant positive correlation with the total score of the Pittsburgh Sleep Quality Index (PSQI). The decreased functional connectivity between the amygdala and insula, striatum, and thalamus suggests that dysfunction in the emotional circuit might contribute to the neurobiological mechanisms underlying PI. The increased functional connectivity of the amygdala with the premotor and sensorimotor cortex demonstrates a compensatory mechanism to overcome the negative effects of sleep deficits and maintain the psychomotor performances in PI patients. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Altered Gray Matter Volume and Resting-State Connectivity in Individuals With Internet Gaming Disorder: A Voxel-Based Morphometry and Resting-State Functional Magnetic Resonance Imaging Study

PubMed Central

Seok, Ji-Woo; Sohn, Jin-Hun

2018-01-01

Neuroimaging studies on the characteristics of individuals with Internet gaming disorder (IGD) have been accumulating due to growing concerns regarding the psychological and social problems associated with Internet use. However, relatively little is known about the brain characteristics underlying IGD, such as the associated functional connectivity and structure. The aim of this study was to investigate alterations in gray matter (GM) volume and functional connectivity during resting state in individuals with IGD using voxel-based morphometry and a resting-state connectivity analysis. The participants included 20 individuals with IGD and 20 age- and sex-matched healthy controls. Resting-state functional and structural images were acquired for all participants using 3 T magnetic resonance imaging. We also measured the severity of IGD and impulsivity using psychological scales. The results show that IGD severity was positively correlated with GM volume in the left caudate (p < 0.05, corrected for multiple comparisons), and negatively associated with functional connectivity between the left caudate and the right middle frontal gyrus (p < 0.05, corrected for multiple comparisons). This study demonstrates that IGD is associated with neuroanatomical changes in the right middle frontal cortex and the left caudate. These are important brain regions for reward and cognitive control processes, and structural and functional abnormalities in these regions have been reported for other addictions, such as substance abuse and pathological gambling. The findings suggest that structural deficits and resting-state functional impairments in the frontostriatal network may be associated with IGD and provide new insights into the underlying neural mechanisms of IGD. PMID:29636704

Correcting for Blood Arrival Time in Global Mean Regression Enhances Functional Connectivity Analysis of Resting State fMRI-BOLD Signals.

PubMed

Erdoğan, Sinem B; Tong, Yunjie; Hocke, Lia M; Lindsey, Kimberly P; deB Frederick, Blaise

2016-01-01

Resting state functional connectivity analysis is a widely used method for mapping intrinsic functional organization of the brain. Global signal regression (GSR) is commonly employed for removing systemic global variance from resting state BOLD-fMRI data; however, recent studies have demonstrated that GSR may introduce spurious negative correlations within and between functional networks, calling into question the meaning of anticorrelations reported between some networks. In the present study, we propose that global signal from resting state fMRI is composed primarily of systemic low frequency oscillations (sLFOs) that propagate with cerebral blood circulation throughout the brain. We introduce a novel systemic noise removal strategy for resting state fMRI data, "dynamic global signal regression" (dGSR), which applies a voxel-specific optimal time delay to the global signal prior to regression from voxel-wise time series. We test our hypothesis on two functional systems that are suggested to be intrinsically organized into anticorrelated networks: the default mode network (DMN) and task positive network (TPN). We evaluate the efficacy of dGSR and compare its performance with the conventional "static" global regression (sGSR) method in terms of (i) explaining systemic variance in the data and (ii) enhancing specificity and sensitivity of functional connectivity measures. dGSR increases the amount of BOLD signal variance being modeled and removed relative to sGSR while reducing spurious negative correlations introduced in reference regions by sGSR, and attenuating inflated positive connectivity measures. We conclude that incorporating time delay information for sLFOs into global noise removal strategies is of crucial importance for optimal noise removal from resting state functional connectivity maps.

Resting-state functional connectivity of the bed nucleus of the stria terminalis in post-traumatic stress disorder and its dissociative subtype.

PubMed

Rabellino, Daniela; Densmore, Maria; Harricharan, Sherain; Jean, Théberge; McKinnon, Margaret C; Lanius, Ruth A

2018-03-01

The bed nucleus of the stria terminals (BNST) is a subcortical structure involved in anticipatory and sustained reactivity to threat and is thus essential to the understanding of anxiety and stress responses. Although chronic stress and anxiety represent a hallmark of post-traumatic stress disorder (PTSD), to date, few studies have examined the functional connectivity of the BNST in PTSD. Here, we used resting state functional Magnetic Resonance Imaging (fMRI) to investigate the functional connectivity of the BNST in PTSD (n = 70), its dissociative subtype (PTSD + DS) (n = 41), and healthy controls (n = 50). In comparison to controls, PTSD showed increased functional connectivity of the BNST with regions of the reward system (ventral and dorsal striatum), possibly underlying stress-induced reward-seeking behaviors in PTSD. By contrast, comparing PTSD + DS to controls, we observed increased functional connectivity of the BNST with the claustrum, a brain region implicated in consciousness and a primary site of kappa-opioid receptors, which are critical to the dynorphin-mediated dysphoric stress response. Moreover, PTSD + DS showed increased functional connectivity of the BNST with brain regions involved in attention and salience detection (anterior insula and caudate nucleus) as compared to PTSD and controls. Finally, BNST functional connectivity positively correlated with default-mode network regions as a function of state identity dissociation, suggesting a role of BNST networks in the disruption of self-relevant processing characterizing the dissociative subtype. These findings represent an important first step in elucidating the role of the BNST in aberrant functional networks underlying PTSD and its dissociative subtype. © 2017 Wiley Periodicals, Inc.

Hyperconnective and hypoconnective cortical and subcortical functional networks in multiple system atrophy.

PubMed

Rosskopf, Johannes; Gorges, Martin; Müller, Hans-Peter; Pinkhardt, Elmar H; Ludolph, Albert C; Kassubek, Jan

2018-04-01

In multiple system atrophy (MSA), the organization of the functional brain connectivity within cortical and subcortical networks and its clinical correlates remains to be investigated. Whole-brain based 'resting-state' fMRI data were obtained from 22 MSA patients (11 MSA-C, 11 MSA-P) and 22 matched healthy controls, together with standardized clinical assessment and video-oculographic recordings (EyeLink ® ). MSA patients vs. controls showed significantly higher ponto-cerebellar functional connectivity and lower default mode network connectivity (p < .05, corrected). No differences were observed in the motor network and in the control network. The higher the ponto-cerebellar network functional connectivity was, the more pronounced was smooth pursuit impairment. This functional connectivity analysis supports a network-dependent combination of hyper- and hypoconnectivity states in MSA, in agreement with adaptive compensatory responses (hyperconnectivity) and a function disconnection syndrome (hypoconnectivity) that may occur in a consecutive sequence. Copyright © 2018 Elsevier Ltd. All rights reserved.

Recursive feature elimination for biomarker discovery in resting-state functional connectivity.

PubMed

Ravishankar, Hariharan; Madhavan, Radhika; Mullick, Rakesh; Shetty, Teena; Marinelli, Luca; Joel, Suresh E

2016-08-01

Biomarker discovery involves finding correlations between features and clinical symptoms to aid clinical decision. This task is especially difficult in resting state functional magnetic resonance imaging (rs-fMRI) data due to low SNR, high-dimensionality of images, inter-subject and intra-subject variability and small numbers of subjects compared to the number of derived features. Traditional univariate analysis suffers from the problem of multiple comparisons. Here, we adopt an alternative data-driven method for identifying population differences in functional connectivity. We propose a machine-learning approach to down-select functional connectivity features associated with symptom severity in mild traumatic brain injury (mTBI). Using this approach, we identified functional regions with altered connectivity in mTBI. including the executive control, visual and precuneus networks. We compared functional connections at multiple resolutions to determine which scale would be more sensitive to changes related to patient recovery. These modular network-level features can be used as diagnostic tools for predicting disease severity and recovery profiles.

A supplementary functional connectivity microstate attached to the default mode network in depression revealed by resting-state magnetoencephalography.

PubMed

Zhang, Siqi; Tian, Shui; Chattun, Mohammad Ridwan; Tang, Hao; Yan, Rui; Bi, Kun; Yao, Zhijian; Lu, Qing

2018-04-20

Default mode network (DMN) has discernable involvement in the representation of negative, self-referential information in depression. Both increased and decreased resting-state functional connectivity between the anterior and posterior DMN have been observed in depression. These conflicting connectivity differences necessitated further exploration of the resting-state DMN dysfunction in depression. Hence, we investigated the time-varying dynamic interactions within the DMN via functional connectivity microstates in a sub-second level. 25 patients with depression and 25 matched healthy controls were enrolled in the MEG analysis. Spherical K-means algorithms embedded within an iterative optimization frame were applied to sliding windowed correlation matrices, resulting in sub-second alternations of two functional connectivity microstates for groups and highlighting the presence of functional variability. In the power dominant state, depressed patients showed a transient decreased pattern that reflected inter/intra-subnetwork deregulation. A supplementary negatively correlated state simultaneously presented with increased connectivity between the ventromedial prefrontal cortex (vmPFC) and the posterior cingulate cortex (PCC), two core nodes for the anterior and posterior DMN respectively. Additionally, depressed patients stayed longer in the supplementary microstate compared to healthy controls. During the time spent in the supplementary microstate, an attempt to compensate for the aberrant effect of vmPFC on PCC across DMN subnetworks was possibly made to balance the self-related processes disturbed by the dominant pattern. The functional compensation mechanism of the supplementary microstate attached to the dominant disrupted one provided a possible explanation to the existing inconsistent findings between the anterior and posterior DMN in depression. Copyright © 2018 Elsevier Inc. All rights reserved.

Brain functional connectivity network studies of acupuncture: a systematic review on resting-state fMRI.

PubMed

Cai, Rong-Lin; Shen, Guo-Ming; Wang, Hao; Guan, Yuan-Yuan

2018-01-01

Functional magnetic resonance imaging (fMRI) is a novel method for studying the changes of brain networks due to acupuncture treatment. In recent years, more and more studies have focused on the brain functional connectivity network of acupuncture stimulation. To offer an overview of the different influences of acupuncture on the brain functional connectivity network from studies using resting-state fMRI. The authors performed a systematic search according to PRISMA guidelines. The database PubMed was searched from January 1, 2006 to December 31, 2016 with restriction to human studies in English language. Electronic searches were conducted in PubMed using the keywords "acupuncture" and "neuroimaging" or "resting-state fMRI" or "functional connectivity". Selection of included articles, data extraction and methodological quality assessments were respectively conducted by two review authors. Forty-four resting-state fMRI studies were included in this systematic review according to inclusion criteria. Thirteen studies applied manual acupuncture vs. sham, four studies applied electro-acupuncture vs. sham, two studies also compared transcutaneous electrical acupoint stimulation vs. sham, and nine applied sham acupoint as control. Nineteen studies with a total number of 574 healthy subjects selected to perform fMRI only considered healthy adult volunteers. The brain functional connectivity of the patients had varying degrees of change. Compared with sham acupuncture, verum acupuncture could increase default mode network and sensorimotor network connectivity with pain-, affective- and memory-related brain areas. It has significantly greater connectivity of genuine acupuncture between the periaqueductal gray, anterior cingulate cortex, left posterior cingulate cortex, right anterior insula, limbic/paralimbic and precuneus compared with sham acupuncture. Some research had also shown that acupuncture could adjust the limbic-paralimbic-neocortical network, brainstem, cerebellum, subcortical and hippocampus brain areas. It can be presumed that the functional connectivity network is closely related to the mechanism of acupuncture, and central integration plays a critical role in the acupuncture mechanism. Copyright © 2017 Shanghai Changhai Hospital. Published by Elsevier B.V. All rights reserved.

A Flexible Approach for Assessing Functional Landscape Connectivity, with Application to Greater Sage-Grouse (Centrocercus urophasianus)

PubMed Central

Harju, Seth M.; Olson, Chad V.; Dzialak, Matthew R.; Mudd, James P.; Winstead, Jeff B.

2013-01-01

Connectivity of animal populations is an increasingly prominent concern in fragmented landscapes, yet existing methodological and conceptual approaches implicitly assume the presence of, or need for, discrete corridors. We tested this assumption by developing a flexible conceptual approach that does not assume, but allows for, the presence of discrete movement corridors. We quantified functional connectivity habitat for greater sage-grouse (Centrocercus urophasianus) across a large landscape in central western North America. We assigned sample locations to a movement state (encamped, traveling and relocating), and used Global Positioning System (GPS) location data and conditional logistic regression to estimate state-specific resource selection functions. Patterns of resource selection during different movement states reflected selection for sagebrush and general avoidance of rough topography and anthropogenic features. Distinct connectivity corridors were not common in the 5,625 km2 study area. Rather, broad areas functioned as generally high or low quality connectivity habitat. A comprehensive map predicting the quality of connectivity habitat across the study area validated well based on a set of GPS locations from independent greater sage-grouse. The functional relationship between greater sage-grouse and the landscape did not always conform to the idea of a discrete corridor. A more flexible consideration of landscape connectivity may improve the efficacy of management actions by aligning those actions with the spatial patterns by which animals interact with the landscape. PMID:24349241

A flexible approach for assessing functional landscape connectivity, with application to greater sage-grouse (Centrocercus urophasianus).

PubMed

Harju, Seth M; Olson, Chad V; Dzialak, Matthew R; Mudd, James P; Winstead, Jeff B

2013-01-01

Connectivity of animal populations is an increasingly prominent concern in fragmented landscapes, yet existing methodological and conceptual approaches implicitly assume the presence of, or need for, discrete corridors. We tested this assumption by developing a flexible conceptual approach that does not assume, but allows for, the presence of discrete movement corridors. We quantified functional connectivity habitat for greater sage-grouse (Centrocercus urophasianus) across a large landscape in central western North America. We assigned sample locations to a movement state (encamped, traveling and relocating), and used Global Positioning System (GPS) location data and conditional logistic regression to estimate state-specific resource selection functions. Patterns of resource selection during different movement states reflected selection for sagebrush and general avoidance of rough topography and anthropogenic features. Distinct connectivity corridors were not common in the 5,625 km(2) study area. Rather, broad areas functioned as generally high or low quality connectivity habitat. A comprehensive map predicting the quality of connectivity habitat across the study area validated well based on a set of GPS locations from independent greater sage-grouse. The functional relationship between greater sage-grouse and the landscape did not always conform to the idea of a discrete corridor. A more flexible consideration of landscape connectivity may improve the efficacy of management actions by aligning those actions with the spatial patterns by which animals interact with the landscape.

Impaired Long Distance Functional Connectivity and Weighted Network Architecture in Alzheimer's Disease

PubMed Central

Liu, Yong; Yu, Chunshui; Zhang, Xinqing; Liu, Jieqiong; Duan, Yunyun; Alexander-Bloch, Aaron F.; Liu, Bing; Jiang, Tianzi; Bullmore, Ed

2014-01-01

Alzheimer's disease (AD) is increasingly recognized as a disconnection syndrome, which leads to cognitive impairment due to the disruption of functional activity across large networks or systems of interconnected brain regions. We explored abnormal functional magnetic resonance imaging (fMRI) resting-state dynamics, functional connectivity, and weighted functional networks, in a sample of patients with severe AD (N = 18) and age-matched healthy volunteers (N = 21). We found that patients had reduced amplitude and regional homogeneity of low-frequency fMRI oscillations, and reduced the strength of functional connectivity, in several regions previously described as components of the default mode network, for example, medial posterior parietal cortex and dorsal medial prefrontal cortex. In patients with severe AD, functional connectivity was particularly attenuated between regions that were separated by a greater physical distance; and loss of long distance connectivity was associated with less efficient global and nodal network topology. This profile of functional abnormality in severe AD was consistent with the results of a comparable analysis of data on 2 additional groups of patients with mild AD (N = 17) and amnestic mild cognitive impairment (MCI; N = 18). A greater degree of cognitive impairment, measured by the mini-mental state examination across all patient groups, was correlated with greater attenuation of functional connectivity, particularly over long connection distances, for example, between anterior and posterior components of the default mode network, and greater reduction of global and nodal network efficiency. These results indicate that neurodegenerative disruption of fMRI oscillations and connectivity in AD affects long-distance connections to hub nodes, with the consequent loss of network efficiency. This profile was evident also to a lesser degree in the patients with less severe cognitive impairment, indicating that the potential of resting-state fMRI measures as biomarkers or predictors of disease progression in AD. PMID:23314940

Intrinsic Functional Connectivity in the Adult Brain and Success in Second-Language Learning.

PubMed

Chai, Xiaoqian J; Berken, Jonathan A; Barbeau, Elise B; Soles, Jennika; Callahan, Megan; Chen, Jen-Kai; Klein, Denise

2016-01-20

There is considerable variability in an individual's ability to acquire a second language (L2) during adulthood. Using resting-state fMRI data acquired before training in English speakers who underwent a 12 week intensive French immersion training course, we investigated whether individual differences in intrinsic resting-state functional connectivity relate to a person's ability to acquire an L2. We focused on two key aspects of language processing--lexical retrieval in spontaneous speech and reading speed--and computed whole-brain functional connectivity from two regions of interest in the language network, namely the left anterior insula/frontal operculum (AI/FO) and the visual word form area (VWFA). Connectivity between the left AI/FO and left posterior superior temporal gyrus (STG) and between the left AI/FO and dorsal anterior cingulate cortex correlated positively with improvement in L2 lexical retrieval in spontaneous speech. Connectivity between the VWFA and left mid-STG correlated positively with improvement in L2 reading speed. These findings are consistent with the different language functions subserved by subcomponents of the language network and suggest that the human capacity to learn an L2 can be predicted by an individual's intrinsic functional connectivity within the language network. Significance statement: There is considerable variability in second-language learning abilities during adulthood. We investigated whether individual differences in intrinsic functional connectivity in the adult brain relate to success in second-language learning, using resting-state functional magnetic resonance imaging in English speakers who underwent a 12 week intensive French immersion training course. We found that pretraining functional connectivity within two different language subnetworks correlated strongly with learning outcome in two different language skills: lexical retrieval in spontaneous speech and reading speed. Our results suggest that the human capacity to learn a second language can be predicted by an individual's intrinsic functional connectivity within the language network. Copyright © 2016 the authors 0270-6474/16/360755-07$15.00/0.

Resting-state functional connectivity imaging of the mouse brain using photoacoustic tomography

NASA Astrophysics Data System (ADS)

Nasiriavanaki, Mohammadreza; Xia, Jun; Wan, Hanlin; Bauer, Adam Q.; Culver, Joseph P.; Wang, Lihong V.

2014-03-01

Resting-state functional connectivity (RSFC) imaging is an emerging neuroimaging approach that aims to identify spontaneous cerebral hemodynamic fluctuations and their associated functional connections. Clinical studies have demonstrated that RSFC is altered in brain disorders such as stroke, Alzheimer's, autism, and epilepsy. However, conventional neuroimaging modalities cannot easily be applied to mice, the most widely used model species for human brain disease studies. For instance, functional magnetic resonance imaging (fMRI) of mice requires a very high magnetic field to obtain a sufficient signal-to-noise ratio and spatial resolution. Functional connectivity mapping with optical intrinsic signal imaging (fcOIS) is an alternative method. Due to the diffusion of light in tissue, the spatial resolution of fcOIS is limited, and experiments have been performed using an exposed skull preparation. In this study, we show for the first time, the use of photoacoustic computed tomography (PACT) to noninvasively image resting-state functional connectivity in the mouse brain, with a large field of view and a high spatial resolution. Bilateral correlations were observed in eight regions, as well as several subregions. These findings agreed well with the Paxinos mouse brain atlas. This study showed that PACT is a promising, non-invasive modality for small-animal functional brain imaging.

Assessing dynamic brain graphs of time-varying connectivity in fMRI data: application to healthy controls and patients with schizophrenia

PubMed Central

Yu, Qingbao; Erhardt, Erik B.; Sui, Jing; Du, Yuhui; He, Hao; Hjelm, Devon; Cetin, Mustafa S.; Rachakonda, Srinivas; Miller, Robyn L.; Pearlson, Godfrey; Calhoun, Vince D.

2014-01-01

Graph theory-based analysis has been widely employed in brain imaging studies, and altered topological properties of brain connectivity have emerged as important features of mental diseases such as schizophrenia. However, most previous studies have focused on graph metrics of stationary brain graphs, ignoring that brain connectivity exhibits fluctuations over time. Here we develop a new framework for accessing dynamic graph properties of time-varying functional brain connectivity in resting state fMRI data and apply it to healthy controls (HCs) and patients with schizophrenia (SZs). Specifically, nodes of brain graphs are defined by intrinsic connectivity networks (ICNs) identified by group independent component analysis (ICA). Dynamic graph metrics of the time-varying brain connectivity estimated by the correlation of sliding time-windowed ICA time courses of ICNs are calculated. First- and second-level connectivity states are detected based on the correlation of nodal connectivity strength between time-varying brain graphs. Our results indicate that SZs show decreased variance in the dynamic graph metrics. Consistent with prior stationary functional brain connectivity works, graph measures of identified first-level connectivity states show lower values in SZs. In addition, more first-level connectivity states are disassociated with the second-level connectivity state which resembles the stationary connectivity pattern computed by the entire scan. Collectively, the findings provide new evidence about altered dynamic brain graphs in schizophrenia which may underscore the abnormal brain performance in this mental illness. PMID:25514514

Altered Amygdala Resting-State Functional Connectivity in Maintenance Hemodialysis End-Stage Renal Disease Patients with Depressive Mood.

PubMed

Chen, Hui Juan; Wang, Yun Fei; Qi, Rongfeng; Schoepf, U Joseph; Varga-Szemes, Akos; Ball, B Devon; Zhang, Zhe; Kong, Xiang; Wen, Jiqiu; Li, Xue; Lu, Guang Ming; Zhang, Long Jiang

2017-04-01

The purpose of this study was to investigate patterns in the amygdala-based emotional processing circuit of hemodialysis patients using resting-state functional MR imaging (rs-fMRI). Fifty hemodialysis patients (25 with depressed mood and 25 without depressed mood) and 26 healthy controls were included. All subjects underwent neuropsychological tests and rs-fMRI, and patients also underwent laboratory tests. Functional connectivity of the bilateral amygdala was compared among the three groups. The relationship between functional connectivity and clinical markers was investigated. Depressed patients showed increased positive functional connectivity of the left amygdala with the left superior temporal gyrus and right parahippocampal gyrus (PHG) but decreased amygdala functional connectivity with the left precuneus, angular gyrus, posterior cingulate cortex (PCC), and left inferior parietal lobule compared with non-depressed patients (P < 0.05, AlphaSim corrected). Depressed patients had increased positive functional connectivity of the right amygdala with bilateral supplementary motor areas and PHG but decreased amygdala functional connectivity with the right superior frontal gyrus, superior parietal lobule, bilateral precuneus, and PCC (P < 0.05, AlphaSim corrected). After including anxiety as a covariate, we discovered additional decreased functional connectivity with anterior cingulate cortex (ACC) for bilateral amygdala (P < 0.05, AlphaSim corrected). For the depressed, neuropsychological test scores were correlated with functional connectivity of multiple regions (P < 0.05, AlphaSim corrected). In conclusion, functional connectivity in the amygdala-prefrontal-PCC-limbic circuits was impaired in depressive hemodialysis patients, with a gradual decrease in ACC between controls, non-depressed, and depressed patients for the right amygdala. This indicates that ACC plays a role in amygdala-based emotional regulatory circuits in these patients.

Large-scale changes in network interactions as a physiological signature of spatial neglect

PubMed Central

Baldassarre, Antonello; Ramsey, Lenny; Hacker, Carl L.; Callejas, Alicia; Astafiev, Serguei V.; Metcalf, Nicholas V.; Zinn, Kristi; Rengachary, Jennifer; Snyder, Abraham Z.; Carter, Alex R.; Shulman, Gordon L.

2014-01-01

The relationship between spontaneous brain activity and behaviour following focal injury is not well understood. Here, we report a large-scale study of resting state functional connectivity MRI and spatial neglect following stroke in a large (n = 84) heterogeneous sample of first-ever stroke patients (within 1–2 weeks). Spatial neglect, which is typically more severe after right than left hemisphere injury, includes deficits of spatial attention and motor actions contralateral to the lesion, and low general attention due to impaired vigilance/arousal. Patients underwent structural and resting state functional MRI scans, and spatial neglect was measured using the Posner spatial cueing task, and Mesulam and Behavioural Inattention Test cancellation tests. A principal component analysis of the behavioural tests revealed a main factor accounting for 34% of variance that captured three correlated behavioural deficits: visual neglect of the contralesional visual field, visuomotor neglect of the contralesional field, and low overall performance. In an independent sample (21 healthy subjects), we defined 10 resting state networks consisting of 169 brain regions: visual-fovea and visual-periphery, sensory-motor, auditory, dorsal attention, ventral attention, language, fronto-parietal control, cingulo-opercular control, and default mode. We correlated the neglect factor score with the strength of resting state functional connectivity within and across the 10 resting state networks. All damaged brain voxels were removed from the functional connectivity:behaviour correlational analysis. We found that the correlated behavioural deficits summarized by the factor score were associated with correlated multi-network patterns of abnormal functional connectivity involving large swaths of cortex. Specifically, dorsal attention and sensory-motor networks showed: (i) reduced interhemispheric functional connectivity; (ii) reduced anti-correlation with fronto-parietal and default mode networks in the right hemisphere; and (iii) increased intrahemispheric connectivity with the basal ganglia. These patterns of functional connectivity:behaviour correlations were stronger in patients with right- as compared to left-hemisphere damage and were independent of lesion volume. Our findings identify large-scale changes in resting state network interactions that are a physiological signature of spatial neglect and may relate to its right hemisphere lateralization. PMID:25367028

Functional organization of intrinsic connectivity networks in Chinese-chess experts.

PubMed

Duan, Xujun; Long, Zhiliang; Chen, Huafu; Liang, Dongmei; Qiu, Lihua; Huang, Xiaoqi; Liu, Timon Cheng-Yi; Gong, Qiyong

2014-04-16

The functional architecture of the human brain has been extensively described in terms of functional connectivity networks, detected from the low-frequency coherent neuronal fluctuations during a resting state condition. Accumulating evidence suggests that the overall organization of functional connectivity networks is associated with individual differences in cognitive performance and prior experience. Such an association raises the question of how cognitive expertise exerts an influence on the topological properties of large-scale functional networks. To address this question, we examined the overall organization of brain functional networks in 20 grandmaster and master level Chinese-chess players (GM/M) and twenty novice players, by means of resting-state functional connectivity and graph theoretical analyses. We found that, relative to novices, functional connectivity was increased in GM/Ms between basal ganglia, thalamus, hippocampus, and several parietal and temporal areas, suggesting the influence of cognitive expertise on intrinsic connectivity networks associated with learning and memory. Furthermore, we observed economical small-world topology in the whole-brain functional connectivity networks in both groups, but GM/Ms exhibited significantly increased values of normalized clustering coefficient which resulted in increased small-world topology. These findings suggest an association between the functional organization of brain networks and individual differences in cognitive expertise, which might provide further evidence of the mechanisms underlying expert behavior. Copyright © 2014 Elsevier B.V. All rights reserved.

Simultaneous tDCS-fMRI Identifies Resting State Networks Correlated with Visual Search Enhancement.

PubMed

Callan, Daniel E; Falcone, Brian; Wada, Atsushi; Parasuraman, Raja

2016-01-01

This study uses simultaneous transcranial direct current stimulation (tDCS) and functional MRI (fMRI) to investigate tDCS modulation of resting state activity and connectivity that underlies enhancement in behavioral performance. The experiment consisted of three sessions within the fMRI scanner in which participants conducted a visual search task: Session 1: Pre-training (no performance feedback), Session 2: Training (performance feedback given), Session 3: Post-training (no performance feedback). Resting state activity was recorded during the last 5 min of each session. During the 2nd session one group of participants underwent 1 mA tDCS stimulation and another underwent sham stimulation over the right posterior parietal cortex. Resting state spontaneous activity, as measured by fractional amplitude of low frequency fluctuations (fALFF), for session 2 showed significant differences between the tDCS stim and sham groups in the precuneus. Resting state functional connectivity from the precuneus to the substantia nigra, a subcortical dopaminergic region, was found to correlate with future improvement in visual search task performance for the stim over the sham group during active stimulation in session 2. The after-effect of stimulation on resting state functional connectivity was measured following a post-training experimental session (session 3). The left cerebellum Lobule VIIa Crus I showed performance related enhancement in resting state functional connectivity for the tDCS stim over the sham group. The ability to determine the relationship that the relative strength of resting state functional connectivity for an individual undergoing tDCS has on future enhancement in behavioral performance has wide ranging implications for neuroergonomic as well as therapeutic, and rehabilitative applications.

Evoked itch perception is associated with changes in functional brain connectivity.

PubMed

Desbordes, Gaëlle; Li, Ang; Loggia, Marco L; Kim, Jieun; Schalock, Peter C; Lerner, Ethan; Tran, Thanh N; Ring, Johannes; Rosen, Bruce R; Kaptchuk, Ted J; Pfab, Florian; Napadow, Vitaly

2015-01-01

Chronic itch, a highly debilitating condition, has received relatively little attention in the neuroimaging literature. Recent studies suggest that brain regions supporting itch in chronic itch patients encompass sensorimotor and salience networks, and corticostriatal circuits involved in motor preparation for scratching. However, how these different brain areas interact with one another in the context of itch is still unknown. We acquired BOLD fMRI scans in 14 atopic dermatitis patients to investigate resting-state functional connectivity before and after allergen-induced itch exacerbated the clinical itch perception in these patients. A seed-based analysis revealed decreased functional connectivity from baseline resting state to the evoked-itch state between several itch-related brain regions, particularly the insular and cingulate cortices and basal ganglia, where decreased connectivity was significantly correlated with increased levels of perceived itch. In contrast, evoked itch increased connectivity between key nodes of the frontoparietal control network (superior parietal lobule and dorsolateral prefrontal cortex), where higher increase in connectivity was correlated with a lesser increase in perceived itch, suggesting that greater interaction between nodes of this executive attention network serves to limit itch sensation via enhanced top-down regulation. Overall, our results provide the first evidence of itch-dependent changes in functional connectivity across multiple brain regions.

Altered functional connectivity of the language network in ASD: Role of classical language areas and cerebellum☆

PubMed Central

Verly, Marjolein; Verhoeven, Judith; Zink, Inge; Mantini, Dante; Peeters, Ronald; Deprez, Sabine; Emsell, Louise; Boets, Bart; Noens, Ilse; Steyaert, Jean; Lagae, Lieven; De Cock, Paul; Rommel, Nathalie; Sunaert, Stefan

2014-01-01

The development of language, social interaction and communicative skills is remarkably different in the child with autism spectrum disorder (ASD). Atypical brain connectivity has frequently been reported in this patient population. However, the neural correlates underlying their disrupted language development and functioning are still poorly understood. Using resting state fMRI, we investigated the functional connectivity properties of the language network in a group of ASD patients with clear comorbid language impairment (ASD-LI; N = 19) and compared them to the language related connectivity properties of 23 age-matched typically developing children. A verb generation task was used to determine language components commonly active in both groups. Eight joint language components were identified and subsequently used as seeds in a resting state analysis. Interestingly, both the interregional and the seed-based whole brain connectivity analysis showed preserved connectivity between the classical intrahemispheric language centers, Wernicke's and Broca's areas. In contrast however, a marked loss of functional connectivity was found between the right cerebellar region and the supratentorial regulatory language areas. Also, the connectivity between the interhemispheric Broca regions and modulatory control dorsolateral prefrontal region was found to be decreased. This disruption of normal modulatory control and automation function by the cerebellum may underlie the abnormal language function in children with ASD-LI. PMID:24567909

Abnormal cerebral functional connectivity in esophageal cancer patients with theory of mind deficits in resting state.

PubMed

Cao, Yin; Xiang, JianBo; Qian, Nong; Sun, SuPing; Hu, LiJun; Yuan, YongGui

2015-01-01

To explore the function of the default mode network (DMN) in the psychopathological mechanisms of theory of mind deficits in patients with an esophageal cancer concomitant with depression in resting the state. Twenty-five cases of esophageal cancer with theory of mind deficits (test group) that meet the diagnostic criteria of esophageal cancer and neuropsychological tests, including Beck depression inventory, reading the mind in the eyes, and Faux pas, were included, Another 25 cases of esophageal cancer patients but without theory of mind deficits (control group) were enrolled. Each patient completed a resting-state functional magnetic resonance imaging. The functional connectivity intensities within the cerebral regions in the DMN of all the enrolled patients were analyzed. The results of each group were compared. The functional connectivity of the bilateral prefrontal central region with the precuneus, bilateral posterior cingulate gyrus and bilateral ventral anterior cingulate gyrus in the patients of the test group were all reduced significantly (P < 0.05). In the resting state, the functional connectivity is abnormal in the cerebral regions in the DMN of esophageal cancer patients with theory of mind deficits. The theory of mind deficits might have an important function in the pathogenesis of esophageal cancer.

A posteriori model validation for the temporal order of directed functional connectivity maps

PubMed Central

Beltz, Adriene M.; Molenaar, Peter C. M.

2015-01-01

A posteriori model validation for the temporal order of neural directed functional connectivity maps is rare. This is striking because models that require sequential independence among residuals are regularly implemented. The aim of the current study was (a) to apply to directed functional connectivity maps of functional magnetic resonance imaging data an a posteriori model validation procedure (i.e., white noise tests of one-step-ahead prediction errors combined with decision criteria for revising the maps based upon Lagrange Multiplier tests), and (b) to demonstrate how the procedure applies to single-subject simulated, single-subject task-related, and multi-subject resting state data. Directed functional connectivity was determined by the unified structural equation model family of approaches in order to map contemporaneous and first order lagged connections among brain regions at the group- and individual-levels while incorporating external input, then white noise tests were run. Findings revealed that the validation procedure successfully detected unmodeled sequential dependencies among residuals and recovered higher order (greater than one) simulated connections, and that the procedure can accommodate task-related input. Findings also revealed that lags greater than one were present in resting state data: With a group-level network that contained only contemporaneous and first order connections, 44% of subjects required second order, individual-level connections in order to obtain maps with white noise residuals. Results have broad methodological relevance (e.g., temporal validation is necessary after directed functional connectivity analyses because the presence of unmodeled higher order sequential dependencies may bias parameter estimates) and substantive implications (e.g., higher order lags may be common in resting state data). PMID:26379489

Resting state brain network function in major depression - Depression symptomatology, antidepressant treatment effects, future research.

PubMed

Brakowski, Janis; Spinelli, Simona; Dörig, Nadja; Bosch, Oliver Gero; Manoliu, Andrei; Holtforth, Martin Grosse; Seifritz, Erich

2017-09-01

The alterations of functional connectivity brain networks in major depressive disorder (MDD) have been subject of a large number of studies. Using different methodologies and focusing on diverse aspects of the disease, research shows heterogeneous results lacking integration. Disrupted network connectivity has been found in core MDD networks like the default mode network (DMN), the central executive network (CEN), and the salience network, but also in cerebellar and thalamic circuitries. Here we review literature published on resting state brain network function in MDD focusing on methodology, and clinical characteristics including symptomatology and antidepressant treatment related findings. There are relatively few investigations concerning the qualitative aspects of symptomatology of MDD, whereas most studies associate quantitative aspects with distinct resting state functional connectivity alterations. Such depression severity associated alterations are found in the DMN, frontal, cerebellar and thalamic brain regions as well as the insula and the subgenual anterior cingulate cortex. Similarly, different therapeutical options in MDD and their effects on brain function showed patchy results. Herein, pharmaceutical treatments reveal functional connectivity alterations throughout multiple brain regions notably the DMN, fronto-limbic, and parieto-temporal regions. Psychotherapeutical interventions show significant functional connectivity alterations in fronto-limbic networks, whereas electroconvulsive therapy and repetitive transcranial magnetic stimulation result in alterations of the subgenual anterior cingulate cortex, the DMN, the CEN and the dorsal lateral prefrontal cortex. While it appears clear that functional connectivity alterations are associated with the pathophysiology and treatment of MDD, future research should also generate a common strategy for data acquisition and analysis, as a least common denominator, to set the basis for comparability across studies and implementation of functional connectivity as a scientifically and clinically useful biomarker. Copyright © 2017 Elsevier Ltd. All rights reserved.

Resting state functional connectivity magnetic resonance imaging integrated with intraoperative neuronavigation for functional mapping after aborted awake craniotomy

PubMed Central

Batra, Prag; Bandt, S. Kathleen; Leuthardt, Eric C.

2016-01-01

Background: Awake craniotomy is currently the gold standard for aggressive tumor resections in eloquent cortex. However, a significant subset of patients is unable to tolerate this procedure, particularly the very young or old or those with psychiatric comorbidities, cardiopulmonary comorbidities, or obesity, among other conditions. In these cases, typical alternative procedures include biopsy alone or subtotal resection, both of which are associated with diminished surgical outcomes. Case Description: Here, we report the successful use of a preoperatively obtained resting state functional connectivity magnetic resonance imaging (MRI) integrated with intraoperative neuronavigation software in order to perform functional cortical mapping in the setting of an aborted awake craniotomy due to loss of airway. Conclusion: Resting state functional connectivity MRI integrated with intraoperative neuronavigation software can provide an alternative option for functional cortical mapping in the setting of an aborted awake craniotomy. PMID:26958419

Resting-state connectivity of pre-motor cortex reflects disability in multiple sclerosis.

PubMed

Dogonowski, A-M; Siebner, H R; Soelberg Sørensen, P; Paulson, O B; Dyrby, T B; Blinkenberg, M; Madsen, K H

2013-11-01

To characterize the relationship between motor resting-state connectivity of the dorsal pre-motor cortex (PMd) and clinical disability in patients with multiple sclerosis (MS). A total of 27 patients with relapsing-remitting MS (RR-MS) and 15 patients with secondary progressive MS (SP-MS) underwent functional resting-state magnetic resonance imaging. Clinical disability was assessed using the Expanded Disability Status Scale (EDSS). Independent component analysis was used to characterize motor resting-state connectivity. Multiple regression analysis was performed in SPM8 between the individual expression of motor resting-state connectivity in PMd and EDSS scores including age as covariate. Separate post hoc analyses were performed for patients with RR-MS and SP-MS. The EDSS scores ranged from 0 to 7 with a median score of 4.3. Motor resting-state connectivity of left PMd showed a positive linear relation with clinical disability in patients with MS. This effect was stronger when considering the group of patients with RR-MS alone, whereas patients with SP-MS showed no increase in coupling strength between left PMd and the motor resting-state network with increasing clinical disability. No significant relation between motor resting-state connectivity of the right PMd and clinical disability was detected in MS. The increase in functional coupling between left PMd and the motor resting-state network with increasing clinical disability can be interpreted as adaptive reorganization of the motor system to maintain motor function, which appears to be limited to the relapsing-remitting stage of the disease. © 2013 John Wiley & Sons A/S.

Transdiagnostic differences in the resting-state functional connectivity of the prefrontal cortex in depression and schizophrenia.

PubMed

Chen, Xi; Liu, Chang; He, Hui; Chang, Xin; Jiang, Yuchao; Li, Yingjia; Duan, Mingjun; Li, Jianfu; Luo, Cheng; Yao, Dezhong

2017-08-01

Depression and schizophrenia are two of the most serious psychiatric disorders. They share similar symptoms but the pathology-specific commonalities and differences remain unknown. This study was conducted to acquire a full picture of the functional alterations in schizophrenia and depression patients. The resting-state fMRI data from 20 patients with schizophrenia, 20 patients with depression and 20 healthy control subjects were collected. A data-driven approach that included local functional connectivity density (FCD) analysis combined with multivariate pattern analysis (MVPA) was used to compare the three groups. Based on the results of the MVPA, the local FCD value in the orbitofrontal cortex (OFC) can differentiate depression patients from schizophrenia patients. The patients with depression had a higher local FCD value in the medial and anterior parts of the OFC than the subjects in the other two groups, which suggested altered abstract and reward reinforces processing in depression patients. Subsequent functional connectivity analysis indicated that the connection in the prefrontal cortex was significantly lower in people with schizophrenia compared to people with depression and healthy controls. The systematically different medications for schizophrenia and depression may have different effects on functional connectivity. These results suggested that the resting-state functional connectivity pattern in the prefrontal cortex may be a transdiagnostic difference between depression and schizophrenia patients. Copyright © 2017 Elsevier B.V. All rights reserved.

Distinct patterns of functional brain connectivity correlate with objective performance and subjective beliefs

PubMed Central

Barttfeld, Pablo; Wicker, Bruno; McAleer, Phil; Belin, Pascal; Cojan, Yann; Graziano, Martín; Leiguarda, Ramón; Sigman, Mariano

2013-01-01

The degree of correspondence between objective performance and subjective beliefs varies widely across individuals. Here we demonstrate that functional brain network connectivity measured before exposure to a perceptual decision task covaries with individual objective (type-I performance) and subjective (type-II performance) accuracy. Increases in connectivity with type-II performance were observed in networks measured while participants directed attention inward (focus on respiration), but not in networks measured during states of neutral (resting state) or exogenous attention. Measures of type-I performance were less sensitive to the subjects’ specific attentional states from which the networks were derived. These results suggest the existence of functional brain networks indexing objective performance and accuracy of subjective beliefs distinctively expressed in a set of stable mental states. PMID:23801762

Functional connectivity of dissociation in patients with psychogenic non-epileptic seizures.

PubMed

van der Kruijs, Sylvie J M; Bodde, Nynke M G; Vaessen, Maarten J; Lazeron, Richard H C; Vonck, Kristl; Boon, Paul; Hofman, Paul A M; Backes, Walter H; Aldenkamp, Albert P; Jansen, Jacobus F A

2012-03-01

Psychogenic non-epileptic seizures (PNES) resemble epileptic seizures, but lack epileptiform brain activity. Instead, the cause is assumed to be psychogenic. An abnormal coping strategy may be exhibited by PNES patients, as indicated by their increased tendency to dissociate. Investigation of resting-state networks may reveal altered routes of information and emotion processing in PNES patients. The authors therefore investigated whether PNES patients differ from healthy controls in their resting-state functional connectivity characteristics and whether these connections are associated with the tendency to dissociate. 11 PNES patients without psychiatric comorbidity and 12 healthy controls underwent task-related paradigms (picture-encoding and Stroop paradigms) and resting-state functional MRI (rsfMRI). Global cognitive performance was tested using the Raven's Matrices test and participants completed questionnaires for evaluating dissociation. Functional connectivity analysis on rsfMRI was based on seed regions extracted from task-related fMRI activation maps. The patients displayed a significantly lower cognitive performance and significantly higher dissociation scores. No significant differences were found between the picture-encoding and Stroop colour-naming activation maps between controls and patients with PNES. However, functional connectivity maps from the rsfMRI were statistically different. For PNES patients, stronger connectivity values between areas involved in emotion (insula), executive control (inferior frontal gyrus and parietal cortex) and movement (precentral sulcus) were observed, which were significantly associated with dissociation scores. The abnormal, strong functional connectivity in PNES patients provides a neurophysiological correlate for the underlying psychoform and somatoform dissociation mechanism where emotion can influence executive control, resulting in altered motor function (eg, seizure-like episodes).

Resting-state networks associated with cognitive processing show more age-related decline than those associated with emotional processing.

PubMed

Nashiro, Kaoru; Sakaki, Michiko; Braskie, Meredith N; Mather, Mara

2017-06-01

Correlations in activity across disparate brain regions during rest reveal functional networks in the brain. Although previous studies largely agree that there is an age-related decline in the "default mode network," how age affects other resting-state networks, such as emotion-related networks, is still controversial. Here we used a dual-regression approach to investigate age-related alterations in resting-state networks. The results revealed age-related disruptions in functional connectivity in all 5 identified cognitive networks, namely the default mode network, cognitive-auditory, cognitive-speech (or speech-related somatosensory), and right and left frontoparietal networks, whereas such age effects were not observed in the 3 identified emotion networks. In addition, we observed age-related decline in functional connectivity in 3 visual and 3 motor/visuospatial networks. Older adults showed greater functional connectivity in regions outside 4 out of the 5 identified cognitive networks, consistent with the dedifferentiation effect previously observed in task-based functional magnetic resonance imaging studies. Both reduced within-network connectivity and increased out-of-network connectivity were correlated with poor cognitive performance, providing potential biomarkers for cognitive aging. Copyright © 2017 Elsevier Inc. All rights reserved.

Resting State Functional Connectivity within the Cingulate Cortex Jointly Predicts Agreeableness and Stressor-Evoked Cardiovascular Reactivity

PubMed Central

Ryan, John P.; Sheu, Lei K.; Gianaros, Peter J.

2010-01-01

Exaggerated cardiovascular reactivity to stress confers risk for cardiovascular disease. Further, individual differences in stressor-evoked cardiovascular reactivity covary with the functionality of cortical and limbic brain areas, particularly within the cingulate cortex. What remains unclear, however, is how individual differences in personality traits interact with cingulate functionality in the prediction of stressor-evoked cardiovascular reactivity. Accordingly, we tested the associations between (i) a particular personality trait, Agreeableness, which is associated with emotional reactions to conflict, (ii) resting state functional connectivity within the cingulate cortex, and (iii) stressor-evoked blood pressure (BP) reactivity. Participants (N=39, 19 men, aged 20–37 yrs) completed a resting functional connectivity MRI protocol, followed by two standardized stressor tasks that engaged conflict processing and evoked BP reactivity. Agreeableness covaried positively with BP reactivity across individuals. Moreover, connectivity analyses demonstrated that a more positive functional connectivity between the posterior cingulate (BA31) and the perigenual anterior cingulate (BA32) covaried positively with Agreeableness and with BP reactivity. Finally, statistical mediation analyses demonstrated that BA31–BA32 connectivity mediated the covariation between Agreeableness and BP reactivity. Functional connectivity within the cingulate appears to link Agreeableness and a risk factor for cardiovascular disease, stressor-evoked BP reactivity. PMID:21130172

Identifying dynamic functional connectivity biomarkers using GIG-ICA: application to schizophrenia, schizoaffective disorder and psychotic bipolar disorder

PubMed Central

Du, Yuhui; Pearlson, Godfrey D; Lin, Dongdong; Sui, Jing; Chen, Jiayu; Salman, Mustafa; Tamminga, Carol A.; Ivleva, Elena I.; Sweeney, John A.; Keshavan, Matcheri S.; Clementz, Brett A.; Bustillo, Juan; Calhoun, Vince D.

2017-01-01

Functional magnetic resonance imaging (fMRI) studies have shown altered brain dynamic functional connectivity (DFC) in mental disorders. Here we aim to explore DFC across a spectrum of symptomatically-related disorders including bipolar disorder with psychosis (BPP), schizoaffective disorder (SAD) and schizophrenia (SZ). We introduce a group information guided independent component analysis (GIG-ICA) procedure to estimate both group-level and subject-specific connectivity states from DFC. Using resting-state fMRI data of 238 healthy controls (HCs), 140 BPP, 132 SAD and 113 SZ patients, we identified measures differentiating groups from the whole-brain DFC and traditional static functional connectivity (SFC), separately. Results show that DFC provided more informative measures than SFC. Diagnosis-related connectivity states were evident using DFC analysis. For the dominant state consistent across groups, we found 22 instances of hypoconnectivity (with decreasing trends from HC to BPP to SAD to SZ) mainly involving post-central, frontal and cerebellar cortices as well as 34 examples of hyperconnectivity (with increasing trends HC through SZ) primarily involving thalamus and temporal cortices. Hypoconnectivities/hyperconnectivities also showed negative/positive correlations, respectively, with clinical symptom scores. Specifically, hypoconnectivities linking postcentral and frontal gyri were significantly negatively correlated with the PANSS positive/negative scores. For frontal connectivities, BPP resembled HC while SAD and SZ were more similar. Three connectivities involving the left cerebellar crus differentiated SZ from other groups and one connection linking frontal and fusiform cortices showed a SAD-unique change. In summary, our method is promising for assessing DFC and may yield imaging biomarkers for quantifying the dimension of psychosis. PMID:28294459

Changes in interhemispheric motor connectivity after muscle fatigue

NASA Astrophysics Data System (ADS)

Peltier, Scott; LaConte, Stephen M.; Niyazov, Dmitriy; Liu, Jing; Sahgal, Vinod; Yue, Guang; Hu, Xiaoping

2005-04-01

Synchronized oscillations in resting state timecourses have been detected in recent fMRI studies. These oscillations are low frequency in nature (< 0.08 Hz), and seem to be a property of symmetric cortices. These fluctuations are important as a potential signal of interest, which could indicate connectivity between functionally related areas of the brain. It has also been shown that the synchronized oscillations decrease in some spontaneous pathological states. Thus, detection of these functional connectivity patterns may help to serve as a gauge of normal brain activity. The cognitive effects of muscle fatigue are not well characterized. Sustained fatigue has the potential to dynamically alter activity in brain networks. In this work, we examined the interhemispheric correlations in the left and right primary motor cortices and how they change with muscle fatigue. Resting-state functional MRI imaging was done before and after a repetitive unilateral fatigue task. We find that the number of significant correlations in the bilateral motor network decreases with fatigue. These results suggest that resting-state interhemispheric motor cortex functional connectivity is affected by muscle fatigue.

Cerebro-cerebellar Resting-State Functional Connectivity in Children and Adolescents with Autism Spectrum Disorder.

PubMed

Khan, Amanda J; Nair, Aarti; Keown, Christopher L; Datko, Michael C; Lincoln, Alan J; Müller, Ralph-Axel

2015-11-01

The cerebellum plays important roles in sensori-motor and supramodal cognitive functions. Cellular, volumetric, and functional abnormalities of the cerebellum have been found in autism spectrum disorders (ASD), but no comprehensive investigation of cerebro-cerebellar connectivity in ASD is available. We used resting-state functional connectivity magnetic resonance imaging in 56 children and adolescents (28 subjects with ASD, 28 typically developing subjects) 8-17 years old. Partial and total correlation analyses were performed for unilateral regions of interest (ROIs), distinguished in two broad domains as sensori-motor (premotor/primary motor, somatosensory, superior temporal, and occipital) and supramodal (prefrontal, posterior parietal, and inferior and middle temporal). There were three main findings: 1) Total correlation analyses showed predominant cerebro-cerebellar functional overconnectivity in the ASD group; 2) partial correlation analyses that emphasized domain specificity (sensori-motor vs. supramodal) indicated a pattern of robustly increased connectivity in the ASD group (compared with the typically developing group) for sensori-motor ROIs but predominantly reduced connectivity for supramodal ROIs; and 3) this atypical pattern of connectivity was supported by significantly increased noncanonical connections (between sensori-motor cerebral and supramodal cerebellar ROIs and vice versa) in the ASD group. Our findings indicate that sensori-motor intrinsic functional connectivity is atypically increased in ASD, at the expense of connectivity supporting cerebellar participation in supramodal cognition. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Phenotypic Variability in Resting-State Functional Connectivity: Current Status

PubMed Central

Gordon, Evan M.

2013-01-01

Abstract We reviewed the extant literature with the goal of assessing the extent to which resting-state functional connectivity is associated with phenotypic variability in healthy and disordered populations. A large corpus of work has accumulated to date (125 studies), supporting the association between intrinsic functional connectivity and individual differences in a wide range of domains—not only in cognitive, perceptual, motoric, and linguistic performance, but also in behavioral traits (e.g., impulsiveness, risky decision making, personality, and empathy) and states (e.g., anxiety and psychiatric symptoms) that are distinguished by cognitive and affective functioning, and in neurological conditions with cognitive and motor sequelae. Further, intrinsic functional connectivity is sensitive to remote (e.g., early-life stress) and enduring (e.g., duration of symptoms) life experience, and it exhibits plasticity in response to recent experience (e.g., learning and adaptation) and pharmacological treatment. The most pervasive associations were observed with the default network; associations were also widespread between the cingulo-opercular network and both cognitive and affective behaviors, while the frontoparietal network was associated primarily with cognitive functions. Associations of somatomotor, frontotemporal, auditory, and amygdala networks were relatively restricted to the behaviors linked to their respective putative functions. Surprisingly, visual network associations went beyond visual function to include a variety of behavioral traits distinguished by affective function. Together, the reviewed evidence sets the stage for testing causal hypothesis about the functional role of intrinsic connectivity and augments its potential as a biomarker for healthy and disordered brain function. PMID:23294010

Connectomic markers of symptom severity in sport-related concussion: Whole-brain analysis of resting-state fMRI.

PubMed

Churchill, Nathan W; Hutchison, Michael G; Graham, Simon J; Schweizer, Tom A

2018-01-01

Concussion is associated with significant adverse effects within the first week post-injury, including physical complaints and altered cognition, sleep and mood. It is currently unknown whether these subjective disturbances have reliable functional brain correlates. Resting-state functional magnetic resonance imaging (rs-fMRI) has been used to measure functional connectivity of individuals after traumatic brain injury, but less is known about the relationship between functional connectivity and symptom assessments after a sport concussion. In this study, rs-fMRI was used to evaluate whole-brain functional connectivity for seventy (70) university-level athletes, including 35 with acute concussion and 35 healthy matched controls. Univariate analyses showed that greater symptom severity was mainly associated with lower pairwise connectivity in frontal, temporal and insular regions, along with higher connectivity in a sparser set of cerebellar regions. A novel multivariate approach also extracted two components that showed reliable covariation with symptom severity: (1) a network of frontal, temporal and insular regions where connectivity was negatively correlated with symptom severity (replicating the univariate findings); and (2) a network with anti-correlated elements of the default-mode network and sensorimotor system, where connectivity was positively correlated with symptom severity. These findings support the presence of connectomic signatures of symptom complaints following a sport-related concussion, including both increased and decreased functional connectivity within distinct functional brain networks.

Resting-State Network Topology Differentiates Task Signals across the Adult Life Span.

PubMed

Chan, Micaela Y; Alhazmi, Fahd H; Park, Denise C; Savalia, Neil K; Wig, Gagan S

2017-03-08

Brain network connectivity differs across individuals. For example, older adults exhibit less segregated resting-state subnetworks relative to younger adults (Chan et al., 2014). It has been hypothesized that individual differences in network connectivity impact the recruitment of brain areas during task execution. While recent studies have described the spatial overlap between resting-state functional correlation (RSFC) subnetworks and task-evoked activity, it is unclear whether individual variations in the connectivity pattern of a brain area (topology) relates to its activity during task execution. We report data from 238 cognitively normal participants (humans), sampled across the adult life span (20-89 years), to reveal that RSFC-based network organization systematically relates to the recruitment of brain areas across two functionally distinct tasks (visual and semantic). The functional activity of brain areas (network nodes) were characterized according to their patterns of RSFC: nodes with relatively greater connections to nodes in their own functional system ("non-connector" nodes) exhibited greater activity than nodes with relatively greater connections to nodes in other systems ("connector" nodes). This "activation selectivity" was specific to those brain systems that were central to each of the tasks. Increasing age was accompanied by less differentiated network topology and a corresponding reduction in activation selectivity (or differentiation) across relevant network nodes. The results provide evidence that connectional topology of brain areas quantified at rest relates to the functional activity of those areas during task. Based on these findings, we propose a novel network-based theory for previous reports of the "dedifferentiation" in brain activity observed in aging. SIGNIFICANCE STATEMENT Similar to other real-world networks, the organization of brain networks impacts their function. As brain network connectivity patterns differ across individuals, we hypothesized that individual differences in network connectivity would relate to differences in brain activity. Using functional MRI in a group of individuals sampled across the adult life span (20-89 years), we measured correlations at rest and related the functional connectivity patterns to measurements of functional activity during two independent tasks. Brain activity varied in relation to connectivity patterns revealed by large-scale network analysis. This relationship tracked the differences in connectivity patterns accompanied by older age, providing important evidence for a link between the topology of areal connectivity measured at rest and the functional recruitment of these areas during task performance. Copyright © 2017 Chan et al.

Patterns of resting state connectivity in human primary visual cortical areas: a 7T fMRI study.

PubMed

Raemaekers, Mathijs; Schellekens, Wouter; van Wezel, Richard J A; Petridou, Natalia; Kristo, Gert; Ramsey, Nick F

2014-01-01

The nature and origin of fMRI resting state fluctuations and connectivity are still not fully known. More detailed knowledge on the relationship between resting state patterns and brain function may help to elucidate this matter. We therefore performed an in depth study of how resting state fluctuations map to the well known architecture of the visual system. We investigated resting state connectivity at both a fine and large scale within and across visual areas V1, V2 and V3 in ten human subjects using a 7Tesla scanner. We found evidence for several coexisting and overlapping connectivity structures at different spatial scales. At the fine-scale level we found enhanced connectivity between the same topographic locations in the fieldmaps of V1, V2 and V3, enhanced connectivity to the contralateral functional homologue, and to a lesser extent enhanced connectivity between iso-eccentric locations within the same visual area. However, by far the largest proportion of the resting state fluctuations occurred within large-scale bilateral networks. These large-scale networks mapped to some extent onto the architecture of the visual system and could thereby obscure fine-scale connectivity. In fact, most of the fine-scale connectivity only became apparent after the large-scale network fluctuations were filtered from the timeseries. We conclude that fMRI resting state fluctuations in the visual cortex may in fact be a composite signal of different overlapping sources. Isolating the different sources could enhance correlations between BOLD and electrophysiological correlates of resting state activity. © 2013 Elsevier Inc. All rights reserved.

Network topology and functional connectivity disturbances precede the onset of Huntington’s disease

PubMed Central

Harrington, Deborah L.; Rubinov, Mikail; Durgerian, Sally; Mourany, Lyla; Reece, Christine; Koenig, Katherine; Bullmore, Ed; Long, Jeffrey D.; Paulsen, Jane S.

2015-01-01

Cognitive, motor and psychiatric changes in prodromal Huntington’s disease have nurtured the emergent need for early interventions. Preventive clinical trials for Huntington’s disease, however, are limited by a shortage of suitable measures that could serve as surrogate outcomes. Measures of intrinsic functional connectivity from resting-state functional magnetic resonance imaging are of keen interest. Yet recent studies suggest circumscribed abnormalities in resting-state functional magnetic resonance imaging connectivity in prodromal Huntington’s disease, despite the spectrum of behavioural changes preceding a manifest diagnosis. The present study used two complementary analytical approaches to examine whole-brain resting-state functional magnetic resonance imaging connectivity in prodromal Huntington’s disease. Network topology was studied using graph theory and simple functional connectivity amongst brain regions was explored using the network-based statistic. Participants consisted of gene-negative controls (n = 16) and prodromal Huntington’s disease individuals (n = 48) with various stages of disease progression to examine the influence of disease burden on intrinsic connectivity. Graph theory analyses showed that global network interconnectivity approximated a random network topology as proximity to diagnosis neared and this was associated with decreased connectivity amongst highly-connected rich-club network hubs, which integrate processing from diverse brain regions. However, functional segregation within the global network (average clustering) was preserved. Functional segregation was also largely maintained at the local level, except for the notable decrease in the diversity of anterior insula intermodular-interconnections (participation coefficient), irrespective of disease burden. In contrast, network-based statistic analyses revealed patterns of weakened frontostriatal connections and strengthened frontal-posterior connections that evolved as disease burden increased. These disturbances were often related to long-range connections involving peripheral nodes and interhemispheric connections. A strong association was found between weaker connectivity and decreased rich-club organization, indicating that whole-brain simple connectivity partially expressed disturbances in the communication of highly-connected hubs. However, network topology and network-based statistic connectivity metrics did not correlate with key markers of executive dysfunction (Stroop Test, Trail Making Test) in prodromal Huntington’s disease, which instead were related to whole-brain connectivity disturbances in nodes (right inferior parietal, right thalamus, left anterior cingulate) that exhibited multiple aberrant connections and that mediate executive control. Altogether, our results show for the first time a largely disease burden-dependent functional reorganization of whole-brain networks in prodromal Huntington’s disease. Both analytic approaches provided a unique window into brain reorganization that was not related to brain atrophy or motor symptoms. Longitudinal studies currently in progress will chart the course of functional changes to determine the most sensitive markers of disease progression. PMID:26059655

Network topology and functional connectivity disturbances precede the onset of Huntington's disease.

PubMed

Harrington, Deborah L; Rubinov, Mikail; Durgerian, Sally; Mourany, Lyla; Reece, Christine; Koenig, Katherine; Bullmore, Ed; Long, Jeffrey D; Paulsen, Jane S; Rao, Stephen M

2015-08-01

Cognitive, motor and psychiatric changes in prodromal Huntington's disease have nurtured the emergent need for early interventions. Preventive clinical trials for Huntington's disease, however, are limited by a shortage of suitable measures that could serve as surrogate outcomes. Measures of intrinsic functional connectivity from resting-state functional magnetic resonance imaging are of keen interest. Yet recent studies suggest circumscribed abnormalities in resting-state functional magnetic resonance imaging connectivity in prodromal Huntington's disease, despite the spectrum of behavioural changes preceding a manifest diagnosis. The present study used two complementary analytical approaches to examine whole-brain resting-state functional magnetic resonance imaging connectivity in prodromal Huntington's disease. Network topology was studied using graph theory and simple functional connectivity amongst brain regions was explored using the network-based statistic. Participants consisted of gene-negative controls (n = 16) and prodromal Huntington's disease individuals (n = 48) with various stages of disease progression to examine the influence of disease burden on intrinsic connectivity. Graph theory analyses showed that global network interconnectivity approximated a random network topology as proximity to diagnosis neared and this was associated with decreased connectivity amongst highly-connected rich-club network hubs, which integrate processing from diverse brain regions. However, functional segregation within the global network (average clustering) was preserved. Functional segregation was also largely maintained at the local level, except for the notable decrease in the diversity of anterior insula intermodular-interconnections (participation coefficient), irrespective of disease burden. In contrast, network-based statistic analyses revealed patterns of weakened frontostriatal connections and strengthened frontal-posterior connections that evolved as disease burden increased. These disturbances were often related to long-range connections involving peripheral nodes and interhemispheric connections. A strong association was found between weaker connectivity and decreased rich-club organization, indicating that whole-brain simple connectivity partially expressed disturbances in the communication of highly-connected hubs. However, network topology and network-based statistic connectivity metrics did not correlate with key markers of executive dysfunction (Stroop Test, Trail Making Test) in prodromal Huntington's disease, which instead were related to whole-brain connectivity disturbances in nodes (right inferior parietal, right thalamus, left anterior cingulate) that exhibited multiple aberrant connections and that mediate executive control. Altogether, our results show for the first time a largely disease burden-dependent functional reorganization of whole-brain networks in prodromal Huntington's disease. Both analytic approaches provided a unique window into brain reorganization that was not related to brain atrophy or motor symptoms. Longitudinal studies currently in progress will chart the course of functional changes to determine the most sensitive markers of disease progression. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Multivariate Classification of Major Depressive Disorder Using the Effective Connectivity and Functional Connectivity

PubMed Central

Geng, Xiangfei; Xu, Junhai; Liu, Baolin; Shi, Yonggang

2018-01-01

Major depressive disorder (MDD) is a mental disorder characterized by at least 2 weeks of low mood, which is present across most situations. Diagnosis of MDD using rest-state functional magnetic resonance imaging (fMRI) data faces many challenges due to the high dimensionality, small samples, noisy and individual variability. To our best knowledge, no studies aim at classification with effective connectivity and functional connectivity measures between MDD patients and healthy controls. In this study, we performed a data-driving classification analysis using the whole brain connectivity measures which included the functional connectivity from two brain templates and effective connectivity measures created by the default mode network (DMN), dorsal attention network (DAN), frontal-parietal network (FPN), and silence network (SN). Effective connectivity measures were extracted using spectral Dynamic Causal Modeling (spDCM) and transformed into a vectorial feature space. Linear Support Vector Machine (linear SVM), non-linear SVM, k-Nearest Neighbor (KNN), and Logistic Regression (LR) were used as the classifiers to identify the differences between MDD patients and healthy controls. Our results showed that the highest accuracy achieved 91.67% (p < 0.0001) when using 19 effective connections and 89.36% when using 6,650 functional connections. The functional connections with high discriminative power were mainly located within or across the whole brain resting-state networks while the discriminative effective connections located in several specific regions, such as posterior cingulate cortex (PCC), ventromedial prefrontal cortex (vmPFC), dorsal cingulate cortex (dACC), and inferior parietal lobes (IPL). To further compare the discriminative power of functional connections and effective connections, a classification analysis only using the functional connections from those four networks was conducted and the highest accuracy achieved 78.33% (p < 0.0001). Our study demonstrated that the effective connectivity measures might play a more important role than functional connectivity in exploring the alterations between patients and health controls and afford a better mechanistic interpretability. Moreover, our results showed a diagnostic potential of the effective connectivity for the diagnosis of MDD patients with high accuracies allowing for earlier prevention or intervention. PMID:29515348

The Semantic Network at Work and Rest: Differential Connectivity of Anterior Temporal Lobe Subregions.

PubMed

Jackson, Rebecca L; Hoffman, Paul; Pobric, Gorana; Lambon Ralph, Matthew A

2016-02-03

The anterior temporal lobe (ATL) makes a critical contribution to semantic cognition. However, the functional connectivity of the ATL and the functional network underlying semantic cognition has not been elucidated. In addition, subregions of the ATL have distinct functional properties and thus the potential differential connectivity between these subregions requires investigation. We explored these aims using both resting-state and active semantic task data in humans in combination with a dual-echo gradient echo planar imaging (EPI) paradigm designed to ensure signal throughout the ATL. In the resting-state analysis, the ventral ATL (vATL) and anterior middle temporal gyrus (MTG) were shown to connect to areas responsible for multimodal semantic cognition, including bilateral ATL, inferior frontal gyrus, medial prefrontal cortex, angular gyrus, posterior MTG, and medial temporal lobes. In contrast, the anterior superior temporal gyrus (STG)/superior temporal sulcus was connected to a distinct set of auditory and language-related areas, including bilateral STG, precentral and postcentral gyri, supplementary motor area, supramarginal gyrus, posterior temporal cortex, and inferior and middle frontal gyri. Complementary analyses of functional connectivity during an active semantic task were performed using a psychophysiological interaction (PPI) analysis. The PPI analysis highlighted the same semantic regions suggesting a core semantic network active during rest and task states. This supports the necessity for semantic cognition in internal processes occurring during rest. The PPI analysis showed additional connectivity of the vATL to regions of occipital and frontal cortex. These areas strongly overlap with regions found to be sensitive to executively demanding, controlled semantic processing. Previous studies have shown that semantic cognition depends on subregions of the anterior temporal lobe (ATL). However, the network of regions functionally connected to these subregions has not been demarcated. Here, we show that these ventrolateral anterior temporal subregions form part of a network responsible for semantic processing during both rest and an explicit semantic task. This demonstrates the existence of a core functional network responsible for multimodal semantic cognition regardless of state. Distinct connectivity is identified in the superior ATL, which is connected to auditory and language areas. Understanding the functional connectivity of semantic cognition allows greater understanding of how this complex process may be performed and the role of distinct subregions of the anterior temporal cortex. Copyright © 2016 Jackson et al.

The Semantic Network at Work and Rest: Differential Connectivity of Anterior Temporal Lobe Subregions

PubMed Central

Jackson, Rebecca L.; Hoffman, Paul; Pobric, Gorana

2016-01-01

The anterior temporal lobe (ATL) makes a critical contribution to semantic cognition. However, the functional connectivity of the ATL and the functional network underlying semantic cognition has not been elucidated. In addition, subregions of the ATL have distinct functional properties and thus the potential differential connectivity between these subregions requires investigation. We explored these aims using both resting-state and active semantic task data in humans in combination with a dual-echo gradient echo planar imaging (EPI) paradigm designed to ensure signal throughout the ATL. In the resting-state analysis, the ventral ATL (vATL) and anterior middle temporal gyrus (MTG) were shown to connect to areas responsible for multimodal semantic cognition, including bilateral ATL, inferior frontal gyrus, medial prefrontal cortex, angular gyrus, posterior MTG, and medial temporal lobes. In contrast, the anterior superior temporal gyrus (STG)/superior temporal sulcus was connected to a distinct set of auditory and language-related areas, including bilateral STG, precentral and postcentral gyri, supplementary motor area, supramarginal gyrus, posterior temporal cortex, and inferior and middle frontal gyri. Complementary analyses of functional connectivity during an active semantic task were performed using a psychophysiological interaction (PPI) analysis. The PPI analysis highlighted the same semantic regions suggesting a core semantic network active during rest and task states. This supports the necessity for semantic cognition in internal processes occurring during rest. The PPI analysis showed additional connectivity of the vATL to regions of occipital and frontal cortex. These areas strongly overlap with regions found to be sensitive to executively demanding, controlled semantic processing. SIGNIFICANCE STATEMENT Previous studies have shown that semantic cognition depends on subregions of the anterior temporal lobe (ATL). However, the network of regions functionally connected to these subregions has not been demarcated. Here, we show that these ventrolateral anterior temporal subregions form part of a network responsible for semantic processing during both rest and an explicit semantic task. This demonstrates the existence of a core functional network responsible for multimodal semantic cognition regardless of state. Distinct connectivity is identified in the superior ATL, which is connected to auditory and language areas. Understanding the functional connectivity of semantic cognition allows greater understanding of how this complex process may be performed and the role of distinct subregions of the anterior temporal cortex. PMID:26843633

Limbic hyperconnectivity in the vegetative state.

PubMed

Di Perri, Carol; Bastianello, Stefano; Bartsch, Andreas J; Pistarini, Caterina; Maggioni, Giorgio; Magrassi, Lorenzo; Imberti, Roberto; Pichiecchio, Anna; Vitali, Paolo; Laureys, Steven; Di Salle, Francesco

2013-10-15

To investigate functional connectivity between the default mode network (DMN) and other networks in disorders of consciousness. We analyzed MRI data from 11 patients in a vegetative state and 7 patients in a minimally conscious state along with age- and sex-matched healthy control subjects. MRI data analysis included nonlinear spatial normalization to compensate for disease-related anatomical distortions. We studied brain connectivity data from resting-state MRI temporal series, combining noninferential (independent component analysis) and inferential (seed-based general linear model) methods. In DMN hypoconnectivity conditions, a patient's DMN functional connectivity shifts and paradoxically increases in limbic structures, including the orbitofrontal cortex, insula, hypothalamus, and the ventral tegmental area. Concurrently with DMN hypoconnectivity, we report limbic hyperconnectivity in patients in vegetative and minimally conscious states. This hyperconnectivity may reflect the persistent engagement of residual neural activity in self-reinforcing neural loops, which, in turn, could disrupt normal patterns of connectivity.

Sedation of Patients With Disorders of Consciousness During Neuroimaging: Effects on Resting State Functional Brain Connectivity.

PubMed

Kirsch, Muriëlle; Guldenmund, Pieter; Ali Bahri, Mohamed; Demertzi, Athena; Baquero, Katherine; Heine, Lizette; Charland-Verville, Vanessa; Vanhaudenhuyse, Audrey; Bruno, Marie-Aurélie; Gosseries, Olivia; Di Perri, Carol; Ziegler, Erik; Brichant, Jean-François; Soddu, Andrea; Bonhomme, Vincent; Laureys, Steven

2017-02-01

To reduce head movement during resting state functional magnetic resonance imaging, post-coma patients with disorders of consciousness (DOC) are frequently sedated with propofol. However, little is known about the effects of this sedation on the brain connectivity patterns in the damaged brain essential for differential diagnosis. In this study, we aimed to assess these effects. Using resting state functional magnetic resonance imaging 3T data obtained over several years of scanning patients for diagnostic and research purposes, we employed a seed-based approach to examine resting state connectivity in higher-order (default mode, bilateral external control, and salience) and lower-order (auditory, sensorimotor, and visual) resting state networks and connectivity with the thalamus, in 20 healthy unsedated controls, 8 unsedated patients with DOC, and 8 patients with DOC sedated with propofol. The DOC groups were matched for age at onset, etiology, time spent in DOC, diagnosis, standardized behavioral assessment scores, movement intensities, and pattern of structural brain injury (as assessed with T1-based voxel-based morphometry). DOC were associated with severely impaired resting state network connectivity in all but the visual network. Thalamic connectivity to higher-order network regions was also reduced. Propofol administration to patients was associated with minor further decreases in thalamic and insular connectivity. Our findings indicate that connectivity decreases associated with propofol sedation, involving the thalamus and insula, are relatively small compared with those already caused by DOC-associated structural brain injury. Nonetheless, given the known importance of the thalamus in brain arousal, its disruption could well reflect the diminished movement obtained in these patients. However, more research is needed on this topic to fully address the research question.

The neural basis of trait self-esteem revealed by the amplitude of low-frequency fluctuations and resting state functional connectivity

PubMed Central

Pan, Weigang; Liu, Congcong; Yang, Qian; Gu, Yan; Yin, Shouhang

2016-01-01

Self-esteem is an affective, self-evaluation of oneself and has a significant effect on mental and behavioral health. Although research has focused on the neural substrates of self-esteem, little is known about the spontaneous brain activity that is associated with trait self-esteem (TSE) during the resting state. In this study, we used the resting-state functional magnetic resonance imaging (fMRI) signal of the amplitude of low-frequency fluctuations (ALFFs) and resting state functional connectivity (RSFC) to identify TSE-related regions and networks. We found that a higher level of TSE was associated with higher ALFFs in the left ventral medial prefrontal cortex (vmPFC) and lower ALFFs in the left cuneus/lingual gyrus and right lingual gyrus. RSFC analyses revealed that the strengths of functional connectivity between the left vmPFC and bilateral hippocampus were positively correlated with TSE; however, the connections between the left vmPFC and right inferior frontal gyrus and posterior superior temporal sulcus were negatively associated with TSE. Furthermore, the strengths of functional connectivity between the left cuneus/lingual gyrus and right dorsolateral prefrontal cortex and anterior cingulate cortex were positively related to TSE. These findings indicate that TSE is linked to core regions in the default mode network and social cognition network, which is involved in self-referential processing, autobiographical memory and social cognition. PMID:26400859

Abnormal resting-state connectivity of motor and cognitive networks in early manifest Huntington's disease.

PubMed

Wolf, R C; Sambataro, F; Vasic, N; Depping, M S; Thomann, P A; Landwehrmeyer, G B; Süssmuth, S D; Orth, M

2014-11-01

Functional magnetic resonance imaging (fMRI) of multiple neural networks during the brain's 'resting state' could facilitate biomarker development in patients with Huntington's disease (HD) and may provide new insights into the relationship between neural dysfunction and clinical symptoms. To date, however, very few studies have examined the functional integrity of multiple resting state networks (RSNs) in manifest HD, and even less is known about whether concomitant brain atrophy affects neural activity in patients. Using MRI, we investigated brain structure and RSN function in patients with early HD (n = 20) and healthy controls (n = 20). For resting-state fMRI data a group-independent component analysis identified spatiotemporally distinct patterns of motor and prefrontal RSNs of interest. We used voxel-based morphometry to assess regional brain atrophy, and 'biological parametric mapping' analyses to investigate the impact of atrophy on neural activity. Compared with controls, patients showed connectivity changes within distinct neural systems including lateral prefrontal, supplementary motor, thalamic, cingulate, temporal and parietal regions. In patients, supplementary motor area and cingulate cortex connectivity indices were associated with measures of motor function, whereas lateral prefrontal connectivity was associated with cognition. This study provides evidence for aberrant connectivity of RSNs associated with motor function and cognition in early manifest HD when controlling for brain atrophy. This suggests clinically relevant changes of RSN activity in the presence of HD-associated cortical and subcortical structural abnormalities.

Time-frequency dynamics of resting-state brain connectivity measured with fMRI.

PubMed

Chang, Catie; Glover, Gary H

2010-03-01

Most studies of resting-state functional connectivity using fMRI employ methods that assume temporal stationarity, such as correlation and data-driven decompositions computed across the duration of the scan. However, evidence from both task-based fMRI studies and animal electrophysiology suggests that functional connectivity may exhibit dynamic changes within time scales of seconds to minutes. In the present study, we investigated the dynamic behavior of resting-state connectivity across the course of a single scan, performing a time-frequency coherence analysis based on the wavelet transform. We focused on the connectivity of the posterior cingulate cortex (PCC), a primary node of the default-mode network, examining its relationship with both the "anticorrelated" ("task-positive") network as well as other nodes of the default-mode network. It was observed that coherence and phase between the PCC and the anticorrelated network was variable in time and frequency, and statistical testing based on Monte Carlo simulations revealed the presence of significant scale-dependent temporal variability. In addition, a sliding-window correlation procedure identified other regions across the brain that exhibited variable connectivity with the PCC across the scan, which included areas previously implicated in attention and salience processing. Although it is unclear whether the observed coherence and phase variability can be attributed to residual noise or modulation of cognitive state, the present results illustrate that resting-state functional connectivity is not static, and it may therefore prove valuable to consider measures of variability, in addition to average quantities, when characterizing resting-state networks. Copyright (c) 2009 Elsevier Inc. All rights reserved.

Abnormal functional brain connectivity and personality traits in myotonic dystrophy type 1.

PubMed

Serra, Laura; Silvestri, Gabriella; Petrucci, Antonio; Basile, Barbara; Masciullo, Marcella; Makovac, Elena; Torso, Mario; Spanò, Barbara; Mastropasqua, Chiara; Harrison, Neil A; Bianchi, Maria L E; Giacanelli, Manlio; Caltagirone, Carlo; Cercignani, Mara; Bozzali, Marco

2014-05-01

Myotonic dystrophy type 1 (DM1), the most common muscular dystrophy observed in adults, is a genetic multisystem disorder affecting several other organs besides skeletal muscle, including the brain. Cognitive and personality abnormalities have been reported; however, no studies have investigated brain functional networks and their relationship with personality traits/disorders in patients with DM1. To use resting-state functional magnetic resonance imaging to assess the potential relationship between personality traits/disorders and changes to functional connectivity within the default mode network (DMN) in patients with DM1. We enrolled 27 patients with genetically confirmed DM1 and 16 matched healthy control individuals. Patients underwent personality assessment using clinical interview and Minnesota Multiphasic Personality Inventory-2 administration; all participants underwent resting-state functional magnetic resonance imaging. Investigations were conducted at the Istituto di Ricovero e Cura a Carattere Scientifico Santa Lucia Foundation, Catholic University of Sacred Heart, and Azienda Ospedaliera San Camillo Forlanini. Resting-state functional magnetic resonance imaging. Measures of personality traits in patients and changes in functional connectivity within the DMN in patients and controls. Changes in functional connectivity and atypical personality traits in patients were correlated. We combined results obtained from the Minnesota Multiphasic Personality Inventory-2 and clinical interview to identify a continuum of atypical personality profiles ranging from schizotypal personality traits to paranoid personality disorder within our DM1 patients. We also demonstrated an increase in functional connectivity in the bilateral posterior cingulate and left parietal DMN nodes in DM1 patients compared with controls. Moreover, patients with DM1 showed strong associations between DMN functional connectivity and schizotypal-paranoid traits. Our findings provide novel biological evidence that DM1 is a clinical condition that also involves an alteration of functional connectivity of the brain. We speculate that these functional brain abnormalities, similarly to frank psychiatric disorders, may account for the atypical personality traits observed in patients with DM1.

Functional Connectivity of the Precuneus in Female University Students with Long-Term Musical Training.

PubMed

Tanaka, Shoji; Kirino, Eiji

2016-01-01

Conceiving concrete mental imagery is critical for skillful musical expression and performance. The precuneus, a core component of the default mode network (DMN), is a hub of mental image processing that participates in functions such as episodic memory retrieval and imagining future events. The precuneus connects with many brain regions in the frontal, parietal, temporal, and occipital cortices. The aim of this study was to examine the effects of long-term musical training on the resting-state functional connectivity of the precuneus. Our hypothesis was that the functional connectivity of the precuneus is altered in musicians. We analyzed the functional connectivity of the precuneus using resting-state functional magnetic resonance imaging (fMRI) data recorded in female university students majoring in music and nonmusic disciplines. The results show that the music students had higher functional connectivity of the precuneus with opercular/insular regions, which are associated with interoceptive and emotional processing; Heschl's gyrus (HG) and the planum temporale (PT), which process complex tonal information; and the lateral occipital cortex (LOC), which processes visual information. Connectivity of the precuneus within the DMN did not differ between the two groups. Our finding suggests that functional connections between the precuneus and the regions outside of the DMN play an important role in musical performance. We propose that a neural network linking the precuneus with these regions contributes to translate mental imagery into information relevant to musical performance.

Functional Connectivity of the Precuneus in Female University Students with Long-Term Musical Training

PubMed Central

Tanaka, Shoji; Kirino, Eiji

2016-01-01

Conceiving concrete mental imagery is critical for skillful musical expression and performance. The precuneus, a core component of the default mode network (DMN), is a hub of mental image processing that participates in functions such as episodic memory retrieval and imagining future events. The precuneus connects with many brain regions in the frontal, parietal, temporal, and occipital cortices. The aim of this study was to examine the effects of long-term musical training on the resting-state functional connectivity of the precuneus. Our hypothesis was that the functional connectivity of the precuneus is altered in musicians. We analyzed the functional connectivity of the precuneus using resting-state functional magnetic resonance imaging (fMRI) data recorded in female university students majoring in music and nonmusic disciplines. The results show that the music students had higher functional connectivity of the precuneus with opercular/insular regions, which are associated with interoceptive and emotional processing; Heschl’s gyrus (HG) and the planum temporale (PT), which process complex tonal information; and the lateral occipital cortex (LOC), which processes visual information. Connectivity of the precuneus within the DMN did not differ between the two groups. Our finding suggests that functional connections between the precuneus and the regions outside of the DMN play an important role in musical performance. We propose that a neural network linking the precuneus with these regions contributes to translate mental imagery into information relevant to musical performance. PMID:27445765

Identifying Individuals with Antisocial Personality Disorder Using Resting-State fMRI

PubMed Central

Tang, Yan; Jiang, Weixiong; Liao, Jian; Wang, Wei; Luo, Aijing

2013-01-01

Antisocial personality disorder (ASPD) is closely connected to criminal behavior. A better understanding of functional connectivity in the brains of ASPD patients will help to explain abnormal behavioral syndromes and to perform objective diagnoses of ASPD. In this study we designed an exploratory data-driven classifier based on machine learning to investigate changes in functional connectivity in the brains of patients with ASPD using resting state functional magnetic resonance imaging (fMRI) data in 32 subjects with ASPD and 35 controls. The results showed that the classifier achieved satisfactory performance (86.57% accuracy, 77.14% sensitivity and 96.88% specificity) and could extract stabile information regarding functional connectivity that could be used to discriminate ASPD individuals from normal controls. More importantly, we found that the greatest change in the ASPD subjects was uncoupling between the default mode network and the attention network. Moreover, the precuneus, superior parietal gyrus and cerebellum exhibited high discriminative power in classification. A voxel-based morphometry analysis was performed and showed that the gray matter volumes in the parietal lobule and white matter volumes in the precuneus were abnormal in ASPD compared to controls. To our knowledge, this study was the first to use resting-state fMRI to identify abnormal functional connectivity in ASPD patients. These results not only demonstrated good performance of the proposed classifier, which can be used to improve the diagnosis of ASPD, but also elucidate the pathological mechanism of ASPD from a resting-state functional integration viewpoint. PMID:23593272

Identifying individuals with antisocial personality disorder using resting-state FMRI.

PubMed

Tang, Yan; Jiang, Weixiong; Liao, Jian; Wang, Wei; Luo, Aijing

2013-01-01

Antisocial personality disorder (ASPD) is closely connected to criminal behavior. A better understanding of functional connectivity in the brains of ASPD patients will help to explain abnormal behavioral syndromes and to perform objective diagnoses of ASPD. In this study we designed an exploratory data-driven classifier based on machine learning to investigate changes in functional connectivity in the brains of patients with ASPD using resting state functional magnetic resonance imaging (fMRI) data in 32 subjects with ASPD and 35 controls. The results showed that the classifier achieved satisfactory performance (86.57% accuracy, 77.14% sensitivity and 96.88% specificity) and could extract stabile information regarding functional connectivity that could be used to discriminate ASPD individuals from normal controls. More importantly, we found that the greatest change in the ASPD subjects was uncoupling between the default mode network and the attention network. Moreover, the precuneus, superior parietal gyrus and cerebellum exhibited high discriminative power in classification. A voxel-based morphometry analysis was performed and showed that the gray matter volumes in the parietal lobule and white matter volumes in the precuneus were abnormal in ASPD compared to controls. To our knowledge, this study was the first to use resting-state fMRI to identify abnormal functional connectivity in ASPD patients. These results not only demonstrated good performance of the proposed classifier, which can be used to improve the diagnosis of ASPD, but also elucidate the pathological mechanism of ASPD from a resting-state functional integration viewpoint.

A SVM-based quantitative fMRI method for resting-state functional network detection.

PubMed

Song, Xiaomu; Chen, Nan-kuei

2014-09-01

Resting-state functional magnetic resonance imaging (fMRI) aims to measure baseline neuronal connectivity independent of specific functional tasks and to capture changes in the connectivity due to neurological diseases. Most existing network detection methods rely on a fixed threshold to identify functionally connected voxels under the resting state. Due to fMRI non-stationarity, the threshold cannot adapt to variation of data characteristics across sessions and subjects, and generates unreliable mapping results. In this study, a new method is presented for resting-state fMRI data analysis. Specifically, the resting-state network mapping is formulated as an outlier detection process that is implemented using one-class support vector machine (SVM). The results are refined by using a spatial-feature domain prototype selection method and two-class SVM reclassification. The final decision on each voxel is made by comparing its probabilities of functionally connected and unconnected instead of a threshold. Multiple features for resting-state analysis were extracted and examined using an SVM-based feature selection method, and the most representative features were identified. The proposed method was evaluated using synthetic and experimental fMRI data. A comparison study was also performed with independent component analysis (ICA) and correlation analysis. The experimental results show that the proposed method can provide comparable or better network detection performance than ICA and correlation analysis. The method is potentially applicable to various resting-state quantitative fMRI studies. Copyright © 2014 Elsevier Inc. All rights reserved.

The development of regional functional connectivity in preterm infants into early childhood.

PubMed

Lee, Wayne; Morgan, Benjamin R; Shroff, Manohar M; Sled, John G; Taylor, Margot J

2013-09-01

Resting state networks are proposed to reflect the neuronal connectivity that underlies cognitive processes. Consequently, abnormal behaviour of these networks due to disease or altered development may predict poor cognitive outcome. To understand how very preterm birth may affect the development of resting state connectivity, we followed a cohort of very preterm-born infants from birth through to 4 years of age using resting state functional MRI. From a larger longitudinal cohort of infants born very preterm (<32 weeks gestational age), 36 at birth, 30 at term, 21 two-year and 22 four-year resting state fMRI datasets were acquired. Using seed-based connectivity analyses with seeds in the anterior cingulate cortex, posterior cingulate cortex, left and right motor-hand regions and left and right temporal lobes, we investigated local and inter-region connectivity as a function of group and age. We found strong local connectivity during the preterm period, which matured into inter-hemispheric and preliminary default-mode network correlations by 4 years of age. This development is comparable to the resting state networks found in term-born infants of equivalent age. The results of this study suggest that differences in developmental trajectory between preterm-born and term-born infants are small and, if present, would require a large sample from both populations to be detected.

Dose-Dependent Effects of Theta Burst rTMS on Cortical Excitability and Resting-State Connectivity of the Human Motor System

PubMed Central

Nettekoven, Charlotte; Volz, Lukas J.; Kutscha, Martha; Pool, Eva-Maria; Rehme, Anne K.; Eickhoff, Simon B.; Fink, Gereon R.

2014-01-01

Theta burst stimulation (TBS), a specific protocol of repetitive transcranial magnetic stimulation (rTMS), induces changes in cortical excitability that last beyond stimulation. TBS-induced aftereffects, however, vary between subjects, and the mechanisms underlying these aftereffects to date remain poorly understood. Therefore, the purpose of this study was to investigate whether increasing the number of pulses of intermittent TBS (iTBS) (1) increases cortical excitability as measured by motor-evoked potentials (MEPs) and (2) alters functional connectivity measured using resting-state fMRI, in a dose-dependent manner. Sixteen healthy, human subjects received three serially applied iTBS blocks of 600 pulses over the primary motor cortex (M1 stimulation) and the parieto-occipital vertex (sham stimulation) to test for dose-dependent iTBS effects on cortical excitability and functional connectivity (four sessions in total). iTBS over M1 increased MEP amplitudes compared with sham stimulation after each stimulation block. Although the increase in MEP amplitudes did not differ between the first and second block of M1 stimulation, we observed a significant increase after three blocks (1800 pulses). Furthermore, iTBS enhanced resting-state functional connectivity between the stimulated M1 and premotor regions in both hemispheres. Functional connectivity between M1 and ipsilateral dorsal premotor cortex further increased dose-dependently after 1800 pulses of iTBS over M1. However, no correlation between changes in MEP amplitudes and functional connectivity was detected. In summary, our data show that increasing the number of iTBS stimulation blocks results in dose-dependent effects at the local level (cortical excitability) as well as at a systems level (functional connectivity) with a dose-dependent enhancement of dorsal premotor cortex-M1 connectivity. PMID:24828639

Reproducibility of resting state spinal cord networks in healthy volunteers at 7 Tesla.

PubMed

Barry, Robert L; Rogers, Baxter P; Conrad, Benjamin N; Smith, Seth A; Gore, John C

2016-06-01

We recently reported our findings of resting state functional connectivity in the human spinal cord: in a cohort of healthy volunteers we observed robust functional connectivity between left and right ventral (motor) horns and between left and right dorsal (sensory) horns (Barry et al., 2014). Building upon these results, we now quantify the within-subject reproducibility of bilateral motor and sensory networks (intraclass correlation coefficient=0.54-0.56) and explore the impact of including frequencies up to 0.13Hz. Our results suggest that frequencies above 0.08Hz may enhance the detectability of these resting state networks, which would be beneficial for practical studies of spinal cord functional connectivity. Copyright © 2016 Elsevier Inc. All rights reserved.

Functional Connectivity Magnetic Resonance Imaging Classification of Autism

ERIC Educational Resources Information Center

Anderson, Jeffrey S.; Nielsen, Jared A.; Froehlich, Alyson L.; DuBray, Molly B.; Druzgal, T. Jason; Cariello, Annahir N.; Cooperrider, Jason R.; Zielinski, Brandon A.; Ravichandran, Caitlin; Fletcher, P. Thomas; Alexander, Andrew L.; Bigler, Erin D.; Lange, Nicholas; Lainhart, Janet E.

2011-01-01

Group differences in resting state functional magnetic resonance imaging connectivity between individuals with autism and typically developing controls have been widely replicated for a small number of discrete brain regions, yet the whole-brain distribution of connectivity abnormalities in autism is not well characterized. It is also unclear…

Cerebellar tDCS as a novel treatment for aphasia? Evidence from behavioral and resting-state functional connectivity data in healthy adults.

PubMed

Turkeltaub, Peter E; Swears, Mary K; D'Mello, Anila M; Stoodley, Catherine J

2016-05-24

Aphasia is an acquired deficit in the ability to communicate through language. Noninvasive neuromodulation offers the potential to boost neural function and recovery, yet the optimal site of neuromodulation for aphasia has yet to be established. The right posterolateral cerebellum is involved in multiple language functions, interconnects with left-hemisphere language cortices, and is crucial for optimization of function and skill acquisition, suggesting that cerebellar neuromodulation could enhance aphasia rehabilitation. To provide preliminary behavioral and functional connectivity evidence from healthy participants that cerebellar neuromodulation may be useful for rehabilitation of aphasia. In Experiment 1, 76 healthy adults performed articulation and verbal fluency tasks before and after anodal, cathodal or sham transcranial direct current stimulation (tDCS) was applied over two cerebellar locations (anterior, right posterolateral). In Experiment 2, we examined whether anodal tDCS over the right posterolateral cerebellum modulated resting-state functional connectivity in language networks in 27 healthy adults. TDCS over the right posterolateral cerebellum significantly improved phonemic fluency. Cerebellar neuromodulation increased functional connectivity between the cerebellum and areas involved in the motor control of speech, and enhanced the correlations between left-hemisphere language and speech-motor regions. We provide proof-of-principle evidence that cerebellar neuromodulation improves verbal fluency and impacts resting-state connectivity in language circuits. These findings suggest that the cerebellum is a viable candidate for neuromodulation in people with aphasia.

Resting-State Connectivity of the Left Frontal Cortex to the Default Mode and Dorsal Attention Network Supports Reserve in Mild Cognitive Impairment.

PubMed

Franzmeier, Nicolai; Göttler, Jens; Grimmer, Timo; Drzezga, Alexander; Áraque-Caballero, Miguel A; Simon-Vermot, Lee; Taylor, Alexander N W; Bürger, Katharina; Catak, Cihan; Janowitz, Daniel; Müller, Claudia; Duering, Marco; Sorg, Christian; Ewers, Michael

2017-01-01

Reserve refers to the phenomenon of relatively preserved cognition in disproportion to the extent of neuropathology, e.g., in Alzheimer's disease. A putative functional neural substrate underlying reserve is global functional connectivity of the left lateral frontal cortex (LFC, Brodmann Area 6/44). Resting-state fMRI-assessed global LFC-connectivity is associated with protective factors (education) and better maintenance of memory in mild cognitive impairment (MCI). Since the LFC is a hub of the fronto-parietal control network that regulates the activity of other networks, the question arises whether LFC-connectivity to specific networks rather than the whole-brain may underlie reserve. We assessed resting-state fMRI in 24 MCI and 16 healthy controls (HC) and in an independent validation sample (23 MCI/32 HC). Seed-based LFC-connectivity to seven major resting-state networks (i.e., fronto-parietal, limbic, dorsal-attention, somatomotor, default-mode, ventral-attention, visual) was computed, reserve was quantified as residualized memory performance after accounting for age and hippocampal atrophy. In both samples of MCI, LFC-activity was anti-correlated with the default-mode network (DMN), but positively correlated with the dorsal-attention network (DAN). Greater education predicted stronger LFC-DMN-connectivity (anti-correlation) and LFC-DAN-connectivity. Stronger LFC-DMN and LFC-DAN-connectivity each predicted higher reserve, consistently in both MCI samples. No associations were detected for LFC-connectivity to other networks. These novel results extend our previous findings on global functional connectivity of the LFC, showing that LFC-connectivity specifically to the DAN and DMN, two core memory networks, enhances reserve in the memory domain in MCI.

Brain Connectivity and Visual Attention

PubMed Central

Parks, Emily L.

2013-01-01

Abstract Emerging hypotheses suggest that efficient cognitive functioning requires the integration of separate, but interconnected cortical networks in the brain. Although task-related measures of brain activity suggest that a frontoparietal network is associated with the control of attention, little is known regarding how components within this distributed network act together or with other networks to achieve various attentional functions. This review considers both functional and structural studies of brain connectivity, as complemented by behavioral and task-related neuroimaging data. These studies show converging results: The frontal and parietal cortical regions are active together, over time, and identifiable frontoparietal networks are active in relation to specific task demands. However, the spontaneous, low-frequency fluctuations of brain activity that occur in the resting state, without specific task demands, also exhibit patterns of connectivity that closely resemble the task-related, frontoparietal attention networks. Both task-related and resting-state networks exhibit consistent relations to behavioral measures of attention. Further, anatomical structure, particularly white matter pathways as defined by diffusion tensor imaging, places constraints on intrinsic functional connectivity. Lastly, connectivity analyses applied to investigate cognitive differences across individuals in both healthy and diseased states suggest that disconnection of attentional networks is linked to deficits in cognitive functioning, and in extreme cases, to disorders of attention. Thus, comprehensive theories of visual attention and their clinical translation depend on the continued integration of behavioral, task-related neuroimaging, and brain connectivity measures. PMID:23597177

An information theory framework for dynamic functional domain connectivity.

PubMed

Vergara, Victor M; Miller, Robyn; Calhoun, Vince

2017-06-01

Dynamic functional network connectivity (dFNC) analyzes time evolution of coherent activity in the brain. In this technique dynamic changes are considered for the whole brain. This paper proposes an information theory framework to measure information flowing among subsets of functional networks call functional domains. Our method aims at estimating bits of information contained and shared among domains. The succession of dynamic functional states is estimated at the domain level. Information quantity is based on the probabilities of observing each dynamic state. Mutual information measurement is then obtained from probabilities across domains. Thus, we named this value the cross domain mutual information (CDMI). Strong CDMIs were observed in relation to the subcortical domain. Domains related to sensorial input, motor control and cerebellum form another CDMI cluster. Information flow among other domains was seldom found. Other methods of dynamic connectivity focus on whole brain dFNC matrices. In the current framework, information theory is applied to states estimated from pairs of multi-network functional domains. In this context, we apply information theory to measure information flow across functional domains. Identified CDMI clusters point to known information pathways in the basal ganglia and also among areas of sensorial input, patterns found in static functional connectivity. In contrast, CDMI across brain areas of higher level cognitive processing follow a different pattern that indicates scarce information sharing. These findings show that employing information theory to formally measured information flow through brain domains reveals additional features of functional connectivity. Copyright © 2017 Elsevier B.V. All rights reserved.

Decreased long- and short-range functional connectivity at rest in drug-naive major depressive disorder.

PubMed

Guo, Wenbin; Liu, Feng; Chen, Jindong; Wu, Renrong; Zhang, Zhikun; Yu, Miaoyu; Xue, Zhimin; Zhao, Jingping

2016-08-01

Abnormal functional connectivity has been observed in major depressive disorder. Anatomical distance may affect functional connectivity in patients with major depressive disorder. However, whether and how anatomical distance affects functional connectivity at rest remains unclear in drug-naive patients with major depressive disorder. Forty-four patients with major depressive disorder, as well as 44 age-, sex- and education-matched healthy controls, underwent resting-state functional magnetic resonance imaging scanning. Regional functional connectivity strength was calculated for each voxel in the whole brain, which was further divided into short- and long-range functional connectivity strength. The patients showed decreased long-range positive functional connectivity strength in the right inferior parietal lobule, as well as decreased short-range positive functional connectivity strength in the right insula and right superior temporal gyrus relative to those of the controls. No significant correlations existed between abnormal functional connectivity strength and the clinical variables of the patients. The findings revealed that anatomical distance decreases long- and short-range functional connectivity strength in patients with major depressive disorder, which may underlie the neurobiology of major depressive disorder. © The Royal Australian and New Zealand College of Psychiatrists 2015.

Estimation of Dynamic Sparse Connectivity Patterns From Resting State fMRI.

PubMed

Cai, Biao; Zille, Pascal; Stephen, Julia M; Wilson, Tony W; Calhoun, Vince D; Wang, Yu Ping

2018-05-01

Functional connectivity (FC) estimated from functional magnetic resonance imaging (fMRI) time series, especially during resting state periods, provides a powerful tool to assess human brain functional architecture in health, disease, and developmental states. Recently, the focus of connectivity analysis has shifted toward the subnetworks of the brain, which reveals co-activating patterns over time. Most prior works produced a dense set of high-dimensional vectors, which are hard to interpret. In addition, their estimations to a large extent were based on an implicit assumption of spatial and temporal stationarity throughout the fMRI scanning session. In this paper, we propose an approach called dynamic sparse connectivity patterns (dSCPs), which takes advantage of both matrix factorization and time-varying fMRI time series to improve the estimation power of FC. The feasibility of analyzing dynamic FC with our model is first validated through simulated experiments. Then, we use our framework to measure the difference between young adults and children with real fMRI data set from the Philadelphia Neurodevelopmental Cohort (PNC). The results from the PNC data set showed significant FC differences between young adults and children in four different states. For instance, young adults had reduced connectivity between the default mode network and other subnetworks, as well as hyperconnectivity within the visual system in states 1 and 3, and hypoconnectivity in state 2. Meanwhile, they exhibited temporal correlation patterns that changed over time within functional subnetworks. In addition, the dSCPs model indicated that older people tend to spend more time within a relatively connected FC pattern. Overall, the proposed method provides a valid means to assess dynamic FC, which could facilitate the study of brain networks.

Habenula functional resting-state connectivity in pediatric CRPS.

PubMed

Erpelding, Nathalie; Sava, Simona; Simons, Laura E; Lebel, Alyssa; Serrano, Paul; Becerra, Lino; Borsook, David

2014-01-01

The habenula (Hb) is a small brain structure located in the posterior end of the medial dorsal thalamus and through medial (MHb) and lateral (LHb) Hb connections, it acts as a conduit of information between forebrain and brainstem structures. The role of the Hb in pain processing is well documented in animals and recently also in acute experimental pain in humans. However, its function remains unknown in chronic pain disorders. Here, we investigated Hb resting-state functional connectivity (rsFC) in patients with complex regional pain syndrome (CRPS) compared with healthy controls. Twelve pediatric patients with unilateral lower-extremity CRPS (9 females; 10-17 yr) and 12 age- and sex-matched healthy controls provided informed consent to participate in the study. In healthy controls, Hb functional connections largely overlapped with previously described anatomical connections in cortical, subcortical, and brainstem structures. Compared with controls, patients exhibited an overall Hb rsFC reduction with the rest of the brain and, specifically, with the anterior midcingulate cortex, dorsolateral prefrontal cortex, supplementary motor cortex, primary motor cortex, and premotor cortex. Our results suggest that Hb rsFC parallels anatomical Hb connections in the healthy state and that overall Hb rsFC is reduced in patients, particularly connections with forebrain areas. Patients' decreased Hb rsFC to brain regions implicated in motor, affective, cognitive, and pain inhibitory/modulatory processes may contribute to their symptomatology.

Effect of deafferentation from spinal anesthesia on pain sensitivity and resting-state functional brain connectivity in healthy male volunteers.

PubMed

Niesters, Marieke; Sitsen, Elske; Oudejans, Linda; Vuyk, Jaap; Aarts, Leon P H J; Rombouts, Serge A R B; de Rover, Mischa; Khalili-Mahani, Najmeh; Dahan, Albert

2014-08-01

Patients may perceive paradoxical heat sensation during spinal anesthesia. This could be due to deafferentation-related functional changes at cortical, subcortical, or spinal levels. In the current study, the effect of spinal deafferentation on sensory (pain) sensitivity was studied and linked to whole-brain functional connectivity as assessed by resting-state functional magnetic resonance imaging (RS-fMRI) imaging. Deafferentation was induced by sham or spinal anesthesia (15 mg bupivacaine injected at L3-4) in 12 male volunteers. RS-fMRI brain connectivity was determined in relation to eight predefined and seven thalamic resting-state networks (RSNs) and measured before, and 1 and 2 h after spinal/sham injection. To measure the effect of deafferentation on pain sensitivity, responses to heat pain were measured at 15-min intervals on nondeafferented skin and correlated to RS-fMRI connectivity data. Spinal anesthesia altered functional brain connectivity within brain regions involved in the sensory discriminative (i.e., pain intensity related) and affective dimensions of pain perception in relation to somatosensory and thalamic RSNs. A significant enhancement of pain sensitivity on nondeafferented skin was observed after spinal anesthesia compared to sham (area-under-the-curve [mean (SEM)]: 190.4 [33.8] versus 13.7 [7.2]; p<0.001), which significantly correlated to functional connectivity changes observed within the thalamus in relation to the thalamo-prefrontal network, and in the anterior cingulate cortex and insula in relation to the thalamo-parietal network. Enhanced pain sensitivity from spinal deafferentation correlated with functional connectivity changes within brain regions involved in affective and sensory pain processing and areas involved in descending control of pain.

Non-parametric model selection for subject-specific topological organization of resting-state functional connectivity.

PubMed

Ferrarini, Luca; Veer, Ilya M; van Lew, Baldur; Oei, Nicole Y L; van Buchem, Mark A; Reiber, Johan H C; Rombouts, Serge A R B; Milles, J

2011-06-01

In recent years, graph theory has been successfully applied to study functional and anatomical connectivity networks in the human brain. Most of these networks have shown small-world topological characteristics: high efficiency in long distance communication between nodes, combined with highly interconnected local clusters of nodes. Moreover, functional studies performed at high resolutions have presented convincing evidence that resting-state functional connectivity networks exhibits (exponentially truncated) scale-free behavior. Such evidence, however, was mostly presented qualitatively, in terms of linear regressions of the degree distributions on log-log plots. Even when quantitative measures were given, these were usually limited to the r(2) correlation coefficient. However, the r(2) statistic is not an optimal estimator of explained variance, when dealing with (truncated) power-law models. Recent developments in statistics have introduced new non-parametric approaches, based on the Kolmogorov-Smirnov test, for the problem of model selection. In this work, we have built on this idea to statistically tackle the issue of model selection for the degree distribution of functional connectivity at rest. The analysis, performed at voxel level and in a subject-specific fashion, confirmed the superiority of a truncated power-law model, showing high consistency across subjects. Moreover, the most highly connected voxels were found to be consistently part of the default mode network. Our results provide statistically sound support to the evidence previously presented in literature for a truncated power-law model of resting-state functional connectivity. Copyright © 2010 Elsevier Inc. All rights reserved.

Identifying dynamic functional connectivity biomarkers using GIG-ICA: Application to schizophrenia, schizoaffective disorder, and psychotic bipolar disorder.

PubMed

Du, Yuhui; Pearlson, Godfrey D; Lin, Dongdong; Sui, Jing; Chen, Jiayu; Salman, Mustafa; Tamminga, Carol A; Ivleva, Elena I; Sweeney, John A; Keshavan, Matcheri S; Clementz, Brett A; Bustillo, Juan; Calhoun, Vince D

2017-05-01

Functional magnetic resonance imaging (fMRI) studies have shown altered brain dynamic functional connectivity (DFC) in mental disorders. Here, we aim to explore DFC across a spectrum of symptomatically-related disorders including bipolar disorder with psychosis (BPP), schizoaffective disorder (SAD), and schizophrenia (SZ). We introduce a group information guided independent component analysis procedure to estimate both group-level and subject-specific connectivity states from DFC. Using resting-state fMRI data of 238 healthy controls (HCs), 140 BPP, 132 SAD, and 113 SZ patients, we identified measures differentiating groups from the whole-brain DFC and traditional static functional connectivity (SFC), separately. Results show that DFC provided more informative measures than SFC. Diagnosis-related connectivity states were evident using DFC analysis. For the dominant state consistent across groups, we found 22 instances of hypoconnectivity (with decreasing trends from HC to BPP to SAD to SZ) mainly involving post-central, frontal, and cerebellar cortices as well as 34 examples of hyperconnectivity (with increasing trends HC through SZ) primarily involving thalamus and temporal cortices. Hypoconnectivities/hyperconnectivities also showed negative/positive correlations, respectively, with clinical symptom scores. Specifically, hypoconnectivities linking postcentral and frontal gyri were significantly negatively correlated with the PANSS positive/negative scores. For frontal connectivities, BPP resembled HC while SAD and SZ were more similar. Three connectivities involving the left cerebellar crus differentiated SZ from other groups and one connection linking frontal and fusiform cortices showed a SAD-unique change. In summary, our method is promising for assessing DFC and may yield imaging biomarkers for quantifying the dimension of psychosis. Hum Brain Mapp 38:2683-2708, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

GABA content within medial prefrontal cortex predicts the variability of fronto-limbic effective connectivity

PubMed Central

Pizzi, Stefano Delli; Chiacchieretta, Piero; Mantini, Dante; Bubbico, Giovanna; Edden, Richard A.; Onofrj, Marco; Ferretti, Antonio

2017-01-01

The amygdala-medial prefrontal cortex (mPFC) circuit plays a key role in social behavior. The amygdala and mPFC are bidirectionally connected, functionally and anatomically, via the uncinate fasciculus. Recent evidence suggests that GABA-ergic neurotransmission within the mPFC could be central to the regulation of amygdala activity related to emotions and anxiety processing. However, the functional and neurochemical interactions within amygdala-mPFC circuits are unclear. In the current study, multimodal magnetic resonance imaging techniques were combined to investigate effective connectivity within the amygdala-mPFC network and its relationship with mPFC neurotransmission in 22 healthy subjects aged between 41 and 88 years. Effective connectivity in the amygdala-mPFC circuit was assessed on resting-state functional magnetic resonance imaging data using spectral dynamic causal modelling. State and trait anxiety were also assessed. The mPFC was shown to be the target of incoming outputs from the amygdalae and the source of exciting inputs to the limbic system. The amygdalae were reciprocally connected by excitatory projections. About half of the variance relating to the strength of top–down endogenous connection between right amygdala and mPFC was explained by mPFC GABA levels. State anxiety was correlated with the strength of the endogenous connections between right amygdala and mPFC. We suggest that mPFC GABA content predicts variability in the effective connectivity within the mPFC-amygdala circuit, providing new insights on emotional physiology and the underlying functional and neurochemical interactions. PMID:28386778

Altered basal ganglia-cortical functional connections in frontal lobe epilepsy: A resting-state fMRI study.

PubMed

Dong, Li; Wang, Pu; Peng, Rui; Jiang, Sisi; Klugah-Brown, Benjamin; Luo, Cheng; Yao, Dezhong

2016-12-01

The purpose of this study was to investigate alterations of basal ganglia-cortical functional connections in patients with frontal lobe epilepsy (FLE). Resting-state functional magnetic resonance imaging (fMRI) data were gathered from 19 FLE patients and 19 age- and gender-matched healthy controls. Functional connectivity (FC) analysis was used to assess the functional connections between basal ganglia and cerebral cortex. Regions of interest, including the left/right caudate, putamen, pallidum and thalamus, were selected as the seeds. Two sample t-test was used to determine the difference between patients and controls, while controlling the age, gender and head motions. Compared with controls, FLE patients demonstrated increased FCs between basal ganglia and regions including the right fusiform gyrus, the bilateral cingulate gyrus, the precuneus and anterior cingulate gyrus. Reduced FCs were mainly located in a range of brain regions including the bilateral middle occipital gyrus, the ventral frontal lobe, the right putamen, the left fusiform gyrus and right rolandic operculum. In addition, the relationships between basal ganglia-cingulate connections and durations of epilepsy were also found. The alterations of functional integrity within the basal ganglia, as well as its connections to limbic and ventral frontal areas, indicate the important roles of the basal ganglia-cortical functional connections in FLE, and provide new insights in the pathophysiological mechanism of FLE. Copyright © 2016 Elsevier B.V. All rights reserved.

Dynamic functional connectivity reveals altered variability in functional connectivity among patients with major depressive disorder.

PubMed

Demirtaş, Murat; Tornador, Cristian; Falcón, Carles; López-Solà, Marina; Hernández-Ribas, Rosa; Pujol, Jesús; Menchón, José M; Ritter, Petra; Cardoner, Narcis; Soriano-Mas, Carles; Deco, Gustavo

2016-08-01

Resting-state fMRI (RS-fMRI) has become a useful tool to investigate the connectivity structure of mental health disorders. In the case of major depressive disorder (MDD), recent studies regarding the RS-fMRI have found abnormal connectivity in several regions of the brain, particularly in the default mode network (DMN). Thus, the relevance of the DMN to self-referential thoughts and ruminations has made the use of the resting-state approach particularly important for MDD. The majority of such research has relied on the grand averaged functional connectivity measures based on the temporal correlations between the BOLD time series of various brain regions. We, in our study, investigated the variations in the functional connectivity over time at global and local level using RS-fMRI BOLD time series of 27 MDD patients and 27 healthy control subjects. We found that global synchronization and temporal stability were significantly increased in the MDD patients. Furthermore, the participants with MDD showed significantly increased overall average (static) functional connectivity (sFC) but decreased variability of functional connectivity (vFC) within specific networks. Static FC increased to predominance among the regions pertaining to the default mode network (DMN), while the decreased variability of FC was observed in the connections between the DMN and the frontoparietal network. Hum Brain Mapp 37:2918-2930, 2016. © 2016 Wiley Periodicals, Inc. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

Disrupted Cerebro-cerebellar Intrinsic Functional Connectivity in Young Adults with High-functioning Autism Spectrum Disorder: A Data-driven, Whole-brain, High Temporal Resolution fMRI Study.

PubMed

Arnold Anteraper, Sheeba; Guell, Xavier; D'Mello, Anila; Joshi, Neha; Whitfield-Gabrieli, Susan; Joshi, Gagan

2018-06-13

To examine the resting-state functional-connectivity (RsFc) in young adults with high-functioning autism spectrum disorder (HF-ASD) using state-of-the-art fMRI data acquisition and analysis techniques. Simultaneous multi-slice, high temporal resolution fMRI acquisition; unbiased whole-brain connectome-wide multivariate pattern analysis (MVPA) techniques for assessing RsFc; and post-hoc whole-brain seed-to-voxel analyses using MVPA results as seeds. MVPA revealed two clusters of abnormal connectivity in the cerebellum. Whole-brain seed-based functional connectivity analyses informed by MVPA-derived clusters showed significant under connectivity between the cerebellum and social, emotional, and language brain regions in the HF-ASD group compared to healthy controls. The results we report are coherent with existing structural, functional, and RsFc literature in autism, extend previous literature reporting cerebellar abnormalities in the neuropathology of autism, and highlight the cerebellum as a potential target for therapeutic, diagnostic, predictive, and prognostic developments in ASD. The description of functional connectivity abnormalities using whole-brain, data-driven analyses as reported in the present study may crucially advance the development of ASD biomarkers, targets for therapeutic interventions, and neural predictors for measuring treatment response.

Flexible modulation of network connectivity related to cognition in Alzheimer's disease.

PubMed

McLaren, Donald G; Sperling, Reisa A; Atri, Alireza

2014-10-15

Functional neuroimaging tools, such as fMRI methods, may elucidate the neural correlates of clinical, behavioral, and cognitive performance. Most functional imaging studies focus on regional task-related activity or resting state connectivity rather than how changes in functional connectivity across conditions and tasks are related to cognitive and behavioral performance. To investigate the promise of characterizing context-dependent connectivity-behavior relationships, this study applies the method of generalized psychophysiological interactions (gPPI) to assess the patterns of associative-memory-related fMRI hippocampal functional connectivity in Alzheimer's disease (AD) associated with performance on memory and other cognitively demanding neuropsychological tests and clinical measures. Twenty-four subjects with mild AD dementia (ages 54-82, nine females) participated in a face-name paired-associate encoding memory study. Generalized PPI analysis was used to estimate the connectivity between the hippocampus and the whole brain during encoding. The difference in hippocampal-whole brain connectivity between encoding novel and encoding repeated face-name pairs was used in multiple-regression analyses as an independent predictor for 10 behavioral, neuropsychological and clinical tests. The analysis revealed connectivity-behavior relationships that were distributed, dynamically overlapping, and task-specific within and across intrinsic networks; hippocampal-whole brain connectivity-behavior relationships were not isolated to single networks, but spanned multiple brain networks. Importantly, these spatially distributed performance patterns were unique for each measure. In general, out-of-network behavioral associations with encoding novel greater than repeated face-name pairs hippocampal-connectivity were observed in the default-mode network, while correlations with encoding repeated greater than novel face-name pairs hippocampal-connectivity were observed in the executive control network (p<0.05, cluster corrected). Psychophysiological interactions revealed significantly more extensive and robust associations between paired-associate encoding task-dependent hippocampal-whole brain connectivity and performance on memory and behavioral/clinical measures than previously revealed by standard activity-behavior analysis. Compared to resting state and task-activation methods, gPPI analyses may be more sensitive to reveal additional complementary information regarding subtle within- and between-network relations. The patterns of robust correlations between hippocampal-whole brain connectivity and behavioral measures identified here suggest that there are 'coordinated states' in the brain; that the dynamic range of these states is related to behavior and cognition; and that these states can be observed and quantified, even in individuals with mild AD. Copyright © 2014 Elsevier Inc. All rights reserved.

Medial reward and lateral non-reward orbitofrontal cortex circuits change in opposite directions in depression.

PubMed

Cheng, Wei; Rolls, Edmund T; Qiu, Jiang; Liu, Wei; Tang, Yanqing; Huang, Chu-Chung; Wang, XinFa; Zhang, Jie; Lin, Wei; Zheng, Lirong; Pu, JunCai; Tsai, Shih-Jen; Yang, Albert C; Lin, Ching-Po; Wang, Fei; Xie, Peng; Feng, Jianfeng

2016-12-01

The first brain-wide voxel-level resting state functional connectivity neuroimaging analysis of depression is reported, with 421 patients with major depressive disorder and 488 control subjects. Resting state functional connectivity between different voxels reflects correlations of activity between those voxels and is a fundamental tool in helping to understand the brain regions with altered connectivity and function in depression. One major circuit with altered functional connectivity involved the medial orbitofrontal cortex Brodmann area 13, which is implicated in reward, and which had reduced functional connectivity in depression with memory systems in the parahippocampal gyrus and medial temporal lobe, especially involving the perirhinal cortex Brodmann area 36 and entorhinal cortex Brodmann area 28. The Hamilton Depression Rating Scale scores were correlated with weakened functional connectivity of the medial orbitofrontal cortex Brodmann area 13. Thus in depression there is decreased reward-related and memory system functional connectivity, and this is related to the depressed symptoms. The lateral orbitofrontal cortex Brodmann area 47/12, involved in non-reward and punishing events, did not have this reduced functional connectivity with memory systems. Second, the lateral orbitofrontal cortex Brodmann area 47/12 had increased functional connectivity with the precuneus, the angular gyrus, and the temporal visual cortex Brodmann area 21. This enhanced functional connectivity of the non-reward/punishment system (Brodmann area 47/12) with the precuneus (involved in the sense of self and agency), and the angular gyrus (involved in language) is thus related to the explicit affectively negative sense of the self, and of self-esteem, in depression. A comparison of the functional connectivity in 185 depressed patients not receiving medication and 182 patients receiving medication showed that the functional connectivity of the lateral orbitofrontal cortex Brodmann area 47/12 with these three brain areas was lower in the medicated than the unmedicated patients. This is consistent with the hypothesis that the increased functional connectivity of the lateral orbitofrontal cortex Brodmann area 47/12 is related to depression. Relating the changes in cortical connectivity to our understanding of the functions of different parts of the orbitofrontal cortex in emotion helps to provide new insight into the brain changes related to depression. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Changes in functional connectivity dynamics associated with vigilance network in taxi drivers.

PubMed

Shen, Hui; Li, Zhenfeng; Qin, Jian; Liu, Qiang; Wang, Lubin; Zeng, Ling-Li; Li, Hong; Hu, Dewen

2016-01-01

An increasing number of neuroimaging studies have suggested that the fluctuations of low-frequency resting-state functional connectivity (FC) are not noise but are instead linked to the shift between distinct cognitive states. However, there is very limited knowledge about whether and how the fluctuations of FC at rest are influenced by long-term training and experience. Here, we investigated how the dynamics of resting-state FC are linked to driving behavior by comparing 20 licensed taxi drivers with 20 healthy non-drivers using a sliding window approach. We found that the driving experience could be effectively decoded with 90% (p<0.001) accuracy by the amplitude of low-frequency fluctuations in some specific connections, based on a multivariate pattern analysis technique. Interestingly, the majority of these connections fell within a set of distributed regions named "the vigilance network". Moreover, the decreased amplitude of the FC fluctuations within the vigilance network in the drivers was negatively correlated with the number of years that they had driven a taxi. Furthermore, temporally quasi-stable functional connectivity segmentation revealed significant differences between the drivers and non-drivers in the dwell time of specific vigilance-related transient brain states, although the brain's repertoire of functional states was preserved. Overall, these results suggested a significant link between the changes in the time-dependent aspects of resting-state FC within the vigilance network and long-term driving experiences. The results not only improve our understanding of how the brain supports driving behavior but also shed new light on the relationship between the dynamics of functional brain networks and individual behaviors. Copyright © 2015 Elsevier Inc. All rights reserved.

Resting state functional connectivity of the nucleus accumbens in youth with a family history of alcoholism

PubMed Central

Cservenka, Anita; Casimo, Kaitlyn; Fair, Damien; Nagel, Bonnie

2014-01-01

Adolescents with a family history of alcoholism (FHP) are at heightened risk for developing alcohol use disorders (AUDs). The nucleus accumbens (NAcc), a key brain region for reward processing, is implicated in the development of AUDs. Thus, functional connectivity of the NAcc may be an important marker of risk in FHP youth. Resting state functional magnetic resonance imaging (rs-fcMRI) was used to examine the intrinsic connectivity of the NAcc in 47 FHP and 50 family history negative (FHN) youth, ages 10–16 years old. FHP and FHN adolescents showed significant group differences in resting state synchrony between the left NAcc and bilateral inferior frontal gyri and the left postcentral gyrus (PG). Additionally, FHP youth differed from FHN youth in right NAcc functional connectivity with the left orbitofrontal cortex (OFC), left superior temporal gyrus, right cerebellum, left PG, and right occipital cortex. These results indicate that FHP youth have less segregation between the NAcc and executive functioning brain regions, and less integration with reward-related brain areas, such as the OFC. The findings of the current study highlight that premorbid atypical connectivity of appetitive systems, in the absence of heavy alcohol use, may be a risk marker in FHP adolescents. PMID:24440571

Mapping the changed hubs and corresponding functional connectivity in idiopathic restless legs syndrome.

PubMed

Liu, Chunyan; Wang, Jiaojian; Hou, Yue; Qi, Zhigang; Wang, Li; Zhan, Shuqin; Wang, Rong; Wang, Yuping

2018-05-01

The hubs of the brain network play a key role in integrating and transferring information between different functional modules. However, whether the changed pattern in functional network hubs contributes to the onset of leg discomfort symptoms in restless legs syndrome (RLS) patients remains unclear. Using resting-state functional magnetic resonance imaging (rs-fMRI) and graph theory methods, we investigated whether alterations of hubs can be detected in RLS. First, we constructed the whole-brain voxelwise functional connectivity and calculated a functional connectivity strength (FCS) map in each of 16 drug-naive idiopathic RLS patients and 26 gender- and age-matched healthy control (HC) subjects. Next, a two-sample t test was applied to compare the FCS maps between HC and RLS patients, and to identify significant changes in FCS in RLS patients. To further elucidate the corresponding changes in the functional connectivity patterns of the aberrant hubs in RLS patients, whole-brain resting-state functional connectivity analyses for the hub areas were performed. The hub analysis revealed decreased FCS in the cuneus, fusiform gyrus, paracentral lobe, and precuneus, and increased FCS in the superior frontal gyrus and thalamus in idiopathic drug-naive RLS patients. Subsequent functional connectivity analyses revealed decreased functional connectivity in sensorimotor and visual processing networks and increased functional connectivity in the affective cognitive network and cerebellar-thalamic circuit. Furthermore, the mean FCS value in the superior frontal gyrus was significantly correlated with Hamilton Anxiety Rating Scale scores in RLS patients, and the mean FCS value in the fusiform gyrus was significantly correlated with Hamilton Depression Rating Scale scores. These findings may provide novel insight into the pathophysiology of RLS. Copyright © 2018 Elsevier B.V. All rights reserved.

Unsupervised classification of major depression using functional connectivity MRI.

PubMed

Zeng, Ling-Li; Shen, Hui; Liu, Li; Hu, Dewen

2014-04-01

The current diagnosis of psychiatric disorders including major depressive disorder based largely on self-reported symptoms and clinical signs may be prone to patients' behaviors and psychiatrists' bias. This study aims at developing an unsupervised machine learning approach for the accurate identification of major depression based on single resting-state functional magnetic resonance imaging scans in the absence of clinical information. Twenty-four medication-naive patients with major depression and 29 demographically similar healthy individuals underwent resting-state functional magnetic resonance imaging. We first clustered the voxels within the perigenual cingulate cortex into two subregions, a subgenual region and a pregenual region, according to their distinct resting-state functional connectivity patterns and showed that a maximum margin clustering-based unsupervised machine learning approach extracted sufficient information from the subgenual cingulate functional connectivity map to differentiate depressed patients from healthy controls with a group-level clustering consistency of 92.5% and an individual-level classification consistency of 92.5%. It was also revealed that the subgenual cingulate functional connectivity network with the highest discriminative power primarily included the ventrolateral and ventromedial prefrontal cortex, superior temporal gyri and limbic areas, indicating that these connections may play critical roles in the pathophysiology of major depression. The current study suggests that subgenual cingulate functional connectivity network signatures may provide promising objective biomarkers for the diagnosis of major depression and that maximum margin clustering-based unsupervised machine learning approaches may have the potential to inform clinical practice and aid in research on psychiatric disorders. Copyright © 2013 Wiley Periodicals, Inc.

AICHA: An atlas of intrinsic connectivity of homotopic areas.

PubMed

Joliot, Marc; Jobard, Gaël; Naveau, Mikaël; Delcroix, Nicolas; Petit, Laurent; Zago, Laure; Crivello, Fabrice; Mellet, Emmanuel; Mazoyer, Bernard; Tzourio-Mazoyer, Nathalie

2015-10-30

Atlases of brain anatomical ROIs are widely used for functional MRI data analysis. Recently, it was proposed that an atlas of ROIs derived from a functional brain parcellation could be advantageous, in particular for understanding how different regions share information. However, functional atlases so far proposed do not account for a crucial aspect of cerebral organization, namely homotopy, i.e. that each region in one hemisphere has a homologue in the other hemisphere. We present AICHA (for Atlas of Intrinsic Connectivity of Homotopic Areas), a functional brain ROIs atlas based on resting-state fMRI data acquired in 281 individuals. AICHA ROIs cover the whole cerebrum, each having 1-homogeneity of its constituting voxels intrinsic activity, and 2-a unique homotopic contralateral counterpart with which it has maximal intrinsic connectivity. AICHA was built in 4 steps: (1) estimation of resting-state networks (RSNs) using individual resting-state fMRI independent components, (2) k-means clustering of voxel-wise group level profiles of connectivity, (3) homotopic regional grouping based on maximal inter-hemispheric functional correlation, and (4) ROI labeling. AICHA includes 192 homotopic region pairs (122 gyral, 50 sulcal, and 20 gray nuclei). As an application, we report inter-hemispheric (homotopic and heterotopic) and intra-hemispheric connectivity patterns at different sparsities. ROI functional homogeneity was higher for AICHA than for anatomical ROI atlases, but slightly lower than for another functional ROI atlas not accounting for homotopy. AICHA is ideally suited for intrinsic/effective connectivity analyses, as well as for investigating brain hemispheric specialization. Copyright © 2015 Elsevier B.V. All rights reserved.

Large-scale changes in network interactions as a physiological signature of spatial neglect.

PubMed

Baldassarre, Antonello; Ramsey, Lenny; Hacker, Carl L; Callejas, Alicia; Astafiev, Serguei V; Metcalf, Nicholas V; Zinn, Kristi; Rengachary, Jennifer; Snyder, Abraham Z; Carter, Alex R; Shulman, Gordon L; Corbetta, Maurizio

2014-12-01

The relationship between spontaneous brain activity and behaviour following focal injury is not well understood. Here, we report a large-scale study of resting state functional connectivity MRI and spatial neglect following stroke in a large (n=84) heterogeneous sample of first-ever stroke patients (within 1-2 weeks). Spatial neglect, which is typically more severe after right than left hemisphere injury, includes deficits of spatial attention and motor actions contralateral to the lesion, and low general attention due to impaired vigilance/arousal. Patients underwent structural and resting state functional MRI scans, and spatial neglect was measured using the Posner spatial cueing task, and Mesulam and Behavioural Inattention Test cancellation tests. A principal component analysis of the behavioural tests revealed a main factor accounting for 34% of variance that captured three correlated behavioural deficits: visual neglect of the contralesional visual field, visuomotor neglect of the contralesional field, and low overall performance. In an independent sample (21 healthy subjects), we defined 10 resting state networks consisting of 169 brain regions: visual-fovea and visual-periphery, sensory-motor, auditory, dorsal attention, ventral attention, language, fronto-parietal control, cingulo-opercular control, and default mode. We correlated the neglect factor score with the strength of resting state functional connectivity within and across the 10 resting state networks. All damaged brain voxels were removed from the functional connectivity:behaviour correlational analysis. We found that the correlated behavioural deficits summarized by the factor score were associated with correlated multi-network patterns of abnormal functional connectivity involving large swaths of cortex. Specifically, dorsal attention and sensory-motor networks showed: (i) reduced interhemispheric functional connectivity; (ii) reduced anti-correlation with fronto-parietal and default mode networks in the right hemisphere; and (iii) increased intrahemispheric connectivity with the basal ganglia. These patterns of functional connectivity:behaviour correlations were stronger in patients with right- as compared to left-hemisphere damage and were independent of lesion volume. Our findings identify large-scale changes in resting state network interactions that are a physiological signature of spatial neglect and may relate to its right hemisphere lateralization. © The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Impaired insula functional connectivity associated with persistent pain perception in patients with complex regional pain syndrome

PubMed Central

Jang, Joon Hwan; Lee, Do-Hyeong; Lee, Kyung-Jun; Lee, Won Joon; Moon, Jee Youn; Kim, Yong Chul

2017-01-01

Given that the insula plays a contributory role in the perception of chronic pain, we examined the resting-state functional connectivity between the insular cortex and other brain regions to investigate neural underpinnings of persisting perception of background pain in patients with complex regional pain syndrome (CRPS). A total of 25 patients with CRPS and 25 matched healthy controls underwent functional magnetic resonance imaging at rest. With the anterior and posterior insular cortices as seed regions, we compared the strength of the resting-state functional connectivity between the two groups. Functional connectivity between the anterior and posterior insular cortices and the postcentral and inferior frontal gyri, cingulate cortices was reduced in patients with CRPS compared with controls. Additionally, greater reductions in functional connectivity between the anterior insula and right postcentral gyrus were associated with more severe sensory pain in patients with CRPS (short-form McGill Pain Questionnaire sensory subscores, r = -.517, P = .023). The present results imply a possible role of the insula in aberrant processing of pain information in patients with CRPS. The findings suggest that a functional derangement of the connection between one of the somatosensory cortical functions of perception and one of the insular functions of awareness can play a significant role in the persistent experience of regional pain that is not confined to a specific nerve territory. PMID:28692702

Discriminant analysis of resting-state functional connectivity patterns on the Grassmann manifold

NASA Astrophysics Data System (ADS)

Fan, Yong; Liu, Yong; Jiang, Tianzi; Liu, Zhening; Hao, Yihui; Liu, Haihong

2010-03-01

The functional networks, extracted from fMRI images using independent component analysis, have been demonstrated informative for distinguishing brain states of cognitive functions and neurological diseases. In this paper, we propose a novel algorithm for discriminant analysis of functional networks encoded by spatial independent components. The functional networks of each individual are used as bases for a linear subspace, referred to as a functional connectivity pattern, which facilitates a comprehensive characterization of temporal signals of fMRI data. The functional connectivity patterns of different individuals are analyzed on the Grassmann manifold by adopting a principal angle based subspace distance. In conjunction with a support vector machine classifier, a forward component selection technique is proposed to select independent components for constructing the most discriminative functional connectivity pattern. The discriminant analysis method has been applied to an fMRI based schizophrenia study with 31 schizophrenia patients and 31 healthy individuals. The experimental results demonstrate that the proposed method not only achieves a promising classification performance for distinguishing schizophrenia patients from healthy controls, but also identifies discriminative functional networks that are informative for schizophrenia diagnosis.

Determination of Vascular Dementia Brain in Distinct Frequency Bands with Whole Brain Functional Connectivity Patterns

PubMed Central

Zhang, Delong; Liu, Bo; Chen, Jun; Peng, Xiaoling; Liu, Xian; Fan, Yuanyuan; Liu, Ming; Huang, Ruiwang

2013-01-01

Recent studies have shown that multivariate pattern analysis (MVPA) can be useful for distinguishing brain disorders into categories. Such analyses can substantially enrich and facilitate clinical diagnoses. Using MPVA methods, whole brain functional networks, especially those derived using different frequency windows, can be applied to detect brain states. We constructed whole brain functional networks for groups of vascular dementia (VaD) patients and controls using resting state BOLD-fMRI (rsfMRI) data from three frequency bands - slow-5 (0.01∼0.027 Hz), slow-4 (0.027∼0.073 Hz), and whole-band (0.01∼0.073 Hz). Then we used the support vector machine (SVM), a type of MVPA classifier, to determine the patterns of functional connectivity. Our results showed that the brain functional networks derived from rsfMRI data (19 VaD patients and 20 controls) in these three frequency bands appear to reflect neurobiological changes in VaD patients. Such differences could be used to differentiate the brain states of VaD patients from those of healthy individuals. We also found that the functional connectivity patterns of the human brain in the three frequency bands differed, as did their ability to differentiate brain states. Specifically, the ability of the functional connectivity pattern to differentiate VaD brains from healthy ones was more efficient in the slow-5 (0.01∼0.027 Hz) band than in the other two frequency bands. Our findings suggest that the MVPA approach could be used to detect abnormalities in the functional connectivity of VaD patients in distinct frequency bands. Identifying such abnormalities may contribute to our understanding of the pathogenesis of VaD. PMID:23359801

In vivo Visuotopic Brain Mapping with Manganese-Enhanced MRI and Resting-State Functional Connectivity MRI

PubMed Central

Chan, Kevin C.; Fan, Shu-Juan; Chan, Russell W.; Cheng, Joe S.; Zhou, Iris Y.; Wu, Ed X.

2014-01-01

The rodents are an increasingly important model for understanding the mechanisms of development, plasticity, functional specialization and disease in the visual system. However, limited tools have been available for assessing the structural and functional connectivity of the visual brain network globally, in vivo and longitudinally. There are also ongoing debates on whether functional brain connectivity directly reflects structural brain connectivity. In this study, we explored the feasibility of manganese-enhanced MRI (MEMRI) via 3 different routes of Mn2+ administration for visuotopic brain mapping and understanding of physiological transport in normal and visually deprived adult rats. In addition, resting-state functional connectivity MRI (RSfcMRI) was performed to evaluate the intrinsic functional network and structural-functional relationships in the corresponding anatomical visual brain connections traced by MEMRI. Upon intravitreal, subcortical, and intracortical Mn2+ injection, different topographic and layer-specific Mn enhancement patterns could be revealed in the visual cortex and subcortical visual nuclei along retinal, callosal, cortico-subcortical, transsynaptic and intracortical horizontal connections. Loss of visual input upon monocular enucleation to adult rats appeared to reduce interhemispheric polysynaptic Mn2+ transfer but not intra- or inter-hemispheric monosynaptic Mn2+ transport after Mn2+ injection into visual cortex. In normal adults, both structural and functional connectivity by MEMRI and RSfcMRI was stronger interhemispherically between bilateral primary/secondary visual cortex (V1/V2) transition zones (TZ) than between V1/V2 TZ and other cortical nuclei. Intrahemispherically, structural and functional connectivity was stronger between visual cortex and subcortical visual nuclei than between visual cortex and other subcortical nuclei. The current results demonstrated the sensitivity of MEMRI and RSfcMRI for assessing the neuroarchitecture, neurophysiology and structural-functional relationships of the visual brains in vivo. These may possess great potentials for effective monitoring and understanding of the basic anatomical and functional connections in the visual system during development, plasticity, disease, pharmacological interventions and genetic modifications in future studies. PMID:24394694

Identifying Dynamic Functional Connectivity Changes in Dementia with Lewy Bodies Based on Product Hidden Markov Models.

PubMed

Sourty, Marion; Thoraval, Laurent; Roquet, Daniel; Armspach, Jean-Paul; Foucher, Jack; Blanc, Frédéric

2016-01-01

Exploring time-varying connectivity networks in neurodegenerative disorders is a recent field of research in functional MRI. Dementia with Lewy bodies (DLB) represents 20% of the neurodegenerative forms of dementia. Fluctuations of cognition and vigilance are the key symptoms of DLB. To date, no dynamic functional connectivity (DFC) investigations of this disorder have been performed. In this paper, we refer to the concept of connectivity state as a piecewise stationary configuration of functional connectivity between brain networks. From this concept, we propose a new method for group-level as well as for subject-level studies to compare and characterize connectivity state changes between a set of resting-state networks (RSNs). Dynamic Bayesian networks, statistical and graph theory-based models, enable one to learn dependencies between interacting state-based processes. Product hidden Markov models (PHMM), an instance of dynamic Bayesian networks, are introduced here to capture both statistical and temporal aspects of DFC of a set of RSNs. This analysis was based on sliding-window cross-correlations between seven RSNs extracted from a group independent component analysis performed on 20 healthy elderly subjects and 16 patients with DLB. Statistical models of DFC differed in patients compared to healthy subjects for the occipito-parieto-frontal network, the medial occipital network and the right fronto-parietal network. In addition, pairwise comparisons of DFC of RSNs revealed a decrease of dependency between these two visual networks (occipito-parieto-frontal and medial occipital networks) and the right fronto-parietal control network. The analysis of DFC state changes thus pointed out networks related to the cognitive functions that are known to be impaired in DLB: visual processing as well as attentional and executive functions. Besides this context, product HMM applied to RSNs cross-correlations offers a promising new approach to investigate structural and temporal aspects of brain DFC.

Altered task-based and resting-state amygdala functional connectivity following real-time fMRI amygdala neurofeedback training in major depressive disorder.

PubMed

Young, Kymberly D; Siegle, Greg J; Misaki, Masaya; Zotev, Vadim; Phillips, Raquel; Drevets, Wayne C; Bodurka, Jerzy

2018-01-01

We have previously shown that in participants with major depressive disorder (MDD) trained to upregulate their amygdala hemodynamic response during positive autobiographical memory (AM) recall with real-time fMRI neurofeedback (rtfMRI-nf) training, depressive symptoms diminish. Here, we assessed the effect of rtfMRI-nf on amygdala functional connectivity during both positive AM recall and rest. The current manuscript consists of a secondary analysis on data from our published clinical trial of neurofeedback. Patients with MDD completed two rtfMRI-nf sessions (18 received amygdala rtfMRI-nf, 16 received control parietal rtfMRI-nf). One-week prior-to and following training participants also completed a resting-state fMRI scan. A GLM-based functional connectivity analysis was applied using a seed ROI in the left amygdala. We compared amygdala functional connectivity changes while recalling positive AMs from the baseline run to the final transfer run during rtfMRI-nf training, as well during rest from the baseline to the one-week follow-up visit. Finally, we assessed the correlation between change in depression scores and change in amygdala connectivity, as well as correlations between amygdala regulation success and connectivity changes. Following training, amygdala connectivity during positive AM recall increased with widespread regions in the frontal and limbic network. During rest, amygdala connectivity increased following training within the fronto-temporal-limbic network. During both task and resting-state analyses, amygdala-temporal pole connectivity decreased. We identified increased amygdala-precuneus and amygdala-inferior frontal gyrus connectivity during positive memory recall and increased amygdala-precuneus and amygdala-thalamus connectivity during rest as functional connectivity changes that explained significant variance in symptom improvement. Amygdala-precuneus connectivity changes also explain a significant amount of variance in neurofeedback regulation success. Neurofeedback training to increase amygdala hemodynamic activity during positive AM recall increased amygdala connectivity with regions involved in self-referential, salience, and reward processing. Results suggest future targets for neurofeedback interventions, particularly interventions involving the precuneus.

Multi-subject hierarchical inverse covariance modelling improves estimation of functional brain networks.

PubMed

Colclough, Giles L; Woolrich, Mark W; Harrison, Samuel J; Rojas López, Pedro A; Valdes-Sosa, Pedro A; Smith, Stephen M

2018-05-07

A Bayesian model for sparse, hierarchical, inver-covariance estimation is presented, and applied to multi-subject functional connectivity estimation in the human brain. It enables simultaneous inference of the strength of connectivity between brain regions at both subject and population level, and is applicable to fMRI, MEG and EEG data. Two versions of the model can encourage sparse connectivity, either using continuous priors to suppress irrelevant connections, or using an explicit description of the network structure to estimate the connection probability between each pair of regions. A large evaluation of this model, and thirteen methods that represent the state of the art of inverse covariance modelling, is conducted using both simulated and resting-state functional imaging datasets. Our novel Bayesian approach has similar performance to the best extant alternative, Ng et al.'s Sparse Group Gaussian Graphical Model algorithm, which also is based on a hierarchical structure. Using data from the Human Connectome Project, we show that these hierarchical models are able to reduce the measurement error in MEG beta-band functional networks by 10%, producing concomitant increases in estimates of the genetic influence on functional connectivity. Copyright © 2018. Published by Elsevier Inc.

Fronto-temporal interactions are functionally relevant for semantic control in language processing.

PubMed

Wawrzyniak, Max; Hoffstaedter, Felix; Klingbeil, Julian; Stockert, Anika; Wrede, Katrin; Hartwigsen, Gesa; Eickhoff, Simon B; Classen, Joseph; Saur, Dorothee

2017-01-01

Semantic cognition, i.e. processing of meaning is based on semantic representations and their controlled retrieval. Semantic control has been shown to be implemented in a network that consists of left inferior frontal (IFG), and anterior and posterior middle temporal gyri (a/pMTG). We aimed to disrupt semantic control processes with continuous theta burst stimulation (cTBS) over left IFG and pMTG and to study whether behavioral effects are moderated by induced alterations in resting-state functional connectivity. To this end, we applied real cTBS over left IFG and left pMTG as well as sham stimulation on 20 healthy participants in a within-subject design. Stimulation was followed by resting-state functional magnetic resonance imaging and a semantic priming paradigm. Resting-state functional connectivity of regions of interest in left IFG, pMTG and aMTG revealed highly interconnected left-lateralized fronto-temporal networks representing the semantic system. We did not find any significant direct modulation of either task performance or resting-state functional connectivity by effective cTBS. However, after sham cTBS, functional connectivity between IFG and pMTG correlated with task performance under high semantic control demands in the semantic priming paradigm. These findings provide evidence for the functional relevance of interactions between IFG and pMTG for semantic control processes. This interaction was functionally less relevant after cTBS over aIFG which might be interpretable in terms of an indirect disruptive effect of cTBS.

Detecting brain dynamics during resting state: a tensor based evolutionary clustering approach

NASA Astrophysics Data System (ADS)

Al-sharoa, Esraa; Al-khassaweneh, Mahmood; Aviyente, Selin

2017-08-01

Human brain is a complex network with connections across different regions. Understanding the functional connectivity (FC) of the brain is important both during resting state and task; as disruptions in connectivity patterns are indicators of different psychopathological and neurological diseases. In this work, we study the resting state functional connectivity networks (FCNs) of the brain from fMRI BOLD signals. Recent studies have shown that FCNs are dynamic even during resting state and understanding the temporal dynamics of FCNs is important for differentiating between different conditions. Therefore, it is important to develop algorithms to track the dynamic formation and dissociation of FCNs of the brain during resting state. In this paper, we propose a two step tensor based community detection algorithm to identify and track the brain network community structure across time. First, we introduce an information-theoretic function to reduce the dynamic FCN and identify the time points that are similar topologically to combine them into a tensor. These time points will be used to identify the different FC states. Second, a tensor based spectral clustering approach is developed to identify the community structure of the constructed tensors. The proposed algorithm applies Tucker decomposition to the constructed tensors and extract the orthogonal factor matrices along the connectivity mode to determine the common subspace within each FC state. The detected community structure is summarized and described as FC states. The results illustrate the dynamic structure of resting state networks (RSNs), including the default mode network, somatomotor network, subcortical network and visual network.

Investigating the effects of nitrous oxide sedation on frontal-parietal interactions.

PubMed

Ryu, Ji-Ho; Kim, Pil-Jong; Kim, Hong-Gee; Koo, Yong-Seo; Shin, Teo Jeon

2017-06-09

Although functional connectivity has received considerable attention in the study of consciousness, few studies have investigated functional connectivity limited to the sedated state where consciousness is maintained but impaired. The aim of the present study was to investigate changes in functional connectivity of the parietal-frontal network resulting from nitrous oxide-induced sedation, and to determine the neural correlates of cognitive impairment during consciousness transition states. Electroencephalography was acquired from healthy adult patients who underwent nitrous oxide inhalation to induce cognitive impairment, and was analyzed using Granger causality (GC). Periods of awake, sedation and recovery for GC between frontal and parietal areas in the delta, theta, alpha, beta, gamma and total frequency bands were obtained. The Friedman test with post-hoc analysis was conducted for GC values of each period for comparison. As a sedated state was induced by nitrous oxide inhalation, power in the low frequency band showed increased activity in frontal regions that was reversed with discontinuation of nitrous oxide. Feedback and feedforward connections analyzed in spectral GC were changed differently in accordance with EEG frequency bands in the sedated state by nitrous oxide administration. Calculated spectral GC of the theta, alpha, and beta frequency regions in the parietal-to-frontal direction was significantly decreased in the sedated state while spectral GC in the reverse direction did not show significant change. Frontal-parietal functional connectivity is significantly affected by nitrous oxide inhalation. Significantly decreased parietal-to-frontal interaction may induce a sedated state. Copyright © 2017 Elsevier B.V. All rights reserved.

Dexmedetomidine Disrupts the Local and Global Efficiencies of Large-scale Brain Networks.

PubMed

Hashmi, Javeria A; Loggia, Marco L; Khan, Sheraz; Gao, Lei; Kim, Jieun; Napadow, Vitaly; Brown, Emery N; Akeju, Oluwaseun

2017-03-01

A clear understanding of the neural basis of consciousness is fundamental to research in clinical and basic neuroscience disciplines and anesthesia. Recently, decreased efficiency of information integration was suggested as a core network feature of propofol-induced unconsciousness. However, it is unclear whether this finding can be generalized to dexmedetomidine, which has a different molecular target. Dexmedetomidine was administered as a 1-μg/kg bolus over 10 min, followed by a 0.7-μg · kg · h infusion to healthy human volunteers (age range, 18 to 36 yr; n = 15). Resting-state functional magnetic resonance imaging data were acquired during baseline, dexmedetomidine-induced altered arousal, and recovery states. Zero-lag correlations between resting-state functional magnetic resonance imaging signals extracted from 131 brain parcellations were used to construct weighted brain networks. Network efficiency, degree distribution, and node strength were computed using graph analysis. Parcellated brain regions were also mapped to known resting-state networks to study functional connectivity changes. Dexmedetomidine significantly reduced the local and global efficiencies of graph theory-derived networks. Dexmedetomidine also reduced the average brain connectivity strength without impairing the degree distribution. Functional connectivity within and between all resting-state networks was modulated by dexmedetomidine. Dexmedetomidine is associated with a significant drop in the capacity for efficient information transmission at both the local and global levels. These changes result from reductions in the strength of connectivity and also manifest as reduced within and between resting-state network connectivity. These findings strengthen the hypothesis that conscious processing relies on an efficient system of information transfer in the brain.

The neural basis of trait self-esteem revealed by the amplitude of low-frequency fluctuations and resting state functional connectivity.

PubMed

Pan, Weigang; Liu, Congcong; Yang, Qian; Gu, Yan; Yin, Shouhang; Chen, Antao

2016-03-01

Self-esteem is an affective, self-evaluation of oneself and has a significant effect on mental and behavioral health. Although research has focused on the neural substrates of self-esteem, little is known about the spontaneous brain activity that is associated with trait self-esteem (TSE) during the resting state. In this study, we used the resting-state functional magnetic resonance imaging (fMRI) signal of the amplitude of low-frequency fluctuations (ALFFs) and resting state functional connectivity (RSFC) to identify TSE-related regions and networks. We found that a higher level of TSE was associated with higher ALFFs in the left ventral medial prefrontal cortex (vmPFC) and lower ALFFs in the left cuneus/lingual gyrus and right lingual gyrus. RSFC analyses revealed that the strengths of functional connectivity between the left vmPFC and bilateral hippocampus were positively correlated with TSE; however, the connections between the left vmPFC and right inferior frontal gyrus and posterior superior temporal sulcus were negatively associated with TSE. Furthermore, the strengths of functional connectivity between the left cuneus/lingual gyrus and right dorsolateral prefrontal cortex and anterior cingulate cortex were positively related to TSE. These findings indicate that TSE is linked to core regions in the default mode network and social cognition network, which is involved in self-referential processing, autobiographical memory and social cognition. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

White matter lesions relate to tract-specific reductions in functional connectivity.

PubMed

Langen, Carolyn D; Zonneveld, Hazel I; White, Tonya; Huizinga, Wyke; Cremers, Lotte G M; de Groot, Marius; Ikram, Mohammad Arfan; Niessen, Wiro J; Vernooij, Meike W

2017-03-01

White matter lesions play a role in cognitive decline and dementia. One presumed pathway is through disconnection of functional networks. Little is known about location-specific effects of lesions on functional connectivity. This study examined location-specific effects within anatomically-defined white matter tracts in 1584 participants of the Rotterdam Study, aged 50-95. Tracts were delineated from diffusion magnetic resonance images using probabilistic tractography. Lesions were segmented on fluid-attenuated inversion recovery images. Functional connectivity was defined across each tract on resting-state functional magnetic resonance images by using gray matter parcellations corresponding to the tract ends and calculating the correlation of the mean functional activity between the gray matter regions. A significant relationship between both local and brain-wide lesion load and tract-specific functional connectivity was found in several tracts using linear regressions, also after Bonferroni correction. Indirect connectivity analyses revealed that tract-specific functional connectivity is affected by lesions in several tracts simultaneously. These results suggest that local white matter lesions can decrease tract-specific functional connectivity, both in direct and indirect connections. Copyright © 2016 Elsevier Inc. All rights reserved.

Differences on Brain Connectivity in Adulthood Are Present in Subjects with Iron Deficiency Anemia in Infancy

PubMed Central

Algarin, Cecilia; Karunakaran, Keerthana Deepti; Reyes, Sussanne; Morales, Cristian; Lozoff, Betsy; Peirano, Patricio; Biswal, Bharat

2017-01-01

Iron deficiency continues to be the most prevalent micronutrient deficit worldwide. Since iron is involved in several processes including myelination, dopamine neurotransmission and neuronal metabolism, the presence of iron deficiency anemia (IDA) in infancy relates to long-lasting neurofunctional effects. There is scarce data regarding whether these effects would extend to former iron deficient anemic human adults. Resting state functional magnetic resonance imaging (fMRI) is a novel technique to explore patterns of functional connectivity. Default Mode Network (DMN), one of the resting state networks, is deeply involved in memory, social cognition and self-referential processes. The four core regions consistently identified in the DMN are the medial prefrontal cortex, posterior cingulate/retrosplenial cortex and left and right inferior parietal cortex. Therefore to investigate the DMN in former iron deficient anemic adults is a particularly useful approach to elucidate de long term effects on functional brain. We conducted this research to explore the connection between IDA in infancy and altered patterns of resting state brain functional networks in young adults. Resting-state fMRI studies were performed to 31 participants that belong to a follow-up study since infancy. Of them, 14 participants were former iron deficient anemic in infancy and 17 were controls, with mean age of 21.5 years (±1.5) and 54.8% were males. Resting-state fMRI protocol was used and the data was analyzed using the seed based connectivity statistical analysis to assess the DMN. We found that compared to controls, former iron deficient anemic subjects showed posterior DMN decreased connectivity to the left posterior cingulate cortex (PCC), whereas they exhibited increased anterior DMN connectivity to the right PCC. Differences between groups were also apparent in the left medial frontal gyrus, with former iron deficient anemic participants having increased connectivity with areas included in DMN and dorsal attention networks. These preliminary results suggest different patterns of functional connectivity between former iron deficient anemic and control young adults. Indeed, IDA in infancy, a common nutritional problem among human infants, may turn out to be important for understanding the mechanisms of cognitive alterations, common in adulthood. PMID:28326037

Altered Intrinsic Functional Brain Architecture in Children at Familial Risk of Major Depression

PubMed Central

Chai, Xiaoqian J.; Hirshfeld-Becker, Dina; Biederman, Joseph; Uchida, Mai; Doehrmann, Oliver; Leonard, Julia; Salvatore, John; Kenworthy, Tara; Brown, Ariel; Kagan, Elana; de los Angeles, Carlo; Gabrieli, John D.E.; Whitfield-Gabrieli, Susan

2015-01-01

Background Neuroimaging studies of patients with major depression have revealed abnormal intrinsic functional connectivity measured during the resting state in multiple, distributed networks. However, it is unclear whether these findings reflect the state of major depression or reflect trait neurobiological underpinnings of risk for major depression. Methods We compared resting-state functional connectivity, measured with functional magnetic resonance imaging (fMRI), between unaffected children of parents who had documented histories of major depression (at-risk, n = 27; 8–14 years of age) and age-matched children of parents with no lifetime history of depression (controls, n = 16). Results At-risk children exhibited hyperconnectivity between the default mode network (DMN) and subgenual anterior cingulate cortex (sgACC) / orbital frontal cortex (OFC), and the magnitude of connectivity positively correlated with individual symptom scores. At-risk children also exhibited (1) hypoconnectivity within the cognitive control network, which also lacked the typical anticorrelation with the DMN; (2) hypoconnectivity between left dorsolateral prefrontal cortex (DLPFC) and sgACC; and (3) hyperconnectivity between the right amygdala and right inferior frontal gyrus, a key region for top-down modulation of emotion. Classification between at-risk children and controls based on resting-state connectivity yielded high accuracy with high sensitivity and specificity that was superior to clinical rating scales. Conclusions Children at familial risk for depression exhibited atypical functional connectivity in the default-mode, cognitive-control, and affective networks. Such task-independent functional brain measures of risk for depression in children could be used to promote early intervention to reduce the likelihood of developing depression. PMID:26826874

Altered Intrinsic Functional Brain Architecture in Children at Familial Risk of Major Depression.

PubMed

Chai, Xiaoqian J; Hirshfeld-Becker, Dina; Biederman, Joseph; Uchida, Mai; Doehrmann, Oliver; Leonard, Julia A; Salvatore, John; Kenworthy, Tara; Brown, Ariel; Kagan, Elana; de Los Angeles, Carlo; Gabrieli, John D E; Whitfield-Gabrieli, Susan

2016-12-01

Neuroimaging studies of patients with major depression have revealed abnormal intrinsic functional connectivity measured during the resting state in multiple distributed networks. However, it is unclear whether these findings reflect the state of major depression or reflect trait neurobiological underpinnings of risk for major depression. We compared resting-state functional connectivity, measured with functional magnetic resonance imaging, between unaffected children of parents who had documented histories of major depression (at-risk, n = 27; 8-14 years of age) and age-matched children of parents with no lifetime history of depression (control subjects, n = 16). At-risk children exhibited hyperconnectivity between the default mode network and subgenual anterior cingulate cortex/orbital frontal cortex, and the magnitude of connectivity positively correlated with individual symptom scores. At-risk children also exhibited 1) hypoconnectivity within the cognitive control network, which also lacked the typical anticorrelation with the default mode network; 2) hypoconnectivity between left dorsolateral prefrontal cortex and subgenual anterior cingulate cortex; and 3) hyperconnectivity between the right amygdala and right inferior frontal gyrus, a key region for top-down modulation of emotion. Classification between at-risk children and control subjects based on resting-state connectivity yielded high accuracy with high sensitivity and specificity that was superior to clinical rating scales. Children at familial risk for depression exhibited atypical functional connectivity in the default mode, cognitive control, and affective networks. Such task-independent functional brain measures of risk for depression in children could be used to promote early intervention to reduce the likelihood of developing depression. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Exercise alters resting state functional connectivity of motor circuits in Parkinsonian rats

PubMed Central

Wang, Zhuo; Guo, Yumei; Myers, Kalisa G.; Heintz, Ryan; Peng, Yu-Hao; Maarek, Jean-Michel I.; Holschneider, Daniel P.

2014-01-01

Few studies have examined changes in functional connectivity after long-term aerobic exercise. We examined the effects of 4 weeks of forced running wheel exercise on the resting-state functional connectivity (rsFC) of motor circuits of rats subjected to bilateral 6-hydroxydopamine lesion of the dorsal striatum. Our results showed substantial similarity between lesion-induced changes in rsFC in the rats and alterations in rsFC reported in Parkinson’s disease subjects, including disconnection of the dorsolateral striatum. Exercise in lesioned rats resulted in: (a) normalization of many of the lesion-induced alterations in rsFC, including reintegration of the dorsolateral striatum into the motor network; (b) emergence of the ventrolateral striatum as a new broadly connected network hub; (c) increased rsFC among the motor cortex, motor thalamus, basal ganglia, and cerebellum. Our results showed for the first time that long-term exercise training partially reversed lesion-induced alterations in rsFC of the motor circuits, and in addition enhanced functional connectivity in specific motor pathways in the Parkinsonian rats, which could underlie recovery in motor functions observed in these rats. PMID:25219465

Resting-state functional connectivity predicts longitudinal pain symptom change in urologic chronic pelvic pain syndrome: a MAPP network study.

PubMed

Kutch, Jason J; Labus, Jennifer S; Harris, Richard E; Martucci, Katherine T; Farmer, Melissa A; Fenske, Sonja; Fling, Connor; Ichesco, Eric; Peltier, Scott; Petre, Bogdan; Guo, Wensheng; Hou, Xiaoling; Stephens, Alisa J; Mullins, Chris; Clauw, Daniel J; Mackey, Sean C; Apkarian, A Vania; Landis, J Richard; Mayer, Emeran A

2017-06-01

Chronic pain symptoms often change over time, even in individuals who have had symptoms for years. Studying biological factors that predict trends in symptom change in chronic pain may uncover novel pathophysiological mechanisms and potential therapeutic targets. In this study, we investigated whether brain functional connectivity measures obtained from resting-state functional magnetic resonance imaging at baseline can predict longitudinal symptom change (3, 6, and 12 months after scan) in urologic chronic pelvic pain syndrome. We studied 52 individuals with urologic chronic pelvic pain syndrome (34 women, 18 men) who had baseline neuroimaging followed by symptom tracking every 2 weeks for 1 year as part of the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network study. We found that brain functional connectivity can make a significant prediction of short-term (3 month) pain reduction with 73.1% accuracy (69.2% sensitivity and 75.0% precision). In addition, we found that the brain regions with greatest contribution to the classification were preferentially aligned with the left frontoparietal network. Resting-state functional magnetic resonance imaging measures seemed to be less informative about 6- or 12-month symptom change. Our study provides the first evidence that future trends in symptom change in patients in a state of chronic pain may be linked to functional connectivity within specific brain networks.

The reorganization of functional architecture in the early-stages of Parkinson's disease.

PubMed

Tuovinen, Noora; Seppi, Klaus; de Pasquale, Francesco; Müller, Christoph; Nocker, Michael; Schocke, Michael; Gizewski, Elke R; Kremser, Christian; Wenning, Gregor K; Poewe, Werner; Djamshidian, Atbin; Scherfler, Christoph; Seki, Morinobu

2018-05-01

The study aim was to identify longitudinal abnormalities of functional connectivity and its relation with motor disability in early to moderately advanced stages of Parkinson's disease patients. 3.0T structural and resting-state functional MRI was performed in healthy subjects (n = 16) and Parkinson's disease patients (n = 16) with mean disease duration of 2.2 ± 1.2 years at baseline with a clinical follow-up of 1.5 ± 0.3 years. Resting-state fMRI analysis included region-to-region connectivity in correlation with UPDRS-III scores and computation of Global Efficiency and Degree Centrality. At baseline, patients' connectivity increased between the cerebellum and somatomotor network, and decreased between motor regions (Rolandic operculum, precentral gyrus, supplementary motor area, postcentral gyrus) and cingulate connectivity. At 1.5 years follow-up, connectivity remained altered in the same regions identified at baseline. The cerebellum showed additional hyperconnectivity within itself and to the caudate nucleus, thalamus and amygdala compared to controls. These differences correlated with UPDRS-III scores. Seed-based connectivity revealed increased involvement of the default mode network with precentral gyrus in patients at follow-up investigation. Resting-state fMRI identified marked disturbances of the overall architecture of connectivity in Parkinson's disease. The noted alterations in cortical motor areas were associated with cerebellar hyperconnectivity in early to moderately advanced stages of Parkinson's disease suggesting ongoing attempts of recovery and compensatory mechanism for affected functions. The potential to identify connectivity alterations in regions related to both motor and attentional functions requires further evaluation as an objective marker to monitor disease progression, and medical, as well as surgical interventions. Copyright © 2018 Elsevier Ltd. All rights reserved.

Alterations of resting state networks and structural connectivity in relation to the prefrontal and anterior cingulate cortices in late prematurity.

PubMed

Degnan, Andrew J; Wisnowski, Jessica L; Choi, SoYoung; Ceschin, Rafael; Bhushan, Chitresh; Leahy, Richard M; Corby, Patricia; Schmithorst, Vincent J; Panigrahy, Ashok

2015-01-07

Late preterm birth is increasingly recognized as a risk factor for cognitive and social deficits. The prefrontal cortex is particularly vulnerable to injury in late prematurity because of its protracted development and extensive cortical connections. Our study examined children born late preterm without access to advanced postnatal care to assess structural and functional connectivity related to the prefrontal cortex. Thirty-eight preadolescents [19 born late preterm (34-36 /7 weeks gestational age) and 19 at term] were recruited from a developing community in Brazil. Participants underwent neuropsychological testing. Individuals underwent three-dimensional T1-weighted, diffusion-weighted, and resting state functional MRI. Probabilistic tractography and functional connectivity analyses were carried out using unilateral seeds combining the medial prefrontal cortex and the anterior cingulate cortex. Late preterm children showed increased functional connectivity within regions of the default mode, salience, and central-executive networks from both right and left frontal cortex seeds. Decreased functional connectivity was observed within the right parahippocampal region from left frontal seeding. Probabilistic tractography showed a pattern of decreased streamlines in frontal white matter pathways and the corpus callosum, but also increased streamlines in the left orbitofrontal white matter and the right frontal white matter when seeded from the right. Late preterm children and term control children scored similarly on neuropsychological testing. Prefrontal cortical connectivity is altered in late prematurity, with hyperconnectivity observed in key resting state networks in the absence of neuropsychological deficits. Abnormal structural connectivity indicated by probabilistic tractography suggests subtle changes in white matter development, implying disruption of normal maturation during the late gestational period.

Atomoxetine Treatment Strengthens an Anti-Correlated Relationship between Functional Brain Networks in Medication-Naïve Adults with Attention-Deficit Hyperactivity Disorder: A Randomized Double-Blind Placebo-Controlled Clinical Trial

PubMed Central

Lin, Hsiang-Yuan

2016-01-01

Background: Although atomoxetine demonstrates efficacy in individuals with attention-deficit hyperactivity disorder, its treatment effects on brain resting-state functional connectivity remain unknown. Therefore, we aimed to investigate major brain functional networks in medication-naïve adults with attention-deficit hyperactivity disorder and the efficacy of atomoxetine treatment on resting-state functional connectivity. Methods: After collecting baseline resting-state functional MRI scans from 24 adults with attention-deficit hyperactivity disorder (aged 18–52 years) and 24 healthy controls (matched in demographic characteristics), the participants with attention-deficit hyperactivity disorder were randomly assigned to atomoxetine (n=12) and placebo (n=12) arms in an 8-week, double-blind, placebo-controlled trial. The primary outcome was functional connectivity assessed by a resting-state functional MRI. Seed-based functional connectivity was calculated and compared for the affective, attention, default, and cognitive control networks. Results: At baseline, we found atypical cross talk between the default, cognitive control, and dorsal attention networks and hypoconnectivity within the dorsal attention and default networks in adults with attention-deficit hyperactivity disorder. Our first-ever placebo-controlled clinical trial incorporating resting-state functional MRI showed that treatment with atomoxetine strengthened an anticorrelated relationship between the default and task-positive networks and modulated all major brain networks. The strengthened anticorrelations were associated with improving clinical symptoms in the atomoxetine-treated adults. Conclusions: Our results support the idea that atypical default mode network task-positive network interaction plays an important role in the pathophysiology of adult attention-deficit hyperactivity disorder. Strengthening this atypical relationship following atomoxetine treatment suggests an important pathway to treat attention-deficit hyperactivity disorder. PMID:26377368

Atomoxetine Treatment Strengthens an Anti-Correlated Relationship between Functional Brain Networks in Medication-Naïve Adults with Attention-Deficit Hyperactivity Disorder: A Randomized Double-Blind Placebo-Controlled Clinical Trial.

PubMed

Lin, Hsiang-Yuan; Gau, Susan Shur-Fen

2015-09-16

Although atomoxetine demonstrates efficacy in individuals with attention-deficit hyperactivity disorder, its treatment effects on brain resting-state functional connectivity remain unknown. Therefore, we aimed to investigate major brain functional networks in medication-naïve adults with attention-deficit hyperactivity disorder and the efficacy of atomoxetine treatment on resting-state functional connectivity. After collecting baseline resting-state functional MRI scans from 24 adults with attention-deficit hyperactivity disorder (aged 18-52 years) and 24 healthy controls (matched in demographic characteristics), the participants with attention-deficit hyperactivity disorder were randomly assigned to atomoxetine (n=12) and placebo (n=12) arms in an 8-week, double-blind, placebo-controlled trial. The primary outcome was functional connectivity assessed by a resting-state functional MRI. Seed-based functional connectivity was calculated and compared for the affective, attention, default, and cognitive control networks. At baseline, we found atypical cross talk between the default, cognitive control, and dorsal attention networks and hypoconnectivity within the dorsal attention and default networks in adults with attention-deficit hyperactivity disorder. Our first-ever placebo-controlled clinical trial incorporating resting-state functional MRI showed that treatment with atomoxetine strengthened an anticorrelated relationship between the default and task-positive networks and modulated all major brain networks. The strengthened anticorrelations were associated with improving clinical symptoms in the atomoxetine-treated adults. Our results support the idea that atypical default mode network task-positive network interaction plays an important role in the pathophysiology of adult attention-deficit hyperactivity disorder. Strengthening this atypical relationship following atomoxetine treatment suggests an important pathway to treat attention-deficit hyperactivity disorder. © The Author 2015. Published by Oxford University Press on behalf of CINP.

Altered affective, executive and sensorimotor resting state networks in patients with pediatric mania

PubMed Central

Wu, Minjie; Lu, Lisa H.; Passarotti, Alessandra M.; Wegbreit, Ezra; Fitzgerald, Jacklynn; Pavuluri, Mani N.

2013-01-01

Background The aim of the present study was to map the pathophysiology of resting state functional connectivity accompanying structural and functional abnormalities in children with bipolar disorder. Methods Children with bipolar disorder and demographically matched healthy controls underwent resting-state functional magnetic resonance imaging. A model-free independent component analysis was performed to identify intrinsically interconnected networks. Results We included 34 children with bipolar disorder and 40 controls in our analysis. Three distinct resting state networks corresponding to affective, executive and sensorimotor functions emerged as being significantly different between the pediatric bipolar disorder (PBD) and control groups. All 3 networks showed hyperconnectivity in the PBD relative to the control group. Specifically, the connectivity of the dorsal anterior cingulate cortex (ACC) differentiated the PBD from the control group in both the affective and the executive networks. Exploratory analysis suggests that greater connectivity of the right amygdala within the affective network is associated with better executive function in children with bipolar disorder, but not in controls. Limitations Unique clinical characteristics of the study sample allowed us to evaluate the pathophysiology of resting state connectivity at an early state of PBD, which led to the lack of generalizability in terms of comorbid disorders existing in a typical PBD population. Conclusion Abnormally engaged resting state affective, executive and sensorimotor networks observed in children with bipolar disorder may reflect a biological context in which abnormal task-based brain activity can occur. Dual engagement of the dorsal ACC in affective and executive networks supports the neuroanatomical interface of these networks, and the amygdala’s engagement in moderating executive function illustrates the intricate interplay of these neural operations at rest. PMID:23735583

Hearing voices in the resting brain: A review of intrinsic functional connectivity research on auditory verbal hallucinations

PubMed Central

Alderson-Day, Ben; McCarthy-Jones, Simon; Fernyhough, Charles

2018-01-01

Resting state networks (RSNs) are thought to reflect the intrinsic functional connectivity of brain regions. Alterations to RSNs have been proposed to underpin various kinds of psychopathology, including the occurrence of auditory verbal hallucinations (AVH). This review outlines the main hypotheses linking AVH and the resting state, and assesses the evidence for alterations to intrinsic connectivity provided by studies of resting fMRI in AVH. The influence of hallucinations during data acquisition, medication confounds, and movement are also considered. Despite a large variety of analytic methods and designs being deployed, it is possible to conclude that resting connectivity in the left temporal lobe in general and left superior temporal gyrus in particular are disrupted in AVH. There is also preliminary evidence of atypical connectivity in the default mode network and its interaction with other RSNs. Recommendations for future research include the adoption of a common analysis protocol to allow for more overlapping datasets and replication of intrinsic functional connectivity alterations. PMID:25956256

Brain correlates of hypnotic paralysis-a resting-state fMRI study.

PubMed

Pyka, M; Burgmer, M; Lenzen, T; Pioch, R; Dannlowski, U; Pfleiderer, B; Ewert, A W; Heuft, G; Arolt, V; Konrad, C

2011-06-15

Hypnotic paralysis has been used since the times of Charcot to study altered states of consciousness; however, the underlying neurobiological correlates are poorly understood. We investigated human brain function during hypnotic paralysis using resting-state functional magnetic resonance imaging (fMRI), focussing on two core regions of the default mode network and the representation of the paralysed hand in the primary motor cortex. Hypnotic suggestion induced an observable left-hand paralysis in 19 participants. Resting-state fMRI at 3T was performed in pseudo-randomised order awake and in the hypnotic condition. Functional connectivity analyses revealed increased connectivity of the precuneus with the right dorsolateral prefrontal cortex, angular gyrus, and a dorsal part of the precuneus. Functional connectivity of the medial frontal cortex and the primary motor cortex remained unchanged. Our results reveal that the precuneus plays a pivotal role during maintenance of an altered state of consciousness. The increased coupling of selective cortical areas with the precuneus supports the concept that hypnotic paralysis may be mediated by a modified representation of the self which impacts motor abilities. Copyright © 2011 Elsevier Inc. All rights reserved.

Clinical Applications of Resting State Functional Connectivity

PubMed Central

Fox, Michael D.; Greicius, Michael

2010-01-01

During resting conditions the brain remains functionally and metabolically active. One manifestation of this activity that has become an important research tool is spontaneous fluctuations in the blood oxygen level-dependent (BOLD) signal of functional magnetic resonance imaging (fMRI). The identification of correlation patterns in these spontaneous fluctuations has been termed resting state functional connectivity (fcMRI) and has the potential to greatly increase the translation of fMRI into clinical care. In this article we review the advantages of the resting state signal for clinical applications including detailed discussion of signal to noise considerations. We include guidelines for performing resting state research on clinical populations, outline the different areas for clinical application, and identify important barriers to be addressed to facilitate the translation of resting state fcMRI into the clinical realm. PMID:20592951

Functional connectivity structure of cortical calcium dynamics in anesthetized and awake mice.

PubMed

Wright, Patrick W; Brier, Lindsey M; Bauer, Adam Q; Baxter, Grant A; Kraft, Andrew W; Reisman, Matthew D; Bice, Annie R; Snyder, Abraham Z; Lee, Jin-Moo; Culver, Joseph P

2017-01-01

The interplay between hemodynamic-based markers of cortical activity (e.g. fMRI and optical intrinsic signal imaging), which are an indirect and relatively slow report of neural activity, and underlying synaptic electrical and metabolic activity through neurovascular coupling is a topic of ongoing research and debate. As application of resting state functional connectivity measures is extended further into topics such as brain development, aging and disease, the importance of understanding the fundamental physiological basis for functional connectivity will grow. Here we extend functional connectivity analysis from hemodynamic- to calcium-based imaging. Transgenic mice (n = 7) expressing a fluorescent calcium indicator (GCaMP6) driven by the Thy1 promoter in glutamatergic neurons were imaged transcranially in both anesthetized (using ketamine/xylazine) and awake states. Sequential LED illumination (λ = 454, 523, 595, 640nm) enabled concurrent imaging of both GCaMP6 fluorescence emission (corrected for hemoglobin absorption) and hemodynamics. Functional connectivity network maps were constructed for infraslow (0.009-0.08Hz), intermediate (0.08-0.4Hz), and high (0.4-4.0Hz) frequency bands. At infraslow and intermediate frequencies, commonly used in BOLD fMRI and fcOIS studies of functional connectivity and implicated in neurovascular coupling mechanisms, GCaMP6 and HbO2 functional connectivity structures were in high agreement, both qualitatively and also quantitatively through a measure of spatial similarity. The spontaneous dynamics of both contrasts had the highest correlation when the GCaMP6 signal was delayed with a ~0.6-1.5s temporal offset. Within the higher-frequency delta band, sensitive to slow wave sleep oscillations in non-REM sleep and anesthesia, we evaluate the speed with which the connectivity analysis stabilized and found that the functional connectivity maps captured putative network structure within time window lengths as short as 30 seconds. Homotopic GCaMP6 functional connectivity maps at 0.4-4.0Hz in the anesthetized states show a striking correlated and anti-correlated structure along the anterior to posterior axis. This structure is potentially explained in part by observed propagation of delta-band activity from frontal somatomotor regions to visuoparietal areas. During awake imaging, this spatio-temporal quality is altered, and a more complex and detailed functional connectivity structure is observed. The combined calcium/hemoglobin imaging technique described here will enable the dissociation of changes in ionic and hemodynamic functional structure and neurovascular coupling and provide a framework for subsequent studies of neurological disease such as stroke.

Functional connectivity structure of cortical calcium dynamics in anesthetized and awake mice

PubMed Central

Wright, Patrick W.; Brier, Lindsey M.; Bauer, Adam Q.; Baxter, Grant A.; Kraft, Andrew W.; Reisman, Matthew D.; Bice, Annie R.; Snyder, Abraham Z.; Lee, Jin-Moo; Culver, Joseph P.

2017-01-01

The interplay between hemodynamic-based markers of cortical activity (e.g. fMRI and optical intrinsic signal imaging), which are an indirect and relatively slow report of neural activity, and underlying synaptic electrical and metabolic activity through neurovascular coupling is a topic of ongoing research and debate. As application of resting state functional connectivity measures is extended further into topics such as brain development, aging and disease, the importance of understanding the fundamental physiological basis for functional connectivity will grow. Here we extend functional connectivity analysis from hemodynamic- to calcium-based imaging. Transgenic mice (n = 7) expressing a fluorescent calcium indicator (GCaMP6) driven by the Thy1 promoter in glutamatergic neurons were imaged transcranially in both anesthetized (using ketamine/xylazine) and awake states. Sequential LED illumination (λ = 454, 523, 595, 640nm) enabled concurrent imaging of both GCaMP6 fluorescence emission (corrected for hemoglobin absorption) and hemodynamics. Functional connectivity network maps were constructed for infraslow (0.009–0.08Hz), intermediate (0.08–0.4Hz), and high (0.4–4.0Hz) frequency bands. At infraslow and intermediate frequencies, commonly used in BOLD fMRI and fcOIS studies of functional connectivity and implicated in neurovascular coupling mechanisms, GCaMP6 and HbO2 functional connectivity structures were in high agreement, both qualitatively and also quantitatively through a measure of spatial similarity. The spontaneous dynamics of both contrasts had the highest correlation when the GCaMP6 signal was delayed with a ~0.6–1.5s temporal offset. Within the higher-frequency delta band, sensitive to slow wave sleep oscillations in non-REM sleep and anesthesia, we evaluate the speed with which the connectivity analysis stabilized and found that the functional connectivity maps captured putative network structure within time window lengths as short as 30 seconds. Homotopic GCaMP6 functional connectivity maps at 0.4–4.0Hz in the anesthetized states show a striking correlated and anti-correlated structure along the anterior to posterior axis. This structure is potentially explained in part by observed propagation of delta-band activity from frontal somatomotor regions to visuoparietal areas. During awake imaging, this spatio-temporal quality is altered, and a more complex and detailed functional connectivity structure is observed. The combined calcium/hemoglobin imaging technique described here will enable the dissociation of changes in ionic and hemodynamic functional structure and neurovascular coupling and provide a framework for subsequent studies of neurological disease such as stroke. PMID:29049297

Mindfulness and dynamic functional neural connectivity in children and adolescents.

PubMed

Marusak, Hilary A; Elrahal, Farrah; Peters, Craig A; Kundu, Prantik; Lombardo, Michael V; Calhoun, Vince D; Goldberg, Elimelech K; Cohen, Cindy; Taub, Jeffrey W; Rabinak, Christine A

2018-01-15

Interventions that promote mindfulness consistently show salutary effects on cognition and emotional wellbeing in adults, and more recently, in children and adolescents. However, we lack understanding of the neurobiological mechanisms underlying mindfulness in youth that should allow for more judicious application of these interventions in clinical and educational settings. Using multi-echo multi-band fMRI, we examined dynamic (i.e., time-varying) and conventional static resting-state connectivity between core neurocognitive networks (i.e., salience/emotion, default mode, central executive) in 42 children and adolescents (ages 6-17). We found that trait mindfulness in youth relates to dynamic but not static resting-state connectivity. Specifically, more mindful youth transitioned more between brain states over the course of the scan, spent overall less time in a certain connectivity state, and showed a state-specific reduction in connectivity between salience/emotion and central executive networks. The number of state transitions mediated the link between higher mindfulness and lower anxiety, providing new insights into potential neural mechanisms underlying benefits of mindfulness on psychological health in youth. Our results provide new evidence that mindfulness in youth relates to functional neural dynamics and interactions between neurocognitive networks, over time. Copyright © 2017 Elsevier B.V. All rights reserved.

The Responsive Amygdala: Treatment-induced Alterations in Functional Connectivity in Pediatric Complex Regional Pain Syndrome

PubMed Central

Simons, LE; Pielech, M; Erpelding, N; Linnman, C; Moulton, E; Sava, S; Lebel, A; Serrano, P; Sethna, N; Berde, C; Becerra, L; Borsook, D

2014-01-01

The amygdala is a key brain region with efferent and afferent neural connections that involve complex behaviors such as pain, reward, fear and anxiety. This study evaluated resting state functional connectivity of the amygdala with cortical and subcortical regions in a group of chronic pain patients (pediatric complex regional pain syndrome) with age-gender matched controls before and after intensive physical-biobehavioral pain treatment. Our main findings include (1) enhanced functional connectivity from the amygdala to multiple cortical, subcortical, and cerebellar regions in patients compared to controls, with differences predominantly in the left amygdala in the pre-treated condition (disease state); (2) dampened hyperconnectivity from the left amygdala to the motor cortex, parietal lobe, and cingulate cortex after intensive pain rehabilitation treatment within patients with nominal differences observed among healthy controls from Time 1 to Time 2 (treatment effects); (3) functional connectivity to several regions key to fear circuitry (prefrontal cortex, bilateral middle temporal lobe, bilateral cingulate, hippocampus) correlated with higher pain-related fear scores and (4) decreases in pain-related fear associated with decreased connectivity between the amygdala and the motor and somatosensory cortex, cingulate, and frontal areas. Our data suggest that there are rapid changes in amygdala connectivity following an aggressive treatment program in children with chronic pain and intrinsic amygdala functional connectivity activity serving as a potential indicator of treatment response. PMID:24861582

Characterizing Individual Differences in Functional Connectivity Using Dual-Regression and Seed-Based Approaches

PubMed Central

Smith, David V.; Utevsky, Amanda V.; Bland, Amy R.; Clement, Nathan; Clithero, John A.; Harsch, Anne E. W.; Carter, R. McKell; Huettel, Scott A.

2014-01-01

A central challenge for neuroscience lies in relating inter-individual variability to the functional properties of specific brain regions. Yet, considerable variability exists in the connectivity patterns between different brain areas, potentially producing reliable group differences. Using sex differences as a motivating example, we examined two separate resting-state datasets comprising a total of 188 human participants. Both datasets were decomposed into resting-state networks (RSNs) using a probabilistic spatial independent components analysis (ICA). We estimated voxelwise functional connectivity with these networks using a dual-regression analysis, which characterizes the participant-level spatiotemporal dynamics of each network while controlling for (via multiple regression) the influence of other networks and sources of variability. We found that males and females exhibit distinct patterns of connectivity with multiple RSNs, including both visual and auditory networks and the right frontal-parietal network. These results replicated across both datasets and were not explained by differences in head motion, data quality, brain volume, cortisol levels, or testosterone levels. Importantly, we also demonstrate that dual-regression functional connectivity is better at detecting inter-individual variability than traditional seed-based functional connectivity approaches. Our findings characterize robust—yet frequently ignored—neural differences between males and females, pointing to the necessity of controlling for sex in neuroscience studies of individual differences. Moreover, our results highlight the importance of employing network-based models to study variability in functional connectivity. PMID:24662574

Altered functional connectivity architecture of the brain in medication overuse headache using resting state fMRI.

PubMed

Chen, Zhiye; Chen, Xiaoyan; Liu, Mengqi; Dong, Zhao; Ma, Lin; Yu, Shengyuan

2017-12-01

Functional connectivity density (FCD) could identify the abnormal intrinsic and spontaneous activity over the whole brain, and a seed-based resting-state functional connectivity (RSFC) could further reveal the altered functional network with the identified brain regions. This may be an effective assessment strategy for headache research. This study is to investigate the RSFC architecture changes of the brain in the patients with medication overuse headache (MOH) using FCD and RSFC methods. 3D structure images and resting-state functional MRI data were obtained from 37 MOH patients, 18 episodic migraine (EM) patients and 32 normal controls (NCs). FCD was calculated to detect the brain regions with abnormal functional activity over the whole brain, and the seed-based RSFC was performed to explore the functional network changes in MOH and EM. The decreased FCD located in right parahippocampal gyrus, and the increased FCD located in left inferior parietal gyrus and right supramarginal gyrus in MOH compared with NC, and in right caudate and left insula in MOH compared with EM. RSFC revealed that decreased functional connectivity of the brain regions with decreased FCD anchored in the right dorsal-lateral prefrontal cortex, right frontopolar cortex in MOH, and in left temporopolar cortex and bilateral visual cortices in EM compared with NC, and in frontal-temporal-parietal pattern in MOH compared with EM. These results provided evidence that MOH and EM suffered from altered intrinsic functional connectivity architecture, and the current study presented a new perspective for understanding the neuromechanism of MOH and EM pathogenesis.

Neurobiological changes of schizotypy: evidence from both volume-based morphometric analysis and resting-state functional connectivity.

PubMed

Wang, Yi; Yan, Chao; Yin, Da-zhi; Fan, Ming-xia; Cheung, Eric F C; Pantelis, Christos; Chan, Raymond C K

2015-03-01

The current study sought to examine the underlying brain changes in individuals with high schizotypy by integrating networks derived from brain structural and functional imaging. Individuals with high schizotypy (n = 35) and low schizotypy (n = 34) controls were screened using the Schizotypal Personality Questionnaire and underwent brain structural and resting-state functional magnetic resonance imaging on a 3T scanner. Voxel-based morphometric analysis and graph theory-based functional network analysis were conducted. Individuals with high schizotypy showed reduced gray matter (GM) density in the insula and the dorsolateral prefrontal gyrus. The graph theoretical analysis showed that individuals with high schizotypy showed similar global properties in their functional networks as low schizotypy individuals. Several hubs of the functional network were identified in both groups, including the insula, the lingual gyrus, the postcentral gyrus, and the rolandic operculum. More hubs in the frontal lobe and fewer hubs in the occipital lobe were identified in individuals with high schizotypy. By comparing the functional connectivity between clusters with abnormal GM density and the whole brain, individuals with high schizotypy showed weaker functional connectivity between the left insula and the putamen, but stronger connectivity between the cerebellum and the medial frontal gyrus. Taken together, our findings suggest that individuals with high schizotypy present changes in terms of GM and resting-state functional connectivity, especially in the frontal lobe. © The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Stomach-brain synchrony reveals a novel, delayed-connectivity resting-state network in humans

PubMed Central

Devauchelle, Anne-Dominique; Béranger, Benoît; Tallon-Baudry, Catherine

2018-01-01

Resting-state networks offer a unique window into the brain’s functional architecture, but their characterization remains limited to instantaneous connectivity thus far. Here, we describe a novel resting-state network based on the delayed connectivity between the brain and the slow electrical rhythm (0.05 Hz) generated in the stomach. The gastric network cuts across classical resting-state networks with partial overlap with autonomic regulation areas. This network is composed of regions with convergent functional properties involved in mapping bodily space through touch, action or vision, as well as mapping external space in bodily coordinates. The network is characterized by a precise temporal sequence of activations within a gastric cycle, beginning with somato-motor cortices and ending with the extrastriate body area and dorsal precuneus. Our results demonstrate that canonical resting-state networks based on instantaneous connectivity represent only one of the possible partitions of the brain into coherent networks based on temporal dynamics. PMID:29561263

A computational study of whole-brain connectivity in resting state and task fMRI

PubMed Central

Goparaju, Balaji; Rana, Kunjan D.; Calabro, Finnegan J.; Vaina, Lucia Maria

2014-01-01

Background We compared the functional brain connectivity produced during resting-state in which subjects were not actively engaged in a task with that produced while they actively performed a visual motion task (task-state). Material/Methods In this paper we employed graph-theoretical measures and network statistics in novel ways to compare, in the same group of human subjects, functional brain connectivity during resting-state fMRI with brain connectivity during performance of a high level visual task. We performed a whole-brain connectivity analysis to compare network statistics in resting and task states among anatomically defined Brodmann areas to investigate how brain networks spanning the cortex changed when subjects were engaged in task performance. Results In the resting state, we found strong connectivity among the posterior cingulate cortex (PCC), precuneus, medial prefrontal cortex (MPFC), lateral parietal cortex, and hippocampal formation, consistent with previous reports of the default mode network (DMN). The connections among these areas were strengthened while subjects actively performed an event-related visual motion task, indicating a continued and strong engagement of the DMN during task processing. Regional measures such as degree (number of connections) and betweenness centrality (number of shortest paths), showed that task performance induces stronger inter-regional connections, leading to a denser processing network, but that this does not imply a more efficient system as shown by the integration measures such as path length and global efficiency, and from global measures such as small-worldness. Conclusions In spite of the maintenance of connectivity and the “hub-like” behavior of areas, our results suggest that the network paths may be rerouted when performing the task condition. PMID:24947491

A Longitudinal Study on Resting State Functional Connectivity in Behavioral Variant Frontotemporal Dementia and Alzheimer's Disease.

PubMed

Hafkemeijer, Anne; Möller, Christiane; Dopper, Elise G P; Jiskoot, Lize C; van den Berg-Huysmans, Annette A; van Swieten, John C; van der Flier, Wiesje M; Vrenken, Hugo; Pijnenburg, Yolande A L; Barkhof, Frederik; Scheltens, Philip; van der Grond, Jeroen; Rombouts, Serge A R B

2017-01-01

Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD) are the most common types of early-onset dementia. We applied longitudinal resting state functional magnetic resonance imaging (fMRI) to delineate functional brain connections relevant for disease progression and diagnostic accuracy. We used two-center resting state fMRI data of 20 AD patients (65.1±8.0 years), 12 bvFTD patients (64.7±5.4 years), and 22 control subjects (63.8±5.0 years) at baseline and 1.8-year follow-up. We used whole-network and voxel-based network-to-region analyses to study group differences in functional connectivity at baseline and follow-up, and longitudinal changes in connectivity within and between groups. At baseline, connectivity between paracingulate gyrus and executive control network, between cuneal cortex and medial visual network, and between paracingulate gyrus and salience network was higher in AD compared with controls. These differences were also present after 1.8 years. At follow-up, connectivity between angular gyrus and right frontoparietal network, and between paracingulate gyrus and default mode network was lower in bvFTD compared with controls, and lower compared with AD between anterior cingulate gyrus and executive control network, and between lateral occipital cortex and medial visual network. Over time, connectivity decreased in AD between precuneus and right frontoparietal network and in bvFTD between inferior frontal gyrus and left frontoparietal network. Longitudinal changes in connectivity between supramarginal gyrus and right frontoparietal network differ between both patient groups and controls. We found disease-specific brain regions with longitudinal connectivity changes. This suggests the potential of longitudinal resting state fMRI to delineate regions relevant for disease progression and for diagnostic accuracy, although no group differences in longitudinal changes in the direct comparison of AD and bvFTD were found.

Changes in Neural Connectivity and Memory Following a Yoga Intervention for Older Adults: A Pilot Study.

PubMed

Eyre, Harris A; Acevedo, Bianca; Yang, Hongyu; Siddarth, Prabha; Van Dyk, Kathleen; Ercoli, Linda; Leaver, Amber M; Cyr, Natalie St; Narr, Katherine; Baune, Bernhard T; Khalsa, Dharma S; Lavretsky, Helen

2016-01-01

No study has explored the effect of yoga on cognitive decline and resting-state functional connectivity. This study explored the relationship between performance on memory tests and resting-state functional connectivity before and after a yoga intervention versus active control for subjects with mild cognitive impairment (MCI). Participants ( ≥ 55 y) with MCI were randomized to receive a yoga intervention or active "gold-standard" control (i.e., memory enhancement training (MET)) for 12 weeks. Resting-state functional magnetic resonance imaging was used to map correlations between brain networks and memory performance changes over time. Default mode networks (DMN), language and superior parietal networks were chosen as networks of interest to analyze the association with changes in verbal and visuospatial memory performance. Fourteen yoga and 11 MET participants completed the study. The yoga group demonstrated a statistically significant improvement in depression and visuospatial memory. We observed improved verbal memory performance correlated with increased connectivity between the DMN and frontal medial cortex, pregenual anterior cingulate cortex, right middle frontal cortex, posterior cingulate cortex, and left lateral occipital cortex. Improved verbal memory performance positively correlated with increased connectivity between the language processing network and the left inferior frontal gyrus. Improved visuospatial memory performance correlated inversely with connectivity between the superior parietal network and the medial parietal cortex. Yoga may be as effective as MET in improving functional connectivity in relation to verbal memory performance. These findings should be confirmed in larger prospective studies.

Unravelling the Intrinsic Functional Organization of the Human Striatum: A Parcellation and Connectivity Study Based on Resting-State fMRI

PubMed Central

Jung, Wi Hoon; Jang, Joon Hwan; Park, Jin Woo; Kim, Euitae; Goo, Eun-Hoe; Im, Oh-Soo; Kwon, Jun Soo

2014-01-01

As the main input hub of the basal ganglia, the striatum receives projections from the cerebral cortex. Many studies have provided evidence for multiple parallel corticostriatal loops based on the structural and functional connectivity profiles of the human striatum. A recent resting-state fMRI study revealed the topography of striatum by assigning each voxel in the striatum to its most strongly correlated cortical network among the cognitive, affective, and motor networks. However, it remains unclear what patterns of striatal parcellation would result from performing the clustering without subsequent assignment to cortical networks. Thus, we applied unsupervised clustering algorithms to parcellate the human striatum based on its functional connectivity patterns to other brain regions without any anatomically or functionally defined cortical targets. Functional connectivity maps of striatal subdivisions, identified through clustering analyses, were also computed. Our findings were consistent with recent accounts of the functional distinctions of the striatum as well as with recent studies about its functional and anatomical connectivity. For example, we found functional connections between dorsal and ventral striatal clusters and the areas involved in cognitive and affective processes, respectively, and between rostral and caudal putamen clusters and the areas involved in cognitive and motor processes, respectively. This study confirms prior findings, showing similar striatal parcellation patterns between the present and prior studies. Given such striking similarity, it is suggested that striatal subregions are functionally linked to cortical networks involving specific functions rather than discrete portions of cortical regions. Our findings also demonstrate that the clustering of functional connectivity patterns is a reliable feature in parcellating the striatum into anatomically and functionally meaningful subdivisions. The striatal subdivisions identified here may have important implications for understanding the relationship between corticostriatal dysfunction and various neurodegenerative and psychiatric disorders. PMID:25203441

Resting-state functional connectivity between amygdala and the ventromedial prefrontal cortex following fear reminder predicts fear extinction

PubMed Central

Feng, Pan; Zheng, Yong

2016-01-01

Investigations of fear conditioning have elucidated the neural mechanisms of fear acquisition, consolidation and extinction, but it is not clear how the neural activation following fear reminder influence the following extinction. To address this question, we measured human brain activity following fear reminder using resting-state functional magnetic resonance imaging, and investigated whether the extinction effect can be predicted by resting-state functional connectivity (RSFC). Behaviorally, we found no significant differences of fear ratings between the reminder group and the no reminder group at the fear acquisition and extinction stages, but spontaneous recovery during re-extinction stage appeared only in the no reminder group. Imaging data showed that functional connectivity between ventromedial prefrontal cortex (vmPFC) and amygdala in the reminder group was greater than that in the no reminder group after fear memory reactivation. More importantly, the functional connectivity between amygdala and vmPFC of the reminder group after fear memory reactivation was positively correlated with extinction effect. These results suggest RSFC between amygdala and the vmPFC following fear reminder can predict fear extinction, which provide important insight into the neural mechanisms of fear memory after fear memory reactivation. PMID:27013104

Global and regional functional connectivity maps of neural oscillations in focal epilepsy

PubMed Central

Englot, Dario J.; Hinkley, Leighton B.; Kort, Naomi S.; Imber, Brandon S.; Mizuiri, Danielle; Honma, Susanne M.; Findlay, Anne M.; Garrett, Coleman; Cheung, Paige L.; Mantle, Mary; Tarapore, Phiroz E.; Knowlton, Robert C.; Chang, Edward F.; Nagarajan, Srikantan S.

2015-01-01

Intractable focal epilepsy is a devastating disorder with profound effects on cognition and quality of life. Epilepsy surgery can lead to seizure freedom in patients with focal epilepsy; however, sometimes it fails due to an incomplete delineation of the epileptogenic zone. Brain networks in epilepsy can be studied with resting-state functional connectivity analysis, yet previous investigations using functional magnetic resonance imaging or electrocorticography have produced inconsistent results. Magnetoencephalography allows non-invasive whole-brain recordings, and can be used to study both long-range network disturbances in focal epilepsy and regional connectivity at the epileptogenic zone. In magnetoencephalography recordings from presurgical epilepsy patients, we examined: (i) global functional connectivity maps in patients versus controls; and (ii) regional functional connectivity maps at the region of resection, compared to the homotopic non-epileptogenic region in the contralateral hemisphere. Sixty-one patients were studied, including 30 with mesial temporal lobe epilepsy and 31 with focal neocortical epilepsy. Compared with a group of 31 controls, patients with epilepsy had decreased resting-state functional connectivity in widespread regions, including perisylvian, posterior temporo-parietal, and orbitofrontal cortices (P < 0.01, t-test). Decreased mean global connectivity was related to longer duration of epilepsy and higher frequency of consciousness-impairing seizures (P < 0.01, linear regression). Furthermore, patients with increased regional connectivity within the resection site (n = 24) were more likely to achieve seizure postoperative seizure freedom (87.5% with Engel I outcome) than those with neutral (n = 15, 64.3% seizure free) or decreased (n = 23, 47.8% seizure free) regional connectivity (P < 0.02, chi-square). Widespread global decreases in functional connectivity are observed in patients with focal epilepsy, and may reflect deleterious long-term effects of recurrent seizures. Furthermore, enhanced regional functional connectivity at the area of resection may help predict seizure outcome and aid surgical planning. PMID:25981965

Altered Resting State Functional Connectivity in Young Survivors of Acute Lymphoblastic Leukemia

PubMed Central

Kesler, Shelli R.; Gugel, Meike; Pritchard-Berman, Mika; Lee, Clement; Kutner, Emily; Hosseini, S.M. Hadi; Dahl, Gary; Lacayo, Norman

2014-01-01

Background Chemotherapy treatment for pediatric acute lymphoblastic leukemia (ALL) has been associated with long-term cognitive impairments in some patients. However, the neurobiologic mechanisms underlying these impairments, particularly in young survivors, are not well understood. This study aimed to examine intrinsic functional brain connectivity in pediatric ALL and its relationship with cognitive status. Procedure We obtained resting state functional magnetic resonance imaging (rsfMRI) and cognitive testing data from 15 ALL survivors age 8–15 years and 14 matched healthy children. The ALL group had a history of intrathecal chemotherapy treatment but were off-therapy for at least 6 months at the time of enrollment. We used seed-based analyses to compare intrinsic functional brain network connectivity between the groups. We also explored correlations between connectivity and cognitive performance, demographic, medical, and treatment variables. Results We demonstrated significantly reduced connectivity between bilateral hippocampus, left inferior occipital, left lingual gyrus, bilateral calcarine sulcus, and right amygdala in the ALL group compared to controls. The ALL group also showed regions of functional hyperconnectivity including right lingual gyrus, precuneus, bilateral superior occipital lobe, and right inferior occipital lobe. Functional hypoconnectivity was associated with reduced cognitive function as well as younger age at diagnosis in the ALL group. Conclusions This is the first study to demonstrate that intrinsic functional brain connectivity is disrupted in pediatric ALL following chemotherapy treatment. These results help explain cognitive dysfunction even when objective test performance is seemingly normal. Children diagnosed at a younger age may show increased vulnerability to altered functional brain connectivity. PMID:24619953

Spontaneous brain activity following fear reminder of fear conditioning by using resting-state functional MRI

PubMed Central

Feng, Pan; Zheng, Yong; Feng, Tingyong

2015-01-01

Although disrupting reconsolidation may be a promising approach to attenuate or erase the expression of fear memory, it is not clear how the neural state following fear reminder contribute to the following fear extinction. To address this question, we used resting-state functional magnetic resonance imaging (rs-fMRI) to measure spontaneous neuronal activity and functional connectivity (RSFC) following fear reminder. Some brain regions such as dorsal anterior cingulate (dACC) and ventromedial prefrontal cortex (vmPFC) showed increased amplitude of LFF (ALFF) in the fear reminder group than the no reminder group following fear reminder. More importantly, there was much stronger functional connectivity between the amygdala and vmPFC in the fear reminder group than those in the no reminder group. These findings suggest that the strong functional connectivity between vmPFC and amygdala following a fear reminder could serve as a key role in the followed-up fear extinction stages, which may contribute to the erasing of fear memory. PMID:26576733

Spontaneous brain activity following fear reminder of fear conditioning by using resting-state functional MRI.

PubMed

Feng, Pan; Zheng, Yong; Feng, Tingyong

2015-11-18

Although disrupting reconsolidation may be a promising approach to attenuate or erase the expression of fear memory, it is not clear how the neural state following fear reminder contribute to the following fear extinction. To address this question, we used resting-state functional magnetic resonance imaging (rs-fMRI) to measure spontaneous neuronal activity and functional connectivity (RSFC) following fear reminder. Some brain regions such as dorsal anterior cingulate (dACC) and ventromedial prefrontal cortex (vmPFC) showed increased amplitude of LFF (ALFF) in the fear reminder group than the no reminder group following fear reminder. More importantly, there was much stronger functional connectivity between the amygdala and vmPFC in the fear reminder group than those in the no reminder group. These findings suggest that the strong functional connectivity between vmPFC and amygdala following a fear reminder could serve as a key role in the followed-up fear extinction stages, which may contribute to the erasing of fear memory.

Higher body mass index is associated with reduced posterior default mode connectivity in older adults.

PubMed

Beyer, Frauke; Kharabian Masouleh, Sharzhad; Huntenburg, Julia M; Lampe, Leonie; Luck, Tobias; Riedel-Heller, Steffi G; Loeffler, Markus; Schroeter, Matthias L; Stumvoll, Michael; Villringer, Arno; Witte, A Veronica

2017-04-11

Obesity is a complex neurobehavioral disorder that has been linked to changes in brain structure and function. However, the impact of obesity on functional connectivity and cognition in aging humans is largely unknown. Therefore, the association of body mass index (BMI), resting-state network connectivity, and cognitive performance in 712 healthy, well-characterized older adults of the Leipzig Research Center for Civilization Diseases (LIFE) cohort (60-80 years old, mean BMI 27.6 kg/m 2  ± 4.2 SD, main sample: n = 521, replication sample: n = 191) was determined. Statistical analyses included a multivariate model selection approach followed by univariate analyses to adjust for possible confounders. Results showed that a higher BMI was significantly associated with lower default mode functional connectivity in the posterior cingulate cortex and precuneus. The effect remained stable after controlling for age, sex, head motion, registration quality, cardiovascular, and genetic factors as well as in replication analyses. Lower functional connectivity in BMI-associated areas correlated with worse executive function. In addition, higher BMI correlated with stronger head motion. Using 3T neuroimaging in a large cohort of healthy older adults, independent negative associations of obesity and functional connectivity in the posterior default mode network were observed. In addition, a subtle link between lower resting-state connectivity in BMI-associated regions and cognitive function was found. The findings might indicate that obesity is associated with patterns of decreased default mode connectivity similar to those seen in populations at risk for Alzheimer's disease. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Exploring the Associations Between Intrinsic Brain Connectivity and Creative Ability Using Functional Connectivity Strength and Connectome Analysis.

PubMed

Gao, Zhenni; Zhang, Delong; Liang, Aiying; Liang, Bishan; Wang, Zengjian; Cai, Yuxuan; Li, Junchao; Gao, Mengxia; Liu, Xiaojin; Chang, Song; Jiao, Bingqing; Huang, Ruiwang; Liu, Ming

2017-11-01

The present study aimed to explore the association between resting-state functional connectivity and creativity ability. Toward this end, the figural Torrance Tests of Creative Thinking (TTCT) scores were collected from 180 participants. Based on the figural TTCT measures, we collected resting-state functional magnetic resonance imaging data for participants with two different levels of creativity ability (a high-creativity group [HG, n = 22] and a low-creativity group [LG, n = 20]). For the aspect of group difference, this study combined voxel-wise functional connectivity strength (FCS) and seed-based functional connectivity to identify brain regions with group-change functional connectivity. Furthermore, the connectome properties of the identified regions and their associations with creativity were investigated using the permutation test, discriminative analysis, and brain-behavior correlation analysis. The results indicated that there were 4 regions with group differences in FCS, and these regions were linked to 30 other regions, demonstrating different functional connectivity between the groups. Together, these regions form a creativity-related network, and we observed higher network efficiency in the HG compared with the LG. The regions involved in the creativity network were widely distributed across the modality-specific/supramodality cerebral cortex, subcortex, and cerebellum. Notably, properties of regions in the supramodality networks (i.e., the default mode network and attention network) carried creativity-level discriminative information and were significantly correlated with the creativity performance. Together, these findings demonstrate a link between intrinsic brain connectivity and creative ability, which should provide new insights into the neural basis of creativity.

Mindfulness Meditation Training and Executive Control Network Resting State Functional Connectivity: A Randomized Controlled Trial.

PubMed

Taren, Adrienne A; Gianaros, Peter J; Greco, Carol M; Lindsay, Emily K; Fairgrieve, April; Brown, Kirk Warren; Rosen, Rhonda K; Ferris, Jennifer L; Julson, Erica; Marsland, Anna L; Creswell, J David

Mindfulness meditation training has been previously shown to enhance behavioral measures of executive control (e.g., attention, working memory, cognitive control), but the neural mechanisms underlying these improvements are largely unknown. Here, we test whether mindfulness training interventions foster executive control by strengthening functional connections between dorsolateral prefrontal cortex (dlPFC)-a hub of the executive control network-and frontoparietal regions that coordinate executive function. Thirty-five adults with elevated levels of psychological distress participated in a 3-day randomized controlled trial of intensive mindfulness meditation or relaxation training. Participants completed a resting state functional magnetic resonance imaging scan before and after the intervention. We tested whether mindfulness meditation training increased resting state functional connectivity (rsFC) between dlPFC and frontoparietal control network regions. Left dlPFC showed increased connectivity to the right inferior frontal gyrus (T = 3.74), right middle frontal gyrus (MFG) (T = 3.98), right supplementary eye field (T = 4.29), right parietal cortex (T = 4.44), and left middle temporal gyrus (T = 3.97, all p < .05) after mindfulness training relative to the relaxation control. Right dlPFC showed increased connectivity to right MFG (T = 4.97, p < .05). We report that mindfulness training increases rsFC between dlPFC and dorsal network (superior parietal lobule, supplementary eye field, MFG) and ventral network (right IFG, middle temporal/angular gyrus) regions. These findings extend previous work showing increased functional connectivity among brain regions associated with executive function during active meditation by identifying specific neural circuits in which rsFC is enhanced by a mindfulness intervention in individuals with high levels of psychological distress. Clinicaltrials.gov,NCT01628809.

Default network connectivity decodes brain states with simulated microgravity.

PubMed

Zeng, Ling-Li; Liao, Yang; Zhou, Zongtan; Shen, Hui; Liu, Yadong; Liu, Xufeng; Hu, Dewen

2016-04-01

With great progress of space navigation technology, it becomes possible to travel beyond Earth's gravity. So far, it remains unclear whether the human brain can function normally within an environment of microgravity and confinement. Particularly, it is a challenge to figure out some neuroimaging-based markers for rapid screening diagnosis of disrupted brain function in microgravity environment. In this study, a 7-day -6° head down tilt bed rest experiment was used to simulate the microgravity, and twenty healthy male participants underwent resting-state functional magnetic resonance imaging scans at baseline and after the simulated microgravity experiment. We used a multivariate pattern analysis approach to distinguish the brain states with simulated microgravity from normal gravity based on the functional connectivity within the default network, resulting in an accuracy of no less than 85 % via cross-validation. Moreover, most discriminative functional connections were mainly located between the limbic system and cortical areas and were enhanced after simulated microgravity, implying a self-adaption or compensatory enhancement to fulfill the need of complex demand in spatial navigation and motor control functions in microgravity environment. Overall, the findings suggest that the brain states in microgravity are likely different from those in normal gravity and that brain connectome could act as a biomarker to indicate the brain state in microgravity.

Functional Connectivity of Insula, Basal Ganglia, and Prefrontal Executive Control Networks during Hypoglycemia in Type 1 Diabetes

PubMed Central

Simonson, Donald C.; Nickerson, Lisa D.; Flores, Veronica L.; Siracusa, Tamar; Hager, Brandon; Lyoo, In Kyoon; Renshaw, Perry F.; Jacobson, Alan M.

2015-01-01

Human brain networks mediating interoceptive, behavioral, and cognitive aspects of glycemic control are not well studied. Using group independent component analysis with dual-regression approach of functional magnetic resonance imaging data, we examined the functional connectivity changes of large-scale resting state networks during sequential euglycemic–hypoglycemic clamp studies in patients with type 1 diabetes and nondiabetic controls and how these changes during hypoglycemia were related to symptoms of hypoglycemia awareness and to concurrent glycosylated hemoglobin (HbA1c) levels. During hypoglycemia, diabetic patients showed increased functional connectivity of the right anterior insula and the prefrontal cortex within the executive control network, which was associated with higher HbA1c. Controls showed decreased functional connectivity of the right anterior insula with the cerebellum/basal ganglia network and of temporal regions within the temporal pole network and increased functional connectivity in the default mode and sensorimotor networks. Functional connectivity reductions in the right basal ganglia were correlated with increases of self-reported hypoglycemic symptoms in controls but not in patients. Resting state networks that showed different group functional connectivity during hypoglycemia may be most sensitive to glycemic environment, and their connectivity patterns may have adapted to repeated glycemic excursions present in type 1 diabetes. Our results suggest that basal ganglia and insula mediation of interoceptive awareness during hypoglycemia is altered in type 1 diabetes. These changes could be neuroplastic adaptations to frequent hypoglycemic experiences. Functional connectivity changes in the insula and prefrontal cognitive networks could also reflect an adaptation to changes in brain metabolic pathways associated with chronic hyperglycemia. SIGNIFICANCE STATEMENT The major factor limiting improved glucose control in type 1 diabetes is the significant increase in hypoglycemia associated with insulin treatment. Repeated exposure to hypoglycemia alters patients' ability to recognize the autonomic and neuroglycopenic symptoms associated with low plasma glucose levels. We examined brain resting state networks during the induction of hypoglycemia in diabetic and control subjects and found differences in networks involved in sensorimotor function, cognition, and interoceptive awareness that were related to chronic levels of glycemic control. These findings identify brain regions that are sensitive to variations in plasma glucose levels and may also provide a basis for understanding the mechanisms underlying the increased incidence of cognitive impairment and affective disorders seen in patients with diabetes. PMID:26245963

Aberrant functional connectivity between motor and language networks in rolandic epilepsy.

PubMed

Besseling, René M H; Overvliet, Geke M; Jansen, Jacobus F A; van der Kruijs, Sylvie J M; Vles, Johannes S H; Ebus, Saskia C M; Hofman, Paul A M; de Louw, Anton J A; Aldenkamp, Albert P; Backes, Walter H

2013-12-01

Rolandic epilepsy (RE) is an idiopathic focal childhood epilepsy with a well-established neuropsychological profile of language impairment. The aim of this study is to provide a functional correlate that links rolandic (sensorimotor) pathology to language problems using functional MRI. Twenty-three children with RE (8-14 years old) and 21 matched controls underwent extensive language assessment (Clinical Evaluation of Language Fundamentals). fMRI was performed at rest and using word generation, reading, and finger tapping paradigms. Since no activation group differences were found, regions of interest (ROIs) were defined at pooled (patients and controls combined) activation maxima and in contralateral homotopic cortex, and used to assess language lateralization as well as for a resting-state connectivity analysis. Furthermore, the association between connection strength and language performance was investigated. Reduced language performance was found in the children with RE. Bilateral activation was found for both language tasks with some predominance of the left hemisphere in both groups. Compared to controls, patient connectivity was decreased between the left sensorimotor area and right inferior frontal gyrus (p<0.01). For this connection, lower connectivity was associated with lower language scores in the patient group (r=0.49, p=0.02), but not in the controls. Language laterality analysis revealed bilateral language representation in the age range under study (8-14 years). As a consequence, the connection of reduced functional connectivity we found represents an impaired interplay between motor and language networks, and aberrant functional connectivity associated with poorer language performance. These findings provide a first neuronal correlate in terms of aberrant resting-state functional connectivity for language impairment in RE. Copyright © 2013 Elsevier B.V. All rights reserved.

Aberrant corticostriatal functional circuits in adolescents with Internet addiction disorder

PubMed Central

Lin, Fuchun; Zhou, Yan; Du, Yasong; Zhao, Zhimin; Qin, Lindi; Xu, Jianrong; Lei, Hao

2015-01-01

Abnormal structure and function in the striatum and prefrontal cortex (PFC) have been revealed in Internet addiction disorder (IAD). However, little is known about alterations of corticostriatal functional circuits in IAD. The aim of this study was to investigate the integrity of corticostriatal functional circuits and their relations to neuropsychological measures in IAD by resting-state functional connectivity (FC). Fourteen IAD adolescents and 15 healthy controls underwent resting-state fMRI scans. Using six predefined bilateral striatal regions-of-interest, voxel-wise correlation maps were computed and compared between groups. Relationships between alterations of corticostriatal connectivity and clinical measurements were examined in the IAD group. Compared to controls, IAD subjects exhibited reduced connectivity between the inferior ventral striatum and bilateral caudate head, subgenual anterior cingulate cortex (ACC), and posterior cingulate cortex, and between the superior ventral striatum and bilateral dorsal/rostral ACC, ventral anterior thalamus, and putamen/pallidum/insula/inferior frontal gyrus (IFG), and between the dorsal caudate and dorsal/rostral ACC, thalamus, and IFG, and between the left ventral rostral putamen and right IFG. IAD subjects also showed increased connectivity between the left dorsal caudal putamen and bilateral caudal cigulate motor area. Moreover, altered cotricostriatal functional circuits were significantly correlated with neuropsychological measures. This study directly provides evidence that IAD is associated with alterations of corticostriatal functional circuits involved in the affective and motivation processing, and cognitive control. These findings emphasize that functional connections in the corticostriatal circuits are modulated by affective/motivational/cognitive states and further suggest that IAD may have abnormalities of such modulation in this network. PMID:26136677

Decoding Lifespan Changes of the Human Brain Using Resting-State Functional Connectivity MRI

PubMed Central

Wang, Lubin; Su, Longfei; Shen, Hui; Hu, Dewen

2012-01-01

The development of large-scale functional brain networks is a complex, lifelong process that can be investigated using resting-state functional connectivity MRI (rs-fcMRI). In this study, we aimed to decode the developmental dynamics of the whole-brain functional network in seven decades (8–79 years) of the human lifespan. We first used parametric curve fitting to examine linear and nonlinear age effect on the resting human brain, and then combined manifold learning and support vector machine methods to predict individuals' “brain ages” from rs-fcMRI data. We found that age-related changes in interregional functional connectivity exhibited spatially and temporally specific patterns. During brain development from childhood to senescence, functional connections tended to linearly increase in the emotion system and decrease in the sensorimotor system; while quadratic trajectories were observed in functional connections related to higher-order cognitive functions. The complex patterns of age effect on the whole-brain functional network could be effectively represented by a low-dimensional, nonlinear manifold embedded in the functional connectivity space, which uncovered the inherent structure of brain maturation and aging. Regression of manifold coordinates with age further showed that the manifold representation extracted sufficient information from rs-fcMRI data to make prediction about individual brains' functional development levels. Our study not only gives insights into the neural substrates that underlie behavioral and cognitive changes over age, but also provides a possible way to quantitatively describe the typical and atypical developmental progression of human brain function using rs-fcMRI. PMID:22952990

Decoding lifespan changes of the human brain using resting-state functional connectivity MRI.

PubMed

Wang, Lubin; Su, Longfei; Shen, Hui; Hu, Dewen

2012-01-01

The development of large-scale functional brain networks is a complex, lifelong process that can be investigated using resting-state functional connectivity MRI (rs-fcMRI). In this study, we aimed to decode the developmental dynamics of the whole-brain functional network in seven decades (8-79 years) of the human lifespan. We first used parametric curve fitting to examine linear and nonlinear age effect on the resting human brain, and then combined manifold learning and support vector machine methods to predict individuals' "brain ages" from rs-fcMRI data. We found that age-related changes in interregional functional connectivity exhibited spatially and temporally specific patterns. During brain development from childhood to senescence, functional connections tended to linearly increase in the emotion system and decrease in the sensorimotor system; while quadratic trajectories were observed in functional connections related to higher-order cognitive functions. The complex patterns of age effect on the whole-brain functional network could be effectively represented by a low-dimensional, nonlinear manifold embedded in the functional connectivity space, which uncovered the inherent structure of brain maturation and aging. Regression of manifold coordinates with age further showed that the manifold representation extracted sufficient information from rs-fcMRI data to make prediction about individual brains' functional development levels. Our study not only gives insights into the neural substrates that underlie behavioral and cognitive changes over age, but also provides a possible way to quantitatively describe the typical and atypical developmental progression of human brain function using rs-fcMRI.

Corticostriatal Connectivity in Antisocial Personality Disorder by MAO-A Genotype and Its Relationship to Aggressive Behavior.

PubMed

Kolla, Nathan J; Dunlop, Katharine; Meyer, Jeffrey H; Downar, Jonathan

2018-05-09

The influence of genetic variation on resting-state neural networks represents a burgeoning line of inquiry in psychiatric research. Monoamine oxidase A, an X-linked gene, is one example of a molecular target linked to brain activity in psychiatric illness. Monoamine oxidase A genetic variants, including the high and low variable nucleotide tandem repeat polymorphisms, have been shown to differentially affect brain functional connectivity in healthy humans. However, it is currently unknown whether these same polymorphisms influence resting-state brain activity in clinical conditions. Given its high burden on society and strong connection to violent behavior, antisocial personality disorder is a logical condition to study, since in vivo markers of monoamine oxidase A brain enzyme are reduced in key affect-modulating regions, and striatal levels of monoamine oxidase A show a relation with the functional connectivity of this same region. We utilized monoamine oxidase A genotyping and seed-to-voxel-based functional connectivity to investigate the relationship between genotype and corticostriatal connectivity in 21 male participants with severe antisocial personality disorder and 19 male healthy controls. Dorsal striatal connectivity to the frontal pole and anterior cingulate gyrus differentiated antisocial personality disorder subjects and healthy controls by monoamine oxidase A genotype. Furthermore, the linear relationship of proactive aggression to superior ventral striatal-angular gyrus functional connectivity differed by monoamine oxidase A genotype in the antisocial personality disorder groups. These results suggest that monoamine oxidase A genotype may affect corticostriatal connectivity in antisocial personality disorder and that these functional connections may also underlie use of proactive aggression in a genotype-specific manner.

Disruption of thalamic functional connectivity is a neural correlate of dexmedetomidine-induced unconsciousness

PubMed Central

Akeju, Oluwaseun; Loggia, Marco L; Catana, Ciprian; Pavone, Kara J; Vazquez, Rafael; Rhee, James; Contreras Ramirez, Violeta; Chonde, Daniel B; Izquierdo-Garcia, David; Arabasz, Grae; Hsu, Shirley; Habeeb, Kathleen; Hooker, Jacob M; Napadow, Vitaly; Brown, Emery N; Purdon, Patrick L

2014-01-01

Understanding the neural basis of consciousness is fundamental to neuroscience research. Disruptions in cortico-cortical connectivity have been suggested as a primary mechanism of unconsciousness. By using a novel combination of positron emission tomography and functional magnetic resonance imaging, we studied anesthesia-induced unconsciousness and recovery using the α2-agonist dexmedetomidine. During unconsciousness, cerebral metabolic rate of glucose and cerebral blood flow were preferentially decreased in the thalamus, the Default Mode Network (DMN), and the bilateral Frontoparietal Networks (FPNs). Cortico-cortical functional connectivity within the DMN and FPNs was preserved. However, DMN thalamo-cortical functional connectivity was disrupted. Recovery from this state was associated with sustained reduction in cerebral blood flow and restored DMN thalamo-cortical functional connectivity. We report that loss of thalamo-cortical functional connectivity is sufficient to produce unconsciousness. DOI: http://dx.doi.org/10.7554/eLife.04499.001 PMID:25432022

Effects of resting state condition on reliability, trait specificity, and network connectivity of brain function measured with arterial spin labeled perfusion MRI.

PubMed

Li, Zhengjun; Vidorreta, Marta; Katchmar, Natalie; Alsop, David C; Wolf, Daniel H; Detre, John A

2018-06-01

Resting state fMRI (rs-fMRI) provides imaging biomarkers of task-independent brain function that can be associated with clinical variables or modulated by interventions such as behavioral training or pharmacological manipulations. These biomarkers include time-averaged regional brain function as manifested by regional cerebral blood flow (CBF) measured using arterial spin labeled (ASL) perfusion MRI and correlated temporal fluctuations of function across brain networks with either ASL or blood oxygenation level dependent (BOLD) fMRI. Resting-state studies are typically carried out using just one of several prescribed state conditions such as eyes closed (EC), eyes open (EO), or visual fixation on a cross-hair (FIX), which may affect the reliability and specificity of rs-fMRI. In this study, we collected test-retest ASL MRI data during 4 resting-state task conditions: EC, EO, FIX and PVT (low-frequency psychomotor vigilance task), and examined the effects of these task conditions on reliability and reproducibility as well as trait specificity of regional brain function. We also acquired resting-state BOLD fMRI under FIX and compared the network connectivity reliabilities between the four ASL conditions and the BOLD FIX condition. For resting-state ASL data, EC provided the highest CBF reliability, reproducibility, trait specificity, and network connectivity reliability, followed by EO, while FIX was lowest on all of these measures. PVT demonstrated lower CBF reliability, reproducibility and trait specificity than EO and EC. Overall network connectivity reliability was comparable between ASL and BOLD. Our findings confirm ASL CBF as a reliable, stable, and consistent measure of resting-state regional brain function and support the use of EC or EO over FIX and PVT as the resting-state condition. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Brain connectivity aberrations in anabolic-androgenic steroid users.

PubMed

Westlye, Lars T; Kaufmann, Tobias; Alnæs, Dag; Hullstein, Ingunn R; Bjørnebekk, Astrid

2017-01-01

Sustained anabolic-androgenic steroid (AAS) use has adverse behavioral consequences, including aggression, violence and impulsivity. Candidate mechanisms include disruptions of brain networks with high concentrations of androgen receptors and critically involved in emotional and cognitive regulation. Here, we tested the effects of AAS on resting-state functional brain connectivity in the largest sample of AAS-users to date. We collected resting-state functional magnetic resonance imaging (fMRI) data from 151 males engaged in heavy resistance strength training. 50 users tested positive for AAS based on the testosterone to epitestosterone (T/E) ratio and doping substances in urine. 16 previous users and 59 controls tested negative. We estimated brain network nodes and their time-series using ICA and dual regression and defined connectivity matrices as the between-node partial correlations. In line with the emotional and behavioral consequences of AAS, current users exhibited reduced functional connectivity between key nodes involved in emotional and cognitive regulation, in particular reduced connectivity between the amygdala and default-mode network (DMN) and between the dorsal attention network (DAN) and a frontal node encompassing the superior and inferior frontal gyri (SFG/IFG) and the anterior cingulate cortex (ACC), with further reductions as a function of dependency, lifetime exposure, and cycle state (on/off).

Default mode network connectivity indicates episodic memory capacity in mesial temporal lobe epilepsy.

PubMed

McCormick, Cornelia; Quraan, Maher; Cohn, Melanie; Valiante, Taufik A; McAndrews, Mary Pat

2013-05-01

The clinical relevance of resting state functional connectivity in neurologic disorders, including mesial temporal lobe epilepsy (mTLE), remains unclear. This study investigated how connectivity in the default mode network changes with unilateral damage to one of its nodes, the hippocampus (HC), and how such connectivity can be exploited clinically to characterize memory deficits and indicate postsurgical memory change. Functional magnetic resonance imaging (fMRI) resting state scans and neuropsychological memory assessments (Warrington Recognition Tests for Words and Faces) were performed on 19 healthy controls, 20 patients with right mTLE, and 18 patients with left mTLE. In addition, postsurgical fMRI resting state and memory change (postsurgical memory performance-presurgical memory performance) data were available for half of these patients. Patients with mTLE showed reduced connectivity from the posterior cingulate cortex (PCC) to the epileptogenic HC and increased PCC connectivity to the contralateral HC. Stronger PCC connectivity to the epileptogenic HC was associated with better presurgical memory and with greater postsurgical memory decline. Stronger PCC connectivity to the contralateral HC was associated with less postsurgical memory decline. Following surgery, PCC connectivity to the remaining HC increased from presurgical values and showed enhanced correlation with postsurgical memory function. It is notable that this index was superior to others (hippocampal volume, preoperative memory scores) in explaining variance in memory change following surgery. Our results demonstrate the striking clinical significance of the brain's intrinsic connectivity in evaluating cognitive capacity and indicating the potential of postsurgical cognitive morbidity in patients with mTLE. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

Reduced connectivity of the auditory cortex in patients with auditory hallucinations: a resting state functional magnetic resonance imaging study.

PubMed

Gavrilescu, M; Rossell, S; Stuart, G W; Shea, T L; Innes-Brown, H; Henshall, K; McKay, C; Sergejew, A A; Copolov, D; Egan, G F

2010-07-01

Previous research has reported auditory processing deficits that are specific to schizophrenia patients with a history of auditory hallucinations (AH). One explanation for these findings is that there are abnormalities in the interhemispheric connectivity of auditory cortex pathways in AH patients; as yet this explanation has not been experimentally investigated. We assessed the interhemispheric connectivity of both primary (A1) and secondary (A2) auditory cortices in n=13 AH patients, n=13 schizophrenia patients without auditory hallucinations (non-AH) and n=16 healthy controls using functional connectivity measures from functional magnetic resonance imaging (fMRI) data. Functional connectivity was estimated from resting state fMRI data using regions of interest defined for each participant based on functional activation maps in response to passive listening to words. Additionally, stimulus-induced responses were regressed out of the stimulus data and the functional connectivity was estimated for the same regions to investigate the reliability of the estimates. AH patients had significantly reduced interhemispheric connectivity in both A1 and A2 when compared with non-AH patients and healthy controls. The latter two groups did not show any differences in functional connectivity. Further, this pattern of findings was similar across the two datasets, indicating the reliability of our estimates. These data have identified a trait deficit specific to AH patients. Since this deficit was characterized within both A1 and A2 it is expected to result in the disruption of multiple auditory functions, for example, the integration of basic auditory information between hemispheres (via A1) and higher-order language processing abilities (via A2).

Dose-dependent effects of theta burst rTMS on cortical excitability and resting-state connectivity of the human motor system.

PubMed

Nettekoven, Charlotte; Volz, Lukas J; Kutscha, Martha; Pool, Eva-Maria; Rehme, Anne K; Eickhoff, Simon B; Fink, Gereon R; Grefkes, Christian

2014-05-14

Theta burst stimulation (TBS), a specific protocol of repetitive transcranial magnetic stimulation (rTMS), induces changes in cortical excitability that last beyond stimulation. TBS-induced aftereffects, however, vary between subjects, and the mechanisms underlying these aftereffects to date remain poorly understood. Therefore, the purpose of this study was to investigate whether increasing the number of pulses of intermittent TBS (iTBS) (1) increases cortical excitability as measured by motor-evoked potentials (MEPs) and (2) alters functional connectivity measured using resting-state fMRI, in a dose-dependent manner. Sixteen healthy, human subjects received three serially applied iTBS blocks of 600 pulses over the primary motor cortex (M1 stimulation) and the parieto-occipital vertex (sham stimulation) to test for dose-dependent iTBS effects on cortical excitability and functional connectivity (four sessions in total). iTBS over M1 increased MEP amplitudes compared with sham stimulation after each stimulation block. Although the increase in MEP amplitudes did not differ between the first and second block of M1 stimulation, we observed a significant increase after three blocks (1800 pulses). Furthermore, iTBS enhanced resting-state functional connectivity between the stimulated M1 and premotor regions in both hemispheres. Functional connectivity between M1 and ipsilateral dorsal premotor cortex further increased dose-dependently after 1800 pulses of iTBS over M1. However, no correlation between changes in MEP amplitudes and functional connectivity was detected. In summary, our data show that increasing the number of iTBS stimulation blocks results in dose-dependent effects at the local level (cortical excitability) as well as at a systems level (functional connectivity) with a dose-dependent enhancement of dorsal premotor cortex-M1 connectivity. Copyright © 2014 the authors 0270-6474/14/346849-11$15.00/0.

Cortical connective field estimates from resting state fMRI activity.

PubMed

Gravel, Nicolás; Harvey, Ben; Nordhjem, Barbara; Haak, Koen V; Dumoulin, Serge O; Renken, Remco; Curčić-Blake, Branislava; Cornelissen, Frans W

2014-01-01

One way to study connectivity in visual cortical areas is by examining spontaneous neural activity. In the absence of visual input, such activity remains shaped by the underlying neural architecture and, presumably, may still reflect visuotopic organization. Here, we applied population connective field (CF) modeling to estimate the spatial profile of functional connectivity in the early visual cortex during resting state functional magnetic resonance imaging (RS-fMRI). This model-based analysis estimates the spatial integration between blood-oxygen level dependent (BOLD) signals in distinct cortical visual field maps using fMRI. Just as population receptive field (pRF) mapping predicts the collective neural activity in a voxel as a function of response selectivity to stimulus position in visual space, CF modeling predicts the activity of voxels in one visual area as a function of the aggregate activity in voxels in another visual area. In combination with pRF mapping, CF locations on the cortical surface can be interpreted in visual space, thus enabling reconstruction of visuotopic maps from resting state data. We demonstrate that V1 ➤ V2 and V1 ➤ V3 CF maps estimated from resting state fMRI data show visuotopic organization. Therefore, we conclude that-despite some variability in CF estimates between RS scans-neural properties such as CF maps and CF size can be derived from resting state data.

Altered functional connectivity between the insula and the cingulate cortex in patients with temporomandibular disorder: a pilot study.

PubMed

Ichesco, Eric; Quintero, Andres; Clauw, Daniel J; Peltier, Scott; Sundgren, Pia M; Gerstner, Geoffrey E; Schmidt-Wilcke, Tobias

2012-03-01

Among the most common chronic pain conditions, yet poorly understood, are temporomandibular disorders (TMDs), with a prevalence estimate of 3-15% for Western populations. Although it is increasingly acknowledged that central nervous system mechanisms contribute to pain amplification and chronicity in TMDs, further research is needed to unravel neural correlates that might abet the development of chronic pain. The insular cortex (IC) and cingulate cortex (CC) are both critically involved in the experience of pain. The current study sought specifically to investigate IC-CC functional connectivity in TMD patients and healthy controls (HCs), both during resting state and during the application of a painful stimulus. Eight patients with TMD, and 8 age- and sex-matched HCs were enrolled in the present study. Functional magnetic resonance imaging data during resting state and during the performance of a pressure pain stimulus to the temple were acquired. Predefined seed regions were placed in the IC (anterior and posterior insular cortices) and the extracted signal was correlated with brain activity throughout the whole brain. Specifically, we were interested whether TMD patients and HCs would show differences in IC-CC connectivity, both during resting state and during the application of a painful stimulus to the face. As a main finding, functional connectivity analyses revealed an increased functional connectivity between the left anterior IC and pregenual anterior cingulate cortex (ACC) in TMD patients, during both resting state and applied pressure pain. Within the patient group, there was a negative correlation between the anterior IC-ACC connectivity and clinical pain intensity as measured by a visual analog scale. Since the pregenual region of the ACC is critically involved in antinociception, we hypothesize that an increase in anterior IC-ACC connectivity is indicative of an adaptation of the pain modulatory system early in the chronification process. © 2011 American Headache Society.

Effect of Resting-State fNIRS Scanning Duration on Functional Brain Connectivity and Graph Theory Metrics of Brain Network.

PubMed

Geng, Shujie; Liu, Xiangyu; Biswal, Bharat B; Niu, Haijing

2017-01-01

As an emerging brain imaging technique, functional near infrared spectroscopy (fNIRS) has attracted widespread attention for advancing resting-state functional connectivity (FC) and graph theoretical analyses of brain networks. However, it remains largely unknown how the duration of the fNIRS signal scanning is related to stable and reproducible functional brain network features. To answer this question, we collected resting-state fNIRS signals (10-min duration, two runs) from 18 participants and then truncated the hemodynamic time series into 30-s time bins that ranged from 1 to 10 min. Measures of nodal efficiency, nodal betweenness, network local efficiency, global efficiency, and clustering coefficient were computed for each subject at each fNIRS signal acquisition duration. Analyses of the stability and between-run reproducibility were performed to identify optimal time length for each measure. We found that the FC, nodal efficiency and nodal betweenness stabilized and were reproducible after 1 min of fNIRS signal acquisition, whereas network clustering coefficient, local and global efficiencies stabilized after 1 min and were reproducible after 5 min of fNIRS signal acquisition for only local and global efficiencies. These quantitative results provide direct evidence regarding the choice of the resting-state fNIRS scanning duration for functional brain connectivity and topological metric stability of brain network connectivity.

Large-Scale Hypoconnectivity Between Resting-State Functional Networks in Unmedicated Adolescent Major Depressive Disorder.

PubMed

Sacchet, Matthew D; Ho, Tiffany C; Connolly, Colm G; Tymofiyeva, Olga; Lewinn, Kaja Z; Han, Laura Km; Blom, Eva H; Tapert, Susan F; Max, Jeffrey E; Frank, Guido Kw; Paulus, Martin P; Simmons, Alan N; Gotlib, Ian H; Yang, Tony T

2016-11-01

Major depressive disorder (MDD) often emerges during adolescence, a critical period of brain development. Recent resting-state fMRI studies of adults suggest that MDD is associated with abnormalities within and between resting-state networks (RSNs). Here we tested whether adolescent MDD is characterized by abnormalities in interactions among RSNs. Participants were 55 unmedicated adolescents diagnosed with MDD and 56 matched healthy controls. Functional connectivity was mapped using resting-state fMRI. We used the network-based statistic (NBS) to compare large-scale connectivity between groups and also compared the groups on graph metrics. We further assessed whether group differences identified using nodes defined from functionally defined RSNs were also evident when using anatomically defined nodes. In addition, we examined relations between network abnormalities and depression severity and duration. Finally, we compared intranetwork connectivity between groups and assessed the replication of previously reported MDD-related abnormalities in connectivity. The NBS indicated that, compared with controls, depressed adolescents exhibited reduced connectivity (p<0.024, corrected) between a specific set of RSNs, including components of the attention, central executive, salience, and default mode networks. The NBS did not identify group differences in network connectivity when using anatomically defined nodes. Longer duration of depression was significantly correlated with reduced connectivity in this set of network interactions (p=0.020, corrected), specifically with reduced connectivity between components of the dorsal attention network. The dorsal attention network was also characterized by reduced intranetwork connectivity in the MDD group. Finally, we replicated previously reported abnormal connectivity in individuals with MDD. In summary, adolescents with MDD show hypoconnectivity between large-scale brain networks compared with healthy controls. Given that connectivity among these networks typically increases during adolescent neurodevelopment, these results suggest that adolescent depression is associated with abnormalities in neural systems that are still developing during this critical period.

Large-Scale Hypoconnectivity Between Resting-State Functional Networks in Unmedicated Adolescent Major Depressive Disorder

PubMed Central

Sacchet, Matthew D; Ho, Tiffany C; Connolly, Colm G; Tymofiyeva, Olga; Lewinn, Kaja Z; Han, Laura KM; Blom, Eva H; Tapert, Susan F; Max, Jeffrey E; Frank, Guido KW; Paulus, Martin P; Simmons, Alan N; Gotlib, Ian H; Yang, Tony T

2016-01-01

Major depressive disorder (MDD) often emerges during adolescence, a critical period of brain development. Recent resting-state fMRI studies of adults suggest that MDD is associated with abnormalities within and between resting-state networks (RSNs). Here we tested whether adolescent MDD is characterized by abnormalities in interactions among RSNs. Participants were 55 unmedicated adolescents diagnosed with MDD and 56 matched healthy controls. Functional connectivity was mapped using resting-state fMRI. We used the network-based statistic (NBS) to compare large-scale connectivity between groups and also compared the groups on graph metrics. We further assessed whether group differences identified using nodes defined from functionally defined RSNs were also evident when using anatomically defined nodes. In addition, we examined relations between network abnormalities and depression severity and duration. Finally, we compared intranetwork connectivity between groups and assessed the replication of previously reported MDD-related abnormalities in connectivity. The NBS indicated that, compared with controls, depressed adolescents exhibited reduced connectivity (p<0.024, corrected) between a specific set of RSNs, including components of the attention, central executive, salience, and default mode networks. The NBS did not identify group differences in network connectivity when using anatomically defined nodes. Longer duration of depression was significantly correlated with reduced connectivity in this set of network interactions (p=0.020, corrected), specifically with reduced connectivity between components of the dorsal attention network. The dorsal attention network was also characterized by reduced intranetwork connectivity in the MDD group. Finally, we replicated previously reported abnormal connectivity in individuals with MDD. In summary, adolescents with MDD show hypoconnectivity between large-scale brain networks compared with healthy controls. Given that connectivity among these networks typically increases during adolescent neurodevelopment, these results suggest that adolescent depression is associated with abnormalities in neural systems that are still developing during this critical period. PMID:27238621

The Psychoactive Designer Drug and Bath Salt Constituent MDPV Causes Widespread Disruption of Brain Functional Connectivity

PubMed Central

Colon-Perez, Luis M; Tran, Kelvin; Thompson, Khalil; Pace, Michael C; Blum, Kenneth; Goldberger, Bruce A; Gold, Mark S; Bruijnzeel, Adriaan W; Setlow, Barry; Febo, Marcelo

2016-01-01

The abuse of ‘bath salts' has raised concerns because of their adverse effects, which include delirium, violent behavior, and suicide ideation in severe cases. The bath salt constituent 3,4-methylenedioxypyrovalerone (MDPV) has been closely linked to these and other adverse effects. The abnormal behavioral pattern produced by acute high-dose MDPV intake suggests possible disruptions of neural communication between brain regions. Therefore, we determined if MDPV exerts disruptive effects on brain functional connectivity, particularly in areas of the prefrontal cortex. Male rats were imaged following administration of a single dose of MDPV (0.3, 1.0, or 3.0 mg/kg) or saline. Resting state brain blood oxygenation level-dependent (BOLD) images were acquired at 4.7 T. To determine the role of dopamine transmission in MDPV-induced changes in functional connectivity, a group of rats received the dopamine D1/D2 receptor antagonist cis-flupenthixol (0.5 mg/kg) 30 min before MDPV. MDPV dose-dependently reduced functional connectivity. Detailed analysis of its effects revealed that connectivity between frontal cortical and striatal areas was reduced. This included connectivity between the prelimbic prefrontal cortex and other areas of the frontal cortex and the insular cortex with hypothalamic, ventral, and dorsal striatal areas. Although the reduced connectivity appeared widespread, connectivity between these regions and somatosensory cortex was not as severely affected. Dopamine receptor blockade did not prevent the MDPV-induced decrease in functional connectivity. The results provide a novel signature of MDPV's in vivo mechanism of action. Reduced brain functional connectivity has been reported in patients suffering from psychosis and has been linked to cognitive dysfunction, audiovisual hallucinations, and negative affective states akin to those reported for MDPV-induced intoxication. The present results suggest that disruption of functional connectivity networks involving frontal cortical and striatal regions could contribute to the adverse effects of MDPV. PMID:26997298

Thalamocortical dysconnectivity in schizophrenia

PubMed Central

Woodward, Neil D.; Karbasforoushan, Haleh; Heckers, Stephan

2013-01-01

Objective The thalamus and cerebral cortex are connected via topographically organized, reciprocal connections. Previous studies revealed thalamic abnormalities in schizophrenia; however, it is not known if thalamocortical networks are differentially affected in the disorder. To explore this possibility, we examined functional connectivity in intrinsic low frequency blood-oxygen-level-dependent (BOLD) signal fluctuations between major divisions of the cortex and thalamus using resting-state functional magnetic resonance imaging. Method 77 healthy subjects and 62 patients with schizophrenia underwent resting-state fMRI. To identify functional subdivisions of the thalamus, we parceled the cortex into six regions-of-interest; prefrontal, motor, somatosensory, temporal, posterior parietal, and occipital cortex. Mean BOLD time-series was extracted from each of the regions-of-interest and entered into a seed-based functional connectivity analysis. Results Consistent with prior reports, activity in distinct cortical areas correlated with specific, largely non-overlapping regions of the thalamus in both healthy subjects and schizophrenia patients. Direct comparison between groups revealed reduced prefrontal-thalamic connectivity and increased motor/somatosensory-thalamic connectivity in schizophrenia. The changes in connectivity were unrelated to local grey matter content within the thalamus and antipsychotic medication dosage. No differences were observed in temporal, posterior parietal, and occipital cortex connectivity with the thalamus. Conclusions This study establishes differential abnormalities of thalamocortical networks in schizophrenia. The etiology of schizophrenia may disrupt the development of prefrontal-thalamic connectivity and refinement of somatomotor connectivity with the thalamus that occurs during brain maturation. PMID:23032387

Information processing architecture of functionally defined clusters in the macaque cortex.

PubMed

Shen, Kelly; Bezgin, Gleb; Hutchison, R Matthew; Gati, Joseph S; Menon, Ravi S; Everling, Stefan; McIntosh, Anthony R

2012-11-28

Computational and empirical neuroimaging studies have suggested that the anatomical connections between brain regions primarily constrain their functional interactions. Given that the large-scale organization of functional networks is determined by the temporal relationships between brain regions, the structural limitations may extend to the global characteristics of functional networks. Here, we explored the extent to which the functional network community structure is determined by the underlying anatomical architecture. We directly compared macaque (Macaca fascicularis) functional connectivity (FC) assessed using spontaneous blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI) to directed anatomical connectivity derived from macaque axonal tract tracing studies. Consistent with previous reports, FC increased with increasing strength of anatomical connection, and FC was also present between regions that had no direct anatomical connection. We observed moderate similarity between the FC of each region and its anatomical connectivity. Notably, anatomical connectivity patterns, as described by structural motifs, were different within and across functional modules: partitioning of the functional network was supported by dense bidirectional anatomical connections within clusters and unidirectional connections between clusters. Together, our data directly demonstrate that the FC patterns observed in resting-state BOLD-fMRI are dictated by the underlying neuroanatomical architecture. Importantly, we show how this architecture contributes to the global organizational principles of both functional specialization and integration.

Altered resting-state amygdala functional connectivity in men with posttraumatic stress disorder

PubMed Central

Sripada, Rebecca K.; King, Anthony P.; Garfinkel, Sarah N.; Wang, Xin; Sripada, Chandra S.; Welsh, Robert C.; Liberzon, Israel

2012-01-01

Background Converging neuroimaging research suggests altered emotion neurocircuitry in individuals with posttraumatic stress disorder (PTSD). Emotion activation studies in these individuals have shown hyperactivation in emotion-related regions, including the amygdala and insula, and hypoactivation in emotion-regulation regions, including the medial prefrontal cortex (mPFC) and anterior cingulate cortex (ACC). However, few studies have examined patterns of connectivity at rest in individuals with PTSD, a potentially powerful method for illuminating brain network structure. Methods Using the amygdala as a seed region, we measured resting-state brain connectivity using 3 T functional magnetic resonance imaging in returning male veterans with PTSD and combat controls without PTSD. Results Fifteen veterans with PTSD and 14 combat controls enrolled in our study. Compared with controls, veterans with PTSD showed greater positive connectivity between the amygdala and insula, reduced positive connectivity between the amygdala and hippocampus, and reduced anticorrelation between the amygdala and dorsal ACC and rostral ACC. Limitations Only male veterans with combat exposure were tested, thus our findings cannot be generalized to women or to individuals with non–combat related PTSD. Conclusion These results demonstrate that studies of functional connectivity during resting state can discern aberrant patterns of coupling within emotion circuits and suggest a possible brain basis for emotion-processing and emotion-regulation deficits in individuals with PTSD. PMID:22313617

Altered resting state functional connectivity of fear and reward circuitry in comorbid PTSD and major depression.

PubMed

Zhu, Xi; Helpman, Liat; Papini, Santiago; Schneier, Franklin; Markowitz, John C; Van Meter, Page E; Lindquist, Martin A; Wager, Tor D; Neria, Yuval

2017-07-01

Individuals with comorbid posttraumatic stress disorder and major depressive disorder (PTSD-MDD) often exhibit greater functional impairment and poorer treatment response than individuals with PTSD alone. Research has not determined whether PTSD-MDD is associated with different network connectivity abnormalities than PTSD alone. We used functional magnetic resonance imaging (fMRI) to measure resting state functional connectivity (rs-FC) patterns of brain regions involved in fear and reward processing in three groups: patients with PTSD-alone (n = 27), PTSD-MDD (n = 21), and trauma-exposed healthy controls (TEHCs, n = 34). Based on previous research, seeds included basolateral amygdala (BLA), centromedial amygdala (CMA), and nucleus accumbens (NAcc). Regardless of MDD comorbidity, PTSD was associated with decreased connectivity of BLA-orbitalfrontal cortex (OFC) and CMA-thalamus pathways, key to fear processing, and fear expression, respectively. PTSD-MDD, compared to PTSD-alone and TEHC, was associated with decreased connectivity across multiple amygdala and striatal-subcortical pathways: BLA-OFC, NAcc-thalamus, and NAcc-hippocampus. Further, while both the BLA-OFC and the NAcc-thalamus pathways were correlated with MDD symptoms, PTSD symptoms correlated with the amygdala pathways (BLA-OFC; CMA-thalamus) only. Comorbid PTSD-MDD may be associated with multifaceted functional connectivity alterations in both fear and reward systems. Clinical implications are discussed. © 2016 Wiley Periodicals, Inc.

Neural traces of stress: cortisol related sustained enhancement of amygdala-hippocampal functional connectivity

PubMed Central

Vaisvaser, Sharon; Lin, Tamar; Admon, Roee; Podlipsky, Ilana; Greenman, Yona; Stern, Naftali; Fruchter, Eyal; Wald, Ilan; Pine, Daniel S.; Tarrasch, Ricardo; Bar-Haim, Yair; Hendler, Talma

2013-01-01

Stressful experiences modulate neuro-circuitry function, and the temporal trajectory of these alterations, elapsing from early disturbances to late recovery, heavily influences resilience and vulnerability to stress. Such effects of stress may depend on processes that are engaged during resting-state, through active recollection of past experiences and anticipation of future events, all known to involve the default mode network (DMN). By inducing social stress and acquiring resting-state functional magnetic resonance imaging (fMRI) before stress, immediately following it, and 2 h later, we expanded the time-window for examining the trajectory of the stress response. Throughout the study repeated cortisol samplings and self-reports of stress levels were obtained from 51 healthy young males. Post-stress alterations were investigated by whole brain resting-state functional connectivity (rsFC) of two central hubs of the DMN: the posterior cingulate cortex (PCC) and hippocampus. Results indicate a ’recovery’ pattern of DMN connectivity, in which all alterations, ascribed to the intervening stress, returned to pre-stress levels. The only exception to this pattern was a stress-induced rise in amygdala-hippocampal connectivity, which was sustained for as long as 2 h following stress induction. Furthermore, this sustained enhancement of limbic connectivity was inversely correlated to individual stress-induced cortisol responsiveness (AUCi) and characterized only the group lacking such increased cortisol (i.e., non-responders). Our observations provide evidence of a prolonged post-stress response profile, characterized by both the comprehensive balance of most DMN functional connections and the distinct time and cortisol dependent ascent of intra-limbic connectivity. These novel insights into neuro-endocrine relations are another milestone in the ongoing search for individual markers in stress-related psychopathologies. PMID:23847492

Functional Connectivity Changes in Systemic Lupus Erythematosus: A Resting-State Study.

PubMed

Nystedt, Jessika; Mannfolk, Peter; Jönsen, Andreas; Bengtsson, Anders; Nilsson, Petra; Sundgren, Pia C; Strandberg, Tor O

2018-05-01

To investigate resting-state functional connectivity of lupus patients and associated subgroups according to the ACR NPSLE case definitions (ACR ad hoc). In addition, we investigated whether or not the observed alterations correlated with disease duration, the systemic lupus erythematosus (SLE)-Disease Activity Index-2000 (SLEDAI-2k), and Systemic Lupus International Collaborating Clinical/ACR organ damage index (SDI)-scores. Anatomical 3T magnetic resonance imaging (MRI) and resting-state functional MRI were performed in 61 female lupus patients (mean age = 37.0 years, range = 18.2-52.0 years) and 20 gender- and age-matched controls (mean age = 36.2 years, range = 23.3-52.2 years) in conjunction with clinical examination and laboratory testing. Whole-brain voxelwise functional connectivity analysis with permutation testing was performed to extract network components that differed in lupus patients relative to healthy controls (HCs). Lupus patients exhibited both inter- and intranetwork hypo- and hyperconnectivity involving several crucial networks. We found reduced connectivity within the default mode network (DMN), the central executive network (CEN), and in-between the DMN and CEN in lupus patients. Increased connectivity was primarily observed within and between the sensory motor network in lupus patients when compared to HCs. Comparing lupus patients with and without neuropsychiatric symptoms, hypoconnectivity was more pronounced in the group with neuropsychiatric complaints. The functional connectivity of SLE patients was both positively and negatively correlated to duration of disease. We conclude that SLE patients in general and neuropsychiatric SLE patients in particular experience altered brain connectivity. These patterns may be due both to direct neuronal damage and compensatory mechanisms through neuronal rewiring and recruitment and may partly explain neuropsychiatric symptoms in SLE patients.

Mining Time-Resolved Functional Brain Graphs to an EEG-Based Chronnectomic Brain Aged Index (CBAI).

PubMed

Dimitriadis, Stavros I; Salis, Christos I

2017-01-01

The brain at rest consists of spatially and temporal distributed but functionally connected regions that called intrinsic connectivity networks (ICNs). Resting state electroencephalography (rs-EEG) is a way to characterize brain networks without confounds associated with task EEG such as task difficulty and performance. A novel framework of how to study dynamic functional connectivity under the notion of functional connectivity microstates (FCμstates) and symbolic dynamics is further discussed. Furthermore, we introduced a way to construct a single integrated dynamic functional connectivity graph (IDFCG) that preserves both the strength of the connections between every pair of sensors but also the type of dominant intrinsic coupling modes (DICM). The whole methodology is demonstrated in a significant and unexplored task for EEG which is the definition of an objective Chronnectomic Brain Aged index (CBAI) extracted from resting-state data ( N = 94 subjects) with both eyes-open and eyes-closed conditions. Novel features have been defined based on symbolic dynamics and the notion of DICM and FCμstates. The transition rate of FCμstates, the symbolic dynamics based on the evolution of FCμstates (the Markovian Entropy, the complexity index), the probability distribution of DICM, the novel Flexibility Index that captures the dynamic reconfiguration of DICM per pair of EEG sensors and the relative signal power constitute a valuable pool of features that can build the proposed CBAI. Here we applied a feature selection technique and Extreme Learning Machine (ELM) classifier to discriminate young adults from middle-aged and a Support Vector Regressor to build a linear model of the actual age based on EEG-based spatio-temporal features. The most significant type of features for both prediction of age and discrimination of young vs. adults age groups was the dynamic reconfiguration of dominant coupling modes derived from a subset of EEG sensor pairs. Specifically, our results revealed a very high prediction of age for eyes-open ( R 2 = 0.60; y = 0.79x + 8.03) and lower for eyes-closed ( R 2 = 0.48; y = 0.71x + 10.91) while we succeeded to correctly classify young vs. middle-age group with 97.8% accuracy in eyes-open and 87.2% for eyes-closed. Our results were reproduced also in a second dataset for further external validation of the whole analysis. The proposed methodology proved valuable for the characterization of the intrinsic properties of dynamic functional connectivity through the age untangling developmental differences using EEG resting-state recordings.

Structural and functional connectional fingerprints in mild cognitive impairment and Alzheimer's disease patients.

PubMed

Son, Seong-Jin; Kim, Jonghoon; Park, Hyunjin

2017-01-01

Regional volume atrophy and functional degeneration are key imaging hallmarks of Alzheimer's disease (AD) in structural and functional magnetic resonance imaging (MRI), respectively. We jointly explored regional volume atrophy and functional connectivity to better characterize neuroimaging data of AD and mild cognitive impairment (MCI). All data were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. We compared regional volume atrophy and functional connectivity in 10 subcortical regions using structural MRI and resting-state functional MRI (rs-fMRI). Neuroimaging data of normal controls (NC) (n = 35), MCI (n = 40), and AD (n = 30) were compared. Significant differences of regional volumes and functional connectivity measures between groups were assessed using permutation tests in 10 regions. The regional volume atrophy and functional connectivity of identified regions were used as features for the random forest classifier to distinguish among three groups. The features of the identified regions were also regarded as connectional fingerprints that could distinctively separate a given group from the others. We identified a few regions with distinctive regional atrophy and functional connectivity patterns for NC, MCI, and AD groups. A three label classifier using the information of regional volume atrophy and functional connectivity of identified regions achieved classification accuracy of 53.33% to distinguish among NC, MCI, and AD. We identified distinctive regional atrophy and functional connectivity patterns that could be regarded as a connectional fingerprint.

Structural and functional connectional fingerprints in mild cognitive impairment and Alzheimer’s disease patients

PubMed Central

Son, Seong-Jin; Kim, Jonghoon

2017-01-01

Regional volume atrophy and functional degeneration are key imaging hallmarks of Alzheimer’s disease (AD) in structural and functional magnetic resonance imaging (MRI), respectively. We jointly explored regional volume atrophy and functional connectivity to better characterize neuroimaging data of AD and mild cognitive impairment (MCI). All data were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. We compared regional volume atrophy and functional connectivity in 10 subcortical regions using structural MRI and resting-state functional MRI (rs-fMRI). Neuroimaging data of normal controls (NC) (n = 35), MCI (n = 40), and AD (n = 30) were compared. Significant differences of regional volumes and functional connectivity measures between groups were assessed using permutation tests in 10 regions. The regional volume atrophy and functional connectivity of identified regions were used as features for the random forest classifier to distinguish among three groups. The features of the identified regions were also regarded as connectional fingerprints that could distinctively separate a given group from the others. We identified a few regions with distinctive regional atrophy and functional connectivity patterns for NC, MCI, and AD groups. A three label classifier using the information of regional volume atrophy and functional connectivity of identified regions achieved classification accuracy of 53.33% to distinguish among NC, MCI, and AD. We identified distinctive regional atrophy and functional connectivity patterns that could be regarded as a connectional fingerprint. PMID:28333946

Resting-state fMRI in sleeping infants more closely resembles adult sleep than adult wakefulness

PubMed Central

Snyder, Abraham Z.; Tagliazucchi, Enzo; Laufs, Helmut; Elison, Jed; Emerson, Robert W.; Shen, Mark D.; Wolff, Jason J.; Botteron, Kelly N.; Dager, Stephen; Estes, Annette M.; Evans, Alan; Gerig, Guido; Hazlett, Heather C.; Paterson, Sarah J.; Schultz, Robert T.; Styner, Martin A.; Zwaigenbaum, Lonnie; Schlaggar, Bradley L.

2017-01-01

Resting state functional magnetic resonance imaging (rs-fMRI) in infants enables important studies of functional brain organization early in human development. However, rs-fMRI in infants has universally been obtained during sleep to reduce participant motion artifact, raising the question of whether differences in functional organization between awake adults and sleeping infants that are commonly attributed to development may instead derive, at least in part, from sleep. This question is especially important as rs-fMRI differences in adult wake vs. sleep are well documented. To investigate this question, we compared functional connectivity and BOLD signal propagation patterns in 6, 12, and 24 month old sleeping infants with patterns in adult wakefulness and non-REM sleep. We find that important functional connectivity features seen during infant sleep closely resemble those seen during adult sleep, including reduced default mode network functional connectivity. However, we also find differences between infant and adult sleep, especially in thalamic BOLD signal propagation patterns. These findings highlight the importance of considering sleep state when drawing developmental inferences in infant rs-fMRI. PMID:29149191

Resting-state fMRI in sleeping infants more closely resembles adult sleep than adult wakefulness.

PubMed

Mitra, Anish; Snyder, Abraham Z; Tagliazucchi, Enzo; Laufs, Helmut; Elison, Jed; Emerson, Robert W; Shen, Mark D; Wolff, Jason J; Botteron, Kelly N; Dager, Stephen; Estes, Annette M; Evans, Alan; Gerig, Guido; Hazlett, Heather C; Paterson, Sarah J; Schultz, Robert T; Styner, Martin A; Zwaigenbaum, Lonnie; Schlaggar, Bradley L; Piven, Joseph; Pruett, John R; Raichle, Marcus

2017-01-01

Resting state functional magnetic resonance imaging (rs-fMRI) in infants enables important studies of functional brain organization early in human development. However, rs-fMRI in infants has universally been obtained during sleep to reduce participant motion artifact, raising the question of whether differences in functional organization between awake adults and sleeping infants that are commonly attributed to development may instead derive, at least in part, from sleep. This question is especially important as rs-fMRI differences in adult wake vs. sleep are well documented. To investigate this question, we compared functional connectivity and BOLD signal propagation patterns in 6, 12, and 24 month old sleeping infants with patterns in adult wakefulness and non-REM sleep. We find that important functional connectivity features seen during infant sleep closely resemble those seen during adult sleep, including reduced default mode network functional connectivity. However, we also find differences between infant and adult sleep, especially in thalamic BOLD signal propagation patterns. These findings highlight the importance of considering sleep state when drawing developmental inferences in infant rs-fMRI.

Resting-state brain networks revealed by granger causal connectivity in frogs.

PubMed

Xue, Fei; Fang, Guangzhan; Yue, Xizi; Zhao, Ermi; Brauth, Steven E; Tang, Yezhong

2016-10-15

Resting-state networks (RSNs) refer to the spontaneous brain activity generated under resting conditions, which maintain the dynamic connectivity of functional brain networks for automatic perception or higher order cognitive functions. Here, Granger causal connectivity analysis (GCCA) was used to explore brain RSNs in the music frog (Babina daunchina) during different behavioral activity phases. The results reveal that a causal network in the frog brain can be identified during the resting state which reflects both brain lateralization and sexual dimorphism. Specifically (1) ascending causal connections from the left mesencephalon to both sides of the telencephalon are significantly higher than those from the right mesencephalon, while the right telencephalon gives rise to the strongest efferent projections among all brain regions; (2) causal connections from the left mesencephalon in females are significantly higher than those in males and (3) these connections are similar during both the high and low behavioral activity phases in this species although almost all electroencephalograph (EEG) spectral bands showed higher power in the high activity phase for all nodes. The functional features of this network match important characteristics of auditory perception in this species. Thus we propose that this causal network maintains auditory perception during the resting state for unexpected auditory inputs as resting-state networks do in other species. These results are also consistent with the idea that females are more sensitive to auditory stimuli than males during the reproductive season. In addition, these results imply that even when not behaviorally active, the frogs remain vigilant for detecting external stimuli. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

A human brain network derived from coma-causing brainstem lesions.

PubMed

Fischer, David B; Boes, Aaron D; Demertzi, Athena; Evrard, Henry C; Laureys, Steven; Edlow, Brian L; Liu, Hesheng; Saper, Clifford B; Pascual-Leone, Alvaro; Fox, Michael D; Geerling, Joel C

2016-12-06

To characterize a brainstem location specific to coma-causing lesions, and its functional connectivity network. We compared 12 coma-causing brainstem lesions to 24 control brainstem lesions using voxel-based lesion-symptom mapping in a case-control design to identify a site significantly associated with coma. We next used resting-state functional connectivity from a healthy cohort to identify a network of regions functionally connected to this brainstem site. We further investigated the cortical regions of this network by comparing their spatial topography to that of known networks and by evaluating their functional connectivity in patients with disorders of consciousness. A small region in the rostral dorsolateral pontine tegmentum was significantly associated with coma-causing lesions. In healthy adults, this brainstem site was functionally connected to the ventral anterior insula (AI) and pregenual anterior cingulate cortex (pACC). These cortical areas aligned poorly with previously defined resting-state networks, better matching the distribution of von Economo neurons. Finally, connectivity between the AI and pACC was disrupted in patients with disorders of consciousness, and to a greater degree than other brain networks. Injury to a small region in the pontine tegmentum is significantly associated with coma. This brainstem site is functionally connected to 2 cortical regions, the AI and pACC, which become disconnected in disorders of consciousness. This network of brain regions may have a role in the maintenance of human consciousness. © 2016 American Academy of Neurology.

Characterizing individual differences in functional connectivity using dual-regression and seed-based approaches.

PubMed

Smith, David V; Utevsky, Amanda V; Bland, Amy R; Clement, Nathan; Clithero, John A; Harsch, Anne E W; McKell Carter, R; Huettel, Scott A

2014-07-15

A central challenge for neuroscience lies in relating inter-individual variability to the functional properties of specific brain regions. Yet, considerable variability exists in the connectivity patterns between different brain areas, potentially producing reliable group differences. Using sex differences as a motivating example, we examined two separate resting-state datasets comprising a total of 188 human participants. Both datasets were decomposed into resting-state networks (RSNs) using a probabilistic spatial independent component analysis (ICA). We estimated voxel-wise functional connectivity with these networks using a dual-regression analysis, which characterizes the participant-level spatiotemporal dynamics of each network while controlling for (via multiple regression) the influence of other networks and sources of variability. We found that males and females exhibit distinct patterns of connectivity with multiple RSNs, including both visual and auditory networks and the right frontal-parietal network. These results replicated across both datasets and were not explained by differences in head motion, data quality, brain volume, cortisol levels, or testosterone levels. Importantly, we also demonstrate that dual-regression functional connectivity is better at detecting inter-individual variability than traditional seed-based functional connectivity approaches. Our findings characterize robust-yet frequently ignored-neural differences between males and females, pointing to the necessity of controlling for sex in neuroscience studies of individual differences. Moreover, our results highlight the importance of employing network-based models to study variability in functional connectivity. Copyright © 2014 Elsevier Inc. All rights reserved.

A human brain network derived from coma-causing brainstem lesions

PubMed Central

Boes, Aaron D.; Demertzi, Athena; Evrard, Henry C.; Laureys, Steven; Edlow, Brian L.; Liu, Hesheng; Saper, Clifford B.; Pascual-Leone, Alvaro; Geerling, Joel C.

2016-01-01

Objective: To characterize a brainstem location specific to coma-causing lesions, and its functional connectivity network. Methods: We compared 12 coma-causing brainstem lesions to 24 control brainstem lesions using voxel-based lesion-symptom mapping in a case-control design to identify a site significantly associated with coma. We next used resting-state functional connectivity from a healthy cohort to identify a network of regions functionally connected to this brainstem site. We further investigated the cortical regions of this network by comparing their spatial topography to that of known networks and by evaluating their functional connectivity in patients with disorders of consciousness. Results: A small region in the rostral dorsolateral pontine tegmentum was significantly associated with coma-causing lesions. In healthy adults, this brainstem site was functionally connected to the ventral anterior insula (AI) and pregenual anterior cingulate cortex (pACC). These cortical areas aligned poorly with previously defined resting-state networks, better matching the distribution of von Economo neurons. Finally, connectivity between the AI and pACC was disrupted in patients with disorders of consciousness, and to a greater degree than other brain networks. Conclusions: Injury to a small region in the pontine tegmentum is significantly associated with coma. This brainstem site is functionally connected to 2 cortical regions, the AI and pACC, which become disconnected in disorders of consciousness. This network of brain regions may have a role in the maintenance of human consciousness. PMID:27815400

Altered default network resting-state functional connectivity in adolescents with Internet gaming addiction.

PubMed

Ding, Wei-na; Sun, Jin-hua; Sun, Ya-wen; Zhou, Yan; Li, Lei; Xu, Jian-rong; Du, Ya-song

2013-01-01

Excessive use of the Internet has been linked to a variety of negative psychosocial consequences. This study used resting-state functional magnetic resonance imaging (fMRI) to investigate whether functional connectivity is altered in adolescents with Internet gaming addiction (IGA). Seventeen adolescents with IGA and 24 normal control adolescents underwent a 7.3 minute resting-state fMRI scan. Posterior cingulate cortex (PCC) connectivity was determined in all subjects by investigating synchronized low-frequency fMRI signal fluctuations using a temporal correlation method. To assess the relationship between IGA symptom severity and PCC connectivity, contrast images representing areas correlated with PCC connectivity were correlated with the scores of the 17 subjects with IGA on the Chen Internet Addiction Scale (CIAS) and Barratt Impulsiveness Scale-11 (BIS-11) and their hours of Internet use per week. There were no significant differences in the distributions of the age, gender, and years of education between the two groups. The subjects with IGA showed longer Internet use per week (hours) (p<0.0001) and higher CIAS (p<0.0001) and BIS-11 (p = 0.01) scores than the controls. Compared with the control group, subjects with IGA exhibited increased functional connectivity in the bilateral cerebellum posterior lobe and middle temporal gyrus. The bilateral inferior parietal lobule and right inferior temporal gyrus exhibited decreased connectivity. Connectivity with the PCC was positively correlated with CIAS scores in the right precuneus, posterior cingulate gyrus, thalamus, caudate, nucleus accumbens, supplementary motor area, and lingual gyrus. It was negatively correlated with the right cerebellum anterior lobe and left superior parietal lobule. Our results suggest that adolescents with IGA exhibit different resting-state patterns of brain activity. As these alterations are partially consistent with those in patients with substance addiction, they support the hypothesis that IGA as a behavioral addiction that may share similar neurobiological abnormalities with other addictive disorders.

Altered Default Network Resting-State Functional Connectivity in Adolescents with Internet Gaming Addiction

PubMed Central

Li, Lei; Xu, Jian-rong

2013-01-01

Purpose Excessive use of the Internet has been linked to a variety of negative psychosocial consequences. This study used resting-state functional magnetic resonance imaging (fMRI) to investigate whether functional connectivity is altered in adolescents with Internet gaming addiction (IGA). Methods Seventeen adolescents with IGA and 24 normal control adolescents underwent a 7.3 minute resting-state fMRI scan. Posterior cingulate cortex (PCC) connectivity was determined in all subjects by investigating synchronized low-frequency fMRI signal fluctuations using a temporal correlation method. To assess the relationship between IGA symptom severity and PCC connectivity, contrast images representing areas correlated with PCC connectivity were correlated with the scores of the 17 subjects with IGA on the Chen Internet Addiction Scale (CIAS) and Barratt Impulsiveness Scale-11 (BIS-11) and their hours of Internet use per week. Results There were no significant differences in the distributions of the age, gender, and years of education between the two groups. The subjects with IGA showed longer Internet use per week (hours) (p<0.0001) and higher CIAS (p<0.0001) and BIS-11 (p = 0.01) scores than the controls. Compared with the control group, subjects with IGA exhibited increased functional connectivity in the bilateral cerebellum posterior lobe and middle temporal gyrus. The bilateral inferior parietal lobule and right inferior temporal gyrus exhibited decreased connectivity. Connectivity with the PCC was positively correlated with CIAS scores in the right precuneus, posterior cingulate gyrus, thalamus, caudate, nucleus accumbens, supplementary motor area, and lingual gyrus. It was negatively correlated with the right cerebellum anterior lobe and left superior parietal lobule. Conclusion Our results suggest that adolescents with IGA exhibit different resting-state patterns of brain activity. As these alterations are partially consistent with those in patients with substance addiction, they support the hypothesis that IGA as a behavioral addiction that may share similar neurobiological abnormalities with other addictive disorders. PMID:23555827

Structural connectivity allows for multi-threading during rest: the structure of the cortex leads to efficient alternation between resting state exploratory behavior and default mode processing.

PubMed

Senden, Mario; Goebel, Rainer; Deco, Gustavo

2012-05-01

Despite the absence of stimulation or task conditions the cortex exhibits highly structured spatio-temporal activity patterns. These patterns are known as resting state networks (RSNs) and emerge as low-frequency fluctuations (<0.1 Hz) observed in the fMRI signal of human subjects during rest. We are interested in the relationship between structural connectivity of the cortex and the fluctuations exhibited during resting conditions. We are especially interested in the effect of degree of connectivity on resting state dynamics as the default mode network (DMN) is highly connected. We find in experimental resting fMRI data that the DMN is the functional network that is most frequently active and for the longest time. In large-scale computational simulations of the cortex based on the corresponding underlying DTI/DSI based neuroanatomical connectivity matrix, we additionally find a strong correlation between the mean degree of functional networks and the proportion of time they are active. By artificially modifying different types of neuroanatomical connectivity matrices in the model, we were able to demonstrate that only models based on structural connectivity containing hubs give rise to this relationship. We conclude that, during rest, the cortex alternates efficiently between explorations of its externally oriented functional repertoire and internally oriented processing as a consequence of the DMN's high degree of connectivity. Copyright © 2012 Elsevier Inc. All rights reserved.

Advanced Connectivity Analysis (ACA): a Large Scale Functional Connectivity Data Mining Environment.

PubMed

Chen, Rong; Nixon, Erika; Herskovits, Edward

2016-04-01

Using resting-state functional magnetic resonance imaging (rs-fMRI) to study functional connectivity is of great importance to understand normal development and function as well as a host of neurological and psychiatric disorders. Seed-based analysis is one of the most widely used rs-fMRI analysis methods. Here we describe a freely available large scale functional connectivity data mining software package called Advanced Connectivity Analysis (ACA). ACA enables large-scale seed-based analysis and brain-behavior analysis. It can seamlessly examine a large number of seed regions with minimal user input. ACA has a brain-behavior analysis component to delineate associations among imaging biomarkers and one or more behavioral variables. We demonstrate applications of ACA to rs-fMRI data sets from a study of autism.

Intrinsic functional connectivity alterations in progressive supranuclear palsy: Differential effects in frontal cortex, motor, and midbrain networks.

PubMed

Rosskopf, Johannes; Gorges, Martin; Müller, Hans-Peter; Lulé, Dorothée; Uttner, Ingo; Ludolph, Albert C; Pinkhardt, Elmar; Juengling, Freimut D; Kassubek, Jan

2017-07-01

The topography of functional network changes in progressive supranuclear palsy can be mapped by intrinsic functional connectivity MRI. The objective of this study was to study functional connectivity and its clinical and behavioral correlates in dedicated networks comprising the cognition-related default mode and the motor and midbrain functional networks in patients with PSP. Whole-brain-based "resting-state" functional MRI and high-resolution T1-weighted magnetic resonance imaging data together with neuropsychological and video-oculographic data from 34 PSP patients (22 with Richardson subtype and 12 with parkinsonian subtype) and 35 matched healthy controls were subjected to network-based functional connectivity and voxel-based morphometry analysis. After correction for global patterns of brain atrophy, the group comparison between PSP patients and controls revealed significantly decreased functional connectivity (P < 0.05, corrected) in the prefrontal cortex, which was significantly correlated with cognitive performance (P = 0.006). Of note, midbrain network connectivity in PSP patients showed increased connectivity with the thalamus, on the one hand, whereas, on the other hand, lower functional connectivity within the midbrain was significantly correlated with vertical gaze impairment, as quantified by video-oculography (P = 0.004). PSP Richardson subtype showed significantly increased functional motor network connectivity with the medial prefrontal gyrus. PSP-associated neurodegeneration was attributed to both decreased and increased functional connectivity. Decreasing functional connectivity was associated with worse behavioral performance (ie, dementia severity and gaze palsy), whereas the pattern of increased functional connectivity may be a potential adaptive mechanism. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

Nekrasov and Argyres-Douglas theories in spherical Hecke algebra representation

NASA Astrophysics Data System (ADS)

Rim, Chaiho; Zhang, Hong

2017-06-01

AGT conjecture connects Nekrasov instanton partition function of 4D quiver gauge theory with 2D Liouville conformal blocks. We re-investigate this connection using the central extension of spherical Hecke algebra in q-coordinate representation, q being the instanton expansion parameter. Based on AFLT basis together with intertwiners we construct gauge conformal state and demonstrate its equivalence to the Liouville conformal state, with careful attention to the proper scaling behavior of the state. Using the colliding limit of regular states, we obtain the formal expression of irregular conformal states corresponding to Argyres-Douglas theory, which involves summation of functions over Young diagrams.

Center-of-Mass Tomography and Wigner Function for Multimode Photon States

NASA Astrophysics Data System (ADS)

Dudinets, Ivan V.; Man'ko, Vladimir I.

2018-06-01

Tomographic probability representation of multimode electromagnetic field states in the scheme of center-of-mass tomography is reviewed. Both connection of the field state Wigner function and observable Weyl symbols with the center-of-mass tomograms as well as connection of the Grönewold kernel with the center-of-mass tomographic kernel determining the noncommutative product of the tomograms are obtained. The dual center-of-mass tomogram of the photon states are constructed and the dual tomographic kernel is obtained. The models of other generalized center-of-mass tomographies are discussed. Example of two-mode even and odd Schrödinger cat states is presented in details.

A study of structural and functional connectivity in early Alzheimer's disease using rest fMRI and diffusion tensor imaging.

PubMed

Balachandar, R; John, J P; Saini, J; Kumar, K J; Joshi, H; Sadanand, S; Aiyappan, S; Sivakumar, P T; Loganathan, S; Varghese, M; Bharath, S

2015-05-01

Alzheimer's disease (AD) is a progressive neurodegenerative condition where in early diagnosis and interventions are key policy priorities in dementia services and research. We studied the functional and structural connectivity in mild AD to determine the nature of connectivity changes that coexist with neurocognitive deficits in the early stages of AD. Fifteen mild AD subjects and 15 cognitively healthy controls (CHc) matched for age and gender, underwent detailed neurocognitive assessment and magnetic resonance imaging (MRI) of resting state functional MRI (rs-fMRI) and diffusion tensor imaging (DTI). Rest fMRI was analyzed using dual regression approach and DTI by voxel wise statistics. Patients with mild AD had significantly lower functional connectivity (FC) within the default mode network and increased FC within the executive network. The mild AD group scored significantly lower in all domains of cognition compared with CHc. But fractional anisotropy did not significantly (p < 0.05) differ between the groups. Resting state functional connectivity alterations are noted during initial stages of cognitive decline in AD, even when there are no significant white matter microstructural changes. Copyright © 2014 John Wiley & Sons, Ltd.

Exercise alters resting-state functional connectivity of motor circuits in parkinsonian rats.

PubMed

Wang, Zhuo; Guo, Yumei; Myers, Kalisa G; Heintz, Ryan; Peng, Yu-Hao; Maarek, Jean-Michel I; Holschneider, Daniel P

2015-01-01

Few studies have examined changes in functional connectivity after long-term aerobic exercise. We examined the effects of 4 weeks of forced running wheel exercise on the resting-state functional connectivity (rsFC) of motor circuits of rats subjected to bilateral 6-hydroxydopamine lesion of the dorsal striatum. Our results showed substantial similarity between lesion-induced changes in rsFC in the rats and alterations in rsFC reported in Parkinson's disease subjects, including disconnection of the dorsolateral striatum. Exercise in lesioned rats resulted in: (1) normalization of many of the lesion-induced alterations in rsFC, including reintegration of the dorsolateral striatum into the motor network; (2) emergence of the ventrolateral striatum as a new broadly connected network hub; and (3) increased rsFC among the motor cortex, motor thalamus, basal ganglia, and cerebellum. Our results showed for the first time that long-term exercise training partially reversed lesion-induced alterations in rsFC of the motor circuits, and in addition enhanced functional connectivity in specific motor pathways in the parkinsonian rats, which could underlie recovery in motor functions observed in these animals. Copyright © 2015 Elsevier Inc. All rights reserved.

The relationship between default mode network connectivity and social functioning in individuals at familial high-risk for schizophrenia.

PubMed

Dodell-Feder, David; Delisi, Lynn E; Hooker, Christine I

2014-06-01

Unaffected first-degree relatives of individuals with schizophrenia (i.e., those at familial high-risk [FHR]), demonstrate social dysfunction qualitatively similar though less severe than that of their affected relatives. These social difficulties may be the consequence of genetically conferred disruption to aspects of the default mode network (DMN), such as the dMPFC subsystem, which overlaps with the network of brain regions recruited during social cognitive processes. In the present study, we investigate this possibility, testing DMN connectivity and its relationship to social functioning in FHR using resting-state fMRI. Twenty FHR individuals and 17 controls underwent fMRI during a resting-state scan. Hypothesis-driven functional connectivity analyses examined ROI-to-ROI correlations between the DMN's hubs, and regions of the dMPFC subsystem and MTL subsystem. Connectivity values were examined in relationship to a measure of social functioning and empathy/perspective-taking. Results demonstrate that FHR exhibit reduced connectivity specifically within the dMPFC subsystem of the DMN. Certain ROI-to-ROI correlations predicted aspects of social functioning and empathy/perspective-taking across all participants. Together, the data indicate that disruption to the dMPFC subsystem of the DMN may be associated with familial risk for schizophrenia, and that these intrinsic connections may carry measurable consequences for social functioning. Copyright © 2014 Elsevier B.V. All rights reserved.

The relationship between default mode network connectivity and social functioning in individuals at familial high-risk for schizophrenia

PubMed Central

Dodell-Feder, David; DeLisi, Lynn E.; Hooker, Christine I.

2014-01-01

Unaffected first-degree relatives of individuals with schizophrenia (i.e., those at familial high-risk [FHR]), demonstrate social dysfunction qualitatively similar though less severe than that of their affected relatives. These social difficulties may be the consequence of genetically conferred disruption to aspects of the default mode network (DMN), such as the dMPFC subsystem, which overlaps with the network of brain regions recruited during social cognitive processes. In the present study, we investigate this possibility, testing DMN connectivity and its relationship to social functioning in FHR using resting-state fMRI. Twenty FHR individuals and 17 controls underwent fMRI during a resting-state scan. Hypothesis-driven functional connectivity analyses examined ROI-to-ROI correlations between the DMN’s hubs, and regions of the dMPFC subsystem and MTL subsystem. Connectivity values were examined in relationship to a measure of social functioning and empathy/perspective-taking. Results demonstrate that FHR exhibit reduced connectivity specifically within the dMPFC subsystem of the DMN. Certain ROI-to-ROI correlations predicted aspects of social functioning and empathy/perspective-taking across all participants. Together, the data indicate that disruption to the dMPFC subsystem of the DMN may be associated with familial risk for schizophrenia, and that these intrinsic connections may carry measurable consequences for social functioning. PMID:24768131

How are different neural networks related to consciousness?

PubMed

Qin, Pengmin; Wu, Xuehai; Huang, Zirui; Duncan, Niall W; Tang, Weijun; Wolff, Annemarie; Hu, Jin; Gao, Liang; Jin, Yi; Wu, Xing; Zhang, Jianfeng; Lu, Lu; Wu, Chunping; Qu, Xiaoying; Mao, Ying; Weng, Xuchu; Zhang, Jun; Northoff, Georg

2015-10-01

We aimed to investigate the roles of different resting-state networks in predicting both the actual level of consciousness and its recovery in brain injury patients. We investigated resting-state functional connectivity within different networks in patients with varying levels of consciousness: unresponsive wakefulness syndrome (UWS; n = 56), minimally conscious state (MCS; n = 29), and patients with brain lesions but full consciousness (BL; n = 48). Considering the actual level of consciousness, we compared the strength of network connectivity among the patient groups. We then checked the presence of connections between specific regions in individual patients and calculated the frequency of this in the different patient groups. Considering the recovery of consciousness, we split the UWS group into 2 subgroups according to recovery: those who emerged from UWS (UWS-E) and those who remained in UWS (UWS-R). The above analyses were repeated on these 2 subgroups. Functional connectivity strength in salience network (SN), especially connectivity between the supragenual anterior cingulate cortex (SACC) and left anterior insula (LAI), was reduced in the unconscious state (UWS) compared to the conscious state (MCS and BL). Moreover, at the individual level, SACC-LAI connectivity was more present in MCS than in UWS. Default-mode network (DMN) connectivity strength, especially between the posterior cingulate cortex (PCC) and left lateral parietal cortex (LLPC), was reduced in UWS-R compared with UWS-E. Furthermore, PCC-LLPC connectivity was more present in UWS-E than in UWS-R. Our findings show that SN (SACC-LAI) connectivity correlates with behavioral signs of consciousness, whereas DMN (PCC-LLPC) connectivity instead predicts recovery of consciousness. © 2015 American Neurological Association.

Hemispheric Lateralization of Resting-State Functional Connectivity of the Anterior Insula: Association with Age, Gender, and a Novelty-Seeking Trait

PubMed Central

Kann, Sarah; Zhang, Sheng; Manza, Peter; Leung, Hoi-Chung

2016-01-01

Abstract Resting-state functional connectivity (rsFC) is widely used to examine cerebral functional organization. The imaging literature has described lateralization of insula activations during cognitive and affective processing. Evidence appears to support a role of the right-hemispheric insula in attentional orientation to salient stimulus, interoception, and physiological arousal, and a role of the left-hemispheric insula in cognitive and affective control, as well as perspective taking. In this study, in a large data set of healthy adults, we examined lateralization of the rsFC of the anterior insula (AI) by computing a laterality index (LI) of connectivity with 54 regions from the Automated Anatomic Labeling atlas. At a corrected threshold (p < 0.001), the AI is left lateralized in connectivity with the dorsomedial prefrontal cortex, superior frontal gyrus, inferior frontal cortex, and posterior orbital gyrus and right lateralized in connectivity with the postcentral gyrus, supramarginal gyrus, and superior parietal lobule. In gender differences, women, but not men, showed right-lateralized connectivity to the thalamus. Furthermore, in a subgroup of participants assessed by the tridimensional personality questionnaire, novelty seeking is correlated with the extent of left lateralization of AI connectivity to the pallidum and putamen in men and with the extent of right lateralization of AI connectivity to the parahippocampal gyrus in women. These findings support hemispheric functional differentiation of the AI. PMID:27604154

Hemispheric Lateralization of Resting-State Functional Connectivity of the Anterior Insula: Association with Age, Gender, and a Novelty-Seeking Trait.

PubMed

Kann, Sarah; Zhang, Sheng; Manza, Peter; Leung, Hoi-Chung; Li, Chiang-Shan R

2016-11-01

Resting-state functional connectivity (rsFC) is widely used to examine cerebral functional organization. The imaging literature has described lateralization of insula activations during cognitive and affective processing. Evidence appears to support a role of the right-hemispheric insula in attentional orientation to salient stimulus, interoception, and physiological arousal, and a role of the left-hemispheric insula in cognitive and affective control, as well as perspective taking. In this study, in a large data set of healthy adults, we examined lateralization of the rsFC of the anterior insula (AI) by computing a laterality index (LI) of connectivity with 54 regions from the Automated Anatomic Labeling atlas. At a corrected threshold (p < 0.001), the AI is left lateralized in connectivity with the dorsomedial prefrontal cortex, superior frontal gyrus, inferior frontal cortex, and posterior orbital gyrus and right lateralized in connectivity with the postcentral gyrus, supramarginal gyrus, and superior parietal lobule. In gender differences, women, but not men, showed right-lateralized connectivity to the thalamus. Furthermore, in a subgroup of participants assessed by the tridimensional personality questionnaire, novelty seeking is correlated with the extent of left lateralization of AI connectivity to the pallidum and putamen in men and with the extent of right lateralization of AI connectivity to the parahippocampal gyrus in women. These findings support hemispheric functional differentiation of the AI.

12-h abstinence-induced functional connectivity density changes and craving in young smokers: a resting-state study.

PubMed

Zhao, Shuzhi; Li, Yangding; Li, Min; Wang, Ruonan; Bi, Yanzhi; Zhang, Yajuan; Lu, Xiaoqi; Yu, Dahua; Yang, Likun; Yuan, Kai

2018-06-20

Studying the neural correlates of craving to smoke is of great importance to improve treatment outcomes in smoking addiction. According to previous studies, the critical roles of striatum and frontal brain regions had been revealed in addiction. However, few studies focused on the hub of brain regions in the 12 h abstinence induced craving in young smokers. Thirty-one young male smokers were enrolled in the present study. A within-subject experiment design was carried out to compare functional connectivity density between 12-h smoking abstinence and smoking satiety conditions during resting state in young adult smokers by using functional connectivity density mapping (FCDM). Then, the functional connectivity density changes during smoking abstinence versus satiety were further used to examine correlations with abstinence-induced changes in subjective craving. We found young adult smokers in abstinence state (vs satiety) had higher local functional connectivity density (lFCD) and global functional connectivity density (gFCD) in brain regions including striatal subregions (i.e., bilateral caudate and putamen), frontal regions (i.e., anterior cingulate cortex (ACC) and orbital frontal cortex (OFC)) and bilateral insula. We also found higher lFCD during smoking abstinence (vs satiety) in bilateral thalamus. Additionally, the lFCD changes of the left ACC, bilateral caudate and right OFC were positively correlated with the changes in craving induced by abstinence (i.e., abstinence minus satiety) in young adult smokers. The present findings improve the understanding of the effects of acute smoking abstinence on the hubs of brain gray matter in the abstinence-induces craving and may contribute new insights into the neural mechanism of abstinence-induced craving in young smokers in smoking addiction.

Altered Functional Connectivity of Insular Subregions in Alzheimer’s Disease

PubMed Central

Liu, Xingyun; Chen, Xiaodan; Zheng, Weimin; Xia, Mingrui; Han, Ying; Song, Haiqing; Li, Kuncheng; He, Yong; Wang, Zhiqun

2018-01-01

Recent researches have demonstrated that the insula is the crucial hub of the human brain networks and most vulnerable region of Alzheimer’s disease (AD). However, little is known about the changes of functional connectivity of insular subregions in the AD patients. In this study, we collected resting-state functional magnetic resonance imaging (fMRI) data including 32 AD patients and 38 healthy controls (HCs). By defining three subregions of insula, we mapped whole-brain resting-state functional connectivity (RSFC) and identified several distinct RSFC patterns of the insular subregions: For positive connectivity, three cognitive-related RSFC patterns were identified within insula that suggest anterior-to-posterior functional subdivisions: (1) an dorsal anterior zone of the insula that exhibits RSFC with executive control network (ECN); (2) a ventral anterior zone of insula, exhibits functional connectivity with the salience network (SN); (3) a posterior zone along the insula exhibits functional connectivity with the sensorimotor network (SMN). In addition, we found significant negative connectivities between the each insular subregion and several special default mode network (DMN) regions. Compared with controls, the AD patients demonstrated distinct disruption of positive RSFCs in the different network (ECN and SMN), suggesting the impairment of the functional integrity. There were no differences of the positive RSFCs in the SN between the two groups. On the other hand, several DMN regions showed increased negative RSFCs to the sub-region of insula in the AD patients, indicating compensatory plasticity. Furthermore, these abnormal insular subregions RSFCs are closely correlated with cognitive performances in the AD patients. Our findings suggested that different insular subregions presented distinct RSFC patterns with various functional networks, which are differently affected in the AD patients. PMID:29695961

Altered Functional Connectivity of Insular Subregions in Alzheimer's Disease.

PubMed

Liu, Xingyun; Chen, Xiaodan; Zheng, Weimin; Xia, Mingrui; Han, Ying; Song, Haiqing; Li, Kuncheng; He, Yong; Wang, Zhiqun

2018-01-01

Recent researches have demonstrated that the insula is the crucial hub of the human brain networks and most vulnerable region of Alzheimer's disease (AD). However, little is known about the changes of functional connectivity of insular subregions in the AD patients. In this study, we collected resting-state functional magnetic resonance imaging (fMRI) data including 32 AD patients and 38 healthy controls (HCs). By defining three subregions of insula, we mapped whole-brain resting-state functional connectivity (RSFC) and identified several distinct RSFC patterns of the insular subregions: For positive connectivity, three cognitive-related RSFC patterns were identified within insula that suggest anterior-to-posterior functional subdivisions: (1) an dorsal anterior zone of the insula that exhibits RSFC with executive control network (ECN); (2) a ventral anterior zone of insula, exhibits functional connectivity with the salience network (SN); (3) a posterior zone along the insula exhibits functional connectivity with the sensorimotor network (SMN). In addition, we found significant negative connectivities between the each insular subregion and several special default mode network (DMN) regions. Compared with controls, the AD patients demonstrated distinct disruption of positive RSFCs in the different network (ECN and SMN), suggesting the impairment of the functional integrity. There were no differences of the positive RSFCs in the SN between the two groups. On the other hand, several DMN regions showed increased negative RSFCs to the sub-region of insula in the AD patients, indicating compensatory plasticity. Furthermore, these abnormal insular subregions RSFCs are closely correlated with cognitive performances in the AD patients. Our findings suggested that different insular subregions presented distinct RSFC patterns with various functional networks, which are differently affected in the AD patients.

Changes in Neural Connectivity and Memory Following a Yoga Intervention for Older Adults: A Pilot Study

PubMed Central

Eyre, Harris A.; Acevedo, Bianca; Yang, Hongyu; Siddarth, Prabha; Van Dyk, Kathleen; Ercoli, Linda; Leaver, Amber M.; Cyr, Natalie St.; Narr, Katherine; Baune, Bernhard T.; Khalsa, Dharma S.; Lavretsky, Helen

2016-01-01

Background: No study has explored the effect of yoga on cognitive decline and resting-state functional connectivity. Objectives: This study explored the relationship between performance on memory tests and resting-state functional connectivity before and after a yoga intervention versus active control for subjects with mild cognitive impairment (MCI). Methods: Participants ( ≥ 55 y) with MCI were randomized to receive a yoga intervention or active “gold-standard” control (i.e., memory enhancement training (MET)) for 12 weeks. Resting-state functional magnetic resonance imaging was used to map correlations between brain networks and memory performance changes over time. Default mode networks (DMN), language and superior parietal networks were chosen as networks of interest to analyze the association with changes in verbal and visuospatial memory performance. Results: Fourteen yoga and 11 MET participants completed the study. The yoga group demonstrated a statistically significant improvement in depression and visuospatial memory. We observed improved verbal memory performance correlated with increased connectivity between the DMN and frontal medial cortex, pregenual anterior cingulate cortex, right middle frontal cortex, posterior cingulate cortex, and left lateral occipital cortex. Improved verbal memory performance positively correlated with increased connectivity between the language processing network and the left inferior frontal gyrus. Improved visuospatial memory performance correlated inversely with connectivity between the superior parietal network and the medial parietal cortex. Conclusion:Yoga may be as effective as MET in improving functional connectivity in relation to verbal memory performance. These findings should be confirmed in larger prospective studies. PMID:27060939

Functional resting-state networks are differentially affected in schizophrenia

PubMed Central

Woodward, Neil D.; Rogers, Baxter; Heckers, Stephan

2011-01-01

Neurobiological theories posit that schizophrenia relates to disturbances in connectivity between brain regions. Resting-state functional magnetic resonance imaging is a powerful tool for examining functional connectivity and has revealed several canonical brain networks, including the default mode, dorsal attention, executive control, and salience networks. The purpose of this study was to examine changes in these networks in schizophrenia. 42 patients with schizophrenia and 61 healthy subjects completed a RS-fMRI scanning session. Seed-based region-of-interest correlation analysis was used to identify the default mode, dorsal attention, executive control, and salience networks. Compared to healthy subjects, individuals with schizophrenia demonstrated greater connectivity between the posterior cingulate cortex, a key hub of the default mode, and the left inferior gyrus, left middle frontal gyrus, and left middle temporal gyrus. Interestingly, these regions were more strongly connected to the executive control network in healthy control subjects. In contrast to the default mode, patients demonstrated less connectivity in the executive control and dorsal attention networks. No differences were observed in the salience network. The results indicate that resting-state networks are differentially affected in schizophrenia. The alterations are characterized by reduced segregation between the default mode and executive control networks in the prefrontal cortex and temporal lobe, and reduced connectivity in the dorsal attention and executive control networks. The changes suggest that the process of functional specialization is altered in schizophrenia. Further work is needed to determine if the alterations are related to disturbances in white matter connectivity, neurodevelopmental abnormalities, and genetic risk for schizophrenia. PMID:21458238

Resting-state fMRI and social cognition: An opportunity to connect.

PubMed

Doruyter, Alex; Groenewold, Nynke A; Dupont, Patrick; Stein, Dan J; Warwick, James M

2017-09-01

Many psychiatric disorders are characterized by altered social cognition. The importance of social cognition has previously been recognized by the National Institute of Mental Health Research Domain Criteria project, in which it features as a core domain. Social task-based functional magnetic resonance imaging (fMRI) currently offers the most direct insight into how the brain processes social information; however, resting-state fMRI may be just as important in understanding the biology and network nature of social processing. Resting-state fMRI allows researchers to investigate the functional relationships between brain regions in a neutral state: so-called resting functional connectivity (RFC). There is evidence that RFC is predictive of how the brain processes information during social tasks. This is important because it shifts the focus from possibly context-dependent aberrations to context-independent aberrations in functional network architecture. Rather than being analysed in isolation, the study of resting-state brain networks shows promise in linking results of task-based fMRI results, structural connectivity, molecular imaging findings, and performance measures of social cognition-which may prove crucial in furthering our understanding of the social brain. Copyright © 2017 John Wiley & Sons, Ltd.

Anti-correlated Networks, Global Signal Regression, and the Effects of Caffeine in Resting-State Functional MRI

PubMed Central

Wong, Chi Wah; Olafsson, Valur; Tal, Omer; Liu, Thomas T.

2012-01-01

Resting-state functional connectivity magnetic resonance imaging is proving to be an essential tool for the characterization of functional networks in the brain. Two of the major networks that have been identified are the default mode network (DMN) and the task positive network (TPN). Although prior work indicates that these two networks are anti-correlated, the findings are controversial because the anti-correlations are often found only after the application of a pre-processing step, known as global signal regression, that can produce artifactual anti-correlations. In this paper, we show that, for subjects studied in an eyes-closed rest state, caffeine can significantly enhance the detection of anti-correlations between the DMN and TPN without the need for global signal regression. In line with these findings, we find that caffeine also leads to widespread decreases in connectivity and global signal amplitude. Using a recently introduced geometric model of global signal effects, we demonstrate that these decreases are consistent with the removal of an additive global signal confound. In contrast to the effects observed in the eyes-closed rest state, caffeine did not lead to significant changes in global functional connectivity in the eyes-open rest state. PMID:22743194

Bayesian network analysis revealed the connectivity difference of the default mode network from the resting-state to task-state

PubMed Central

Wu, Xia; Yu, Xinyu; Yao, Li; Li, Rui

2014-01-01

Functional magnetic resonance imaging (fMRI) studies have converged to reveal the default mode network (DMN), a constellation of regions that display co-activation during resting-state but co-deactivation during attention-demanding tasks in the brain. Here, we employed a Bayesian network (BN) analysis method to construct a directed effective connectivity model of the DMN and compared the organizational architecture and interregional directed connections under both resting-state and task-state. The analysis results indicated that the DMN was consistently organized into two closely interacting subsystems in both resting-state and task-state. The directed connections between DMN regions, however, changed significantly from the resting-state to task-state condition. The results suggest that the DMN intrinsically maintains a relatively stable structure whether at rest or performing tasks but has different information processing mechanisms under varied states. PMID:25309414

Dynamic functional connectivity and its behavioral correlates beyond vigilance.

PubMed

Patanaik, Amiya; Tandi, Jesisca; Ong, Ju Lynn; Wang, Chenhao; Zhou, Juan; Chee, Michael W L

2018-04-25

Fluctuations in resting-state functional connectivity and global signal have been found to correspond with vigilance fluctuations, but their associations with other behavioral measures are unclear. We evaluated 52 healthy adolescents after a week of adequate sleep followed by five nights of sleep restriction to unmask inter-individual differences in cognition and mood. Resting state scans obtained at baseline only, analyzed using sliding window analysis, consistently yielded two polar dynamic functional connectivity states (DCSs) corresponding to previously reported 'low arousal' and 'high arousal' states. We found that the relative temporal preponderance of two dynamic connectivity states (DCS) in well-rested participants, indexed by a median split of participants, based on the relative time spent in these DCS, revealed highly significant group differences in vigilance at baseline and its decline following multiple nights of sleep restriction. Group differences in processing speed and working memory following manipulation but not at baseline suggest utility of DCS in predicting cognitive vulnerabilities unmasked by a stressor like sleep restriction. DCS temporal predominance was uninformative about mood and sleepiness speaking to specificity in its behavioral predictions. Global signal fluctuation provided information confined to vigilance. This appears to be related to head motion, which increases during periods of low arousal. Copyright © 2018. Published by Elsevier Inc.

Electrophysiological resting-state biomarker for diagnosing mesial temporal lobe epilepsy with hippocampal sclerosis.

PubMed

Jin, Seung-Hyun; Chung, Chun Kee

2017-01-01

The main aim of the present study was to evaluate whether resting-state functional connectivity of magnetoencephalography (MEG) signals can differentiate patients with mesial temporal lobe epilepsy (MTLE) from healthy controls (HC) and can differentiate between right and left MTLE as a diagnostic biomarker. To this end, a support vector machine (SVM) method among various machine learning algorithms was employed. We compared resting-state functional networks between 46 MTLE (right MTLE=23; left MTLE=23) patients with histologically proven HS who were free of seizure after surgery, and 46 HC. The optimal SVM group classifier distinguished MTLE patients with a mean accuracy of 95.1% (sensitivity=95.8%; specificity=94.3%). Increased connectivity including the right posterior cingulate gyrus and decreased connectivity including at least one sensory-related resting-state network were key features reflecting the differences between MTLE patients and HC. The optimal SVM model distinguished between right and left MTLE patients with a mean accuracy of 76.2% (sensitivity=76.0%; specificity=76.5%). We showed the potential of electrophysiological resting-state functional connectivity, which reflects brain network reorganization in MTLE patients, as a possible diagnostic biomarker to differentiate MTLE patients from HC and differentiate between right and left MTLE patients. Copyright © 2016 Elsevier B.V. All rights reserved.

Distinct hippocampal functional networks revealed by tractography-based parcellation.

PubMed

Adnan, Areeba; Barnett, Alexander; Moayedi, Massieh; McCormick, Cornelia; Cohn, Melanie; McAndrews, Mary Pat

2016-07-01

Recent research suggests the anterior and posterior hippocampus form part of two distinct functional neural networks. Here we investigate the structural underpinnings of this functional connectivity difference using diffusion-weighted imaging-based parcellation. Using this technique, we substantiated that the hippocampus can be parcellated into distinct anterior and posterior segments. These structurally defined segments did indeed show different patterns of resting state functional connectivity, in that the anterior segment showed greater connectivity with temporal and orbitofrontal cortex, whereas the posterior segment was more highly connected to medial and lateral parietal cortex. Furthermore, we showed that the posterior hippocampal connectivity to memory processing regions, including the dorsolateral prefrontal cortex, parahippocampal, inferior temporal and fusiform gyri and the precuneus, predicted interindividual relational memory performance. These findings provide important support for the integration of structural and functional connectivity in understanding the brain networks underlying episodic memory.

Tracking ongoing cognition in individuals using brief, whole-brain functional connectivity patterns

PubMed Central

Gonzalez-Castillo, Javier; Hoy, Colin W.; Handwerker, Daniel A.; Robinson, Meghan E.; Buchanan, Laura C.; Saad, Ziad S.; Bandettini, Peter A.

2015-01-01

Functional connectivity (FC) patterns in functional MRI exhibit dynamic behavior on the scale of seconds, with rich spatiotemporal structure and limited sets of whole-brain, quasi-stable FC configurations (FC states) recurring across time and subjects. Based on previous evidence linking various aspects of cognition to group-level, minute-to-minute FC changes in localized connections, we hypothesized that whole-brain FC states may reflect the global, orchestrated dynamics of cognitive processing on the scale of seconds. To test this hypothesis, subjects were continuously scanned as they engaged in and transitioned between mental states dictated by tasks. FC states computed within windows as short as 22.5 s permitted robust tracking of cognition in single subjects with near perfect accuracy. Accuracy dropped markedly for subjects with the lowest task performance. Spatially restricting FC information decreased accuracy at short time scales, emphasizing the distributed nature of whole-brain FC dynamics, beyond univariate magnitude changes, as valuable markers of cognition. PMID:26124112

Electrophysiological signatures of atypical intrinsic brain connectivity networks in autism

NASA Astrophysics Data System (ADS)

Shou, Guofa; Mosconi, Matthew W.; Wang, Jun; Ethridge, Lauren E.; Sweeney, John A.; Ding, Lei

2017-08-01

Objective. Abnormal local and long-range brain connectivity have been widely reported in autism spectrum disorder (ASD), yet the nature of these abnormalities and their functional relevance at distinct cortical rhythms remains unknown. Investigations of intrinsic connectivity networks (ICNs) and their coherence across whole brain networks hold promise for determining whether patterns of functional connectivity abnormalities vary across frequencies and networks in ASD. In the present study, we aimed to probe atypical intrinsic brain connectivity networks in ASD from resting-state electroencephalography (EEG) data via characterizing the whole brain network. Approach. Connectivity within individual ICNs (measured by spectral power) and between ICNs (measured by coherence) were examined at four canonical frequency bands via a time-frequency independent component analysis on high-density EEG, which were recorded from 20 ASD and 20 typical developing (TD) subjects during an eyes-closed resting state. Main results. Among twelve identified electrophysiological ICNs, individuals with ASD showed hyper-connectivity in individual ICNs and hypo-connectivity between ICNs. Functional connectivity alterations in ASD were more severe in the frontal lobe and the default mode network (DMN) and at low frequency bands. These functional connectivity measures also showed abnormal age-related associations in ICNs related to frontal, temporal and motor regions in ASD. Significance. Our findings suggest that ASD is characterized by the opposite directions of abnormalities (i.e. hypo- and hyper-connectivity) in the hierarchical structure of the whole brain network, with more impairments in the frontal lobe and the DMN at low frequency bands, which are critical for top-down control of sensory systems, as well as for both cognition and social skills.

Individual variation in functional brain connectivity: implications for personalized approaches to psychiatric disease.

PubMed

Finn, Emily S; Todd Constable, R

2016-09-01

Functional brain connectivity measured with functional magnetic resonance imaging (fMRI) is a popular technique for investigating neural organization in both healthy subjects and patients with mental illness. Despite a rapidly growing body of literature, however, functional connectivity research has yet to deliver biomarkers that can aid psychiatric diagnosis or prognosis at the single-subject level. One impediment to developing such practical tools has been uncertainty regarding the ratio of intra- to interindividual variability in functional connectivity; in other words, how much variance is state- versus trait-related. Here, we review recent evidence that functional connectivity profiles are both reliable within subjects and unique across subjects, and that features of these profiles relate to behavioral phenotypes. Together, these results suggest the potential to discover reliable correlates of present and future illness and/or response to treatment in the strength of an individual's functional brain connections. Ultimately, this work could help develop personalized approaches to psychiatric illness.

Detecting nonlinear dynamics of functional connectivity

NASA Astrophysics Data System (ADS)

LaConte, Stephen M.; Peltier, Scott J.; Kadah, Yasser; Ngan, Shing-Chung; Deshpande, Gopikrishna; Hu, Xiaoping

2004-04-01

Functional magnetic resonance imaging (fMRI) is a technique that is sensitive to correlates of neuronal activity. The application of fMRI to measure functional connectivity of related brain regions across hemispheres (e.g. left and right motor cortices) has great potential for revealing fundamental physiological brain processes. Primarily, functional connectivity has been characterized by linear correlations in resting-state data, which may not provide a complete description of its temporal properties. In this work, we broaden the measure of functional connectivity to study not only linear correlations, but also those arising from deterministic, non-linear dynamics. Here the delta-epsilon approach is extended and applied to fMRI time series. The method of delays is used to reconstruct the joint system defined by a reference pixel and a candidate pixel. The crux of this technique relies on determining whether the candidate pixel provides additional information concerning the time evolution of the reference. As in many correlation-based connectivity studies, we fix the reference pixel. Every brain location is then used as a candidate pixel to estimate the spatial pattern of deterministic coupling with the reference. Our results indicate that measured connectivity is often emphasized in the motor cortex contra-lateral to the reference pixel, demonstrating the suitability of this approach for functional connectivity studies. In addition, discrepancies with traditional correlation analysis provide initial evidence for non-linear dynamical properties of resting-state fMRI data. Consequently, the non-linear characterization provided from our approach may provide a more complete description of the underlying physiology and brain function measured by this type of data.

Dynamic connectivity regression: Determining state-related changes in brain connectivity

PubMed Central

Cribben, Ivor; Haraldsdottir, Ragnheidur; Atlas, Lauren Y.; Wager, Tor D.; Lindquist, Martin A.

2014-01-01

Most statistical analyses of fMRI data assume that the nature, timing and duration of the psychological processes being studied are known. However, often it is hard to specify this information a priori. In this work we introduce a data-driven technique for partitioning the experimental time course into distinct temporal intervals with different multivariate functional connectivity patterns between a set of regions of interest (ROIs). The technique, called Dynamic Connectivity Regression (DCR), detects temporal change points in functional connectivity and estimates a graph, or set of relationships between ROIs, for data in the temporal partition that falls between pairs of change points. Hence, DCR allows for estimation of both the time of change in connectivity and the connectivity graph for each partition, without requiring prior knowledge of the nature of the experimental design. Permutation and bootstrapping methods are used to perform inference on the change points. The method is applied to various simulated data sets as well as to an fMRI data set from a study (N=26) of a state anxiety induction using a socially evaluative threat challenge. The results illustrate the method’s ability to observe how the networks between different brain regions changed with subjects’ emotional state. PMID:22484408

Altered Coupling Between Resting-State Cerebral Blood Flow and Functional Connectivity in Schizophrenia.

PubMed

Zhu, Jiajia; Zhuo, Chuanjun; Xu, Lixue; Liu, Feng; Qin, Wen; Yu, Chunshui

2017-10-21

Respective changes in resting-state cerebral blood flow (CBF) and functional connectivity in schizophrenia have been reported. However, their coupling alterations in schizophrenia remain largely unknown. 89 schizophrenia patients and 90 sex- and age-matched healthy controls underwent resting-state functional MRI to calculate functional connectivity strength (FCS) and arterial spin labeling imaging to compute CBF. The CBF-FCS coupling of the whole gray matter and the CBF/FCS ratio (the amount of blood supply per unit of connectivity strength) of each voxel were compared between the 2 groups. Whole gray matter CBF-FCS coupling was decreased in schizophrenia patients relative to healthy controls. In schizophrenia patients, the decreased CBF/FCS ratio was predominantly located in cognitive- and emotional-related brain regions, including the dorsolateral prefrontal cortex, insula, hippocampus and thalamus, whereas an increased CBF/FCS ratio was mainly identified in the sensorimotor regions, including the putamen, and sensorimotor, mid-cingulate and visual cortices. These findings suggest that the neurovascular decoupling in the brain may be a possible neuropathological mechanism of schizophrenia. © The Author 2017. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com

Resting state functional connectivity of the anterior striatum and prefrontal cortex predicts reading performance in school-age children.

PubMed

Alcauter, Sarael; García-Mondragón, Liliana; Gracia-Tabuenca, Zeus; Moreno, Martha B; Ortiz, Juan J; Barrios, Fernando A

2017-11-01

The current study investigated the neural basis of reading performance in 60 school-age Spanish-speaking children, aged 6 to 9years. By using a data-driven approach and an automated matching procedure, we identified a left-lateralized resting state network that included typical language regions (Wernicke's and Broca's regions), prefrontal cortex, pre- and post-central gyri, superior and middle temporal gyri, cerebellum, and subcortical regions, and explored its relevance for reading performance (accuracy, comprehension and speed). Functional connectivity of the left frontal and temporal cortices and subcortical regions predicted reading speed. These results extend previous findings on the relationship between functional connectivity and reading competence in children, providing new evidence about such relationships in previously unexplored regions in the resting brain, including the left caudate, putamen and thalamus. This work highlights the relevance of a broad network, functionally synchronized in the resting state, for the acquisition and perfecting of reading abilities in young children. Copyright © 2017 Elsevier Inc. All rights reserved.

Dynamic functional connectivity using state-based dynamic community structure: method and application to opioid analgesia.

PubMed

Robinson, Lucy F; Atlas, Lauren Y; Wager, Tor D

2015-03-01

We present a new method, State-based Dynamic Community Structure, that detects time-dependent community structure in networks of brain regions. Most analyses of functional connectivity assume that network behavior is static in time, or differs between task conditions with known timing. Our goal is to determine whether brain network topology remains stationary over time, or if changes in network organization occur at unknown time points. Changes in network organization may be related to shifts in neurological state, such as those associated with learning, drug uptake or experimental conditions. Using a hidden Markov stochastic blockmodel, we define a time-dependent community structure. We apply this approach to data from a functional magnetic resonance imaging experiment examining how contextual factors influence drug-induced analgesia. Results reveal that networks involved in pain, working memory, and emotion show distinct profiles of time-varying connectivity. Copyright © 2014 Elsevier Inc. All rights reserved.

Resting State fMRI Functional Connectivity-Based Classification Using a Convolutional Neural Network Architecture

PubMed Central

Meszlényi, Regina J.; Buza, Krisztian; Vidnyánszky, Zoltán

2017-01-01

Machine learning techniques have become increasingly popular in the field of resting state fMRI (functional magnetic resonance imaging) network based classification. However, the application of convolutional networks has been proposed only very recently and has remained largely unexplored. In this paper we describe a convolutional neural network architecture for functional connectome classification called connectome-convolutional neural network (CCNN). Our results on simulated datasets and a publicly available dataset for amnestic mild cognitive impairment classification demonstrate that our CCNN model can efficiently distinguish between subject groups. We also show that the connectome-convolutional network is capable to combine information from diverse functional connectivity metrics and that models using a combination of different connectivity descriptors are able to outperform classifiers using only one metric. From this flexibility follows that our proposed CCNN model can be easily adapted to a wide range of connectome based classification or regression tasks, by varying which connectivity descriptor combinations are used to train the network. PMID:29089883

Resting State fMRI Functional Connectivity-Based Classification Using a Convolutional Neural Network Architecture.

PubMed

Meszlényi, Regina J; Buza, Krisztian; Vidnyánszky, Zoltán

2017-01-01

Machine learning techniques have become increasingly popular in the field of resting state fMRI (functional magnetic resonance imaging) network based classification. However, the application of convolutional networks has been proposed only very recently and has remained largely unexplored. In this paper we describe a convolutional neural network architecture for functional connectome classification called connectome-convolutional neural network (CCNN). Our results on simulated datasets and a publicly available dataset for amnestic mild cognitive impairment classification demonstrate that our CCNN model can efficiently distinguish between subject groups. We also show that the connectome-convolutional network is capable to combine information from diverse functional connectivity metrics and that models using a combination of different connectivity descriptors are able to outperform classifiers using only one metric. From this flexibility follows that our proposed CCNN model can be easily adapted to a wide range of connectome based classification or regression tasks, by varying which connectivity descriptor combinations are used to train the network.

Resting-state functional connectivity between amygdala and the ventromedial prefrontal cortex following fear reminder predicts fear extinction.

PubMed

Feng, Pan; Zheng, Yong; Feng, Tingyong

2016-06-01

Investigations of fear conditioning have elucidated the neural mechanisms of fear acquisition, consolidation and extinction, but it is not clear how the neural activation following fear reminder influence the following extinction. To address this question, we measured human brain activity following fear reminder using resting-state functional magnetic resonance imaging, and investigated whether the extinction effect can be predicted by resting-state functional connectivity (RSFC). Behaviorally, we found no significant differences of fear ratings between the reminder group and the no reminder group at the fear acquisition and extinction stages, but spontaneous recovery during re-extinction stage appeared only in the no reminder group. Imaging data showed that functional connectivity between ventromedial prefrontal cortex (vmPFC) and amygdala in the reminder group was greater than that in the no reminder group after fear memory reactivation. More importantly, the functional connectivity between amygdala and vmPFC of the reminder group after fear memory reactivation was positively correlated with extinction effect. These results suggest RSFC between amygdala and the vmPFC following fear reminder can predict fear extinction, which provide important insight into the neural mechanisms of fear memory after fear memory reactivation. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

IMAGING OF BRAIN FUNCTION BASED ON THE ANALYSIS OF FUNCTIONAL CONNECTIVITY - IMAGING ANALYSIS OF BRAIN FUNCTION BY FMRI AFTER ACUPUNCTURE AT LR3 IN HEALTHY INDIVIDUALS.

PubMed

Zheng, Yu; Wang, Yuying; Lan, Yujun; Qu, Xiaodong; Lin, Kelin; Zhang, Jiping; Qu, Shanshan; Wang, Yanjie; Tang, Chunzhi; Huang, Yong

2016-01-01

This Study observed the relevant brain areas activated by acupuncture at the Taichong acupoint (LR3) and analyzed the functional connectivity among brain areas using resting state functional magnetic resonance imaging (fMRI) to explore the acupoint specificity of the Taichong acupoint. A total of 45 healthy subjects were randomly divided into the Taichong (LR3) group, sham acupuncture group and sham acupoint group. Subjects received resting state fMRI before acupuncture, after true (sham) acupuncture in each group. Analysis of changes in connectivity among the brain areas was performed using the brain functional connectivity method. The right cerebrum temporal lobe was selected as the seed point to analyze the functional connectivity. It had a functional connectivity with right cerebrum superior frontal gyrus, limbic lobe cingulate gyrus and left cerebrum inferior temporal gyrus (BA 37), inferior parietal lobule compared by before vs. after acupuncture at LR3, and right cerebrum sub-lobar insula and left cerebrum middle frontal gyrus, medial frontal gyrus compared by true vs. sham acupuncture at LR3, and right cerebrum occipital lobe cuneus, occipital lobe sub-gyral, parietal lobe precuneus and left cerebellum anterior lobe culmen by acupuncture at LR3 vs. sham acupoint. Acupuncture at LR3 mainly specifically activated the brain functional network that participates in visual function, associative function, and emotion cognition, which are similar to the features on LR3 in tradition Chinese medicine. These brain areas constituted a neural network structure with specific functions that had specific reference values for the interpretation of the acupoint specificity of the Taichong acupoint.

Tinnitus alters resting state functional connectivity (RSFC) in human auditory and non-auditory brain regions as measured by functional near-infrared spectroscopy (fNIRS)

PubMed Central

Hu, Xiao-Su; Issa, Mohamad; Bisconti, Silvia; Kovelman, Ioulia; Kileny, Paul; Basura, Gregory

2017-01-01

Tinnitus, or phantom sound perception, leads to increased spontaneous neural firing rates and enhanced synchrony in central auditory circuits in animal models. These putative physiologic correlates of tinnitus to date have not been well translated in the brain of the human tinnitus sufferer. Using functional near-infrared spectroscopy (fNIRS) we recently showed that tinnitus in humans leads to maintained hemodynamic activity in auditory and adjacent, non-auditory cortices. Here we used fNIRS technology to investigate changes in resting state functional connectivity between human auditory and non-auditory brain regions in normal-hearing, bilateral subjective tinnitus and controls before and after auditory stimulation. Hemodynamic activity was monitored over the region of interest (primary auditory cortex) and non-region of interest (adjacent non-auditory cortices) and functional brain connectivity was measured during a 60-second baseline/period of silence before and after a passive auditory challenge consisting of alternating pure tones (750 and 8000Hz), broadband noise and silence. Functional connectivity was measured between all channel-pairs. Prior to stimulation, connectivity of the region of interest to the temporal and fronto-temporal region was decreased in tinnitus participants compared to controls. Overall, connectivity in tinnitus was differentially altered as compared to controls following sound stimulation. Enhanced connectivity was seen in both auditory and non-auditory regions in the tinnitus brain, while controls showed a decrease in connectivity following sound stimulation. In tinnitus, the strength of connectivity was increased between auditory cortex and fronto-temporal, fronto-parietal, temporal, occipito-temporal and occipital cortices. Together these data suggest that central auditory and non-auditory brain regions are modified in tinnitus and that resting functional connectivity measured by fNIRS technology may contribute to conscious phantom sound perception and potentially serve as an objective measure of central neural pathology. PMID:28604786

Multimodal Classification of Schizophrenia Patients with MEG and fMRI Data Using Static and Dynamic Connectivity Measures

PubMed Central

Cetin, Mustafa S.; Houck, Jon M.; Rashid, Barnaly; Agacoglu, Oktay; Stephen, Julia M.; Sui, Jing; Canive, Jose; Mayer, Andy; Aine, Cheryl; Bustillo, Juan R.; Calhoun, Vince D.

2016-01-01

Mental disorders like schizophrenia are currently diagnosed by physicians/psychiatrists through clinical assessment and their evaluation of patient's self-reported experiences as the illness emerges. There is great interest in identifying biological markers of prognosis at the onset of illness, rather than relying on the evolution of symptoms across time. Functional network connectivity, which indicates a subject's overall level of “synchronicity” of activity between brain regions, demonstrates promise in providing individual subject predictive power. Many previous studies reported functional connectivity changes during resting-state using only functional magnetic resonance imaging (fMRI). Nevertheless, exclusive reliance on fMRI to generate such networks may limit the inference of the underlying dysfunctional connectivity, which is hypothesized to be a factor in patient symptoms, as fMRI measures connectivity via hemodynamics. Therefore, combination of connectivity assessments using fMRI and magnetoencephalography (MEG), which more directly measures neuronal activity, may provide improved classification of schizophrenia than either modality alone. Moreover, recent evidence indicates that metrics of dynamic connectivity may also be critical for understanding pathology in schizophrenia. In this work, we propose a new framework for extraction of important disease related features and classification of patients with schizophrenia based on using both fMRI and MEG to investigate functional network components in the resting state. Results of this study show that the integration of fMRI and MEG provides important information that captures fundamental characteristics of functional network connectivity in schizophrenia and is helpful for prediction of schizophrenia patient group membership. Combined fMRI/MEG methods, using static functional network connectivity analyses, improved classification accuracy relative to use of fMRI or MEG methods alone (by 15 and 12.45%, respectively), while combined fMRI/MEG methods using dynamic functional network connectivity analyses improved classification up to 5.12% relative to use of fMRI alone and up to 17.21% relative to use of MEG alone. PMID:27807403

Resting state brain networks and their implications in neurodegenerative disease

NASA Astrophysics Data System (ADS)

Sohn, William S.; Yoo, Kwangsun; Kim, Jinho; Jeong, Yong

2012-10-01

Neurons are the basic units of the brain, and form network by connecting via synapses. So far, there have been limited ways to measure the brain networks. Recently, various imaging modalities are widely used for this purpose. In this paper, brain network mapping using resting state fMRI will be introduced with several applications including neurodegenerative disease such as Alzheimer's disease, frontotemporal lobar degeneration and Parkinson's disease. The resting functional connectivity using intrinsic functional connectivity in mouse is useful since we can take advantage of perturbation or stimulation of certain nodes of the network. The study of brain connectivity will open a new era in understanding of brain and diseases thus will be an essential foundation for future research.

Repetitive transcranial magnetic stimulation induced modulations of resting state motor connectivity in writer's cramp.

PubMed

Bharath, R D; Biswal, B B; Bhaskar, M V; Gohel, S; Jhunjhunwala, K; Panda, R; George, L; Gupta, A K; Pal, P K

2015-05-01

Writer's cramp (WC) is a focal task-specific dystonia of the hand which is increasingly being accepted as a network disorder. Non-invasive cortical stimulation using repetitive transcranial magnetic stimulation (rTMS) has produced therapeutic benefits in some of these patients. This study aimed to visualize the motor network abnormalities in WC and also its rTMS induced modulations using resting state functional magnetic resonance imaging (rsfMRI). Nineteen patients with right-sided WC and 20 matched healthy controls (HCs) were prospectively evaluated. All patients underwent a single session of rTMS and rsfMRI was acquired before (R1) and after (R2) rTMS. Seed-based functional connectivity analysis of several regions in the motor network was performed for HCs, R1 and R2 using SPM8 software. Thresholded (P < 0.05, false discovery rate corrected) group level mean correlation maps were used to derive significantly connected region of interest pairs. Writer's cramp showed a significant reduction in resting state functional connectivity in comparison with HCs involving the left cerebellum, thalamus, globus pallidus, putamen, bilateral supplementary motor area, right medial prefrontal lobe and right post central gyrus. After rTMS there was a significant increase in the contralateral resting state functional connectivity through the left thalamus-right globus pallidus-right thalamus-right prefrontal lobe network loop. It is concluded that WC is a network disorder with widespread dysfunction much larger than clinically evident and changes induced by rTMS probably act through subcortical and trans-hemispheric unaffected connections. Longitudinal studies with therapeutic rTMS will be required to ascertain whether such information could be used to select patients prior to rTMS therapy. © 2015 EAN.

A Multimodal Imaging- and Stimulation-based Method of Evaluating Connectivity-related Brain Excitability in Patients with Epilepsy

PubMed Central

Shafi, Mouhsin M.; Whitfield-Gabrieli, Susan; Chu, Catherine J.; Pascual-Leone, Alvaro; Chang, Bernard S.

2017-01-01

Resting-state functional connectivity MRI (rs-fcMRI) is a technique that identifies connectivity between different brain regions based on correlations over time in the blood-oxygenation level dependent signal. rs-fcMRI has been applied extensively to identify abnormalities in brain connectivity in different neurologic and psychiatric diseases. However, the relationship among rs-fcMRI connectivity abnormalities, brain electrophysiology and disease state is unknown, in part because the causal significance of alterations in functional connectivity in disease pathophysiology has not been established. Transcranial Magnetic Stimulation (TMS) is a technique that uses electromagnetic induction to noninvasively produce focal changes in cortical activity. When combined with electroencephalography (EEG), TMS can be used to assess the brain's response to external perturbations. Here we provide a protocol for combining rs-fcMRI, TMS and EEG to assess the physiologic significance of alterations in functional connectivity in patients with neuropsychiatric disease. We provide representative results from a previously published study in which rs-fcMRI was used to identify regions with abnormal connectivity in patients with epilepsy due to a malformation of cortical development, periventricular nodular heterotopia (PNH). Stimulation in patients with epilepsy resulted in abnormal TMS-evoked EEG activity relative to stimulation of the same sites in matched healthy control patients, with an abnormal increase in the late component of the TMS-evoked potential, consistent with cortical hyperexcitability. This abnormality was specific to regions with abnormal resting-state functional connectivity. Electrical source analysis in a subject with previously recorded seizures demonstrated that the origin of the abnormal TMS-evoked activity co-localized with the seizure-onset zone, suggesting the presence of an epileptogenic circuit. These results demonstrate how rs-fcMRI, TMS and EEG can be utilized together to identify and understand the physiological significance of abnormal brain connectivity in human diseases. PMID:27911366

Increased sensitivity to age-related differences in brain functional connectivity during continuous multiple object tracking compared to resting-state.

PubMed

Dørum, Erlend S; Kaufmann, Tobias; Alnæs, Dag; Andreassen, Ole A; Richard, Geneviève; Kolskår, Knut K; Nordvik, Jan Egil; Westlye, Lars T

2017-03-01

Age-related differences in cognitive agility vary greatly between individuals and cognitive functions. This heterogeneity is partly mirrored in individual differences in brain network connectivity as revealed using resting-state functional magnetic resonance imaging (fMRI), suggesting potential imaging biomarkers for age-related cognitive decline. However, although convenient in its simplicity, the resting state is essentially an unconstrained paradigm with minimal experimental control. Here, based on the conception that the magnitude and characteristics of age-related differences in brain connectivity is dependent on cognitive context and effort, we tested the hypothesis that experimentally increasing cognitive load boosts the sensitivity to age and changes the discriminative network configurations. To this end, we obtained fMRI data from younger (n=25, mean age 24.16±5.11) and older (n=22, mean age 65.09±7.53) healthy adults during rest and two load levels of continuous multiple object tracking (MOT). Brain network nodes and their time-series were estimated using independent component analysis (ICA) and dual regression, and the edges in the brain networks were defined as the regularized partial temporal correlations between each of the node pairs at the individual level. Using machine learning based on a cross-validated regularized linear discriminant analysis (rLDA) we attempted to classify groups and cognitive load from the full set of edge-wise functional connectivity indices. While group classification using resting-state data was highly above chance (approx. 70% accuracy), functional connectivity (FC) obtained during MOT strongly increased classification performance, with 82% accuracy for the young and 95% accuracy for the old group at the highest load level. Further, machine learning revealed stronger differentiation between rest and task in young compared to older individuals, supporting the notion of network dedifferentiation in cognitive aging. Task-modulation in edgewise FC was primarily observed between attention- and sensorimotor networks; with decreased negative correlations between attention- and default mode networks in older adults. These results demonstrate that the magnitude and configuration of age-related differences in brain functional connectivity are partly dependent on cognitive context and load, which emphasizes the importance of assessing brain connectivity differences across a range of cognitive contexts beyond the resting-state. Copyright © 2017 Elsevier Inc. All rights reserved.

Disrupted Brain Functional Organization in Epilepsy Revealed by Graph Theory Analysis.

PubMed

Song, Jie; Nair, Veena A; Gaggl, Wolfgang; Prabhakaran, Vivek

2015-06-01

The human brain is a complex and dynamic system that can be modeled as a large-scale brain network to better understand the reorganizational changes secondary to epilepsy. In this study, we developed a brain functional network model using graph theory methods applied to resting-state fMRI data acquired from a group of epilepsy patients and age- and gender-matched healthy controls. A brain functional network model was constructed based on resting-state functional connectivity. A minimum spanning tree combined with proportional thresholding approach was used to obtain sparse connectivity matrices for each subject, which formed the basis of brain networks. We examined the brain reorganizational changes in epilepsy thoroughly at the level of the whole brain, the functional network, and individual brain regions. At the whole-brain level, local efficiency was significantly decreased in epilepsy patients compared with the healthy controls. However, global efficiency was significantly increased in epilepsy due to increased number of functional connections between networks (although weakly connected). At the functional network level, there were significant proportions of newly formed connections between the default mode network and other networks and between the subcortical network and other networks. There was a significant proportion of decreasing connections between the cingulo-opercular task control network and other networks. Individual brain regions from different functional networks, however, showed a distinct pattern of reorganizational changes in epilepsy. These findings suggest that epilepsy alters brain efficiency in a consistent pattern at the whole-brain level, yet alters brain functional networks and individual brain regions differently.

Changes of intranetwork and internetwork functional connectivity in Alzheimer’s disease and mild cognitive impairment

NASA Astrophysics Data System (ADS)

Zhu, Haoze; Zhou, Peng; Alcauter, Sarael; Chen, Yuanyuan; Cao, Hongbao; Tian, Miao; Ming, Dong; Qi, Hongzhi; Wang, Xuemin; Zhao, Xin; He, Feng; Ni, Hongyan; Gao, Wei

2016-08-01

Objective. Alzheimer’s disease (AD) is a serious neurodegenerative disorder characterized by deficits of working memory, attention, language and many other cognitive functions. Although different stages of the disease are relatively well characterized by clinical criteria, stage-specific pathological changes in the brain remain relatively poorly understood, especially at the level of large-scale functional networks. In this study, we aimed to characterize the potential disruptions of large-scale functional brain networks based on a sample including amnestic mild cognition impairment (aMCI) and AD patients to help delineate the underlying stage-dependent AD pathology. Approach. We sought to identify the neural connectivity mechanisms of aMCI and AD through examination of both intranetwork and internetwork interactions among four of the brain’s key networks, namely dorsal attention network (DAN), default mode network (DMN), executive control network (ECN) and salience network (SAL). We analyzed functional connectivity based on resting-state functional magnetic resonance imaging (rs-fMRI) data from 25 Alzheimer’s disease patients, 20 aMCI patients and 35 elderly normal controls (NC). Main results. Intranetwork functional disruptions within the DAN and ECN were detected in both aMCI and AD patients. Disrupted intranetwork connectivity of DMN and anti-correlation between DAN and DMN were observed in AD patients. Moreover, aMCI-specific alterations in the internetwork functional connectivity of SAL were observed. Significance. Our results confirmed previous findings that AD pathology was related to dysconnectivity both within and between resting-state networks but revealed more spatial details. Moreover, the SAL network, reportedly flexibly coupling either with the DAN or DMN networks during different brain states, demonstrated interesting alterations specifically in the early stage of the disease.

Long-term intensive gymnastic training induced changes in intra- and inter-network functional connectivity: an independent component analysis.

PubMed

Huang, Huiyuan; Wang, Junjing; Seger, Carol; Lu, Min; Deng, Feng; Wu, Xiaoyan; He, Yuan; Niu, Chen; Wang, Jun; Huang, Ruiwang

2018-01-01

Long-term intensive gymnastic training can induce brain structural and functional reorganization. Previous studies have identified structural and functional network differences between world class gymnasts (WCGs) and non-athletes at the whole-brain level. However, it is still unclear how interactions within and between functional networks are affected by long-term intensive gymnastic training. We examined both intra- and inter-network functional connectivity of gymnasts relative to non-athletes using resting-state fMRI (R-fMRI). R-fMRI data were acquired from 13 WCGs and 14 non-athlete controls. Group-independent component analysis (ICA) was adopted to decompose the R-fMRI data into spatial independent components and associated time courses. An automatic component identification method was used to identify components of interest associated with resting-state networks (RSNs). We identified nine RSNs, the basal ganglia network (BG), sensorimotor network (SMN), cerebellum (CB), anterior and posterior default mode networks (aDMN/pDMN), left and right fronto-parietal networks (lFPN/rFPN), primary visual network (PVN), and extrastriate visual network (EVN). Statistical analyses revealed that the intra-network functional connectivity was significantly decreased within the BG, aDMN, lFPN, and rFPN, but increased within the EVN in the WCGs compared to the controls. In addition, the WCGs showed uniformly decreased inter-network functional connectivity between SMN and BG, CB, and PVN, BG and PVN, and pDMN and rFPN compared to the controls. We interpret this generally weaker intra- and inter-network functional connectivity in WCGs during the resting state as a result of greater efficiency in the WCGs' brain associated with long-term motor skill training.

Subgenual anterior cingulate-insula resting-state connectivity as a neural correlate to trait and state stress resilience.

PubMed

Shao, Robin; Lau, Way K W; Leung, Mei-Kei; Lee, Tatia M C

2018-07-01

Accumulating evidence indicates important roles of the subgenual anterior cingulate cortex and rostral limbic regions such as the anterior insula, in regulating stress-related affective responses and negative affect states in general. However, research is lacking in simultaneously assessing the inter-relations between trait and state affective responses to stress, and the functional connectivity between the subgenual anterior cingulate and anterior insula. This preliminary research involved matched healthy participants with high (N = 10) and low (N = 10) self-reported trait stress resilience, and assessed their affective and subgenual anterior cingulate-anterior insula resting-state functional connectivity patterns before and after a psychosocial stress task. We found that while the low-resilience group displayed higher trait negative affect and perceived greater task-related stress, only the high-resilience group showed increase of negative affect, along with greater decrease of left subgenual anterior cingulate-right anterior insula connectivity, following stress induction. Moreover, the functional connectivity change mediated group difference in affect change following stress task. We speculate that the contingent increase of negative affect, and the associated temporary decoupling of subgenual anterior cingulate-insula circuitry, may represent a normative and adaptive stress response underpinned by adaptive and dynamic interplay between the default mode and salience networks. Such findings, if consolidated, have important implications for promoting stress resilience and reducing risk for stress-related affective disorders. Copyright © 2018. Published by Elsevier Inc.

Regional homogeneity and functional connectivity patterns in major depressive disorder, cognitive vulnerability to depression and healthy subjects.

PubMed

Sun, Hui; Luo, Lizhu; Yuan, Xinru; Zhang, Lu; He, Yini; Yao, Shuqiao; Wang, Jiaojian; Xiao, Jing

2018-08-01

Cognitive vulnerability to depression (CVD) is a high risk for depressive disorder. Recent studies focus on individuals with CVD to determine the neural basis of major depressive disorder (MDD) neuropathology. However, whether CVD showed specific or similar brain functional activity and connectivity patterns, compared to MDD, remain largely unknown. Here, using resting-state functional magnetic resonance imaging in subjects with CVD, healthy controls (HC) and MDD, regional homogeneity (ReHo) and resting-state functional connectivity (R-FC) analyses were conducted to assess local synchronization and changes in functional connectivity patterns. Significant ReHo differences were found in right posterior lobe of cerebellum (PLC), left lingual gyrus (LG) and precuneus. Compared to HC, CVD subjects showed increased ReHo in the PLC, which was similar to the difference found between MDD and HC. Compared to MDD patients, CVD subjects showed decreased ReHo in PLC, LG, and precuneus. R-FC analyses found increased functional connections between LG and left inferior parietal lobule, posterior cingulate cortex, and dorsolateral prefrontal cortex in CVD compared to both HC and MDD. Moreover, Regional mean ReHo values were positively correlated with Center for Epidemiologic Studies Depression Scale scores. These analyses revealed that PLC and functional connections between LG and left inferior parietal lobule, posterior cingulate cortex, and dorsolateral prefrontal cortex may be a potential marker for CVD. Copyright © 2018 Elsevier B.V. All rights reserved.

Function-specific and Enhanced Brain Structural Connectivity Mapping via Joint Modeling of Diffusion and Functional MRI.

PubMed

Chu, Shu-Hsien; Parhi, Keshab K; Lenglet, Christophe

2018-03-16

A joint structural-functional brain network model is presented, which enables the discovery of function-specific brain circuits, and recovers structural connections that are under-estimated by diffusion MRI (dMRI). Incorporating information from functional MRI (fMRI) into diffusion MRI to estimate brain circuits is a challenging task. Usually, seed regions for tractography are selected from fMRI activation maps to extract the white matter pathways of interest. The proposed method jointly analyzes whole brain dMRI and fMRI data, allowing the estimation of complete function-specific structural networks instead of interactively investigating the connectivity of individual cortical/sub-cortical areas. Additionally, tractography techniques are prone to limitations, which can result in erroneous pathways. The proposed framework explicitly models the interactions between structural and functional connectivity measures thereby improving anatomical circuit estimation. Results on Human Connectome Project (HCP) data demonstrate the benefits of the approach by successfully identifying function-specific anatomical circuits, such as the language and resting-state networks. In contrast to correlation-based or independent component analysis (ICA) functional connectivity mapping, detailed anatomical connectivity patterns are revealed for each functional module. Results on a phantom (Fibercup) also indicate improvements in structural connectivity mapping by rejecting false-positive connections with insufficient support from fMRI, and enhancing under-estimated connectivity with strong functional correlation.

On nodes and modes in resting state fMRI

PubMed Central

Friston, Karl J.; Kahan, Joshua; Razi, Adeel; Stephan, Klaas Enno; Sporns, Olaf

2014-01-01

This paper examines intrinsic brain networks in light of recent developments in the characterisation of resting state fMRI timeseries — and simulations of neuronal fluctuations based upon the connectome. Its particular focus is on patterns or modes of distributed activity that underlie functional connectivity. We first demonstrate that the eigenmodes of functional connectivity – or covariance among regions or nodes – are the same as the eigenmodes of the underlying effective connectivity, provided we limit ourselves to symmetrical connections. This symmetry constraint is motivated by appealing to proximity graphs based upon multidimensional scaling. Crucially, the principal modes of functional connectivity correspond to the dynamically unstable modes of effective connectivity that decay slowly and show long term memory. Technically, these modes have small negative Lyapunov exponents that approach zero from below. Interestingly, the superposition of modes – whose exponents are sampled from a power law distribution – produces classical 1/f (scale free) spectra. We conjecture that the emergence of dynamical instability – that underlies intrinsic brain networks – is inevitable in any system that is separated from external states by a Markov blanket. This conjecture appeals to a free energy formulation of nonequilibrium steady-state dynamics. The common theme that emerges from these theoretical considerations is that endogenous fluctuations are dominated by a small number of dynamically unstable modes. We use this as the basis of a dynamic causal model (DCM) of resting state fluctuations — as measured in terms of their complex cross spectra. In this model, effective connectivity is parameterised in terms of eigenmodes and their Lyapunov exponents — that can also be interpreted as locations in a multidimensional scaling space. Model inversion provides not only estimates of edges or connectivity but also the topography and dimensionality of the underlying scaling space. Here, we focus on conceptual issues with simulated fMRI data and provide an illustrative application using an empirical multi-region timeseries. PMID:24862075

Using Dual Regression to Investigate Network Shape and Amplitude in Functional Connectivity Analyses

PubMed Central

Nickerson, Lisa D.; Smith, Stephen M.; Öngür, Döst; Beckmann, Christian F.

2017-01-01

Independent Component Analysis (ICA) is one of the most popular techniques for the analysis of resting state FMRI data because it has several advantageous properties when compared with other techniques. Most notably, in contrast to a conventional seed-based correlation analysis, it is model-free and multivariate, thus switching the focus from evaluating the functional connectivity of single brain regions identified a priori to evaluating brain connectivity in terms of all brain resting state networks (RSNs) that simultaneously engage in oscillatory activity. Furthermore, typical seed-based analysis characterizes RSNs in terms of spatially distributed patterns of correlation (typically by means of simple Pearson's coefficients) and thereby confounds together amplitude information of oscillatory activity and noise. ICA and other regression techniques, on the other hand, retain magnitude information and therefore can be sensitive to both changes in the spatially distributed nature of correlations (differences in the spatial pattern or “shape”) as well as the amplitude of the network activity. Furthermore, motion can mimic amplitude effects so it is crucial to use a technique that retains such information to ensure that connectivity differences are accurately localized. In this work, we investigate the dual regression approach that is frequently applied with group ICA to assess group differences in resting state functional connectivity of brain networks. We show how ignoring amplitude effects and how excessive motion corrupts connectivity maps and results in spurious connectivity differences. We also show how to implement the dual regression to retain amplitude information and how to use dual regression outputs to identify potential motion effects. Two key findings are that using a technique that retains magnitude information, e.g., dual regression, and using strict motion criteria are crucial for controlling both network amplitude and motion-related amplitude effects, respectively, in resting state connectivity analyses. We illustrate these concepts using realistic simulated resting state FMRI data and in vivo data acquired in healthy subjects and patients with bipolar disorder and schizophrenia. PMID:28348512

Statistical inference of dynamic resting-state functional connectivity using hierarchical observation modeling.

PubMed

Sojoudi, Alireza; Goodyear, Bradley G

2016-12-01

Spontaneous fluctuations of blood-oxygenation level-dependent functional magnetic resonance imaging (BOLD fMRI) signals are highly synchronous between brain regions that serve similar functions. This provides a means to investigate functional networks; however, most analysis techniques assume functional connections are constant over time. This may be problematic in the case of neurological disease, where functional connections may be highly variable. Recently, several methods have been proposed to determine moment-to-moment changes in the strength of functional connections over an imaging session (so called dynamic connectivity). Here a novel analysis framework based on a hierarchical observation modeling approach was proposed, to permit statistical inference of the presence of dynamic connectivity. A two-level linear model composed of overlapping sliding windows of fMRI signals, incorporating the fact that overlapping windows are not independent was described. To test this approach, datasets were synthesized whereby functional connectivity was either constant (significant or insignificant) or modulated by an external input. The method successfully determines the statistical significance of a functional connection in phase with the modulation, and it exhibits greater sensitivity and specificity in detecting regions with variable connectivity, when compared with sliding-window correlation analysis. For real data, this technique possesses greater reproducibility and provides a more discriminative estimate of dynamic connectivity than sliding-window correlation analysis. Hum Brain Mapp 37:4566-4580, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

ABERRANT RESTING-STATE BRAIN ACTIVITY IN POSTTRAUMATIC STRESS DISORDER: A META-ANALYSIS AND SYSTEMATIC REVIEW.

PubMed

Koch, Saskia B J; van Zuiden, Mirjam; Nawijn, Laura; Frijling, Jessie L; Veltman, Dick J; Olff, Miranda

2016-07-01

About 10% of trauma-exposed individuals develop PTSD. Although a growing number of studies have investigated resting-state abnormalities in PTSD, inconsistent results suggest a need for a meta-analysis and a systematic review. We conducted a systematic literature search in four online databases using keywords for PTSD, functional neuroimaging, and resting-state. In total, 23 studies matched our eligibility criteria. For the meta-analysis, we included 14 whole-brain resting-state studies, reporting data on 663 participants (298 PTSD patients and 365 controls). We used the activation likelihood estimation approach to identify concurrence of whole-brain hypo- and hyperactivations in PTSD patients during rest. Seed-based studies could not be included in the quantitative meta-analysis. Therefore, a separate qualitative systematic review was conducted on nine seed-based functional connectivity studies. The meta-analysis showed consistent hyperactivity in the ventral anterior cingulate cortex and the parahippocampus/amygdala, but hypoactivity in the (posterior) insula, cerebellar pyramis and middle frontal gyrus in PTSD patients, compared to healthy controls. Partly concordant with these findings, the systematic review on seed-based functional connectivity studies showed enhanced salience network (SN) connectivity, but decreased default mode network (DMN) connectivity in PTSD. Combined, these altered resting-state connectivity and activity patterns could represent neurobiological correlates of increased salience processing and hypervigilance (SN), at the cost of awareness of internal thoughts and autobiographical memory (DMN) in PTSD. However, several discrepancies between findings of the meta-analysis and systematic review were observed, stressing the need for future studies on resting-state abnormalities in PTSD patients. © 2016 Wiley Periodicals, Inc.

Default Mode Functional Connectivity is Associated with Social Functioning in Schizophrenia

PubMed Central

Fox, Jaclyn M.; Abram, Samantha V.; Reilly, James L.; Eack, Shaun; Goldman, Morris B.; Csernansky, John G.; Wang, Lei; Smith, Matthew J.

2017-01-01

Individuals with schizophrenia display notable deficits in social functioning. Research indicates that neural connectivity within the default mode network (DMN) is related to social cognition and social functioning in healthy and clinical populations. However, the association between DMN connectivity, social cognition, and social functioning has not been studied in schizophrenia. For the present study, we used resting-state neuroimaging data to evaluate connectivity between the main DMN hubs (i.e., the medial prefrontal cortex (mPFC) and the posterior cingulate cortex-anterior precuneus (PPC)) in individuals with schizophrenia (n=28) and controls (n=32). We also examined whether DMN connectivity was associated with social functioning via social attainment (measured by the Specific Levels of Functioning Scale) and social competence (measured by the Social Skills Performance Assessment), and if social cognition mediates the association between DMN connectivity and these measures of social functioning. Results revealed that DMN connectivity did not differ between individuals with schizophrenia and controls. However, connectivity between the mPFC and PCC hubs was significantly associated with social competence and social attainment in individuals with schizophrenia but not in controls as reflected by a significant group-by-connectivity interaction. Social cognition did not mediate the association between social functioning and DMN connectivity in individuals with schizophrenia. Our findings suggest that fronto-parietal DMN connectivity in particular may be differentially associated with social functioning in schizophrenia and controls. As a result, DMN connectivity may be used as a neuroimaging marker to monitor treatment response or as a potential target for interventions that aim to enhance social functioning in schizophrenia. PMID:28358526

Resting-state FMRI confounds and cleanup

PubMed Central

Murphy, Kevin; Birn, Rasmus M.; Bandettini, Peter A.

2013-01-01

The goal of resting-state functional magnetic resonance imaging (FMRI) is to investigate the brain’s functional connections by using the temporal similarity between blood oxygenation level dependent (BOLD) signals in different regions of the brain “at rest” as an indicator of synchronous neural activity. Since this measure relies on the temporal correlation of FMRI signal changes between different parts of the brain, any non-neural activity-related process that affects the signals will influence the measure of functional connectivity, yielding spurious results. To understand the sources of these resting-state FMRI confounds, this article describes the origins of the BOLD signal in terms of MR physics and cerebral physiology. Potential confounds arising from motion, cardiac and respiratory cycles, arterial CO2 concentration, blood pressure/cerebral autoregulation, and vasomotion are discussed. Two classes of techniques to remove confounds from resting-state BOLD time series are reviewed: 1) those utilising external recordings of physiology and 2) data-based cleanup methods that only use the resting-state FMRI data itself. Further methods that remove noise from functional connectivity measures at a group level are also discussed. For successful interpretation of resting-state FMRI comparisons and results, noise cleanup is an often over-looked but essential step in the analysis pipeline. PMID:23571418

Altered Resting State Effective Connectivity of Anterior Insula in Depression.

PubMed

Kandilarova, Sevdalina; Stoyanov, Drozdstoy; Kostianev, Stefan; Specht, Karsten

2018-01-01

Depression has been associated with changes in both functional and effective connectivity of large scale brain networks, including the default mode network, executive network, and salience network. However, studies of effective connectivity by means of spectral dynamic causal modeling (spDCM) are still rare and the interaction between the different resting state networks has not been investigated in detail. Thus, we aimed at exploring differences in effective connectivity among eight right hemisphere brain areas-anterior insula, inferior frontal gyrus, middle frontal gyrus (MFG), frontal eye field, anterior cingulate cortex, superior parietal lobe, amygdala, and hippocampus, between a group of healthy controls ( N  = 20) and medicated depressed patients ( N  = 20). We found that patients not only had significantly reduced strength of the connection from the anterior insula to the MFG (i.e., dorsolateral prefrontal cortex) but also a significant connection between the amygdala and the anterior insula. Moreover, depression severity correlated with connectivity of the hippocampal node. In conclusion, the results from this resting state spDCM study support and enrich previous data on the role of the right anterior insula in the pathophysiology of depression. Furthermore, our findings add to the growing evidence of an association between depression severity and disturbances of the hippocampal function in terms of impaired connectivity with other brain regions.

Altered Resting State Effective Connectivity of Anterior Insula in Depression

PubMed Central

Kandilarova, Sevdalina; Stoyanov, Drozdstoy; Kostianev, Stefan; Specht, Karsten

2018-01-01

Depression has been associated with changes in both functional and effective connectivity of large scale brain networks, including the default mode network, executive network, and salience network. However, studies of effective connectivity by means of spectral dynamic causal modeling (spDCM) are still rare and the interaction between the different resting state networks has not been investigated in detail. Thus, we aimed at exploring differences in effective connectivity among eight right hemisphere brain areas—anterior insula, inferior frontal gyrus, middle frontal gyrus (MFG), frontal eye field, anterior cingulate cortex, superior parietal lobe, amygdala, and hippocampus, between a group of healthy controls (N = 20) and medicated depressed patients (N = 20). We found that patients not only had significantly reduced strength of the connection from the anterior insula to the MFG (i.e., dorsolateral prefrontal cortex) but also a significant connection between the amygdala and the anterior insula. Moreover, depression severity correlated with connectivity of the hippocampal node. In conclusion, the results from this resting state spDCM study support and enrich previous data on the role of the right anterior insula in the pathophysiology of depression. Furthermore, our findings add to the growing evidence of an association between depression severity and disturbances of the hippocampal function in terms of impaired connectivity with other brain regions. PMID:29599728

Potential risk for healthy siblings to develop schizophrenia: evidence from pattern classification with whole-brain connectivity.

PubMed

Liu, Meijie; Zeng, Ling-Li; Shen, Hui; Liu, Zhening; Hu, Dewen

2012-03-28

Recent resting-state functional connectivity MRI studies using group-level statistical analysis have demonstrated the inheritable characters of schizophrenia. The objective of the present study was to use pattern classification as a means to investigate schizophrenia inheritance based on the whole-brain resting-state functional connectivity at the individual subject level. One-against-one pattern classifications were made amongst three groups (i.e. patients diagnosed with schizophrenia, healthy siblings, and healthy controls after preprocessing), resulting in an 80.4% separation between patients with schizophrenia and healthy controls, a 77.6% separation between schizophrenia patients and their healthy siblings, and a 78.7% separation between healthy siblings and healthy controls, respectively. These results suggest that the healthy siblings of schizophrenia patients have an altered resting-state functional connectivity pattern compared with healthy controls. Thus, healthy siblings may have a potential higher risk for developing schizophrenia compared with the general population. Moreover, this pattern differed from that of schizophrenia patients and may contribute to the normal behavior exhibition of healthy siblings in daily life.

Disturbed resting state EEG synchronization in bipolar disorder: A graph-theoretic analysis☆

PubMed Central

Kim, Dae-Jin; Bolbecker, Amanda R.; Howell, Josselyn; Rass, Olga; Sporns, Olaf; Hetrick, William P.; Breier, Alan; O'Donnell, Brian F.

2013-01-01

Disruption of functional connectivity may be a key feature of bipolar disorder (BD) which reflects disturbances of synchronization and oscillations within brain networks. We investigated whether the resting electroencephalogram (EEG) in patients with BD showed altered synchronization or network properties. Resting-state EEG was recorded in 57 BD type-I patients and 87 healthy control subjects. Functional connectivity between pairs of EEG channels was measured using synchronization likelihood (SL) for 5 frequency bands (δ, θ, α, β, and γ). Graph-theoretic analysis was applied to SL over the electrode array to assess network properties. BD patients showed a decrease of mean synchronization in the alpha band, and the decreases were greatest in fronto-central and centro-parietal connections. In addition, the clustering coefficient and global efficiency were decreased in BD patients, whereas the characteristic path length increased. We also found that the normalized characteristic path length and small-worldness were significantly correlated with depression scores in BD patients. These results suggest that BD patients show impaired neural synchronization at rest and a disruption of resting-state functional connectivity. PMID:24179795

Functional Connectivity Substrates for tDCS Response in Minimally Conscious State Patients

PubMed Central

Cavaliere, Carlo; Aiello, Marco; Di Perri, Carol; Amico, Enrico; Martial, Charlotte; Thibaut, Aurore; Laureys, Steven; Soddu, Andrea

2016-01-01

Transcranial direct current stimulation (tDCS) is a non-invasive technique recently employed in disorders of consciousness, and determining a transitory recovery of signs of consciousness in almost half of minimally conscious state (MCS) patients. Although the rising evidences about its possible role in the treatment of many neurological and psychiatric conditions exist, no evidences exist about brain functional connectivity substrates underlying tDCS response. We retrospectively evaluated resting state functional Magnetic Resonance Imaging (fMRI) of 16 sub-acute and chronic MCS patients (6 tDCS responders) who successively received a single left dorsolateral prefrontal cortex (DLPFC) tDCS in a double-blind randomized cross-over trial. A seed-based approach for regions of left extrinsic control network (ECN) and default-mode network (DMN) was performed. tDCS responders showed an increased left intra-network connectivity for regions co-activated with left DLPFC, and significantly with left inferior frontal gyrus. Non-responders (NR) MCS patients showed an increased connectivity between left DLPFC and midline cortical structures, including anterior cingulate cortex and precuneus. Our findings suggest that a prior high connectivity with regions belonging to ECN can facilitate transitory recovery of consciousness in a subgroup of MCS patients that underwent tDCS treatment. Therefore, resting state-fMRI could be very valuable in detecting the neuronal conditions necessary for tDCS to improve behavior in MCS. PMID:27857682

Functional Connectivity Substrates for tDCS Response in Minimally Conscious State Patients.

PubMed

Cavaliere, Carlo; Aiello, Marco; Di Perri, Carol; Amico, Enrico; Martial, Charlotte; Thibaut, Aurore; Laureys, Steven; Soddu, Andrea

2016-01-01

Transcranial direct current stimulation (tDCS) is a non-invasive technique recently employed in disorders of consciousness, and determining a transitory recovery of signs of consciousness in almost half of minimally conscious state (MCS) patients. Although the rising evidences about its possible role in the treatment of many neurological and psychiatric conditions exist, no evidences exist about brain functional connectivity substrates underlying tDCS response. We retrospectively evaluated resting state functional Magnetic Resonance Imaging (fMRI) of 16 sub-acute and chronic MCS patients (6 tDCS responders) who successively received a single left dorsolateral prefrontal cortex (DLPFC) tDCS in a double-blind randomized cross-over trial. A seed-based approach for regions of left extrinsic control network (ECN) and default-mode network (DMN) was performed. tDCS responders showed an increased left intra-network connectivity for regions co-activated with left DLPFC, and significantly with left inferior frontal gyrus. Non-responders (NR) MCS patients showed an increased connectivity between left DLPFC and midline cortical structures, including anterior cingulate cortex and precuneus. Our findings suggest that a prior high connectivity with regions belonging to ECN can facilitate transitory recovery of consciousness in a subgroup of MCS patients that underwent tDCS treatment. Therefore, resting state-fMRI could be very valuable in detecting the neuronal conditions necessary for tDCS to improve behavior in MCS.

Functional connectivity associated with social networks in older adults: A resting-state fMRI study.

PubMed

Pillemer, Sarah; Holtzer, Roee; Blumen, Helena M

2017-06-01

Poor social networks and decreased levels of social support are associated with worse mood, health, and cognition in younger and older adults. Yet, we know very little about the brain substrates associated with social networks and social support, particularly in older adults. This study examined functional brain substrates associated with social networks using the Social Network Index (SNI) and resting-state functional magnetic resonance imaging (fMRI). Resting-state fMRI data from 28 non-demented older adults were analyzed with independent components analyses. As expected, four established resting-state networks-previously linked to motor, vision, speech, and other language functions-correlated with the quality (SNI-1: total number of high-contact roles of a respondent) and quantity (SNI-2: total number of individuals in a respondent's social network) of social networks: a sensorimotor, a visual, a vestibular/insular, and a left frontoparietal network. Moreover, SNI-1 was associated with greater functional connectivity in the lateral prefrontal regions of the left frontoparietal network, while SNI-2 was associated with greater functional connectivity in the medial prefrontal regions of this network. Thus, lateral prefrontal regions may be particularly linked to the quality of social networks while medial prefrontal regions may be particularly linked to the quantity of social networks.

Spatial-temporal-spectral EEG patterns of BOLD functional network connectivity dynamics

NASA Astrophysics Data System (ADS)

Lamoš, Martin; Mareček, Radek; Slavíček, Tomáš; Mikl, Michal; Rektor, Ivan; Jan, Jiří

2018-06-01

Objective. Growing interest in the examination of large-scale brain network functional connectivity dynamics is accompanied by an effort to find the electrophysiological correlates. The commonly used constraints applied to spatial and spectral domains during electroencephalogram (EEG) data analysis may leave part of the neural activity unrecognized. We propose an approach that blindly reveals multimodal EEG spectral patterns that are related to the dynamics of the BOLD functional network connectivity. Approach. The blind decomposition of EEG spectrogram by parallel factor analysis has been shown to be a useful technique for uncovering patterns of neural activity. The simultaneously acquired BOLD fMRI data were decomposed by independent component analysis. Dynamic functional connectivity was computed on the component’s time series using a sliding window correlation, and between-network connectivity states were then defined based on the values of the correlation coefficients. ANOVA tests were performed to assess the relationships between the dynamics of between-network connectivity states and the fluctuations of EEG spectral patterns. Main results. We found three patterns related to the dynamics of between-network connectivity states. The first pattern has dominant peaks in the alpha, beta, and gamma bands and is related to the dynamics between the auditory, sensorimotor, and attentional networks. The second pattern, with dominant peaks in the theta and low alpha bands, is related to the visual and default mode network. The third pattern, also with peaks in the theta and low alpha bands, is related to the auditory and frontal network. Significance. Our previous findings revealed a relationship between EEG spectral pattern fluctuations and the hemodynamics of large-scale brain networks. In this study, we suggest that the relationship also exists at the level of functional connectivity dynamics among large-scale brain networks when no standard spatial and spectral constraints are applied on the EEG data.

Abnormal brain functional connectivity leads to impaired mood and cognition in hyperthyroidism: a resting-state functional MRI study

PubMed Central

Li, Ling; Zhi, Mengmeng; Hou, Zhenghua; Zhang, Yuqun; Yue, Yingying; Yuan, Yonggui

2017-01-01

Patients with hyperthyroidism frequently have neuropsychiatric complaints such as lack of concentration, poor memory, depression, anxiety, nervousness, and irritability, suggesting brain dysfunction. However, the underlying process of these symptoms remains unclear. Using resting-state functional magnetic resonance imaging (rs-fMRI), we depicted the altered graph theoretical metric degree centrality (DC) and seed-based resting-state functional connectivity (FC) in 33 hyperthyroid patients relative to 33 healthy controls. The peak points of significantly altered DC between the two groups were defined as the seed regions to calculate FC to the whole brain. Then, partial correlation analyses were performed between abnormal DC, FC and neuropsychological performances, as well as some clinical indexes. The decreased intrinsic functional connectivity in the posterior lobe of cerebellum (PLC) and medial frontal gyrus (MeFG), as well as the abnormal seed-based FC anchored in default mode network (DMN), attention network, visual network and cognitive network in this study, possibly constitutes the latent mechanism for emotional and cognitive changes in hyperthyroidism, including anxiety and impaired processing speed. PMID:28009983

Abnormal brain functional connectivity leads to impaired mood and cognition in hyperthyroidism: a resting-state functional MRI study.

PubMed

Li, Ling; Zhi, Mengmeng; Hou, Zhenghua; Zhang, Yuqun; Yue, Yingying; Yuan, Yonggui

2017-01-24

Patients with hyperthyroidism frequently have neuropsychiatric complaints such as lack of concentration, poor memory, depression, anxiety, nervousness, and irritability, suggesting brain dysfunction. However, the underlying process of these symptoms remains unclear. Using resting-state functional magnetic resonance imaging (rs-fMRI), we depicted the altered graph theoretical metric degree centrality (DC) and seed-based resting-state functional connectivity (FC) in 33 hyperthyroid patients relative to 33 healthy controls. The peak points of significantly altered DC between the two groups were defined as the seed regions to calculate FC to the whole brain. Then, partial correlation analyses were performed between abnormal DC, FC and neuropsychological performances, as well as some clinical indexes. The decreased intrinsic functional connectivity in the posterior lobe of cerebellum (PLC) and medial frontal gyrus (MeFG), as well as the abnormal seed-based FC anchored in default mode network (DMN), attention network, visual network and cognitive network in this study, possibly constitutes the latent mechanism for emotional and cognitive changes in hyperthyroidism, including anxiety and impaired processing speed.

Alzheimer Classification Using a Minimum Spanning Tree of High-Order Functional Network on fMRI Dataset

PubMed Central

Guo, Hao; Liu, Lei; Chen, Junjie; Xu, Yong; Jie, Xiang

2017-01-01

Functional magnetic resonance imaging (fMRI) is one of the most useful methods to generate functional connectivity networks of the brain. However, conventional network generation methods ignore dynamic changes of functional connectivity between brain regions. Previous studies proposed constructing high-order functional connectivity networks that consider the time-varying characteristics of functional connectivity, and a clustering method was performed to decrease computational cost. However, random selection of the initial clustering centers and the number of clusters negatively affected classification accuracy, and the network lost neurological interpretability. Here we propose a novel method that introduces the minimum spanning tree method to high-order functional connectivity networks. As an unbiased method, the minimum spanning tree simplifies high-order network structure while preserving its core framework. The dynamic characteristics of time series are not lost with this approach, and the neurological interpretation of the network is guaranteed. Simultaneously, we propose a multi-parameter optimization framework that involves extracting discriminative features from the minimum spanning tree high-order functional connectivity networks. Compared with the conventional methods, our resting-state fMRI classification method based on minimum spanning tree high-order functional connectivity networks greatly improved the diagnostic accuracy for Alzheimer's disease. PMID:29249926

Towards mapping the brain connectome in depression: functional connectivity by perfusion SPECT.

PubMed

Gardner, Ann; Åstrand, Disa; Öberg, Johanna; Jacobsson, Hans; Jonsson, Cathrine; Larsson, Stig; Pagani, Marco

2014-08-30

Several studies have demonstrated altered brain functional connectivity in the resting state in depression. However, no study has investigated interregional networking in patients with persistent depressive disorder (PDD). The aim of this study was to assess differences in brain perfusion distribution and connectivity between large groups of patients and healthy controls. Participants comprised 91 patients with PDD and 65 age- and sex-matched healthy controls. Resting state perfusion was investigated by single photon emission computed tomography, and group differences were assessed by Statistical Parametric Mapping. Brain connectivity was explored through a voxel-wise interregional correlation analysis using as covariate of interest the normalized values of clusters of voxels in which perfusion differences were found in group analysis. Significantly increased regional brain perfusion distribution covering a large part of the cerebellum was observed in patients as compared with controls. Patients showed a significant negative functional connectivity between the cerebellar cluster and caudate, bilaterally. This study demonstrated inverse relative perfusion between the cerebellum and the caudate in PDD. Functional uncoupling may be associated with a dysregulation between the role of the cerebellum in action control and of the caudate in action selection, initiation and decision making in the patients. The potential impact of the resting state condition and the possibility of mitochondrial impairment are discussed. Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

A selective involvement of putamen functional connectivity in youth with internet gaming disorder.

PubMed

Hong, Soon-Beom; Harrison, Ben J; Dandash, Orwa; Choi, Eun-Jung; Kim, Seong-Chan; Kim, Ho-Hyun; Shim, Do-Hyun; Kim, Chang-Dai; Kim, Jae-Won; Yi, Soon-Hyung

2015-03-30

Brain cortico-striatal circuits have consistently been implicated in the pathology of addiction related disorders. We applied a reliable seed-based analysis of the resting-state brain activity to comprehensively delineate the subdivisions of striatal functional connectivity implicated in internet gaming disorder. Among twelve right-handed male adolescents with internet gaming disorder and 11 right-handed and gender-matched healthy controls, we examined group differences in the functional connectivity of dorsal and ventral subdivisions of the caudate nucleus and putamen, as well as the association of these connectivity indices with behavioral measures of internet use. Adolescents with internet gaming disorder showed significantly reduced dorsal putamen functional connectivity with the posterior insula-parietal operculum. More time spent playing online games predicted significantly greater functional connectivity between the dorsal putamen and bilateral primary somatosensory cortices in adolescents with internet gaming disorder, and significantly lower functional connectivity between the dorsal putamen and bilateral sensorimotor cortices in healthy controls. The dorsal putamen functional connectivity was significantly and specifically different in adolescents with internet gaming disorder. The findings suggest a possible biomarker of internet gaming disorder. Copyright © 2015. Published by Elsevier B.V.

Early life social stress and resting state functional connectivity in postpartum rat anterior cingulate circuits.

PubMed

Nephew, Benjamin C; Febo, Marcelo; Huang, Wei; Colon-Perez, Luis M; Payne, Laurellee; Poirier, Guillaume L; Greene, Owen; King, Jean A

2018-03-15

Continued development and refinement of resting state functional connectivity (RSFC) fMRI techniques in both animal and clinical studies has enhanced our comprehension of the adverse effects of stress on psychiatric health. The objective of the current study was to assess both maternal behavior and resting state functional connectivity (RSFC) changes in these animals when they were dams caring for their own young. It was hypothesized that ECSS exposed dams would express depressed maternal care and exhibit similar (same networks), yet different specific changes in RSFC (different individual nuclei) than reported when they were adult females. We have developed an ethologically relevant transgenerational model of the role of chronic social stress (CSS) in the etiology of postpartum depression and anxiety. Initial fMRI investigation of the CSS model indicates that early life exposure to CSS (ECSS) induces long term changes in functional connectivity in adult nulliparous female F1 offspring. ECSS in F1 dams resulted in depressed maternal care specifically during early lactation, consistent with previous CSS studies, and induced changes in functional connectivity in regions associated with sensory processing, maternal and emotional responsiveness, memory, and the reward pathway, with robust changes in anterior cingulate circuits. The sample sizes for the fMRI groups were low, limiting statistical power. This behavioral and functional neuroanatomical foundation can now be used to enhance our understanding of the neural etiology of early life stress associated disorders and test preventative measures and treatments for stress related disorders. Copyright © 2018 Elsevier B.V. All rights reserved.

Functional substrate for memory function differences between patients with left and right mesial temporal lobe epilepsy associated with hippocampal sclerosis.

PubMed

Jin, Seung-Hyun; Chung, Chun Kee

2015-10-01

Little is known about the functional substrate for memory function differences in patients with left or right mesial temporal lobe epilepsy (mTLE) associated with hippocampal sclerosis (HS) from an electrophysiological perspective. To characterize these differences, we hypothesized that hippocampal theta connectivity in the resting-state might be different between patients with left and right mTLE with HS and be correlated with memory performance. Resting-state hippocampal theta connectivity, identified via whole-brain magnetoencephalography, was evaluated. Connectivity and memory function in 41 patients with mTLE with HS (left mTLE=22; right mTLE=19) were compared with those in 46 age-matched healthy controls and 28 patients with focal cortical dysplasia (FCD) but without HS. Connectivity between the right hippocampus and the left middle frontal gyrus was significantly stronger in patients with right mTLE than in patients with left mTLE. Moreover, this connectivity was positively correlated with delayed verbal recall and recognition scores in patients with mTLE. Patients with left mTLE had greater delayed recall impairment than patients with right mTLE and FCD. Similarly, delayed recognition performance was worse in patients with left mTLE than in patients with right mTLE and FCD. No significant differences in memory function between patients with right mTLE and FCD were detected. Patients with right mTLE showed significantly stronger hippocampal theta connectivity between the right hippocampus and left middle frontal gyrus than patients with FCD and left mTLE. Our results suggest that right hippocampal-left middle frontal theta connectivity could be a functional substrate that can account for differences in memory function between patients with left and right mTLE. This functional substrate might be related to different compensatory mechanisms against the structural hippocampal lesions in left and right mTLE groups. Given the positive correlation between connectivity and delayed verbal memory function, hemispheric-specific hippocampal-frontal theta connectivity assessment could be useful as an electrophysiological indicator of delayed verbal memory function in patients with mTLE with HS. Copyright © 2015 Elsevier Inc. All rights reserved.

The Posterior Medial Cortex in Urologic Chronic Pelvic Pain Syndrome: Detachment from Default Mode Network. A Resting-State Study from the MAPP Research Network

PubMed Central

Martucci, Katherine T.; Shirer, William R.; Bagarinao, Epifanio; Johnson, Kevin A.; Farmer, Melissa A.; Labus, Jennifer S.; Apkarian, A. Vania; Deutsch, Georg; Harris, Richard E.; Mayer, Emeran A.; Clauw, Daniel J.; Greicius, Michael D.; Mackey, Sean C.

2015-01-01

Altered resting-state brain activity, as a measure of functional connectivity, is commonly observed in chronic pain. Identifying a reliable signature pattern of altered resting-state activity for chronic pain could provide strong mechanistic insights and serve as a highly beneficial neuroimaging-based diagnostic tool. We collected and analyzed resting-state fMRI data from female patients with urologic chronic pelvic pain syndrome (UCPPS, N = 45) and matched healthy participants (N = 45) as part of a NIDDK funded multicenter project (www.mappnetwork.org). Using dual regression and seed-based analyses, we observed significantly decreased functional connectivity of the default mode network (DMN) to two regions in the posterior medial cortex (PMC): the posterior cingulate cortex (PCC) and left precuneus (TFCE, FWE corrected p<0.05). Further investigation revealed that patients demonstrated increased functional connectivity between the PCC and several brain regions implicated in pain, sensory, motor, and emotion regulation processes (e.g., insular cortex, dorsolateral prefrontal cortex, thalamus, globus pallidus, putamen, amygdala, hippocampus). The left precuneus demonstrated decreased functional connectivity to several regions of pain processing, reward, and higher executive functioning within the prefrontal (orbitofrontal, anterior cingulate, ventromedial prefrontal) and parietal cortices (angular gyrus, superior and inferior parietal lobules). The altered PMC connectivity was associated with several phenotype measures, including pain and urologic symptom intensity, depression, anxiety, quality of relationships and self-esteem levels in patients. Collectively, these findings indicate that in UCPPS patients, regions of the PMC are detached from the DMN, while neurological processes of self-referential thought and introspection may be joined to pain and emotion regulatory processes. PMID:26010458

Intranasal insulin enhances brain functional connectivity mediating the relationship between adiposity and subjective feeling of hunger.

PubMed

Kullmann, Stephanie; Heni, Martin; Veit, Ralf; Scheffler, Klaus; Machann, Jürgen; Häring, Hans-Ulrich; Fritsche, Andreas; Preissl, Hubert

2017-05-09

Brain insulin sensitivity is an important link between metabolism and cognitive dysfunction. Intranasal insulin is a promising tool to investigate central insulin action in humans. We evaluated the acute effects of 160 U intranasal insulin on resting-state brain functional connectivity in healthy young adults. Twenty-five lean and twenty-two overweight and obese participants underwent functional magnetic resonance imaging, on two separate days, before and after intranasal insulin or placebo application. Insulin compared to placebo administration resulted in increased functional connectivity between the prefrontal regions of the default-mode network and the hippocampus as well as the hypothalamus. The change in hippocampal functional connectivity significantly correlated with visceral adipose tissue and the change in subjective feeling of hunger after intranasal insulin. Mediation analysis revealed that the intranasal insulin induced hippocampal functional connectivity increase served as a mediator, suppressing the relationship between visceral adipose tissue and hunger. The insulin-induced hypothalamic functional connectivity change showed a significant interaction with peripheral insulin sensitivity. Only participants with high peripheral insulin sensitivity showed a boost in hypothalamic functional connectivity. Hence, brain insulin action may regulate eating behavior and facilitate weight loss by modifying brain functional connectivity within and between cognitive and homeostatic brain regions.

Disrupted directed connectivity along the cingulate cortex determines vigilance after sleep deprivation

PubMed Central

Piantoni, Giovanni; Cheung, Bing Leung P.; Van Veen, Barry D.; Romeijn, Nico; Riedner, Brady A.; Tononi, Giulio; Van Der Werf, Ysbrand D.; Van Someren, Eus J.W.

2013-01-01

The cingulate cortex is regarded as the backbone of structural and functional connectivity of the brain. While its functional connectivity has been intensively studied, little is known about its effective connectivity, its modulation by behavioral states, and its involvement in cognitive performance. Given their previously reported effects on cingulate functional connectivity, we investigated how eye-closure and sleep deprivation changed cingulate effective connectivity, estimated from resting-state high-density electroencephalography (EEG) using a novel method to calculate Granger Causality directly in source space. Effective connectivity along the cingulate cortex was dominant in the forward direction. Eyes-open connectivity in the forward direction was greater compared to eyes-closed, in well-rested participants. The difference between eyes-open and eyes-closed connectivity was attenuated and no longer significant after sleep deprivation. Individual variability in the forward connectivity after sleep deprivation predicted subsequent task performance, such that those subjects who showed a greater increase in forward connectivity between the eyes-open and the eyes-closed periods also performed better on a sustained attention task. Effective connectivity in the opposite, backward, direction was not affected by whether the eyes were open or closed or by sleep deprivation. These findings indicate that the effective connectivity from posterior to anterior cingulate regions is enhanced when a well-rested subject has his eyes open compared to when they are closed. Sleep deprivation impairs this directed information flow, proportional to its deleterious effect on vigilance. Therefore, sleep may play a role in the maintenance of waking effective connectivity. PMID:23643925

Large-Scale Functional Brain Network Reorganization During Taoist Meditation.

PubMed

Jao, Tun; Li, Chia-Wei; Vértes, Petra E; Wu, Changwei Wesley; Achard, Sophie; Hsieh, Chao-Hsien; Liou, Chien-Hui; Chen, Jyh-Horng; Bullmore, Edward T

2016-02-01

Meditation induces a distinct and reversible mental state that provides insights into brain correlates of consciousness. We explored brain network changes related to meditation by graph theoretical analysis of resting-state functional magnetic resonance imaging data. Eighteen Taoist meditators with varying levels of expertise were scanned using a within-subjects counterbalanced design during resting and meditation states. State-related differences in network topology were measured globally and at the level of individual nodes and edges. Although measures of global network topology, such as small-worldness, were unchanged, meditation was characterized by an extensive and expertise-dependent reorganization of the hubs (highly connected nodes) and edges (functional connections). Areas of sensory cortex, especially the bilateral primary visual and auditory cortices, and the bilateral temporopolar areas, which had the highest degree (or connectivity) during the resting state, showed the biggest decrease during meditation. Conversely, bilateral thalamus and components of the default mode network, mainly the bilateral precuneus and posterior cingulate cortex, had low degree in the resting state but increased degree during meditation. Additionally, these changes in nodal degree were accompanied by reorganization of anatomical orientation of the edges. During meditation, long-distance longitudinal (antero-posterior) edges increased proportionally, whereas orthogonal long-distance transverse (right-left) edges connecting bilaterally homologous cortices decreased. Our findings suggest that transient changes in consciousness associated with meditation introduce convergent changes in the topological and spatial properties of brain functional networks, and the anatomical pattern of integration might be as important as the global level of integration when considering the network basis for human consciousness.

Striatal changes in Parkinson disease: An investigation of morphology, functional connectivity and their relationship to clinical symptoms.

PubMed

Owens-Walton, Conor; Jakabek, David; Li, Xiaozhen; Wilkes, Fiona A; Walterfang, Mark; Velakoulis, Dennis; van Westen, Danielle; Looi, Jeffrey C L; Hansson, Oskar

2018-05-30

We sought to investigate morphological and resting state functional connectivity changes to the striatal nuclei in Parkinson disease (PD) and examine whether changes were associated with measures of clinical function. Striatal nuclei were manually segmented on 3T-T1 weighted MRI scans of 74 PD participants and 27 control subjects, quantitatively analysed for volume, shape and also functional connectivity using functional MRI data. Bilateral caudate nuclei and putamen volumes were significantly reduced in the PD cohort compared to controls. When looking at left and right hemispheres, the PD cohort had significantly smaller left caudate nucleus and right putamen volumes compared to controls. A significant correlation was found between greater atrophy of the caudate nucleus and poorer cognitive function, and between greater atrophy of the putamen and more severe motor symptoms. Resting-state functional MRI analysis revealed altered functional connectivity of the striatal structures in the PD group. This research demonstrates that PD involves atrophic changes to the caudate nucleus and putamen that are linked to clinical dysfunction. Our work reveals important information about a key structure-function relationship in the brain and provides support for caudate nucleus and putamen atrophy as neuroimaging biomeasures in PD. Copyright © 2018 Elsevier B.V. All rights reserved.

Abnormal functional connectivity density in children with anisometropic amblyopia at resting-state.

PubMed

Wang, Tianyue; Li, Qian; Guo, Mingxia; Peng, Yanmin; Li, Qingji; Qin, Wen; Yu, Chunshui

2014-05-14

Amblyopia is a developmental disorder resulting from anomalous binocular visual input in early life. Task-based neuroimaging studies have widely investigated cortical functional impairments in amblyopia, but changes in spontaneous neuronal functional activities in amblyopia remain largely unknown. In the present study, functional connectivity density (FCD) mapping, an ultrafast data-driven method based on fMRI, was applied for the first time to investigate changes in cortical functional connectivities in amblyopia during the resting-state. We quantified and compared both short- and long-range FCD in both the brains of children with anisometropic amblyopia (AAC) and normal sighted children (NSC). In contrast to the NSC, the AAC showed significantly decreased short-range FCD in the inferior temporal/fusiform gyri, parieto-occipital and rostrolateral prefrontal cortices, as well as decreased long-range FCD in the premotor cortex, dorsal inferior parietal lobule, frontal-insular and dorsal prefrontal cortices. Furthermore, most regions with reduced long-range FCD in the AAC showed decreased functional connectivity with occipital and posterior parietal cortices in the AAC. The results suggest that chronically poor visual input in amblyopia not only impairs the brain's short-range functional connections in visual pathways and in the frontal cortex, which is important for cognitive control, but also affects long-range functional connections among the visual areas, posterior parietal and frontal cortices that subserve visuomotor and visual-guided actions, visuospatial attention modulation and the integration of salient information. This study provides evidence for abnormal spontaneous brain activities in amblyopia. Copyright © 2014 Elsevier B.V. All rights reserved.

Investigating the Intersession Reliability of Dynamic Brain-State Properties.

PubMed

Smith, Derek M; Zhao, Yrian; Keilholz, Shella D; Schumacher, Eric H

2018-06-01

Dynamic functional connectivity metrics have much to offer to the neuroscience of individual differences of cognition. Yet, despite the recent expansion in dynamic connectivity research, limited resources have been devoted to the study of the reliability of these connectivity measures. To address this, resting-state functional magnetic resonance imaging data from 100 Human Connectome Project subjects were compared across 2 scan days. Brain states (i.e., patterns of coactivity across regions) were identified by classifying each time frame using k means clustering. This was done with and without global signal regression (GSR). Multiple gauges of reliability indicated consistency in the brain-state properties across days and GSR attenuated the reliability of the brain states. Changes in the brain-state properties across the course of the scan were investigated as well. The results demonstrate that summary metrics describing the clustering of individual time frames have adequate test/retest reliability, and thus, these patterns of brain activation may hold promise for individual-difference research.

Systemic inflammation and resting state connectivity of the default mode network.

PubMed

Marsland, Anna L; Kuan, Dora C-H; Sheu, Lei K; Krajina, Katarina; Kraynak, Thomas E; Manuck, Stephen B; Gianaros, Peter J

2017-05-01

The default mode network (DMN) encompasses brain systems that exhibit coherent neural activity at rest. DMN brain systems have been implicated in diverse social, cognitive, and affective processes, as well as risk for forms of dementia and psychiatric disorders that associate with systemic inflammation. Areas of the anterior cingulate cortex (ACC) and surrounding medial prefrontal cortex (mPFC) within the DMN have been implicated specifically in regulating autonomic and neuroendocrine processes that relate to systemic inflammation via bidirectional signaling mechanisms. However, it is still unclear whether indicators of inflammation relate directly to coherent resting state activity of the ACC, mPFC, or other areas within the DMN. Accordingly, we tested whether plasma interleukin (IL)-6, an indicator of systemic inflammation, covaried with resting-state functional connectivity of the DMN among 98 adults aged 30-54 (39% male; 81% Caucasian). Independent component analyses were applied to resting state fMRI data to generate DMN connectivity maps. Voxel-wise regression analyses were then used to test for associations between IL-6 and DMN connectivity across individuals, controlling for age, sex, body mass index, and fMRI signal motion. Within the DMN, IL-6 covaried positively with connectivity of the sub-genual ACC and negatively with a region of the dorsal medial PFC at corrected statistical thresholds. These novel findings offer evidence for a unique association between a marker of systemic inflammation (IL-6) and ACC and mPFC functional connectivity within the DMN, a network that may be important for linking aspects of immune function to psychological and behavioral states in health and disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Multiband multi-echo imaging of simultaneous oxygenation and flow timeseries for resting state connectivity.

PubMed

Cohen, Alexander D; Nencka, Andrew S; Lebel, R Marc; Wang, Yang

2017-01-01

A novel sequence has been introduced that combines multiband imaging with a multi-echo acquisition for simultaneous high spatial resolution pseudo-continuous arterial spin labeling (ASL) and blood-oxygenation-level dependent (BOLD) echo-planar imaging (MBME ASL/BOLD). Resting-state connectivity in healthy adult subjects was assessed using this sequence. Four echoes were acquired with a multiband acceleration of four, in order to increase spatial resolution, shorten repetition time, and reduce slice-timing effects on the ASL signal. In addition, by acquiring four echoes, advanced multi-echo independent component analysis (ME-ICA) denoising could be employed to increase the signal-to-noise ratio (SNR) and BOLD sensitivity. Seed-based and dual-regression approaches were utilized to analyze functional connectivity. Cerebral blood flow (CBF) and BOLD coupling was also evaluated by correlating the perfusion-weighted timeseries with the BOLD timeseries. These metrics were compared between single echo (E2), multi-echo combined (MEC), multi-echo combined and denoised (MECDN), and perfusion-weighted (PW) timeseries. Temporal SNR increased for the MECDN data compared to the MEC and E2 data. Connectivity also increased, in terms of correlation strength and network size, for the MECDN compared to the MEC and E2 datasets. CBF and BOLD coupling was increased in major resting-state networks, and that correlation was strongest for the MECDN datasets. These results indicate our novel MBME ASL/BOLD sequence, which collects simultaneous high-resolution ASL/BOLD data, could be a powerful tool for detecting functional connectivity and dynamic neurovascular coupling during the resting state. The collection of more than two echoes facilitates the use of ME-ICA denoising to greatly improve the quality of resting state functional connectivity MRI.

Resting-state networks link invasive and noninvasive brain stimulation across diverse psychiatric and neurological diseases

PubMed Central

Fox, Michael D.; Buckner, Randy L.; Liu, Hesheng; Chakravarty, M. Mallar; Lozano, Andres M.; Pascual-Leone, Alvaro

2014-01-01

Brain stimulation, a therapy increasingly used for neurological and psychiatric disease, traditionally is divided into invasive approaches, such as deep brain stimulation (DBS), and noninvasive approaches, such as transcranial magnetic stimulation. The relationship between these approaches is unknown, therapeutic mechanisms remain unclear, and the ideal stimulation site for a given technique is often ambiguous, limiting optimization of the stimulation and its application in further disorders. In this article, we identify diseases treated with both types of stimulation, list the stimulation sites thought to be most effective in each disease, and test the hypothesis that these sites are different nodes within the same brain network as defined by resting-state functional-connectivity MRI. Sites where DBS was effective were functionally connected to sites where noninvasive brain stimulation was effective across diseases including depression, Parkinson's disease, obsessive-compulsive disorder, essential tremor, addiction, pain, minimally conscious states, and Alzheimer’s disease. A lack of functional connectivity identified sites where stimulation was ineffective, and the sign of the correlation related to whether excitatory or inhibitory noninvasive stimulation was found clinically effective. These results suggest that resting-state functional connectivity may be useful for translating therapy between stimulation modalities, optimizing treatment, and identifying new stimulation targets. More broadly, this work supports a network perspective toward understanding and treating neuropsychiatric disease, highlighting the therapeutic potential of targeted brain network modulation. PMID:25267639

Resting-state thalamic dysconnectivity in schizophrenia and relationships with symptoms.

PubMed

Ferri, J; Ford, J M; Roach, B J; Turner, J A; van Erp, T G; Voyvodic, J; Preda, A; Belger, A; Bustillo, J; O'Leary, D; Mueller, B A; Lim, K O; McEwen, S C; Calhoun, V D; Diaz, M; Glover, G; Greve, D; Wible, C G; Vaidya, J G; Potkin, S G; Mathalon, D H

2018-02-15

Schizophrenia (SZ) is a severe neuropsychiatric disorder associated with disrupted connectivity within the thalamic-cortico-cerebellar network. Resting-state functional connectivity studies have reported thalamic hypoconnectivity with the cerebellum and prefrontal cortex as well as thalamic hyperconnectivity with sensory cortical regions in SZ patients compared with healthy comparison participants (HCs). However, fundamental questions remain regarding the clinical significance of these connectivity abnormalities. Resting state seed-based functional connectivity was used to investigate thalamus to whole brain connectivity using multi-site data including 183 SZ patients and 178 matched HCs. Statistical significance was based on a voxel-level FWE-corrected height threshold of p < 0.001. The relationships between positive and negative symptoms of SZ and regions of the brain demonstrating group differences in thalamic connectivity were examined. HC and SZ participants both demonstrated widespread positive connectivity between the thalamus and cortical regions. Compared with HCs, SZ patients had reduced thalamic connectivity with bilateral cerebellum and anterior cingulate cortex. In contrast, SZ patients had greater thalamic connectivity with multiple sensory-motor regions, including bilateral pre- and post-central gyrus, middle/inferior occipital gyrus, and middle/superior temporal gyrus. Thalamus to middle temporal gyrus connectivity was positively correlated with hallucinations and delusions, while thalamus to cerebellar connectivity was negatively correlated with delusions and bizarre behavior. Thalamic hyperconnectivity with sensory regions and hypoconnectivity with cerebellar regions in combination with their relationship to clinical features of SZ suggest that thalamic dysconnectivity may be a core neurobiological feature of SZ that underpins positive symptoms.

Increased Functional MEG Connectivity as a Hallmark of MRI-Negative Focal and Generalized Epilepsy.

PubMed

Li Hegner, Yiwen; Marquetand, Justus; Elshahabi, Adham; Klamer, Silke; Lerche, Holger; Braun, Christoph; Focke, Niels K

2018-05-15

Epilepsy is one of the most prevalent neurological diseases with a high morbidity. Accumulating evidence has shown that epilepsy is an archetypical neural network disorder. Here we developed a non-invasive cortical functional connectivity analysis based on magnetoencephalography (MEG) to assess commonalities and differences in the network phenotype in different epilepsy syndromes (non-lesional/cryptogenic focal and idiopathic/genetic generalized epilepsy). Thirty-seven epilepsy patients with normal structural brain anatomy underwent a 30-min resting state MEG measurement with eyes closed. We only analyzed interictal epochs without epileptiform discharges. The imaginary part of coherency was calculated as an indicator of cortical functional connectivity in five classical frequency bands. This connectivity measure was computed between all sources on individually reconstructed cortical surfaces that were surface-aligned to a common template. In comparison to healthy controls, both focal and generalized epilepsy patients showed widespread increased functional connectivity in several frequency bands, demonstrating the potential of elevated functional connectivity as a common pathophysiological hallmark in different epilepsy types. Furthermore, the comparison between focal and generalized epilepsies revealed increased network connectivity in bilateral mesio-frontal and motor regions specifically for the generalized epilepsy patients. Our study indicated that the surface-based normalization of MEG sources of individual brains enables the comparison of imaging findings across subjects and groups on a united platform, which leads to a straightforward and effective disclosure of pathological network characteristics in epilepsy. This approach may allow for the definition of more specific markers of different epilepsy syndromes, and increased MEG-based resting-state functional connectivity seems to be a common feature in MRI-negative epilepsy syndromes.

Connectivity in MEG resting-state networks increases after resective surgery for low-grade glioma and correlates with improved cognitive performance☆

PubMed Central

van Dellen, E.; de Witt Hamer, P.C.; Douw, L.; Klein, M.; Heimans, J.J.; Stam, C.J.; Reijneveld, J.C.; Hillebrand, A.

2012-01-01

Purpose Low-grade glioma (LGG) patients often have cognitive deficits. Several disease- and treatment related factors affect cognitive processing. Cognitive outcome of resective surgery is unpredictable, both for improvement and deterioration, especially for complex domains such as attention and executive functioning. MEG analysis of resting-state networks (RSNs) is a good candidate for presurgical prediction of cognitive outcome. In this study, we explore the relation between alterations in connectivity of RSNs and changes in cognitive processing after resective surgery, as a stepping stone to ultimately predict postsurgical cognitive outcome. Methods Ten patients with LGG were included, who had no adjuvant therapy. MEG recording and neuropsychological assessment were obtained before and after resective surgery. MEG data were recorded during a no-task eyes-closed condition, and projected to the anatomical space of the AAL atlas. Alterations in functional connectivity, as characterized by the phase lag index (PLI), within the default mode network (DMN), executive control network (ECN), and left- and right-sided frontoparietal networks (FPN) were compared to cognitive changes. Results Lower alpha band DMN connectivity was increased after surgery, and this increase was related to improved verbal memory functioning. Similarly, right FPN connectivity was increased after resection in the upper alpha band, which correlated with improved attention, working memory and executive functioning. Discussion Increased alpha band RSN functional connectivity in MEG recordings correlates with improved cognitive outcome after resective surgery. The mechanisms resulting in functional connectivity alterations after resection remain to be elucidated. Importantly, our findings indicate that connectivity of MEG RSNs may be used for presurgical prediction of cognitive outcome in future studies. PMID:24179752

Default mode network connectivity as a function of familial and environmental risk for psychotic disorder.

PubMed

Peeters, Sanne C T; van de Ven, Vincent; Gronenschild, Ed H B M; Patel, Ameera X; Habets, Petra; Goebel, Rainer; van Os, Jim; Marcelis, Machteld

2015-01-01

Research suggests that altered interregional connectivity in specific networks, such as the default mode network (DMN), is associated with cognitive and psychotic symptoms in schizophrenia. In addition, frontal and limbic connectivity alterations have been associated with trauma, drug use and urban upbringing, though these environmental exposures have never been examined in relation to DMN functional connectivity in psychotic disorder. Resting-state functional MRI scans were obtained from 73 patients with psychotic disorder, 83 non-psychotic siblings of patients with psychotic disorder and 72 healthy controls. Posterior cingulate cortex (PCC) seed-based correlation analysis was used to estimate functional connectivity within the DMN. DMN functional connectivity was examined in relation to group (familial risk), group × environmental exposure (to cannabis, developmental trauma and urbanicity) and symptomatology. There was a significant association between group and PCC connectivity with the inferior parietal lobule (IPL), the precuneus (PCu) and the medial prefrontal cortex (MPFC). Compared to controls, patients and siblings had increased PCC connectivity with the IPL, PCu and MPFC. In the IPL and PCu, the functional connectivity of siblings was intermediate to that of controls and patients. No significant associations were found between DMN connectivity and (subclinical) psychotic/cognitive symptoms. In addition, there were no significant interactions between group and environmental exposures in the model of PCC functional connectivity. Increased functional connectivity in individuals with (increased risk for) psychotic disorder may reflect trait-related network alterations. The within-network "connectivity at rest" intermediate phenotype was not associated with (subclinical) psychotic or cognitive symptoms. The association between familial risk and DMN connectivity was not conditional on environmental exposure.

Interaction among subsystems within default mode network diminished in schizophrenia patients: a dynamic connectivity approach

PubMed Central

Du, Yuhui; Pearlson, Godfrey D; Yu, Qingbao; He, Hao; Lin, Dongdong; Sui, Jing; Wu, Lei; Calhoun, Vince D.

2015-01-01

Default mode network (DMN) has been reported altered in schizophrenia (SZ) using static connectivity analysis. However, the studies on dynamic characteristics of DMN in SZ are still limited. In this work, we compare dynamic connectivity within DMN between 82 healthy controls (HC) and 82 SZ patients using resting-state fMRI. Firstly, dynamic DMN was computed using a sliding time window method for each subject. Then, the overall connectivity strengths were compared between two groups. Furthermore, we estimated functional connectivity states using K-means clustering, and then investigated group differences with respect to the connectivity strengths in states, the dwell time in each state, and the transition times between states. Finally, graph metrics of time-varying connectivity patterns and connectivity states were assessed. Results suggest that measured by the overall connectivity, HC showed stronger inter-subsystem interaction than patients. Compared to HC, patients spent less time in the states with nodes tightly connected. For each state, SZ patients presented relatively weaker connectivity strengths mainly in inter-subsystem. Patients also exhibited lower values in averaged node strength, clustering coefficient, global efficiency, and local efficiency than HC. In summary, our findings indicate that SZ showed impaired interaction among DMN subsystems, with a reduced central role for posterior cingulate cortex (PCC) and anterior medial prefrontal cortex (aMPFC) hubs as well as weaker interaction between dorsal medial prefrontal cortex (dMPFC) subsystem and medial temporal lobe (MTL) subsystem. For SZ, decreased integration of DMN may be associated with impaired ability in making self-other distinctions and coordinating present mental states with episodic decisions about future. PMID:26654933

Greater preference consistency during the Willingness-to-Pay task is related to higher resting state connectivity between the ventromedial prefrontal cortex and the ventral striatum.

PubMed

Mackey, Scott; Olafsson, Valur; Aupperle, Robin L; Lu, Kun; Fonzo, Greg A; Parnass, Jason; Liu, Thomas; Paulus, Martin P

2016-09-01

The significance of why a similar set of brain regions are associated with the default mode network and value-related neural processes remains to be clarified. Here, we examined i) whether brain regions exhibiting willingness-to-pay (WTP) task-related activity are intrinsically connected when the brain is at rest, ii) whether these regions overlap spatially with the default mode network, and iii) whether individual differences in choice behavior during the WTP task are reflected in functional brain connectivity at rest. Blood-oxygen-level dependent (BOLD) signal was measured by functional magnetic resonance imaging while subjects performed the WTP task and at rest with eyes open. Brain regions that tracked the value of bids during the WTP task were used as seed regions in an analysis of functional connectivity in the resting state data. The seed in the ventromedial prefrontal cortex was functionally connected to core regions of the WTP task-related network. Brain regions within the WTP task-related network, namely the ventral precuneus, ventromedial prefrontal and posterior cingulate cortex overlapped spatially with publically available maps of the default mode network. Also, those individuals with higher functional connectivity during rest between the ventromedial prefrontal cortex and the ventral striatum showed greater preference consistency during the WTP task. Thus, WTP task-related regions are an intrinsic network of the brain that corresponds spatially with the default mode network, and individual differences in functional connectivity within the WTP network at rest may reveal a priori biases in choice behavior.

Greater preference consistency during the Willingness-to-Pay task is related to higher resting state connectivity between the ventromedial prefrontal cortex and the ventral striatum

PubMed Central

Mackey, Scott; Olafsson, Valur; Aupperle, Robin; Lu, Kun; Fonzo, Greg; Parnass, Jason; Liu, Thomas; Paulus, Martin P.

2015-01-01

The significance of why a similar set of brain regions are associated with the default mode network and value-related neural processes remains to be clarified. Here, we examined i) whether brain regions exhibiting willingness-to-pay (WTP) task-related activity are intrinsically connected when the brain is at rest, ii) whether these regions overlap spatially with the default mode network, and iii) whether individual differences in choice behavior during the WTP task are reflected in functional brain connectivity at rest. Blood-oxygen-level dependent (BOLD) signal was measured by functional magnetic resonance imaging while subjects performed the WTP task and at rest with eyes open. Brain regions that tracked the value of bids during the WTP task were used as seed regions in an analysis of functional connectivity in the resting state data. The seed in the ventromedial prefrontal cortex was functionally connected to core regions of the WTP task-related network. Brain regions within the WTP task-related network, namely the ventral precuneus, ventromedial prefrontal and posterior cingulate cortex overlapped spatially with publically available maps of the default mode network. Also, those individuals with higher functional connectivity during rest between the ventromedial prefrontal cortex and the ventral striatum showed greater preference consistency during the WTP task. Thus, WTP task-related regions are an intrinsic network of the brain that corresponds spatially with the default mode network, and individual differences in functional connectivity within the WTP network at rest may reveal a priori biases in choice behavior. PMID:26271206

Amygdala Functional Connectivity is Reduced After the Cold Pressor Task

PubMed Central

Clewett, David; Schoeke, Andrej; Mather, Mara

2013-01-01

The amygdala forms a crucial link between central pain and stress systems. There is much evidence that psychological stress affects amygdala activity, but it is less clear how painful stressors influence subsequent amygdala functional connectivity. In the present study, we used pulsed arterial spin labeling (PASL) to investigate differences in healthy male adults’ resting-state amygdala functional connectivity following a cold pressor versus control task, with the stressor and control conditions conducted on different days. During the period of peak cortisol response to acute stress (approximately fifteen to thirty minutes after stressor onset), participants were asked to rest for six minutes with their eyes closed during a PASL scanning sequence. The cold pressor task led to reduced resting-state functional connectivity between the amygdalae and orbitofrontal cortex (OFC) and ventromedial prefrontal cortex (VMPFC), which occurred irrespective of cortisol release. The stressor also induced greater inverse connectivity between the left amygdala and dorsal anterior cingulate cortex (dACC), a brain region implicated in the down-regulation of amygdala responsivity. Furthermore, the degree of post-stressor left amygdala decoupling with the lateral OFC varied according to self-reported pain intensity during the cold pressor task. These findings indicate that the cold pressor task alters amygdala interactions with prefrontal and ACC regions 15–30 minutes after the stressor, and that these altered functional connectivity patterns are related to pain perception rather than cortisol feedback. PMID:23645370

Sex differences in normal age trajectories of functional brain networks.

PubMed

Scheinost, Dustin; Finn, Emily S; Tokoglu, Fuyuze; Shen, Xilin; Papademetris, Xenophon; Hampson, Michelle; Constable, R Todd

2015-04-01

Resting-state functional magnetic resonance image (rs-fMRI) is increasingly used to study functional brain networks. Nevertheless, variability in these networks due to factors such as sex and aging is not fully understood. This study explored sex differences in normal age trajectories of resting-state networks (RSNs) using a novel voxel-wise measure of functional connectivity, the intrinsic connectivity distribution (ICD). Males and females showed differential patterns of changing connectivity in large-scale RSNs during normal aging from early adulthood to late middle-age. In some networks, such as the default-mode network, males and females both showed decreases in connectivity with age, albeit at different rates. In other networks, such as the fronto-parietal network, males and females showed divergent connectivity trajectories with age. Main effects of sex and age were found in many of the same regions showing sex-related differences in aging. Finally, these sex differences in aging trajectories were robust to choice of preprocessing strategy, such as global signal regression. Our findings resolve some discrepancies in the literature, especially with respect to the trajectory of connectivity in the default mode, which can be explained by our observed interactions between sex and aging. Overall, results indicate that RSNs show different aging trajectories for males and females. Characterizing effects of sex and age on RSNs are critical first steps in understanding the functional organization of the human brain. © 2014 Wiley Periodicals, Inc.

Reduction of Interhemispheric Functional Brain Connectivity in Early Blindness: A Resting-State fMRI Study

PubMed Central

2017-01-01

Objective The purpose of this study was to investigate the resting-state interhemispheric functional connectivity in early blindness by using voxel-mirrored homotopic connectivity (VMHC). Materials and Methods Sixteen early blind patients (EB group) and sixteen age- and gender-matched sighted control volunteers (SC group) were recruited in this study. We used VMHC to identify brain areas with significant differences in functional connectivity between different groups and used voxel-based morphometry (VBM) to calculate the individual gray matter volume (GMV). Results VMHC analysis showed a significantly lower connectivity in primary visual cortex, visual association cortex, and somatosensory association cortex in EB group compared to sighted controls. Additionally, VBM analysis revealed that GMV was reduced in the left lateral calcarine cortices in EB group compared to sighted controls, while it was increased in the left lateral middle occipital gyri. Statistical analysis showed the duration of blindness negatively correlated with VMHC in the bilateral middle frontal gyri, middle temporal gyri, and inferior temporal gyri. Conclusions Our findings help elucidate the pathophysiological mechanisms of EB. The interhemispheric functional connectivity was impaired in EB patients. Additionally, the middle frontal gyri, middle temporal gyri, and inferior temporal gyri may be potential target regions for rehabilitation. PMID:28656145

Altered functional connectivity of the amygdaloid input nuclei in adolescents and young adults with autism spectrum disorder: a resting state fMRI study.

PubMed

Rausch, Annika; Zhang, Wei; Haak, Koen V; Mennes, Maarten; Hermans, Erno J; van Oort, Erik; van Wingen, Guido; Beckmann, Christian F; Buitelaar, Jan K; Groen, Wouter B

2016-01-01

Amygdala dysfunction is hypothesized to underlie the social deficits observed in autism spectrum disorders (ASD). However, the neurobiological basis of this hypothesis is underspecified because it is unknown whether ASD relates to abnormalities of the amygdaloid input or output nuclei. Here, we investigated the functional connectivity of the amygdaloid social-perceptual input nuclei and emotion-regulation output nuclei in ASD versus controls. We collected resting state functional magnetic resonance imaging (fMRI) data, tailored to provide optimal sensitivity in the amygdala as well as the neocortex, in 20 adolescents and young adults with ASD and 25 matched controls. We performed a regular correlation analysis between the entire amygdala (EA) and the whole brain and used a partial correlation analysis to investigate whole-brain functional connectivity uniquely related to each of the amygdaloid subregions. Between-group comparison of regular EA correlations showed significantly reduced connectivity in visuospatial and superior parietal areas in ASD compared to controls. Partial correlation analysis revealed that this effect was driven by the left superficial and right laterobasal input subregions, but not the centromedial output nuclei. These results indicate reduced connectivity of specifically the amygdaloid sensory input channels in ASD, suggesting that abnormal amygdalo-cortical connectivity can be traced down to the socio-perceptual pathways.

Unique insula subregion resting-state functional connectivity with amygdala complexes in posttraumatic stress disorder and its dissociative subtype.

PubMed

Nicholson, Andrew A; Sapru, Iman; Densmore, Maria; Frewen, Paul A; Neufeld, Richard W J; Théberge, Jean; McKinnon, Margaret C; Lanius, Ruth A

2016-04-30

The insula and amygdala are implicated in the pathophysiology of posttraumatic stress disorder (PTSD), where both have been shown to be hyper/hypoactive in non-dissociative (PTSD-DS) and dissociative subtype (PTSD+DS) PTSD patients, respectively, during symptom provocation. However, the functional connectivity between individual insula subregions and the amygdala has not been investigated in persons with PTSD, with or without the dissociative subtype. We examined insula subregion (anterior, mid, and posterior) functional connectivity with the bilateral amygdala using a region-of-interest seed-based approach via PickAtlas and SPM8. Resting-state fMRI was conducted with (n=61) PTSD patients (n=44 PTSD-DS; n=17 PTSD+DS), and (n=40) age-matched healthy controls. When compared to controls, the PTSD-DS group displayed increased insula connectivity (bilateral anterior, bilateral mid, and left posterior) to basolateral amygdala clusters in both hemispheres, and the PTSD+DS group displayed increased insula connectivity (bilateral anterior, left mid, and left posterior) to the left basolateral amygdala complex. Moreover, as compared to PTSD-DS, increased insula subregion connectivity (bilateral anterior, left mid, and right posterior) to the left basolateral amygdala was found in PTSD+DS. Depersonalization/derealization symptoms and PTSD symptom severity correlated with insula subregion connectivity to the basolateral amygdala within PTSD patients. This study is an important first step in elucidating patterns of neural connectivity associated with unique symptoms of arousal/interoception, emotional processing, and awareness of bodily states, in PTSD and its dissociative subtype. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Resting-State Functional Connectivity Emerges from Structurally and Dynamically Shaped Slow Linear Fluctuations

PubMed Central

Deco, Gustavo; Mantini, Dante; Romani, Gian Luca; Hagmann, Patric; Corbetta, Maurizio

2013-01-01

Brain fluctuations at rest are not random but are structured in spatial patterns of correlated activity across different brain areas. The question of how resting-state functional connectivity (FC) emerges from the brain's anatomical connections has motivated several experimental and computational studies to understand structure–function relationships. However, the mechanistic origin of resting state is obscured by large-scale models' complexity, and a close structure–function relation is still an open problem. Thus, a realistic but simple enough description of relevant brain dynamics is needed. Here, we derived a dynamic mean field model that consistently summarizes the realistic dynamics of a detailed spiking and conductance-based synaptic large-scale network, in which connectivity is constrained by diffusion imaging data from human subjects. The dynamic mean field approximates the ensemble dynamics, whose temporal evolution is dominated by the longest time scale of the system. With this reduction, we demonstrated that FC emerges as structured linear fluctuations around a stable low firing activity state close to destabilization. Moreover, the model can be further and crucially simplified into a set of motion equations for statistical moments, providing a direct analytical link between anatomical structure, neural network dynamics, and FC. Our study suggests that FC arises from noise propagation and dynamical slowing down of fluctuations in an anatomically constrained dynamical system. Altogether, the reduction from spiking models to statistical moments presented here provides a new framework to explicitly understand the building up of FC through neuronal dynamics underpinned by anatomical connections and to drive hypotheses in task-evoked studies and for clinical applications. PMID:23825427

Resting-state functional connectivity emerges from structurally and dynamically shaped slow linear fluctuations.

PubMed

Deco, Gustavo; Ponce-Alvarez, Adrián; Mantini, Dante; Romani, Gian Luca; Hagmann, Patric; Corbetta, Maurizio

2013-07-03

Brain fluctuations at rest are not random but are structured in spatial patterns of correlated activity across different brain areas. The question of how resting-state functional connectivity (FC) emerges from the brain's anatomical connections has motivated several experimental and computational studies to understand structure-function relationships. However, the mechanistic origin of resting state is obscured by large-scale models' complexity, and a close structure-function relation is still an open problem. Thus, a realistic but simple enough description of relevant brain dynamics is needed. Here, we derived a dynamic mean field model that consistently summarizes the realistic dynamics of a detailed spiking and conductance-based synaptic large-scale network, in which connectivity is constrained by diffusion imaging data from human subjects. The dynamic mean field approximates the ensemble dynamics, whose temporal evolution is dominated by the longest time scale of the system. With this reduction, we demonstrated that FC emerges as structured linear fluctuations around a stable low firing activity state close to destabilization. Moreover, the model can be further and crucially simplified into a set of motion equations for statistical moments, providing a direct analytical link between anatomical structure, neural network dynamics, and FC. Our study suggests that FC arises from noise propagation and dynamical slowing down of fluctuations in an anatomically constrained dynamical system. Altogether, the reduction from spiking models to statistical moments presented here provides a new framework to explicitly understand the building up of FC through neuronal dynamics underpinned by anatomical connections and to drive hypotheses in task-evoked studies and for clinical applications.

Altered resting state neuromotor connectivity in men with chronic prostatitis/chronic pelvic pain syndrome: A MAPP

PubMed Central

Kutch, Jason J.; Yani, Moheb S.; Asavasopon, Skulpan; Kirages, Daniel J.; Rana, Manku; Cosand, Louise; Labus, Jennifer S.; Kilpatrick, Lisa A.; Ashe-McNalley, Cody; Farmer, Melissa A.; Johnson, Kevin A.; Ness, Timothy J.; Deutsch, Georg; Harris, Richard E.; Apkarian, A. Vania; Clauw, Daniel J.; Mackey, Sean C.; Mullins, Chris; Mayer, Emeran A.

2015-01-01

Brain network activity associated with altered motor control in individuals with chronic pain is not well understood. Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) is a debilitating condition in which previous studies have revealed altered resting pelvic floor muscle activity in men with CP/CPPS compared to healthy controls. We hypothesized that the brain networks controlling pelvic floor muscles would also show altered resting state function in men with CP/CPPS. Here we describe the results of the first test of this hypothesis focusing on the motor cortical regions, termed pelvic-motor, that can directly activate pelvic floor muscles. A group of men with CP/CPPS (N = 28), as well as group of age-matched healthy male controls (N = 27), had resting state functional magnetic resonance imaging scans as part of the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network study. Brain maps of the functional connectivity of pelvic-motor were compared between groups. A significant group difference was observed in the functional connectivity between pelvic-motor and the right posterior insula. The effect size of this group difference was among the largest effect sizes in functional connectivity between all pairs of 165 anatomically-defined subregions of the brain. Interestingly, many of the atlas region pairs with large effect sizes also involved other subregions of the insular cortices. We conclude that functional connectivity between motor cortex and the posterior insula may be among the most important markers of altered brain function in men with CP/CPPS, and may represent changes in the integration of viscerosensory and motor processing. PMID:26106574

The Effects of Long Duration Bed Rest as a Spaceflight Analogue on Resting State Sensorimotor Network Functional Connectivity and Neurocognitive Performance

NASA Technical Reports Server (NTRS)

Cassady, K.; Koppelmans, V.; Yuan, P.; Cooke, K.; De Dios, Y.; Stepanyan, V.; Szecsy, D.; Gadd, N.; Wood, S.; Reuter-Lorenz, P.;

A Complex Interplay of Vitamin B1 and B6 Metabolism with Cognition, Brain Structure, and Functional Connectivity in Older Adults.

PubMed

Jannusch, Kai; Jockwitz, Christiane; Bidmon, Hans-Jürgen; Moebus, Susanne; Amunts, Katrin; Caspers, Svenja

2017-01-01

Aging is associated with brain atrophy, functional brain network reorganization and decline of cognitive performance, albeit characterized by high interindividual variability. Among environmental influencing factors accounting for this variability, nutrition and particularly vitamin supply is thought to play an important role. While evidence exists that supplementation of vitamins B6 and B1 might be beneficial for cognition and brain structure, at least in deficient states and neurodegenerative diseases, little is known about this relation during healthy aging and in relation to reorganization of functional brain networks. We thus assessed the relation between blood levels of vitamins B1 and B6 and cognitive performance, cortical folding, and functional resting-state connectivity in a large sample of older adults ( N > 600; age: 55-85 years), drawn from the population-based 1000BRAINS study. In addition to blood sampling, subjects underwent structural and functional resting-state neuroimaging as well as extensive neuropsychological testing in the domains of executive functions, (working) memory, attention, and language. Brain regions showing changes in the local gyrification index as calculated using FreeSurfer in relation to vitamin levels were used for subsequent seed-based resting-state functional connectivity analysis. For B6, a positive correlation with local cortical folding was found throughout the brain, while only slight changes in functional connectivity were observed. Contrarily, for B1, a negative correlation with cortical folding as well as problem solving and visuo-spatial working memory performance was found, which was accompanied by pronounced increases of interhemispheric and decreases of intrahemispheric functional connectivity. While the effects for B6 expand previous knowledge on beneficial effects of B6 supplementation on brain structure, they also showed that additional effects on cognition might not be recognizable in healthy older subjects with normal B6 blood levels. The cortical atrophy and pronounced functional reorganization associated with B1, contrarily, was more in line with the theory of a disturbed B1 metabolism in older adults, leading to B1 utilization deficits, and thus, an effective B1 deficiency in the brain, despite normal to high-normal blood levels.

A Complex Interplay of Vitamin B1 and B6 Metabolism with Cognition, Brain Structure, and Functional Connectivity in Older Adults

PubMed Central

Jannusch, Kai; Jockwitz, Christiane; Bidmon, Hans-Jürgen; Moebus, Susanne; Amunts, Katrin; Caspers, Svenja

2017-01-01

Aging is associated with brain atrophy, functional brain network reorganization and decline of cognitive performance, albeit characterized by high interindividual variability. Among environmental influencing factors accounting for this variability, nutrition and particularly vitamin supply is thought to play an important role. While evidence exists that supplementation of vitamins B6 and B1 might be beneficial for cognition and brain structure, at least in deficient states and neurodegenerative diseases, little is known about this relation during healthy aging and in relation to reorganization of functional brain networks. We thus assessed the relation between blood levels of vitamins B1 and B6 and cognitive performance, cortical folding, and functional resting-state connectivity in a large sample of older adults (N > 600; age: 55–85 years), drawn from the population-based 1000BRAINS study. In addition to blood sampling, subjects underwent structural and functional resting-state neuroimaging as well as extensive neuropsychological testing in the domains of executive functions, (working) memory, attention, and language. Brain regions showing changes in the local gyrification index as calculated using FreeSurfer in relation to vitamin levels were used for subsequent seed-based resting-state functional connectivity analysis. For B6, a positive correlation with local cortical folding was found throughout the brain, while only slight changes in functional connectivity were observed. Contrarily, for B1, a negative correlation with cortical folding as well as problem solving and visuo-spatial working memory performance was found, which was accompanied by pronounced increases of interhemispheric and decreases of intrahemispheric functional connectivity. While the effects for B6 expand previous knowledge on beneficial effects of B6 supplementation on brain structure, they also showed that additional effects on cognition might not be recognizable in healthy older subjects with normal B6 blood levels. The cortical atrophy and pronounced functional reorganization associated with B1, contrarily, was more in line with the theory of a disturbed B1 metabolism in older adults, leading to B1 utilization deficits, and thus, an effective B1 deficiency in the brain, despite normal to high-normal blood levels. PMID:29163003

Double-dissociation between the mechanism leading to impulsivity and inattention in Attention Deficit Hyperactivity Disorder: A resting-state functional connectivity study.

PubMed

Sanefuji, Masafumi; Craig, Michael; Parlatini, Valeria; Mehta, Mitul A; Murphy, Declan G; Catani, Marco; Cerliani, Leonardo; Thiebaut de Schotten, Michel

2017-01-01

Two core symptoms characterize Attention Deficit Hyperactivity Disorder (ADHD) subtypes: inattentiveness and hyperactivity-impulsivity. While previous brain imaging research investigated ADHD as if it was a homogenous condition, its two core symptoms may originate from different brain mechanisms. We, therefore, hypothesized that the functional connectivity of cortico-striatal and attentional networks would be different between ADHD subtypes. We studied 165 children (mean age 10.93 years; age range, 7-17 year old) diagnosed as having ADHD based on their revised Conner's rating scale score and 170 typical developing individuals (mean age 11.46 years; age range, 7-17 year old) using resting state functional fMRI. Groups were matched for age, IQ and head motion during the MRI acquisition. We fractionated the ADHD group into predominantly inattentive, hyperactive-impulsive and combined subtypes based on their revised Conner's rating scale score. We then analyzed differences in resting state functional connectivity of the cortico-striatal and attentional networks between these subtypes. We found a double dissociation of functional connectivity in the cortico-striatal and ventral attentional networks, reflecting the subtypes of the ADHD participants. Particularly, the hyperactive-impulsive subtype was associated with increased connectivity in cortico-striatal network, whereas the inattentive subtype was associated with increased connectivity in the right ventral attention network. Our study demonstrated for the first time a right lateralized, double dissociation between specific networks associated with hyperactivity-impulsivity and inattentiveness in ADHD children, providing a biological basis for exploring symptom dimensions and revealing potential targets for more personalized treatments. Copyright © 2016 Elsevier Ltd. All rights reserved.

Multimodal MR-imaging reveals large-scale structural and functional connectivity changes in profound early blindness

PubMed Central

Bauer, Corinna M.; Hirsch, Gabriella V.; Zajac, Lauren; Koo, Bang-Bon; Collignon, Olivier

2017-01-01

In the setting of profound ocular blindness, numerous lines of evidence demonstrate the existence of dramatic anatomical and functional changes within the brain. However, previous studies based on a variety of distinct measures have often provided inconsistent findings. To help reconcile this issue, we used a multimodal magnetic resonance (MR)-based imaging approach to provide complementary structural and functional information regarding this neuroplastic reorganization. This included gray matter structural morphometry, high angular resolution diffusion imaging (HARDI) of white matter connectivity and integrity, and resting state functional connectivity MRI (rsfcMRI) analysis. When comparing the brains of early blind individuals to sighted controls, we found evidence of co-occurring decreases in cortical volume and cortical thickness within visual processing areas of the occipital and temporal cortices respectively. Increases in cortical volume in the early blind were evident within regions of parietal cortex. Investigating white matter connections using HARDI revealed patterns of increased and decreased connectivity when comparing both groups. In the blind, increased white matter connectivity (indexed by increased fiber number) was predominantly left-lateralized, including between frontal and temporal areas implicated with language processing. Decreases in structural connectivity were evident involving frontal and somatosensory regions as well as between occipital and cingulate cortices. Differences in white matter integrity (as indexed by quantitative anisotropy, or QA) were also in general agreement with observed pattern changes in the number of white matter fibers. Analysis of resting state sequences showed evidence of both increased and decreased functional connectivity in the blind compared to sighted controls. Specifically, increased connectivity was evident between temporal and inferior frontal areas. Decreases in functional connectivity were observed between occipital and frontal and somatosensory-motor areas and between temporal (mainly fusiform and parahippocampus) and parietal, frontal, and other temporal areas. Correlations in white matter connectivity and functional connectivity observed between early blind and sighted controls showed an overall high degree of association. However, comparing the relative changes in white matter and functional connectivity between early blind and sighted controls did not show a significant correlation. In summary, these findings provide complimentary evidence, as well as highlight potential contradictions, regarding the nature of regional and large scale neuroplastic reorganization resulting from early onset blindness. PMID:28328939

Age-Related Differences in Dynamic Interactions Among Default Mode, Frontoparietal Control, and Dorsal Attention Networks during Resting-State and Interference Resolution.

PubMed

Avelar-Pereira, Bárbara; Bäckman, Lars; Wåhlin, Anders; Nyberg, Lars; Salami, Alireza

2017-01-01

Resting-state fMRI (rs-fMRI) can identify large-scale brain networks, including the default mode (DMN), frontoparietal control (FPN) and dorsal attention (DAN) networks. Interactions among these networks are critical for supporting complex cognitive functions, yet the way in which they are modulated across states is not well understood. Moreover, it remains unclear whether these interactions are similarly affected in aging regardless of cognitive state. In this study, we investigated age-related differences in functional interactions among the DMN, FPN and DAN during rest and the Multi-Source Interference task (MSIT). Networks were identified using independent component analysis (ICA), and functional connectivity was measured during rest and task. We found that the FPN was more coupled with the DMN during rest and with the DAN during the MSIT. The degree of FPN-DMN connectivity was lower in older compared to younger adults, whereas no age-related differences were observed in FPN-DAN connectivity in either state. This suggests that dynamic interactions of the FPN are stable across cognitive states. The DMN and DAN were anti correlated and age-sensitive during the MSIT only, indicating variation in a task-dependent manner. Increased levels of anticorrelation from rest to task also predicted successful interference resolution. Additional analyses revealed that the degree of DMN-DAN anticorrelation during the MSIT was associated to resting cerebral blood flow (CBF) within the DMN. This suggests that reduced DMN neural activity during rest underlies an impaired ability to achieve higher levels of anticorrelation during a task. Taken together, our results suggest that only parts of age-related differences in connectivity are uncovered at rest and thus, should be studied in the functional connectome across multiple states for a more comprehensive picture.

Age-Related Differences in Dynamic Interactions Among Default Mode, Frontoparietal Control, and Dorsal Attention Networks during Resting-State and Interference Resolution

PubMed Central

Avelar-Pereira, Bárbara; Bäckman, Lars; Wåhlin, Anders; Nyberg, Lars; Salami, Alireza

2017-01-01

Resting-state fMRI (rs-fMRI) can identify large-scale brain networks, including the default mode (DMN), frontoparietal control (FPN) and dorsal attention (DAN) networks. Interactions among these networks are critical for supporting complex cognitive functions, yet the way in which they are modulated across states is not well understood. Moreover, it remains unclear whether these interactions are similarly affected in aging regardless of cognitive state. In this study, we investigated age-related differences in functional interactions among the DMN, FPN and DAN during rest and the Multi-Source Interference task (MSIT). Networks were identified using independent component analysis (ICA), and functional connectivity was measured during rest and task. We found that the FPN was more coupled with the DMN during rest and with the DAN during the MSIT. The degree of FPN-DMN connectivity was lower in older compared to younger adults, whereas no age-related differences were observed in FPN-DAN connectivity in either state. This suggests that dynamic interactions of the FPN are stable across cognitive states. The DMN and DAN were anti correlated and age-sensitive during the MSIT only, indicating variation in a task-dependent manner. Increased levels of anticorrelation from rest to task also predicted successful interference resolution. Additional analyses revealed that the degree of DMN-DAN anticorrelation during the MSIT was associated to resting cerebral blood flow (CBF) within the DMN. This suggests that reduced DMN neural activity during rest underlies an impaired ability to achieve higher levels of anticorrelation during a task. Taken together, our results suggest that only parts of age-related differences in connectivity are uncovered at rest and thus, should be studied in the functional connectome across multiple states for a more comprehensive picture. PMID:28588476

Neural correlates of consciousness in patients who have emerged from a minimally conscious state: a cross-sectional multimodal imaging study.

PubMed

Di Perri, Carol; Bahri, Mohamed Ali; Amico, Enrico; Thibaut, Aurore; Heine, Lizette; Antonopoulos, Georgios; Charland-Verville, Vanessa; Wannez, Sarah; Gomez, Francisco; Hustinx, Roland; Tshibanda, Luaba; Demertzi, Athena; Soddu, Andrea; Laureys, Steven

2016-07-01

Between pathologically impaired consciousness and normal consciousness exists a scarcely researched transition zone, referred to as emergence from minimally conscious state, in which patients regain the capacity for functional communication, object use, or both. We investigated neural correlates of consciousness in these patients compared with patients with disorders of consciousness and healthy controls, by multimodal imaging. In this cross-sectional, multimodal imaging study, patients with unresponsive wakefulness syndrome, patients in a minimally conscious state, and patients who had emerged from a minimally conscious state, diagnosed with the Coma Recovery Scale-Revised, were recruited from the neurology department of the Centre Hospitalier Universitaire de Liège, Belgium. Key exclusion criteria were neuroimaging examination in an acute state, sedation or anaesthesia during scanning, large focal brain damage, motion parameters of more than 3 mm in translation and 3° in rotation, and suboptimal segmentation and normalisation. We acquired resting state functional and structural MRI data and (18)F-fluorodeoxyglucose (FDG) PET data; we used seed-based functional MRI (fMRI) analysis to investigate positive default mode network connectivity (within-network correlations) and negative default mode network connectivity (between-network anticorrelations). We correlated FDG-PET brain metabolism with fMRI connectivity. We used voxel-based morphometry to test the effect of anatomical deformations on functional connectivity. We recruited a convenience sample of 58 patients (21 [36%] with unresponsive wakefulness syndrome, 24 [41%] in a minimally conscious state, and 13 [22%] who had emerged from a minimally conscious state) and 35 healthy controls between Oct 1, 2009, and Oct 31, 2014. We detected consciousness-level-dependent increases (from unresponsive wakefulness syndrome, minimally conscious state, emergence from minimally conscious state, to healthy controls) for positive and negative default mode network connectivity, brain metabolism, and grey matter volume (p<0·05 false discovery rate corrected for multiple comparisons). Positive default mode network connectivity differed between patients and controls but not among patient groups (F test p<0·0001). Negative default mode network connectivity was only detected in healthy controls and in those who had emerged from a minimally conscious state; patients with unresponsive wakefulness syndrome or in a minimally conscious state showed pathological between-network positive connectivity (hyperconnectivity; F test p<0·0001). Brain metabolism correlated with positive default mode network connectivity (Spearman's r=0·50 [95% CI 0·26 to 0·61]; p<0·0001) and negative default mode network connectivity (Spearman's r=-0·52 [-0·35 to -0·67); p<0·0001). Grey matter volume did not differ between the studied groups (F test p=0·06). Partial preservation of between-network anticorrelations, which are seemingly of neuronal origin and cannot be solely explained by morphological deformations, characterise patients who have emerged from a minimally conscious state. Conversely, patients with disorders of consciousness show pathological between-network correlations. Apart from a deeper understanding of the neural correlates of consciousness, these findings have clinical implications and might be particularly relevant for outcome prediction and could inspire new therapeutic options. Belgian National Funds for Scientific Research (FNRS), European Commission, Natural Sciences and Engineering Research Council of Canada, James McDonnell Foundation, European Space Agency, Mind Science Foundation, French Speaking Community Concerted Research Action, Fondazione Europea di Ricerca Biomedica, University and University Hospital of Liège (Liège, Belgium), and University of Western Ontario (London, ON, Canada). Copyright © 2016 Elsevier Ltd. All rights reserved.

Altered frontal inter-hemispheric resting state functional connectivity is associated with bulimic symptoms among restrained eaters.

PubMed

Chen, Shuaiyu; Dong, Debo; Jackson, Todd; Su, Yanhua; Chen, Hong

2016-01-29

Theory and research have indicated that restrained eating (RE) increases risk for binge-eating and eating disorder symptoms. According to the goal conflict model, such risk may result from disrupted hedonic-feeding control and its interaction with reward-driven eating. However, RE-related alterations in functional interactions among associated underlying brain regions, especially between the cerebral hemispheres, have rarely been examined directly. Therefore, we investigated inter-hemispheric resting-state functional connectivity (RSFC) among female restrained eaters (REs) (n=23) and unrestrained eaters (UREs) (n=24) following food deprivation as well as its relation to overall bulimia nervosa (BN) symptoms using voxel-mirrored homotopic connectivity (VMHC). Seed-based RSFC associated with areas exhibiting significant VMHC differences was also assessed. Compared to UREs, REs showed reduced VMHC in the dorsal-lateral prefrontal cortex (DLPFC), an area involved in inhibiting hedonic overeating. REs also displayed decreased RSFC between the right DLPFC and regions associated with reward estimation--the ventromedial prefrontal cortex (VMPFC) and posterior cingulate cortex (PCC). Finally, bulimic tendencies had a negative correlation with VMHC in the DLPFC and a positive correlation with functional connectivity (DLPFC and VMPFC) among REs but not UREs. Findings suggested that reduced inter-hemispheric functional connectivity in appetite inhibition regions and altered functional connectivity in reward related regions may help to explain why some REs fail to control hedonically-motivated feeding and experience higher associated levels of BN symptomatology. Copyright © 2015 Elsevier Ltd. All rights reserved.

Corticostriatal connectivity fingerprints: Probability maps based on resting-state functional connectivity.

PubMed

Jaspers, Ellen; Balsters, Joshua H; Kassraian Fard, Pegah; Mantini, Dante; Wenderoth, Nicole

2017-03-01

Over the last decade, structure-function relationships have begun to encompass networks of brain areas rather than individual structures. For example, corticostriatal circuits have been associated with sensorimotor, limbic, and cognitive information processing, and damage to these circuits has been shown to produce unique behavioral outcomes in Autism, Parkinson's Disease, Schizophrenia and healthy ageing. However, it remains an open question how abnormal or absent connectivity can be detected at the individual level. Here, we provide a method for clustering gross morphological structures into subregions with unique functional connectivity fingerprints, and generate network probability maps usable as a baseline to compare individual cases against. We used connectivity metrics derived from resting-state fMRI (N = 100), in conjunction with hierarchical clustering methods, to parcellate the striatum into functionally distinct clusters. We identified three highly reproducible striatal subregions, across both hemispheres and in an independent replication dataset (N = 100) (dice-similarity values 0.40-1.00). Each striatal seed region resulted in a highly reproducible distinct connectivity fingerprint: the putamen showed predominant connectivity with cortical and cerebellar sensorimotor and language processing areas; the ventromedial striatum cluster had a distinct limbic connectivity pattern; the caudate showed predominant connectivity with the thalamus, frontal and occipital areas, and the cerebellum. Our corticostriatal probability maps agree with existing connectivity data in humans and non-human primates, and showed a high degree of replication. We believe that these maps offer an efficient tool to further advance hypothesis driven research and provide important guidance when investigating deviant connectivity in neurological patient populations suffering from e.g., stroke or cerebral palsy. Hum Brain Mapp 38:1478-1491, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Cannabis and cocaine decrease cognitive impulse control and functional corticostriatal connectivity in drug users with low activity DBH genotypes.

PubMed

Ramaekers, J G; van Wel, J H; Spronk, D; Franke, B; Kenis, G; Toennes, S W; Kuypers, K P C; Theunissen, E L; Stiers, P; Verkes, R J

2016-12-01

The dopamine β-hydroxylase (DβH) enzyme transforms dopamine into noradrenaline. We hypothesized that individuals with low activity DBH genotypes (rs1611115 CT/TT) are more sensitive to the influence of cannabis and cocaine on cognitive impulse control and functional connectivity in the limbic 'reward' circuit because they experience a drug induced hyperdopaminergic state compared to individuals with high activity DBH genotypes (rs1611115 CC). Regular drug users (N = 122) received acute doses of cannabis (450 μg/kg THC), cocaine HCl 300 mg and placebo. Cognitive impulse control was assessed by means of the Matching Familiar Figures Test (MFFT). Resting state fMRI was measured in a subset of participants to determine functional connectivity between the nucleus accumbens (NAc) and (sub)cortical areas. The influence of cannabis and cocaine on impulsivity and functional connectivity significantly interacted with DBH genotype. Both drugs increased cognitive impulsivity in participants with CT/TT genotypes but not in CC participants. Both drugs also reduced functional connectivity between the NAc and the limbic lobe, prefrontal cortex, striatum and thalamus and primarily in individuals with CT/TT genotypes. Correlational analysis indicated a significant negative association between cognitive impulsivity and functional connectivity in subcortical areas of the brain. It is concluded that interference of cannabis and cocaine with cognitive impulse control and functional corticostriatal connectivity depends on DBH genotype. The present data provide a neural substrate and behavioral mechanism by which drug users can progress to drug seeking and may also offer a rationale for targeted pharmacotherapy in chronic drug users with high risk DBH genotypes.

Functional connectivity changes detected with magnetoencephalography after mild traumatic brain injury

PubMed Central

Dimitriadis, Stavros I.; Zouridakis, George; Rezaie, Roozbeh; Babajani-Feremi, Abbas; Papanicolaou, Andrew C.

2015-01-01

Mild traumatic brain injury (mTBI) may affect normal cognition and behavior by disrupting the functional connectivity networks that mediate efficient communication among brain regions. In this study, we analyzed brain connectivity profiles from resting state Magnetoencephalographic (MEG) recordings obtained from 31 mTBI patients and 55 normal controls. We used phase-locking value estimates to compute functional connectivity graphs to quantify frequency-specific couplings between sensors at various frequency bands. Overall, normal controls showed a dense network of strong local connections and a limited number of long-range connections that accounted for approximately 20% of all connections, whereas mTBI patients showed networks characterized by weak local connections and strong long-range connections that accounted for more than 60% of all connections. Comparison of the two distinct general patterns at different frequencies using a tensor representation for the connectivity graphs and tensor subspace analysis for optimal feature extraction showed that mTBI patients could be separated from normal controls with 100% classification accuracy in the alpha band. These encouraging findings support the hypothesis that MEG-based functional connectivity patterns may be used as biomarkers that can provide more accurate diagnoses, help guide treatment, and monitor effectiveness of intervention in mTBI. PMID:26640764

Resting-state functional connectivity of the default mode network associated with happiness

PubMed Central

Luo, Yangmei; Kong, Feng; Qi, Senqing; You, Xuqun

2016-01-01

Happiness refers to people’s cognitive and affective evaluation of their life. Why are some people happier than others? One reason might be that unhappy people are prone to ruminate more than happy people. The default mode network (DMN) is normally active during rest and is implicated in rumination. We hypothesized that unhappiness may be associated with increased default-mode functional connectivity during rest, including the medial prefrontal cortex (MPFC), posterior cingulate cortex (PCC) and inferior parietal lobule (IPL). The hyperconnectivity of these areas may be associated with higher levels of rumination. One hundred forty-eight healthy participants underwent a resting-state fMRI scan. A group-independent component analysis identified the DMNs. Results indicated increased functional connectivity in the DMN was associated with lower levels of happiness. Specifically, relative to happy people, unhappy people exhibited greater functional connectivity in the anterior medial cortex (bilateral MPFC), posterior medial cortex regions (bilateral PCC) and posterior parietal cortex (left IPL). Moreover, the increased functional connectivity of the MPFC, PCC and IPL, correlated positively with the inclination to ruminate. These results highlight the important role of the DMN in the neural correlates of happiness, and suggest that rumination may play an important role in people’s perceived happiness. PMID:26500289

The functional organization of human epileptic hippocampus

PubMed Central

Klimes, Petr; Duque, Juliano J.; Brinkmann, Ben; Van Gompel, Jamie; Stead, Matt; St. Louis, Erik K.; Halamek, Josef; Jurak, Pavel

2016-01-01

The function and connectivity of human brain is disrupted in epilepsy. We previously reported that the region of epileptic brain generating focal seizures, i.e., the seizure onset zone (SOZ), is functionally isolated from surrounding brain regions in focal neocortical epilepsy. The modulatory effect of behavioral state on the spatial and spectral scales over which the reduced functional connectivity occurs, however, is unclear. Here we use simultaneous sleep staging from scalp EEG with intracranial EEG recordings from medial temporal lobe to investigate how behavioral state modulates the spatial and spectral scales of local field potential synchrony in focal epileptic hippocampus. The local field spectral power and linear correlation between adjacent electrodes provide measures of neuronal population synchrony at different spatial scales, ∼1 and 10 mm, respectively. Our results show increased connectivity inside the SOZ and low connectivity between electrodes in SOZ and outside the SOZ. During slow-wave sleep, we observed decreased connectivity for ripple and fast ripple frequency bands within the SOZ at the 10 mm spatial scale, while the local synchrony remained high at the 1 mm spatial scale. Further study of these phenomena may prove useful for SOZ localization and help understand seizure generation, and the functional deficits seen in epileptic eloquent cortex. PMID:27030735

Decreased integration and information capacity in stroke measured by whole brain models of resting state activity.

PubMed

Adhikari, Mohit H; Hacker, Carl D; Siegel, Josh S; Griffa, Alessandra; Hagmann, Patric; Deco, Gustavo; Corbetta, Maurizio

2017-04-01

While several studies have shown that focal lesions affect the communication between structurally normal regions of the brain, and that these changes may correlate with behavioural deficits, their impact on brain's information processing capacity is currently unknown. Here we test the hypothesis that focal lesions decrease the brain's information processing capacity, of which changes in functional connectivity may be a measurable correlate. To measure processing capacity, we turned to whole brain computational modelling to estimate the integration and segregation of information in brain networks. First, we measured functional connectivity between different brain areas with resting state functional magnetic resonance imaging in healthy subjects (n = 26), and subjects who had suffered a cortical stroke (n = 36). We then used a whole-brain network model that coupled average excitatory activities of local regions via anatomical connectivity. Model parameters were optimized in each healthy or stroke participant to maximize correlation between model and empirical functional connectivity, so that the model's effective connectivity was a veridical representation of healthy or lesioned brain networks. Subsequently, we calculated two model-based measures: 'integration', a graph theoretical measure obtained from functional connectivity, which measures the connectedness of brain networks, and 'information capacity', an information theoretical measure that cannot be obtained empirically, representative of the segregative ability of brain networks to encode distinct stimuli. We found that both measures were decreased in stroke patients, as compared to healthy controls, particularly at the level of resting-state networks. Furthermore, we found that these measures, especially information capacity, correlate with measures of behavioural impairment and the segregation of resting-state networks empirically measured. This study shows that focal lesions affect the brain's ability to represent stimuli and task states, and that information capacity measured through whole brain models is a theory-driven measure of processing capacity that could be used as a biomarker of injury for outcome prediction or target for rehabilitation intervention. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Connected Equipment Maturity Model Version 1.0

DOE Office of Scientific and Technical Information (OSTI.GOV)

Butzbaugh, Joshua B.; Mayhorn, Ebony T.; Sullivan, Greg

2017-05-01

The Connected Equipment Maturity Model (CEMM) evaluates the high-level functionality and characteristics that enable equipment to provide the four categories of energy-related services through communication with other entities (e.g., equipment, third parties, utilities, and users). The CEMM will help the U.S. Department of Energy, industry, energy efficiency organizations, and research institutions benchmark the current state of connected equipment and identify capabilities that may be attained to reach a more advanced, future state.

Functional connectivity dynamics: modeling the switching behavior of the resting state.

PubMed

Hansen, Enrique C A; Battaglia, Demian; Spiegler, Andreas; Deco, Gustavo; Jirsa, Viktor K

2015-01-15

Functional connectivity (FC) sheds light on the interactions between different brain regions. Besides basic research, it is clinically relevant for applications in Alzheimer's disease, schizophrenia, presurgical planning, epilepsy, and traumatic brain injury. Simulations of whole-brain mean-field computational models with realistic connectivity determined by tractography studies enable us to reproduce with accuracy aspects of average FC in the resting state. Most computational studies, however, did not address the prominent non-stationarity in resting state FC, which may result in large intra- and inter-subject variability and thus preclude an accurate individual predictability. Here we show that this non-stationarity reveals a rich structure, characterized by rapid transitions switching between a few discrete FC states. We also show that computational models optimized to fit time-averaged FC do not reproduce these spontaneous state transitions and, thus, are not qualitatively superior to simplified linear stochastic models, which account for the effects of structure alone. We then demonstrate that a slight enhancement of the non-linearity of the network nodes is sufficient to broaden the repertoire of possible network behaviors, leading to modes of fluctuations, reminiscent of some of the most frequently observed Resting State Networks. Because of the noise-driven exploration of this repertoire, the dynamics of FC qualitatively change now and display non-stationary switching similar to empirical resting state recordings (Functional Connectivity Dynamics (FCD)). Thus FCD bear promise to serve as a better biomarker of resting state neural activity and of its pathologic alterations. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

The Time Course of Task-Specific Memory Consolidation Effects in Resting State Networks

PubMed Central

Sami, Saber; Robertson, Edwin M.

2014-01-01

Previous studies have reported functionally localized changes in resting-state brain activity following a short period of motor learning, but their relationship with memory consolidation and their dependence on the form of learning is unclear. We investigate these questions with implicit or explicit variants of the serial reaction time task (SRTT). fMRI resting-state functional connectivity was measured in human subjects before the tasks, and 0.1, 0.5, and 6 h after learning. There was significant improvement in procedural skill in both groups, with the group learning under explicit conditions showing stronger initial acquisition, and greater improvement at the 6 h retest. Immediately following acquisition, this group showed enhanced functional connectivity in networks including frontal and cerebellar areas and in the visual cortex. Thirty minutes later, enhanced connectivity was observed between cerebellar nuclei, thalamus, and basal ganglia, whereas at 6 h there was enhanced connectivity in a sensory-motor cortical network. In contrast, immediately after acquisition under implicit conditions, there was increased connectivity in a network including precentral and sensory-motor areas, whereas after 30 min a similar cerebello-thalamo-basal ganglionic network was seen as in explicit learning. Finally, 6 h after implicit learning, we found increased connectivity in medial temporal cortex, but reduction in precentral and sensory-motor areas. Our findings are consistent with predictions that two variants of the SRTT task engage dissociable functional networks, although there are also networks in common. We also show a converging and diverging pattern of flux between prefrontal, sensory-motor, and parietal areas, and subcortical circuits across a 6 h consolidation period. PMID:24623776

Distinct Aging Effects on Functional Networks in Good and Poor Cognitive Performers

PubMed Central

Lee, Annie; Tan, Mingzhen; Qiu, Anqi

2016-01-01

Brain network hubs are susceptible to normal aging processes and disruptions of their functional connectivity are detrimental to decline in cognitive functions in older adults. However, it remains unclear how the functional connectivity of network hubs cope with cognitive heterogeneity in an aging population. This study utilized cognitive and resting-state functional magnetic resonance imaging data, cluster analysis, and graph network analysis to examine age-related alterations in the network hubs’ functional connectivity of good and poor cognitive performers. Our results revealed that poor cognitive performers showed age-dependent disruptions in the functional connectivity of the right insula and posterior cingulate cortex (PCC), while good cognitive performers showed age-related disruptions in the functional connectivity of the left insula and PCC. Additionally, the left PCC had age-related declines in the functional connectivity with the left medial prefrontal cortex (mPFC) and anterior cingulate cortex (ACC). Most interestingly, good cognitive performers showed age-related declines in the functional connectivity of the left insula and PCC with their right homotopic structures. These results may provide insights of neuronal correlates for understanding individual differences in aging. In particular, our study suggests prominent protection roles of the left insula and PCC and bilateral ACC in good performers. PMID:27667972

Long-term effects of musical training and functional plasticity in salience system.

PubMed

Luo, Cheng; Tu, Shipeng; Peng, Yueheng; Gao, Shan; Li, Jianfu; Dong, Li; Li, Gujing; Lai, Yongxiu; Li, Hong; Yao, Dezhong

2014-01-01

Musicians undergoing long-term musical training show improved emotional and cognitive function, which suggests the presence of neuroplasticity. The structural and functional impacts of the human brain have been observed in musicians. In this study, we used data-driven functional connectivity analysis to map local and distant functional connectivity in resting-state functional magnetic resonance imaging data from 28 professional musicians and 28 nonmusicians. Compared with nonmusicians, musicians exhibited significantly greater local functional connectivity density in 10 regions, including the bilateral dorsal anterior cingulate cortex, anterior insula, and anterior temporoparietal junction. A distant functional connectivity analysis demonstrated that most of these regions were included in salience system, which is associated with high-level cognitive control and fundamental attentional process. Additionally, musicians had significantly greater functional integration in this system, especially for connections to the left insula. Increased functional connectivity between the left insula and right temporoparietal junction may be a response to long-term musical training. Our findings indicate that the improvement of salience network is involved in musical training. The salience system may represent a new avenue for exploration regarding the underlying foundations of enhanced higher-level cognitive processes in musicians.

Multi-modal neuroimaging of adolescents with non-suicidal self-injury: Amygdala functional connectivity.

PubMed

Westlund Schreiner, Melinda; Klimes-Dougan, Bonnie; Mueller, Bryon A; Eberly, Lynn E; Reigstad, Kristina M; Carstedt, Patricia A; Thomas, Kathleen M; Hunt, Ruskin H; Lim, Kelvin O; Cullen, Kathryn R

2017-10-15

Non-suicidal self-injury (NSSI) is a significant mental health problem among adolescents. Research is needed to clarify the neurobiology of NSSI and identify candidate neurobiological targets for interventions. Based on prior research implicating heightened negative affect and amygdala hyperactivity in NSSI, we pursued a systems approach to characterize amygdala functional connectivity networks during rest (resting-state functional connectivity [RSFC)]) and a task (task functional connectivity [TFC]) in adolescents with NSSI. We examined amygdala networks in female adolescents with NSSI and healthy controls (n = 45) using resting-state fMRI and a negative emotion face-matching fMRI task designed to activate the amygdala. Connectivity analyses included amygdala RSFC, amygdala TFC, and psychophysiological interactions (PPI) between amygdala connectivity and task conditions. Compared to healthy controls, adolescents with NSSI showed atypical amygdala-frontal connectivity during rest and task; greater amygdala RSFC in supplementary motor area (SMA) and dorsal anterior cingulate; and differential amygdala-occipital connectivity between rest and task. After correcting for depression symptoms, amygdala-SMA RSFC abnormalities, among others, remained significant. This study's limitations include its cross-sectional design and its absence of a psychiatric control group. Using a multi-modal approach, we identified widespread amygdala circuitry anomalies in adolescents with NSSI. While deficits in amygdala-frontal connectivity (driven by depression symptoms) replicates prior work in depression, hyperconnectivity between amygdala and SMA (independent of depression symptoms) has not been previously reported. This circuit may represent an important mechanism underlying the link between negative affect and habitual behaviors. These abnormalities may represent intervention targets for adolescents with NSSI. Copyright © 2017 Elsevier B.V. All rights reserved.

Altered resting-state connectivity in adolescent cannabis users.

PubMed

Orr, Catherine; Morioka, Rowen; Behan, Brendan; Datwani, Sameer; Doucet, Marika; Ivanovic, Jelena; Kelly, Clare; Weierstall, Karen; Watts, Richard; Smyth, Bobby; Garavan, Hugh

2013-11-01

Cannabis is the most commonly used illicit drug in adolescence. Heavy use is associated with deficits on a broad range of cognitive functions and heavy use during adolescence may impact development of gray and white matter. To examine differences in intrinsic brain activity and connectivity associated with cannabis dependence in adolescence using whole-brain voxelwise approaches. Adolescents admitted to a drug-treatment facility for cannabis dependence (n = 17) and age-matched controls (n = 18) were compared on a measure of oscillations in the low-frequency blood oxygen level-dependent signal at rest (the fractional amplitude of low-frequency fluctuations fALFF, 0.01-0.1 Hz) and interhemispheric resting-state functional connectivity (RSFC) using voxel-mirrored homotopic connectivity. The cannabis-dependent population showed increased fALFF activity compared to the control group in right hemisphere regions including the superior parietal gyrus, superior frontal gyrus, inferior frontal gyrus, inferior semilunar lobe of the cerebellum and the inferior temporal gyrus. Post-hoc analyses revealed stronger intra-hemispheric functional connectivity between these functionally defined regions of interest (ROIs) in the cannabis-dependent population than in the controls. Reduced interhemispheric connectivity was observed in the cannabis users compared to controls in the pyramis of the cerebellum and the superior frontal gyrus. Controls showed reduced interhemispheric connectivity compared to users in the supramarginal gyrus. The reduced interhemispheric RSFC in adolescent cannabis users complements previous reports of white matter deficits associated with cannabis use. The evidence of elevated connectivity within the right hemisphere may reflect a compensatory mechanism. Combined, the results suggest that altered intrinsic connectivity may be characteristic of adolescent cannabis dependence.

Resting-state networks in healthy adult subjects: a comparison between a 32-element and an 8-element phased array head coil at 3.0 Tesla.

PubMed

Paolini, Marco; Keeser, Daniel; Ingrisch, Michael; Werner, Natalie; Kindermann, Nicole; Reiser, Maximilian; Blautzik, Janusch

2015-05-01

Little research exists on the influence of a magnetic resonance imaging (MRI) head coil's channel count on measured resting-state functional connectivity. To compare a 32-element (32ch) and an 8-element (8ch) phased array head coil with respect to their potential to detect functional connectivity within resting-state networks. Twenty-six healthy adults (mean age, 21.7 years; SD, 2.1 years) underwent resting-state functional MRI at 3.0 Tesla with both coils using equal standard imaging parameters and a counterbalanced design. Independent component analysis (ICA) at different model orders and a dual regression approach were performed. Voxel-wise non-parametric statistical between-group contrasts were determined using permutation-based non-parametric inference. Phantom measurements demonstrated a generally higher image signal-to-noise ratio using the 32ch head coil. However, the results showed no significant differences between corresponding resting-state networks derived from both coils (p < 0.05, FWE-corrected). Using the identical standard acquisition parameters, the 32ch head coil does not offer any significant advantages in detecting ICA-based functional connectivity within RSNs. © The Foundation Acta Radiologica 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Anti-correlated networks, global signal regression, and the effects of caffeine in resting-state functional MRI.

PubMed

Wong, Chi Wah; Olafsson, Valur; Tal, Omer; Liu, Thomas T

2012-10-15

Resting-state functional connectivity magnetic resonance imaging is proving to be an essential tool for the characterization of functional networks in the brain. Two of the major networks that have been identified are the default mode network (DMN) and the task positive network (TPN). Although prior work indicates that these two networks are anti-correlated, the findings are controversial because the anti-correlations are often found only after the application of a pre-processing step, known as global signal regression, that can produce artifactual anti-correlations. In this paper, we show that, for subjects studied in an eyes-closed rest state, caffeine can significantly enhance the detection of anti-correlations between the DMN and TPN without the need for global signal regression. In line with these findings, we find that caffeine also leads to widespread decreases in connectivity and global signal amplitude. Using a recently introduced geometric model of global signal effects, we demonstrate that these decreases are consistent with the removal of an additive global signal confound. In contrast to the effects observed in the eyes-closed rest state, caffeine did not lead to significant changes in global functional connectivity in the eyes-open rest state. Copyright © 2012 Elsevier Inc. All rights reserved.

Altered Functional Connectivity of the Default Mode Network in Low-Empathy Subjects

PubMed Central

Kim, Seung Jun; Kim, Sung-Eun; Kim, Hyo Eun; Han, Kiwan; Jeong, Bumseok; Kim, Jae-Jin; Namkoong, Kee

2017-01-01

Empathy is the ability to identify with or make a vicariously experience of another person's feelings or thoughts based on memory and/or self-referential mental simulation. The default mode network in particular is related to self-referential empathy. In order to elucidate the possible neural mechanisms underlying empathy, we investigated the functional connectivity of the default mode network in subjects from a general population. Resting state functional magnetic resonance imaging data were acquired from 19 low-empathy subjects and 18 medium-empathy subjects. An independent component analysis was used to identify the default mode network, and differences in functional connectivity strength were compared between the two groups. The low-empathy group showed lower functional connectivity of the medial prefrontal cortex and anterior cingulate cortex (Brodmann areas 9 and 32) within the default mode network, compared to the medium-empathy group. The results of the present study suggest that empathy is related to functional connectivity of the medial prefrontal cortex/anterior cingulate cortex within the default mode network. Functional decreases in connectivity among low-empathy subjects may reflect an impairment of self-referential mental simulation. PMID:28792155

Creativity and the default network: A functional connectivity analysis of the creative brain at rest☆

PubMed Central

Beaty, Roger E.; Benedek, Mathias; Wilkins, Robin W.; Jauk, Emanuel; Fink, Andreas; Silvia, Paul J.; Hodges, Donald A.; Koschutnig, Karl; Neubauer, Aljoscha C.

2014-01-01

The present research used resting-state functional magnetic resonance imaging (fMRI) to examine whether the ability to generate creative ideas corresponds to differences in the intrinsic organization of functional networks in the brain. We examined the functional connectivity between regions commonly implicated in neuroimaging studies of divergent thinking, including the inferior prefrontal cortex and the core hubs of the default network. Participants were prescreened on a battery of divergent thinking tests and assigned to high- and low-creative groups based on task performance. Seed-based functional connectivity analysis revealed greater connectivity between the left inferior frontal gyrus (IFG) and the entire default mode network in the high-creative group. The right IFG also showed greater functional connectivity with bilateral inferior parietal cortex and the left dorsolateral prefrontal cortex in the high-creative group. The results suggest that the ability to generate creative ideas is characterized by increased functional connectivity between the inferior prefrontal cortex and the default network, pointing to a greater cooperation between brain regions associated with cognitive control and low-level imaginative processes. PMID:25245940

Acupuncture-induced changes in functional connectivity of the primary somatosensory cortex varied with pathological stages of Bell's palsy.

PubMed

He, Xiaoxuan; Zhu, Yifang; Li, Chuanfu; Park, Kyungmo; Mohamed, Abdalla Z; Wu, Hongli; Xu, Chunsheng; Zhang, Wei; Wang, Linying; Yang, Jun; Qiu, Bensheng

2014-10-01

Bell's palsy is the most common cause of acute facial nerve paralysis. In China, Bell's palsy is frequently treated with acupuncture. However, its efficacy and underlying mechanism are still controversial. In this study, we used functional MRI to investigate the effect of acupuncture on the functional connectivity of the brain in Bell's palsy patients and healthy individuals. The patients were further grouped according to disease duration and facial motor performance. The results of resting-state functional MRI connectivity show that acupuncture induces significant connectivity changes in the primary somatosensory region of both early and late recovery groups, but no significant changes in either the healthy control group or the recovered group. In the recovery group, the changes also varied with regions and disease duration. Therefore, we propose that the effect of acupuncture stimulation may depend on the functional connectivity status of patients with Bell's palsy.

The mean-variance relationship reveals two possible strategies for dynamic brain connectivity analysis in fMRI.

PubMed

Thompson, William H; Fransson, Peter

2015-01-01

When studying brain connectivity using fMRI, signal intensity time-series are typically correlated with each other in time to compute estimates of the degree of interaction between different brain regions and/or networks. In the static connectivity case, the problem of defining which connections that should be considered significant in the analysis can be addressed in a rather straightforward manner by a statistical thresholding that is based on the magnitude of the correlation coefficients. More recently, interest has come to focus on the dynamical aspects of brain connectivity and the problem of deciding which brain connections that are to be considered relevant in the context of dynamical changes in connectivity provides further options. Since we, in the dynamical case, are interested in changes in connectivity over time, the variance of the correlation time-series becomes a relevant parameter. In this study, we discuss the relationship between the mean and variance of brain connectivity time-series and show that by studying the relation between them, two conceptually different strategies to analyze dynamic functional brain connectivity become available. Using resting-state fMRI data from a cohort of 46 subjects, we show that the mean of fMRI connectivity time-series scales negatively with its variance. This finding leads to the suggestion that magnitude- versus variance-based thresholding strategies will induce different results in studies of dynamic functional brain connectivity. Our assertion is exemplified by showing that the magnitude-based strategy is more sensitive to within-resting-state network (RSN) connectivity compared to between-RSN connectivity whereas the opposite holds true for a variance-based analysis strategy. The implications of our findings for dynamical functional brain connectivity studies are discussed.

Default mode of brain function in monkeys.

PubMed

Mantini, Dante; Gerits, Annelis; Nelissen, Koen; Durand, Jean-Baptiste; Joly, Olivier; Simone, Luciano; Sawamura, Hiromasa; Wardak, Claire; Orban, Guy A; Buckner, Randy L; Vanduffel, Wim

2011-09-07

Human neuroimaging has revealed a specific network of brain regions-the default-mode network (DMN)-that reduces its activity during goal-directed behavior. So far, evidence for a similar network in monkeys is mainly indirect, since, except for one positron emission tomography study, it is all based on functional connectivity analysis rather than activity increases during passive task states. Here, we tested whether a consistent DMN exists in monkeys using its defining property. We performed a meta-analysis of functional magnetic resonance imaging data collected in 10 awake monkeys to reveal areas in which activity consistently decreases when task demands shift from passive tasks to externally oriented processing. We observed task-related spatially specific deactivations across 15 experiments, implying in the monkey a functional equivalent of the human DMN. We revealed by resting-state connectivity that prefrontal and medial parietal regions, including areas 9/46d and 31, respectively, constitute the DMN core, being functionally connected to all other DMN areas. We also detected two distinct subsystems composed of DMN areas with stronger functional connections between each other. These clusters included areas 24/32, 8b, and TPOC and areas 23, v23, and PGm, respectively. Such a pattern of functional connectivity largely fits, but is not completely consistent with anatomical tract tracing data in monkeys. Also, analysis of afferent and efferent connections between DMN areas suggests a multisynaptic network structure. Like humans, monkeys increase activity during passive epochs in heteromodal and limbic association regions, suggesting that they also default to internal modes of processing when not actively interacting with the environment.

Default Mode of Brain Function in Monkeys

PubMed Central

Mantini, Dante; Gerits, Annelis; Nelissen, Koen; Durand, Jean-Baptiste; Joly, Olivier; Simone, Luciano; Sawamura, Hiromasa; Wardak, Claire; Orban, Guy A.; Buckner, Randy L.; Vanduffel, Wim

2013-01-01

Human neuroimaging has revealed a specific network of brain regions—the default-mode network (DMN)—that reduces its activity during goal-directed behavior. So far, evidence for a similar network in monkeys is mainly indirect, since, except for one positron emission tomography study, it is all based on functional connectivity analysis rather than activity increases during passive task states. Here, we tested whether a consistent DMN exists in monkeys using its defining property. We performed a meta-analysis of functional magnetic resonance imaging data collected in 10 awake monkeys to reveal areas in which activity consistently decreases when task demands shift from passive tasks to externally oriented processing. We observed task-related spatially specific deactivations across 15 experiments, implying in the monkey a functional equivalent of the human DMN. We revealed by resting-state connectivity that prefrontal and medial parietal regions, including areas 9/46d and 31, respectively, constitute the DMN core, being functionally connected to all other DMN areas. We also detected two distinct subsystems composed of DMN areas with stronger functional connections between each other. These clusters included areas 24/32, 8b, and TPOC and areas 23, v23, and PGm, respectively. Such a pattern of functional connectivity largely fits, but is not completely consistent with anatomical tract tracing data in monkeys. Also, analysis of afferent and efferent connections between DMN areas suggests a multisynaptic network structure. Like humans, monkeys increase activity during passive epochs in heteromodal and limbic association regions, suggesting that they also default to internal modes of processing when not actively interacting with the environment. PMID:21900574

Altered Brain Functional Connectivity in Betel Quid-Dependent Chewers.

PubMed

Huang, Xiaojun; Pu, Weidan; Liu, Haihong; Li, Xinmin; Greenshaw, Andrew J; Dursun, Serdar M; Xue, Zhimin; Liu, Zhening

2017-01-01

Betel quid (BQ) is a common psychoactive substance worldwide with particularly high usage in many Asian countries. This study aimed to explore the effect of BQ use on functional connectivity by comparing global functional brain networks and their subset between BQ chewers and healthy controls (HCs). Resting-state functional magnetic resonance imaging (fMRI) was obtained from 24 betel quid-dependent (BQD) male chewers and 27 healthy male individuals on a 3.0T scanner. We used independent component analysis (ICA) to determine components that represent the brain's functional networks and their spatial aspects of functional connectivity. Two sample t -tests were used to identify the functional connectivity differences in each network between these two groups. Seventeen networks were identified by ICA. Nine of them showed connectivity differences between BQD and HCs (two sample t -tests, p  < 0.001 uncorrected). We found increased functional connectivity in the orbitofrontal, bilateral frontoparietal, frontotemporal, occipital/parietal, frontotemporal/cerebellum, and temporal/limbic networks, and decreased connectivity in the parietal and medial frontal/anterior cingulate networks in the BQD compared to the HCs. The betel quid dependence scale scores were positively related to the increased functional connectivity in the orbitofrontal ( r  = 0.39, p  = 0.03) while negatively related to the decreased functional connectivity in medial frontal/anterior cingulate networks ( r  = -0.35, p  = 0.02). Our findings provide further evidence that BQ chewing may lead to brain functional connectivity changes, which may play a key role in the psychological and physiological effects of BQ.

Normalisation of brain connectivity through compensatory behaviour, despite congenital hand absence.

PubMed

Hahamy, Avital; Sotiropoulos, Stamatios N; Henderson Slater, David; Malach, Rafael; Johansen-Berg, Heidi; Makin, Tamar R

2015-01-06

Previously we showed, using task-evoked fMRI, that compensatory intact hand usage after amputation facilitates remapping of limb representations in the cortical territory of the missing hand (Makin et al., 2013a). Here we show that compensatory arm usage in individuals born without a hand (one-handers) reflects functional connectivity of spontaneous brain activity in the cortical hand region. Compared with two-handed controls, one-handers showed reduced symmetry of hand region inter-hemispheric resting-state functional connectivity and corticospinal white matter microstructure. Nevertheless, those one-handers who more frequently use their residual (handless) arm for typically bimanual daily tasks also showed more symmetrical functional connectivity of the hand region, demonstrating that adaptive behaviour drives long-range brain organisation. We therefore suggest that compensatory arm usage maintains symmetrical sensorimotor functional connectivity in one-handers. Since variability in spontaneous functional connectivity in our study reflects ecological behaviour, we propose that inter-hemispheric symmetry, typically observed in resting sensorimotor networks, depends on coordinated motor behaviour in daily life.

Differential brain network activity across mood states in bipolar disorder.

PubMed

Brady, Roscoe O; Tandon, Neeraj; Masters, Grace A; Margolis, Allison; Cohen, Bruce M; Keshavan, Matcheri; Öngür, Dost

2017-01-01

This study aimed to identify how the activity of large-scale brain networks differs between mood states in bipolar disorder. The authors measured spontaneous brain activity in subjects with bipolar disorder in mania and euthymia and compared these states to a healthy comparison population. 23 subjects with bipolar disorder type I in a manic episode, 24 euthymic bipolar I subjects, and 23 matched healthy comparison (HC) subjects underwent resting state fMRI scans. Using an existing parcellation of the whole brain, we measured functional connectivity between brain regions and identified significant differences between groups. In unbiased whole-brain analyses, functional connectivity between parietal, occipital, and frontal nodes within the dorsal attention network (DAN) were significantly greater in mania than euthymia or HC subjects. In the default mode network (DMN), connectivity between dorsal frontal nodes and the rest of the DMN differentiated both mood state and diagnosis. The bipolar groups were separate cohorts rather than subjects imaged longitudinally across mood states. Bipolar mood states are associated with highly significant alterations in connectivity in two large-scale brain networks. These same networks also differentiate bipolar mania and euthymia from a HC population. State related changes in DAN and DMN connectivity suggest a circuit based pathology underlying cognitive dysfunction as well as activity/reactivity in bipolar mania. Altered activities in neural networks may be biomarkers of bipolar disorder diagnosis and mood state that are accessible to neuromodulation and are promising novel targets for scientific investigation and possible clinical intervention. Copyright © 2016 Elsevier B.V. All rights reserved.

Reorganization of the Connectivity between Elementary Functions – A Model Relating Conscious States to Neural Connections

PubMed Central

Mogensen, Jesper; Overgaard, Morten

2017-01-01

In the present paper it is argued that the “neural correlate of consciousness” (NCC) does not appear to be a separate “module” – but an aspect of information processing within the neural substrate of various cognitive processes. Consequently, NCC can only be addressed adequately within frameworks that model the general relationship between neural processes and mental states – and take into account the dynamic connectivity of the brain. We presently offer the REFGEN (general reorganization of elementary functions) model as such a framework. This model builds upon and expands the REF (reorganization of elementary functions) and REFCON (of elementary functions and consciousness) models. All three models integrate the relationship between the neural and mental layers of description via the construction of an intermediate level dealing with computational states. The importance of experience based organization of neural and cognitive processes is stressed. The models assume that the mechanisms of consciousness are in principle the same as the basic mechanisms of all aspects of cognition – when information is processed to a sufficiently “high level” it becomes available to conscious experience. The NCC is within the REFGEN model seen as aspects of the dynamic and experience driven reorganizations of the synaptic connectivity between the neurocognitive “building blocks” of the model – the elementary functions. PMID:28473797

Sexually dimorphic functional connectivity in response to high vs. low energy-dense food cues in obese humans: an fMRI study.

PubMed

Atalayer, Deniz; Pantazatos, Spiro P; Gibson, Charlisa D; McOuatt, Haley; Puma, Lauren; Astbury, Nerys M; Geliebter, Allan

2014-10-15

Sexually-dimorphic behavioral and biological aspects of human eating have been described. Using psychophysiological interaction (PPI) analysis, we investigated sex-based differences in functional connectivity with a key emotion-processing region (amygdala, AMG) and a key reward-processing area (ventral striatum, VS) in response to high vs. low energy-dense (ED) food images using blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) in obese persons in fasted and fed states. When fed, in response to high vs. low-ED food cues, obese men (vs. women) had greater functional connectivity with AMG in right subgenual anterior cingulate, whereas obese women had greater functional connectivity with AMG in left angular gyrus and right primary motor areas. In addition, when fed, AMG functional connectivity with pre/post-central gyrus was more associated with BMI in women (vs. men). When fasted, obese men (vs. women) had greater functional connectivity with AMG in bilateral supplementary frontal and primary motor areas, left precuneus, and right cuneus, whereas obese women had greater functional connectivity with AMG in left inferior frontal gyrus, right thalamus, and dorsomedial prefrontal cortex. When fed, greater functional connectivity with VS was observed in men in bilateral supplementary and primary motor areas, left postcentral gyrus, and left precuneus. These sex-based differences in functional connectivity in response to visual food cues may help partly explain differential eating behavior, pathology prevalence, and outcomes in men and women. Published by Elsevier Inc.

Bipolar mood state reflected in cortico-amygdala resting state connectivity: A cohort and longitudinal study.

PubMed

Brady, Roscoe O; Margolis, Allison; Masters, Grace A; Keshavan, Matcheri; Öngür, Dost

2017-08-01

Using resting-state functional magnetic resonance imaging (rsfMRI), we previously compared cohorts of bipolar I subjects in a manic state to those in a euthymic state to identify mood state-specific patterns of cortico-amygdala connectivity. Our results suggested that mania is reflected in the disruption of emotion regulation circuits. We sought to replicate this finding in a group of subjects with bipolar disorder imaged longitudinally across states of mania and euthymia METHODS: We divided our subjects into three groups: 26 subjects imaged in a manic state, 21 subjects imaged in a euthymic state, and 10 subjects imaged longitudinally across both mood states. We measured differences in amygdala connectivity between the mania and euthymia cohorts. We then used these regions of altered connectivity to examine connectivity in the longitudinal bipolar group using a within-subjects design. Our findings in the mania vs euthymia cohort comparison were replicated in the longitudinal analysis. Bipolar mania was differentiated from euthymia by decreased connectivity between the amygdala and pre-genual anterior cingulate cortex. Mania was also characterized by increased connectivity between amygdala and the supplemental motor area, a region normally anti-correlated to the amygdala in emotion regulation tasks. Stringent controls for movement effects limited the number of subjects in the longitudinal sample. In this first report of rsfMRI conducted longitudinally across mood states, we find that previously observed between-group differences in amygdala connectivity are also found longitudinally within subjects. These results suggest resting state cortico-amygdala connectivity is a biomarker of mood state in bipolar disorder. Copyright © 2017 Elsevier B.V. All rights reserved.

Aberrant functional network connectivity in psychopathy from a large (N = 985) forensic sample.

PubMed

Espinoza, Flor A; Vergara, Victor M; Reyes, Daisy; Anderson, Nathaniel E; Harenski, Carla L; Decety, Jean; Rachakonda, Srinivas; Damaraju, Eswar; Rashid, Barnaly; Miller, Robyn L; Koenigs, Michael; Kosson, David S; Harenski, Keith; Kiehl, Kent A; Calhoun, Vince D

2018-06-01

Psychopathy is a personality disorder characterized by antisocial behavior, lack of remorse and empathy, and impaired decision making. The disproportionate amount of crime committed by psychopaths has severe emotional and economic impacts on society. Here we examine the neural correlates associated with psychopathy to improve early assessment and perhaps inform treatments for this condition. Previous resting-state functional magnetic resonance imaging (fMRI) studies in psychopathy have primarily focused on regions of interest. This study examines whole-brain functional connectivity and its association to psychopathic traits. Psychopathy was hypothesized to be characterized by aberrant functional network connectivity (FNC) in several limbic/paralimbic networks. Group-independent component and regression analyses were applied to a data set of resting-state fMRI from 985 incarcerated adult males. We identified resting-state networks (RSNs), estimated FNC between RSNs, and tested their association to psychopathy factors and total summary scores (Factor 1, interpersonal/affective; Factor 2, lifestyle/antisocial). Factor 1 scores showed both increased and reduced functional connectivity between RSNs from seven brain domains (sensorimotor, cerebellar, visual, salience, default mode, executive control, and attentional). Consistent with hypotheses, RSNs from the paralimbic system-insula, anterior and posterior cingulate cortex, amygdala, orbital frontal cortex, and superior temporal gyrus-were related to Factor 1 scores. No significant FNC associations were found with Factor 2 and total PCL-R scores. In summary, results suggest that the affective and interpersonal symptoms of psychopathy (Factor 1) are associated with aberrant connectivity in multiple brain networks, including paralimbic regions. © 2018 Wiley Periodicals, Inc.

Sensation-to-Cognition Cortical Streams in Attention-Deficit/Hyperactivity Disorder

PubMed Central

Carmona, Susana; Hoekzema, Elseline; Castellanos, Francisco X.; García-García, David; Lage-Castellanos, Agustín; Dijk, Koene R.A.Van; Navas-Sánchez, Francisco J.; Martínez, Kenia; Desco, Manuel; Sepulcre, Jorge

2015-01-01

We sought to determine whether functional connectivity streams that link sensory, attentional, and higher-order cognitive circuits are atypical in attention-deficit/hyperactivity disorder (ADHD). We applied a graph-theory method to the resting-state functional magnetic resonance imaging data of 120 children with ADHD and 120 age-matched typically developing children (TDC). Starting in unimodal primary cortex—visual, auditory, and somatosensory—we used stepwise functional connectivity to calculate functional connectivity paths at discrete numbers of relay stations (or link-step distances). First, we characterized the functional connectivity streams that link sensory, attentional, and higher-order cognitive circuits in TDC and found that systems do not reach the level of integration achieved by adults. Second, we searched for stepwise functional connectivity differences between children with ADHD and TDC. We found that, at the initial steps of sensory functional connectivity streams, patients display significant enhancements of connectivity degree within neighboring areas of primary cortex, while connectivity to attention-regulatory areas is reduced. Third, at subsequent link-step distances from primary sensory cortex, children with ADHD show decreased connectivity to executive processing areas and increased degree of connections to default mode regions. Fourth, in examining medication histories in children with ADHD, we found that children medicated with psychostimulants present functional connectivity streams with higher degree of connectivity to regions subserving attentional and executive processes compared to medication-naïve children. We conclude that predominance of local sensory processing and lesser influx of information to attentional and executive regions may reduce the ability to organize and control the balance between external and internal sources of information in ADHD. PMID:25821110

Spinal Cord Stimulation (SCS) and Functional Magnetic Resonance Imaging (fMRI): Modulation of Cortical Connectivity With Therapeutic SCS.

PubMed

Deogaonkar, Milind; Sharma, Mayur; Oluigbo, Chima; Nielson, Dylan M; Yang, Xiangyu; Vera-Portocarrero, Louis; Molnar, Gregory F; Abduljalil, Amir; Sederberg, Per B; Knopp, Michael; Rezai, Ali R

2016-02-01

The neurophysiological basis of pain relief due to spinal cord stimulation (SCS) and the related cortical processing of sensory information are not completely understood. The aim of this study was to use resting state functional magnetic resonance imaging (rs-fMRI) to detect changes in cortical networks and cortical processing related to the stimulator-induced pain relief. Ten patients with complex regional pain syndrome (CRPS) or neuropathic leg pain underwent thoracic epidural spinal cord stimulator implantation. Stimulation parameters associated with "optimal" pain reduction were evaluated prior to imaging studies. Rs-fMRI was obtained on a 3 Tesla, Philips Achieva MRI. Rs-fMRI was performed with stimulator off (300TRs) and stimulator at optimum (Opt, 300 TRs) pain relief settings. Seed-based analysis of the resting state functional connectivity was conducted using seeds in regions established as participating in pain networks or in the default mode network (DMN) in addition to the network analysis. NCUT (normalized cut) parcellation was used to generate 98 cortical and subcortical regions of interest in order to expand our analysis of changes in functional connections to the entire brain. We corrected for multiple comparisons by limiting the false discovery rate to 5%. Significant differences in resting state connectivity between SCS off and optimal state were seen between several regions related to pain perception, including the left frontal insula, right primary and secondary somatosensory cortices, as well as in regions involved in the DMN, such as the precuneus. In examining changes in connectivity across the entire brain, we found decreased connection strength between somatosensory and limbic areas and increased connection strength between somatosensory and DMN with optimal SCS resulting in pain relief. This suggests that pain relief from SCS may be reducing negative emotional processing associated with pain, allowing somatosensory areas to become more integrated into default mode activity. SCS reduces the affective component of pain resulting in optimal pain relief. Study shows a decreased connectivity between somatosensory and limbic areas associated with optimal pain relief due to SCS. © 2015 International Neuromodulation Society.

Default Mode Network Connectivity as a Function of Familial and Environmental Risk for Psychotic Disorder

PubMed Central

Peeters, Sanne C. T.; van de Ven, Vincent; Gronenschild, Ed H. B. M; Patel, Ameera X.; Habets, Petra; Goebel, Rainer; van Os, Jim; Marcelis, Machteld

2015-01-01

Background Research suggests that altered interregional connectivity in specific networks, such as the default mode network (DMN), is associated with cognitive and psychotic symptoms in schizophrenia. In addition, frontal and limbic connectivity alterations have been associated with trauma, drug use and urban upbringing, though these environmental exposures have never been examined in relation to DMN functional connectivity in psychotic disorder. Methods Resting-state functional MRI scans were obtained from 73 patients with psychotic disorder, 83 non-psychotic siblings of patients with psychotic disorder and 72 healthy controls. Posterior cingulate cortex (PCC) seed-based correlation analysis was used to estimate functional connectivity within the DMN. DMN functional connectivity was examined in relation to group (familial risk), group × environmental exposure (to cannabis, developmental trauma and urbanicity) and symptomatology. Results There was a significant association between group and PCC connectivity with the inferior parietal lobule (IPL), the precuneus (PCu) and the medial prefrontal cortex (MPFC). Compared to controls, patients and siblings had increased PCC connectivity with the IPL, PCu and MPFC. In the IPL and PCu, the functional connectivity of siblings was intermediate to that of controls and patients. No significant associations were found between DMN connectivity and (subclinical) psychotic/cognitive symptoms. In addition, there were no significant interactions between group and environmental exposures in the model of PCC functional connectivity. Discussion Increased functional connectivity in individuals with (increased risk for) psychotic disorder may reflect trait-related network alterations. The within-network “connectivity at rest” intermediate phenotype was not associated with (subclinical) psychotic or cognitive symptoms. The association between familial risk and DMN connectivity was not conditional on environmental exposure. PMID:25790002

Thinking About a Task Is Associated with Increased Connectivity in Regions Activated by Task Performance

PubMed Central

Robertson, Edwin M.; Manoach, Dara S.; Stickgold, Robert

2016-01-01

Abstract We investigated whether functional neuroimaging of quiet “rest” can reveal the neural correlates of conscious thought. Using resting-state functional MRI, we measured functional connectivity during a resting scan that immediately followed performance of a finger tapping motor sequence task. Self-reports of the amount of time spent thinking about the task during the resting scan correlated with connectivity between regions of the motor network activated during task performance. Thus, thinking about a task is associated with coordinated activity in brain regions responsible for that task's performance. More generally, this study demonstrates the feasibility of using the combination of functional connectivity MRI and self-reports to examine the neural correlates of thought. PMID:26650337

Effect of phase-encoding direction on group analysis of resting-state functional magnetic resonance imaging.

PubMed

Mori, Yasuo; Miyata, Jun; Isobe, Masanori; Son, Shuraku; Yoshihara, Yujiro; Aso, Toshihiko; Kouchiyama, Takanori; Murai, Toshiya; Takahashi, Hidehiko

2018-05-17

Echo-planar imaging is a common technique used in functional magnetic resonance imaging (fMRI), however it suffers from image distortion and signal loss because of large susceptibility effects that are related to the phase-encoding direction of the scan. Despite this relationship, the majority of neuroimaging studies have not considered the influence of phase-encoding direction. Here, we aimed to clarify how phase-encoding direction can affect the outcome of an fMRI connectivity study of schizophrenia. Resting-state fMRI using anterior to posterior (A-P) and posterior to anterior (P-A) directions was used to examine 25 patients with schizophrenia (SC) and 37 matched healthy controls (HC). We conducted a functional connectivity analysis using independent component analysis and performed three group comparisons: A-P vs. P-A (all participants), SC vs. HC for the A-P and P-A datasets, and the interaction between phase-encoding direction and participant group. The estimated functional connectivity differed between the two phase-encoding directions in areas that were more extensive than those where signal loss has been reported. Although functional connectivity in the SC group was lower than that in the HC group for both directions, the A-P and P-A conditions did not exhibit the same specific pattern of differences. Further, we observed an interaction between participant group and the phase-encoding direction in the left temporo-parietal junction and left fusiform gyrus. Phase-encoding direction can influence the results of functional connectivity studies. Thus, appropriate selection and documentation of phase-encoding direction will be important in future resting-state fMRI studies. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Differences in brain functional connectivity at resting state in neonates born to healthy obese or normal-weight mothers

USDA-ARS?s Scientific Manuscript database

Recent studies have shown associations between maternal obesity at pre- or early pregnancy and long-term neurodevelopment in children, suggesting in utero effects of maternal obesity on offspring brain development. In this study, we examined whether brain functional connectivity to the prefrontal lo...

Control Networks in Paediatric Tourette Syndrome Show Immature and Anomalous Patterns of Functional Connectivity

ERIC Educational Resources Information Center

Church, Jessica A.; Fair, Damien A.; Dosenbach, Nico U. F.; Cohen, Alexander L.; Miezin, Francis M.; Petersen, Steven E.; Schlaggar, Bradley L.

2009-01-01

Tourette syndrome (TS) is a developmental disorder characterized by unwanted, repetitive behaviours that manifest as stereotyped movements and vocalizations called "tics". Operating under the hypothesis that the brain's control systems may be impaired in TS, we measured resting-state functional connectivity MRI (rs-fcMRI) between 39 previously…

Social interactions elicit rapid shifts in functional connectivity in the social decision-making network of zebrafish

PubMed Central

Teles, Magda C.; Almeida, Olinda; Lopes, João S.; Oliveira, Rui F.

2015-01-01

According to the social decision-making (SDM) network hypothesis, SDM is encoded in a network of forebrain and midbrain structures in a distributed and dynamic fashion, such that the expression of a given social behaviour is better reflected by the overall profile of activation across the different loci rather than by the activity of a single node. This proposal has the implicit assumption that SDM relies on integration across brain regions, rather than on regional specialization. Here we tested the occurrence of functional localization and of functional connectivity in the SDM network. For this purpose we used zebrafish to map different social behaviour states into patterns of neuronal activity, as indicated by the expression of the immediate early genes c-fos and egr-1, across the SDM network. The results did not support functional localization, as some loci had similar patterns of activity associated with different social behaviour states, and showed socially driven changes in functional connectivity. Thus, this study provides functional support to the SDM network hypothesis and suggests that the neural context in which a given node of the network is operating (i.e. the state of its interconnected areas) is central to its functional relevance. PMID:26423839

Social interactions elicit rapid shifts in functional connectivity in the social decision-making network of zebrafish.

PubMed

Teles, Magda C; Almeida, Olinda; Lopes, João S; Oliveira, Rui F

2015-10-07

According to the social decision-making (SDM) network hypothesis, SDM is encoded in a network of forebrain and midbrain structures in a distributed and dynamic fashion, such that the expression of a given social behaviour is better reflected by the overall profile of activation across the different loci rather than by the activity of a single node. This proposal has the implicit assumption that SDM relies on integration across brain regions, rather than on regional specialization. Here we tested the occurrence of functional localization and of functional connectivity in the SDM network. For this purpose we used zebrafish to map different social behaviour states into patterns of neuronal activity, as indicated by the expression of the immediate early genes c-fos and egr-1, across the SDM network. The results did not support functional localization, as some loci had similar patterns of activity associated with different social behaviour states, and showed socially driven changes in functional connectivity. Thus, this study provides functional support to the SDM network hypothesis and suggests that the neural context in which a given node of the network is operating (i.e. the state of its interconnected areas) is central to its functional relevance. © 2015 The Author(s).

Contributions of structural connectivity and cerebrovascular parameters to functional magnetic resonance imaging signals in mice at rest and during sensory paw stimulation.

PubMed

Schroeter, Aileen; Grandjean, Joanes; Schlegel, Felix; Saab, Bechara J; Rudin, Markus

2017-07-01

Previously, we reported widespread bilateral increases in stimulus-evoked functional magnetic resonance imaging signals in mouse brain to unilateral sensory paw stimulation. We attributed the pattern to arousal-related cardiovascular changes overruling cerebral autoregulation thereby masking specific signal changes elicited by local neuronal activity. To rule out the possibility that interhemispheric neuronal communication might contribute to bilateral functional magnetic resonance imaging responses, we compared stimulus-evoked functional magnetic resonance imaging responses to unilateral hindpaw stimulation in acallosal I/LnJ, C57BL/6, and BALB/c mice. We found bilateral blood-oxygenation-level dependent signal changes in all three strains, ruling out a dominant contribution of transcallosal communication as reason for bilaterality. Analysis of functional connectivity derived from resting-state functional magnetic resonance imaging, revealed that bilateral cortical functional connectivity is largely abolished in I/LnJ animals. Cortical functional connectivity in all strains correlated with structural connectivity in corpus callosum as revealed by diffusion tensor imaging. Given the profound influence of systemic hemodynamics on stimulus-evoked functional magnetic resonance imaging outcomes, we evaluated whether functional connectivity data might be affected by cerebrovascular parameters, i.e. baseline cerebral blood volume, vascular reactivity, and reserve. We found that effects of cerebral hemodynamics on functional connectivity are largely outweighed by dominating contributions of structural connectivity. In contrast, contributions of transcallosal interhemispheric communication to the occurrence of ipsilateral functional magnetic resonance imaging response of equal amplitude to unilateral stimuli seem negligible.

Diffeomorphic functional brain surface alignment: Functional demons.

PubMed

Nenning, Karl-Heinz; Liu, Hesheng; Ghosh, Satrajit S; Sabuncu, Mert R; Schwartz, Ernst; Langs, Georg

2017-08-01

Aligning brain structures across individuals is a central prerequisite for comparative neuroimaging studies. Typically, registration approaches assume a strong association between the features used for alignment, such as macro-anatomy, and the variable observed, such as functional activation or connectivity. Here, we propose to use the structure of intrinsic resting state fMRI signal correlation patterns as a basis for alignment of the cortex in functional studies. Rather than assuming the spatial correspondence of functional structures between subjects, we have identified locations with similar connectivity profiles across subjects. We mapped functional connectivity relationships within the brain into an embedding space, and aligned the resulting maps of multiple subjects. We then performed a diffeomorphic alignment of the cortical surfaces, driven by the corresponding features in the joint embedding space. Results show that functional alignment based on resting state fMRI identifies functionally homologous regions across individuals with higher accuracy than alignment based on the spatial correspondence of anatomy. Further, functional alignment enables measurement of the strength of the anatomo-functional link across the cortex, and reveals the uneven distribution of this link. Stronger anatomo-functional dissociation was found in higher association areas compared to primary sensory- and motor areas. Functional alignment based on resting state features improves group analysis of task based functional MRI data, increasing statistical power and improving the delineation of task-specific core regions. Finally, a comparison of the anatomo-functional dissociation between cohorts is demonstrated with a group of left and right handed subjects. Copyright © 2017 Elsevier Inc. All rights reserved.

Increased Gray Matter Volume and Resting-State Functional Connectivity in Somatosensory Cortex and their Relationship with Autistic Symptoms in Young Boys with Autism Spectrum Disorder.

PubMed

Wang, Jia; Fu, Kuang; Chen, Lei; Duan, Xujun; Guo, Xiaonan; Chen, Heng; Wu, Qiong; Xia, Wei; Wu, Lijie; Chen, Huafu

2017-01-01

Autism spectrum disorder (ASD) has been widely recognized as a complex neurodevelopmental disorder. A large number of neuroimaging studies suggest abnormalities in brain structure and function of patients with ASD, but there is still no consistent conclusion. We sought to investigate both of the structural and functional brain changes in 3-7-year-old children with ASD compared with typically developing controls (TDs), and to assess whether these alterations are associated with autistic behavioral symptoms. Firstly, we applied an optimized method of voxel-based morphometry (VBM) analysis on structural magnetic resonance imaging (sMRI) data to assess the differences of gray matter volume (GMV) between 31 autistic boys aged 3-7 and 31 age- and handness-matched male TDs. Secondly, we used clusters with between-group differences as seed regions to generate intrinsic functional connectivity maps based on resting-state functional connectivity magnetic resonance imaging (rs-fcMRI) in order to evaluate the functional impairments induced by structural alterations. Brain-behavior correlations were assessed among GMV, functional connectivity and symptom severity in children with ASD. VBM analyses revealed increased GMV in left superior temporal gyrus (STG) and left postcentral gyrus (PCG) in ASD children, comparing with TDs. Using left PCG as a seed region, ASD children displayed significantly higher positive connectivity with right angular gyrus (AG) and greater negative connectivity with right superior parietal gyrus (SPG) and right superior occipital gyrus (SOG), which were associated with the severity of symptoms in social interaction, communication and self-care ability. We suggest that stronger functional connectivity between left PCG and right AG, SPG, and SOG detected in young boys with ASD may serve as important indicators of disease severity. Our study provided preliminary functional evidence that may underlie impaired higher-order multisensory integration in ASD children.

Increased inter-hemispheric resting-state functional connectivity in acute lacunar stroke patients with aphasia.

PubMed

Yang, Haiqing; Bai, Lin; Zhou, Yi; Kang, Shan; Liang, Panpan; Wang, Lihua; Zhu, Yifei

2017-03-01

Aphasia is a devastating neurological condition affecting a person's ability to communicate and reintegrate into the society. It may occur in 20% or more of patients after stroke. The recovery of language function is accompanied by brain reorganization, and identifying the inter-hemispheric interaction post-stroke will conduce to more targeted treatments. Previous studies suggested that robust homotopic resting-state functional connectivity is a key characteristic of the brain's intrinsic functional architecture, and communication between the left and right cerebral hemispheres is important for language processing. In this study, voxel-mirrored homotopic connectivity (VMHC) was used to examine the inter-hemispheric resting-state functional connectivity (RSFC) differences between 37 patients with acute lacunar stroke in the left hemisphere and 28 healthy controls. Besides, correlation analyses were carried out to investigate the relationship between VMHC values of brain regions showing abnormal inter-hemispheric RSFC and clinical variables [i.e., aphasia quotient (AQ) scores, National Institutes of Health Stroke Scale (NIHSS) and Mini-Mental State Examination of patients]. Compared with healthy controls, patients showed significantly increased VMHC in the pars orbitalis of the inferior frontal gyrus, anterior part of the superior temporal gyrus (STG) and lingual gyrus. No brain region showed decreased VMHC in the patient group than in the healthy control group. The AQ scores were negatively correlated with VMHC values in the STG. NIHSS scores were positively correlated with VMHC values in the lingual gyrus. We hope these results could shed new insights into the pathology of aphasia in patients with acute lacunar stroke.

Development of a selective left-hemispheric fronto-temporal network for processing syntactic complexity in language comprehension.

PubMed

Xiao, Yaqiong; Friederici, Angela D; Margulies, Daniel S; Brauer, Jens

2016-03-01

The development of language comprehension abilities in childhood is closely related to the maturation of the brain, especially the ability to process syntactically complex sentences. Recent studies proposed that the fronto-temporal connection within left perisylvian regions, supporting the processing of syntactically complex sentences, is still immature at preschool age. In the current study, resting state functional magnetic resonance imaging data were acquired from typically developing 5-year-old children and adults to shed further light on the brain functional development. Children additionally performed a behavioral syntactic comprehension test outside the scanner. The amplitude of low-frequency fluctuations was analyzed in order to identify the functional correlation networks of language-relevant brain regions. Results showed an intrahemispheric correlation between left inferior frontal gyrus (IFG) and left posterior superior temporal sulcus (pSTS) in adults, whereas an interhemispheric correlation between left IFG and its right-hemispheric homolog was predominant in children. Correlation analysis between resting-state functional connectivity and sentence processing performance in 5-year-olds revealed that local connectivity within the left IFG is associated with competence of processing syntactically simple canonical sentences, while long-range connectivity between IFG and pSTS in left hemisphere is associated with competence of processing syntactically relatively more complex non-canonical sentences. The present developmental data suggest that a selective left fronto-temporal connectivity network for processing complex syntax is already in functional connection at the age of 5 years when measured in a non-task situation. The correlational findings provide new insight into the relationship between intrinsic functional connectivity and syntactic language abilities in preschool children. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Sculpting the Intrinsic Modular Organization of Spontaneous Brain Activity by Art.

PubMed

Lin, Chia-Shu; Liu, Yong; Huang, Wei-Yuan; Lu, Chia-Feng; Teng, Shin; Ju, Tzong-Ching; He, Yong; Wu, Yu-Te; Jiang, Tianzi; Hsieh, Jen-Chuen

2013-01-01

Artistic training is a complex learning that requires the meticulous orchestration of sophisticated polysensory, motor, cognitive, and emotional elements of mental capacity to harvest an aesthetic creation. In this study, we investigated the architecture of the resting-state functional connectivity networks from professional painters, dancers and pianists. Using a graph-based network analysis, we focused on the art-related changes of modular organization and functional hubs in the resting-state functional connectivity network. We report that the brain architecture of artists consists of a hierarchical modular organization where art-unique and artistic form-specific brain states collectively mirror the mind states of virtuosos. We show that even in the resting state, this type of extraordinary and long-lasting training can macroscopically imprint a neural network system of spontaneous activity in which the related brain regions become functionally and topologically modularized in both domain-general and domain-specific manners. The attuned modularity reflects a resilient plasticity nurtured by long-term experience.

Sculpting the Intrinsic Modular Organization of Spontaneous Brain Activity by Art

PubMed Central

Lin, Chia-Shu; Liu, Yong; Huang, Wei-Yuan; Lu, Chia-Feng; Teng, Shin; Ju, Tzong-Ching; He, Yong; Wu, Yu-Te; Jiang, Tianzi; Hsieh, Jen-Chuen

2013-01-01

Artistic training is a complex learning that requires the meticulous orchestration of sophisticated polysensory, motor, cognitive, and emotional elements of mental capacity to harvest an aesthetic creation. In this study, we investigated the architecture of the resting-state functional connectivity networks from professional painters, dancers and pianists. Using a graph-based network analysis, we focused on the art-related changes of modular organization and functional hubs in the resting-state functional connectivity network. We report that the brain architecture of artists consists of a hierarchical modular organization where art-unique and artistic form-specific brain states collectively mirror the mind states of virtuosos. We show that even in the resting state, this type of extraordinary and long-lasting training can macroscopically imprint a neural network system of spontaneous activity in which the related brain regions become functionally and topologically modularized in both domain-general and domain-specific manners. The attuned modularity reflects a resilient plasticity nurtured by long-term experience. PMID:23840527

Schizophrenic patients and their unaffected siblings share increased resting-state connectivity in the task-negative network but not its anticorrelated task-positive network.

PubMed

Liu, Haihong; Kaneko, Yoshio; Ouyang, Xuan; Li, Li; Hao, Yihui; Chen, Eric Y H; Jiang, Tianzi; Zhou, Yuan; Liu, Zhening

2012-03-01

Abnormal connectivity of the anticorrelated intrinsic networks, the task-negative network (TNN), and the task-positive network (TPN) is implicated in schizophrenia. Comparisons between schizophrenic patients and their unaffected siblings enable further understanding of illness susceptibility and pathophysiology. We examined the resting-state connectivity differences in the intrinsic networks between schizophrenic patients, their unaffected siblings, and healthy controls. Resting-state functional magnetic resonance images were obtained from 25 individuals in each subject group. The posterior cingulate cortex/precuneus and right dorsolateral prefrontal cortex were used as seed regions to identify the TNN and TPN through functional connectivity analysis. Interregional connectivity strengths were analyzed using overlapped intrinsic networks composed of regions common to all subject groups. Schizophrenic patients and their unaffected siblings showed increased connectivity in the TNN between the bilateral inferior temporal gyri. By contrast, schizophrenic patients alone demonstrated increased connectivity between the posterior cingulate cortex/precuneus and left inferior temporal gyrus and between the ventral medial prefrontal cortex and right lateral parietal cortex in the TNN. Schizophrenic patients exhibited increased connectivity between the left dorsolateral prefrontal cortex and right inferior frontal gyrus in the TPN relative to their unaffected siblings, though this trend only approached statistical significance in comparison to healthy controls. Resting-state hyperconnectivity of the intrinsic networks may disrupt network coordination and thereby contribute to the pathophysiology of schizophrenia. Similar, though milder, hyperconnectivity of the TNN in unaffected siblings of schizophrenic patients may contribute to the identification of schizophrenia endophenotypes and ultimately to the determination of schizophrenia risk genes.

The contributions of resting state and task-based functional connectivity studies to our understanding of adolescent brain network maturation.

PubMed

Stevens, Michael C

2016-11-01

This review summarizes functional magnetic resonance imaging (fMRI) research done over the past decade that examined changes in the function and organization of brain networks across human adolescence. Its over-arching goal is to highlight how both resting state functional connectivity (rs-fcMRI) and task-based functional connectivity (t-fcMRI) have jointly contributed - albeit in different ways - to our understanding of the scope and types of network organization changes that occur from puberty until young adulthood. These two approaches generally have tested different types of hypotheses using different analysis techniques. This has hampered the convergence of findings. Although much has been learned about system-wide changes to adolescents' neural network organization, if both rs-fcMRI and t-fcMRI approaches draw upon each other's methodology and ask broader questions, it will produce a more detailed connectome-informed theory of adolescent neurodevelopment to guide physiological, clinical, and other lines of research. Copyright © 2016 Elsevier Ltd. All rights reserved.

Microstructural and functional connectivity in the developing preterm brain

PubMed Central

Lubsen, Julia; Vohr, Betty; Myers, Eliza; Hampson, Michelle; Lacadie, Cheryl; Schneider, Karen C.; Katz, Karol H.; Constable, R. Todd; Ment, Laura R.

2011-01-01

Prematurely born children are at increased risk for cognitive deficits, but the neurobiological basis of these findings remains poorly understood. Since variations in neural circuitry may influence performance on cognitive tasks, recent investigations have explored the impact of preterm birth on connectivity in the developing brain. Diffusion tensor imaging studies demonstrate widespread alterations in fractional anisotropy, a measure of axonal integrity and microstructural connectivity, throughout the developing preterm brain. Functional connectivity studies report that preterm neonates, children and adolescents exhibit alterations in both resting state and task-based connectivity when compared to term control subjects. Taken together, these data suggest that neurodevelopmental impairment following preterm birth may represent a disease of neural connectivity. PMID:21255705

Effects of Methylphenidate on Resting-State Functional Connectivity of the Mesocorticolimbic Dopamine Pathways in Cocaine Addiction

PubMed Central

Konova, Anna B.; Moeller, Scott J.; Tomasi, Dardo; Volkow, Nora D.; Goldstein, Rita Z.

2015-01-01

Importance Cocaine addiction is associated with altered resting-state functional connectivity among regions of the mesocorticolimbic dopamine pathways. Methylphenidate hydrochloride, an indirect dopamine agonist, normalizes task-related regional brain activity and associated behavior in cocaine users; however, the neural systems–level effects of methylphenidate in this population have not yet been described. Objective To use resting-state functional magnetic resonance imaging to examine changes in mesocorticolimbic connectivity with methylphenidate and how connectivity of affected pathways relates to severity of cocaine addiction. Design Randomized, placebo-controlled, before-after, crossover study. Setting Clinical research center. Participants Eighteen nonabstaining individuals with cocaine use disorders. Interventions Single doses of oral methylphenidate (20 mg) or placebo were administered at each of 2 study sessions. At each session, resting scans were acquired twice: immediately after drug administration (before the onset of effects [baseline]) and 120 minutes later (within the window of peak effects). Main outcomes and Measures Functional connectivity strength was evaluated using a seed voxel correlation approach. Changes in this measure were examined to characterize the neural systems–level effects of methylphenidate; severity of cocaine addiction was assessed by interview and questionnaire. Results Short-term methylphenidate administration reduced an abnormally strong connectivity of the ventral striatum with the dorsal striatum (putamen/globus pallidus), and lower connectivity between these regions during placebo administration uniquely correlated with less severe addiction. In contrast, methylphenidate strengthened several corticolimbic and corticocortical connections. Conclusions and Relevance These findings help elucidate the neural systems–level effects of methylphenidate and suggest that short-term methylphenidate can, at least transiently, remodel abnormal circuitry relevant to the pathophysiologic characteristics of cocaine addiction. In particular, the effects of methylphenidate within striatal and cortical pathways constitute a potentially viable mechanism by which methylphenidate could facilitate control of behavior in cocaine addiction. PMID:23803700

Effective Connectivity within the Default Mode Network: Dynamic Causal Modeling of Resting-State fMRI Data.

PubMed

Sharaev, Maksim G; Zavyalova, Viktoria V; Ushakov, Vadim L; Kartashov, Sergey I; Velichkovsky, Boris M

2016-01-01

The Default Mode Network (DMN) is a brain system that mediates internal modes of cognitive activity, showing higher neural activation when one is at rest. Nowadays, there is a lot of interest in assessing functional interactions between its key regions, but in the majority of studies only association of Blood-oxygen-level dependent (BOLD) activation patterns is measured, so it is impossible to identify causal influences. There are some studies of causal interactions (i.e., effective connectivity), however often with inconsistent results. The aim of the current work is to find a stable pattern of connectivity between four DMN key regions: the medial prefrontal cortex (mPFC), the posterior cingulate cortex (PCC), left and right intraparietal cortex (LIPC and RIPC). For this purpose functional magnetic resonance imaging (fMRI) data from 30 healthy subjects (1000 time points from each one) was acquired and spectral dynamic causal modeling (DCM) on a resting-state fMRI data was performed. The endogenous brain fluctuations were explicitly modeled by Discrete Cosine Set at the low frequency band of 0.0078-0.1 Hz. The best model at the group level is the one where connections from both bilateral IPC to mPFC and PCC are significant and symmetrical in strength (p < 0.05). Connections between mPFC and PCC are bidirectional, significant in the group and weaker than connections originating from bilateral IPC. In general, all connections from LIPC/RIPC to other DMN regions are much stronger. One can assume that these regions have a driving role within the DMN. Our results replicate some data from earlier works on effective connectivity within the DMN as well as provide new insights on internal DMN relationships and brain's functioning at resting state.

Frontal networks associated with command following after hemorrhagic stroke.

PubMed

Mikell, Charles B; Banks, Garrett P; Frey, Hans-Peter; Youngerman, Brett E; Nelp, Taylor B; Karas, Patrick J; Chan, Andrew K; Voss, Henning U; Connolly, E Sander; Claassen, Jan

2015-01-01

Level of consciousness is frequently assessed by command-following ability in the clinical setting. However, it is unclear what brain circuits are needed to follow commands. We sought to determine what networks differentiate command following from noncommand following patients after hemorrhagic stroke. Structural MRI, resting-state functional MRI, and electroencephalography were performed on 25 awake and unresponsive patients with acute intracerebral and subarachnoid hemorrhage. Structural injury was assessed via volumetric T1-weighted MRI analysis. Functional connectivity differences were analyzed against a template of standard resting-state networks. The default mode network (DMN) and the task-positive network were investigated using seed-based functional connectivity. Networks were interrogated by pairwise coherence of electroencephalograph leads in regions of interest defined by functional MRI. Functional imaging of unresponsive patients identified significant differences in 6 of 16 standard resting-state networks. Significant voxels were found in premotor cortex, dorsal anterior cingulate gyrus, and supplementary motor area. Direct interrogation of the DMN and task-positive network revealed loss of connectivity between the DMN and the orbitofrontal cortex and new connections between the task-positive network and DMN. Coherence between electrodes corresponding to right executive network and visual networks was also decreased in unresponsive patients. Resting-state functional MRI and electroencephalography coherence data support a model in which multiple, chiefly frontal networks are required for command following. Loss of DMN anticorrelation with task-positive network may reflect a loss of inhibitory control of the DMN by motor-executive regions. Frontal networks should thus be a target for future investigations into the mechanism of responsiveness in the intensive care unit environment. © 2014 American Heart Association, Inc.

The Anatomical Distance of Functional Connections Predicts Brain Network Topology in Health and Schizophrenia

PubMed Central

Vértes, Petra E.; Stidd, Reva; Lalonde, François; Clasen, Liv; Rapoport, Judith; Giedd, Jay; Bullmore, Edward T.; Gogtay, Nitin

2013-01-01

The human brain is a topologically complex network embedded in anatomical space. Here, we systematically explored relationships between functional connectivity, complex network topology, and anatomical (Euclidean) distance between connected brain regions, in the resting-state functional magnetic resonance imaging brain networks of 20 healthy volunteers and 19 patients with childhood-onset schizophrenia (COS). Normal between-subject differences in average distance of connected edges in brain graphs were strongly associated with variation in topological properties of functional networks. In addition, a club or subset of connector hubs was identified, in lateral temporal, parietal, dorsal prefrontal, and medial prefrontal/cingulate cortical regions. In COS, there was reduced strength of functional connectivity over short distances especially, and therefore, global mean connection distance of thresholded graphs was significantly greater than normal. As predicted from relationships between spatial and topological properties of normal networks, this disorder-related proportional increase in connection distance was associated with reduced clustering and modularity and increased global efficiency of COS networks. Between-group differences in connection distance were localized specifically to connector hubs of multimodal association cortex. In relation to the neurodevelopmental pathogenesis of schizophrenia, we argue that the data are consistent with the interpretation that spatial and topological disturbances of functional network organization could arise from excessive “pruning” of short-distance functional connections in schizophrenia. PMID:22275481

Resting state fMRI reveals a default mode dissociation between retrosplenial and medial prefrontal subnetworks in ASD despite motion scrubbing.

PubMed

Starck, Tuomo; Nikkinen, Juha; Rahko, Jukka; Remes, Jukka; Hurtig, Tuula; Haapsamo, Helena; Jussila, Katja; Kuusikko-Gauffin, Sanna; Mattila, Marja-Leena; Jansson-Verkasalo, Eira; Pauls, David L; Ebeling, Hanna; Moilanen, Irma; Tervonen, Osmo; Kiviniemi, Vesa J

2013-01-01

In resting state functional magnetic resonance imaging (fMRI) studies of autism spectrum disorders (ASDs) decreased frontal-posterior functional connectivity is a persistent finding. However, the picture of the default mode network (DMN) hypoconnectivity remains incomplete. In addition, the functional connectivity analyses have been shown to be susceptible even to subtle motion. DMN hypoconnectivity in ASD has been specifically called for re-evaluation with stringent motion correction, which we aimed to conduct by so-called scrubbing. A rich set of default mode subnetworks can be obtained with high dimensional group independent component analysis (ICA) which can potentially provide more detailed view of the connectivity alterations. We compared the DMN connectivity in high-functioning adolescents with ASDs to typically developing controls using ICA dual-regression with decompositions from typical to high dimensionality. Dual-regression analysis within DMN subnetworks did not reveal alterations but connectivity between anterior and posterior DMN subnetworks was decreased in ASD. The results were very similar with and without motion scrubbing thus indicating the efficacy of the conventional motion correction methods combined with ICA dual-regression. Specific dissociation between DMN subnetworks was revealed on high ICA dimensionality, where networks centered at the medial prefrontal cortex and retrosplenial cortex showed weakened coupling in adolescents with ASDs compared to typically developing control participants. Generally the results speak for disruption in the anterior-posterior DMN interplay on the network level whereas local functional connectivity in DMN seems relatively unaltered.

The effects of age on resting state functional connectivity of the basal ganglia from young to middle adulthood.

PubMed

Manza, Peter; Zhang, Sheng; Hu, Sien; Chao, Herta H; Leung, Hoi-Chung; Li, Chiang-Shan R

2015-02-15

The basal ganglia nuclei are critical for a variety of cognitive and motor functions. Much work has shown age-related structural changes of the basal ganglia. Yet less is known about how the functional interactions of these regions with the cerebral cortex and the cerebellum change throughout the lifespan. Here, we took advantage of a convenient sample and examined resting state functional magnetic resonance imaging data from 250 adults 18 to 49 years of age, focusing specifically on the caudate nucleus, pallidum, putamen, and ventral tegmental area/substantia nigra (VTA/SN). There are a few main findings to report. First, with age, caudate head connectivity increased with a large region of ventromedial prefrontal/medial orbitofrontal cortex. Second, across all subjects, pallidum and putamen showed negative connectivity with default mode network (DMN) regions such as the ventromedial prefrontal cortex and posterior cingulate cortex, in support of anti-correlation of the "task-positive" network (TPN) and DMN. This negative connectivity was reduced with age. Furthermore, pallidum, posterior putamen and VTA/SN connectivity to other TPN regions, such as somatomotor cortex, decreased with age. These results highlight a distinct effect of age on cerebral functional connectivity of the dorsal striatum and VTA/SN from young to middle adulthood and may help research investigating the etiologies or monitoring outcomes of neuropsychiatric conditions that implicate dopaminergic dysfunction. Copyright © 2014 Elsevier Inc. All rights reserved.

Decreased functional connectivity of insula-based network in young adults with internet gaming disorder.

PubMed

Zhang, Yanzhen; Mei, Wei; Zhang, John X; Wu, Qiulin; Zhang, Wei

2016-09-01

The insula is a region that integrates interoception and drug urges, but little is known about its role in behavioral addiction such as internet addiction. We investigated insula-based functional connectivity in participants with internet gaming disorder (IGD) and healthy controls (HC) using resting-state functional MRI. The right and left insula subregions (posterior, ventroanterior, and dorsoanterior) were used as seed regions in a connectivity analysis. Compared with the HC group, the IGD group showed decreased functional connectivity between left posterior insula and bilateral supplementary motor area and middle cingulated cortex, between right posterior insula and right superior frontal gyrus, and decreased functional integration between insular subregions. The finding of reduced functional connectivity between the interoception and the motor/executive control regions is interpreted to reflect reduced ability to inhibit motor responses to internet gaming or diminished executive control over craving for internet gaming in IGD. The results support the hypothesis that IGD is associated with altered insula-based network, similar to substance addiction such as smoking.

Interferon-α acutely impairs whole-brain functional connectivity network architecture - A preliminary study.

PubMed

Dipasquale, Ottavia; Cooper, Ella A; Tibble, Jeremy; Voon, Valerie; Baglio, Francesca; Baselli, Giuseppe; Cercignani, Mara; Harrison, Neil A

2016-11-01

Interferon-alpha (IFN-α) is a key mediator of antiviral immune responses used to treat Hepatitis C infection. Though clinically effective, IFN-α rapidly impairs mood, motivation and cognition, effects that can appear indistinguishable from major depression and provide powerful empirical support for the inflammation theory of depression. Though inflammation has been shown to modulate activity within discrete brain regions, how it affects distributed information processing and the architecture of whole brain functional connectivity networks have not previously been investigated. Here we use a graph theoretic analysis of resting state functional magnetic resonance imaging (rfMRI) to investigate acute effects of systemic interferon-alpha (IFN-α) on whole brain functional connectivity architecture and its relationship to IFN-α-induced mood change. Twenty-two patients with Hepatitis-C infection, initiating IFN-α-based therapy were scanned at baseline and 4h after their first IFN-α dose. The whole brain network was parcellated into 110 cortical and sub-cortical nodes based on the Oxford-Harvard Atlas and effects assessed on higher-level graph metrics, including node degree, betweenness centrality, global and local efficiency. IFN-α was associated with a significant reduction in global network connectivity (node degree) (p=0.033) and efficiency (p=0.013), indicating a global reduction of information transfer among the nodes forming the whole brain network. Effects were similar for highly connected (hub) and non-hub nodes, with no effect on betweenness centrality (p>0.1). At a local level, we identified regions with reduced efficiency of information exchange and a sub-network with decreased functional connectivity after IFN-α. Changes in local and particularly global functional connectivity correlated with associated changes in mood measured on the Profile of Mood States (POMS) questionnaire. IFN-α rapidly induced a profound shift in whole brain network structure, impairing global functional connectivity and the efficiency of parallel information exchange. Correlations with multiple indices of mood change support a role for global changes in brain functional connectivity architecture in coordinated behavioral responses to IFN-α. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Dissociable connectivity within human angular gyrus and intraparietal sulcus: evidence from functional and structural connectivity.

PubMed

Uddin, Lucina Q; Supekar, Kaustubh; Amin, Hitha; Rykhlevskaia, Elena; Nguyen, Daniel A; Greicius, Michael D; Menon, Vinod

2010-11-01

The inferior parietal lobule (IPL) of the human brain is a heterogeneous region involved in visuospatial attention, memory, and mathematical cognition. Detailed description of connectivity profiles of subdivisions within the IPL is critical for accurate interpretation of functional neuroimaging studies involving this region. We separately examined functional and structural connectivity of the angular gyrus (AG) and the intraparietal sulcus (IPS) using probabilistic cytoarchitectonic maps. Regions-of-interest (ROIs) included anterior and posterior AG subregions (PGa, PGp) and 3 IPS subregions (hIP2, hIP1, and hIP3). Resting-state functional connectivity analyses showed that PGa was more strongly linked to basal ganglia, ventral premotor areas, and ventrolateral prefrontal cortex, while PGp was more strongly connected with ventromedial prefrontal cortex, posterior cingulate, and hippocampus-regions comprising the default mode network. The anterior-most IPS ROIs, hIP2 and hIP1, were linked with ventral premotor and middle frontal gyrus, while the posterior-most IPS ROI, hIP3, showed connectivity with extrastriate visual areas. In addition, hIP1 was connected with the insula. Tractography using diffusion tensor imaging revealed structural connectivity between most of these functionally connected regions. Our findings provide evidence for functional heterogeneity of cytoarchitectonically defined subdivisions within IPL and offer a novel framework for synthesis and interpretation of the task-related activations and deactivations involving the IPL during cognition.

Dissociable Connectivity within Human Angular Gyrus and Intraparietal Sulcus: Evidence from Functional and Structural Connectivity

PubMed Central

Supekar, Kaustubh; Amin, Hitha; Rykhlevskaia, Elena; Nguyen, Daniel A.; Greicius, Michael D.; Menon, Vinod

2010-01-01

The inferior parietal lobule (IPL) of the human brain is a heterogeneous region involved in visuospatial attention, memory, and mathematical cognition. Detailed description of connectivity profiles of subdivisions within the IPL is critical for accurate interpretation of functional neuroimaging studies involving this region. We separately examined functional and structural connectivity of the angular gyrus (AG) and the intraparietal sulcus (IPS) using probabilistic cytoarchitectonic maps. Regions-of-interest (ROIs) included anterior and posterior AG subregions (PGa, PGp) and 3 IPS subregions (hIP2, hIP1, and hIP3). Resting-state functional connectivity analyses showed that PGa was more strongly linked to basal ganglia, ventral premotor areas, and ventrolateral prefrontal cortex, while PGp was more strongly connected with ventromedial prefrontal cortex, posterior cingulate, and hippocampus—regions comprising the default mode network. The anterior-most IPS ROIs, hIP2 and hIP1, were linked with ventral premotor and middle frontal gyrus, while the posterior-most IPS ROI, hIP3, showed connectivity with extrastriate visual areas. In addition, hIP1 was connected with the insula. Tractography using diffusion tensor imaging revealed structural connectivity between most of these functionally connected regions. Our findings provide evidence for functional heterogeneity of cytoarchitectonically defined subdivisions within IPL and offer a novel framework for synthesis and interpretation of the task-related activations and deactivations involving the IPL during cognition. PMID:20154013

Mechanisms of hemispheric specialization: Insights from analyses of connectivity

PubMed Central

Stephan, Klaas Enno; Fink, Gereon R.; Marshall, John C.

2007-01-01

Traditionally, anatomical and physiological descriptions of hemispheric specialization have focused on hemispheric asymmetries of local brain structure or local functional properties, respectively. This article reviews the current state of an alternative approach that aims at unraveling the causes and functional principles of hemispheric specialization in terms of asymmetries in connectivity. Starting with an overview of the historical origins of the concept of lateralization, we briefly review recent evidence from anatomical and developmental studies that asymmetries in structural connectivity may be a critical factor shaping hemispheric specialization. These differences in anatomical connectivity, which are found both at the intra- and inter-regional level, are likely to form the structural substrate of different functional principles of information processing in the two hemispheres. The main goal of this article is to describe how these functional principles can be characterized using functional neuroimaging in combination with models of functional and effective connectivity. We discuss the methodology of established models of connectivity which are applicable to data from positron emission tomography and functional magnetic resonance imaging and review published studies that have applied these approaches to characterize asymmetries of connectivity during lateralized tasks. Adopting a model-based approach enables functional imaging to proceed from mere descriptions of asymmetric activation patterns to mechanistic accounts of how these asymmetries are caused. PMID:16949111

Decreased Functional Brain Connectivity in Adolescents with Internet Addiction

PubMed Central

Hong, Soon-Beom; Zalesky, Andrew; Cocchi, Luca; Fornito, Alex; Choi, Eun-Jung; Kim, Ho-Hyun; Suh, Jeong-Eun; Kim, Chang-Dai; Kim, Jae-Won; Yi, Soon-Hyung

2013-01-01

Background Internet addiction has become increasingly recognized as a mental disorder, though its neurobiological basis is unknown. This study used functional neuroimaging to investigate whole-brain functional connectivity in adolescents diagnosed with internet addiction. Based on neurobiological changes seen in other addiction related disorders, it was predicted that connectivity disruptions in adolescents with internet addiction would be most prominent in cortico-striatal circuitry. Methods Participants were 12 adolescents diagnosed with internet addiction and 11 healthy comparison subjects. Resting-state functional magnetic resonance images were acquired, and group differences in brain functional connectivity were analyzed using the network-based statistic. We also analyzed network topology, testing for between-group differences in key graph-based network measures. Results Adolescents with internet addiction showed reduced functional connectivity spanning a distributed network. The majority of impaired connections involved cortico-subcortical circuits (∼24% with prefrontal and ∼27% with parietal cortex). Bilateral putamen was the most extensively involved subcortical brain region. No between-group difference was observed in network topological measures, including the clustering coefficient, characteristic path length, or the small-worldness ratio. Conclusions Internet addiction is associated with a widespread and significant decrease of functional connectivity in cortico-striatal circuits, in the absence of global changes in brain functional network topology. PMID:23451272

Network discovery with DCM

PubMed Central

Friston, Karl J.; Li, Baojuan; Daunizeau, Jean; Stephan, Klaas E.

2011-01-01

This paper is about inferring or discovering the functional architecture of distributed systems using Dynamic Causal Modelling (DCM). We describe a scheme that recovers the (dynamic) Bayesian dependency graph (connections in a network) using observed network activity. This network discovery uses Bayesian model selection to identify the sparsity structure (absence of edges or connections) in a graph that best explains observed time-series. The implicit adjacency matrix specifies the form of the network (e.g., cyclic or acyclic) and its graph-theoretical attributes (e.g., degree distribution). The scheme is illustrated using functional magnetic resonance imaging (fMRI) time series to discover functional brain networks. Crucially, it can be applied to experimentally evoked responses (activation studies) or endogenous activity in task-free (resting state) fMRI studies. Unlike conventional approaches to network discovery, DCM permits the analysis of directed and cyclic graphs. Furthermore, it eschews (implausible) Markovian assumptions about the serial independence of random fluctuations. The scheme furnishes a network description of distributed activity in the brain that is optimal in the sense of having the greatest conditional probability, relative to other networks. The networks are characterised in terms of their connectivity or adjacency matrices and conditional distributions over the directed (and reciprocal) effective connectivity between connected nodes or regions. We envisage that this approach will provide a useful complement to current analyses of functional connectivity for both activation and resting-state studies. PMID:21182971

Resting-State Functional Connectivity in Individuals with Down Syndrome and Williams Syndrome Compared with Typically Developing Controls.

PubMed

Vega, Jennifer N; Hohman, Timothy J; Pryweller, Jennifer R; Dykens, Elisabeth M; Thornton-Wells, Tricia A

2015-10-01

The emergence of resting-state functional connectivity (rsFC) analysis, which examines temporal correlations of low-frequency (<0.1 Hz) blood oxygen level-dependent signal fluctuations between brain regions, has dramatically improved our understanding of the functional architecture of the typically developing (TD) human brain. This study examined rsFC in Down syndrome (DS) compared with another neurodevelopmental disorder, Williams syndrome (WS), and TD. Ten subjects with DS, 18 subjects with WS, and 40 subjects with TD each participated in a 3-Tesla MRI scan. We tested for group differences (DS vs. TD, DS vs. WS, and WS vs. TD) in between- and within-network rsFC connectivity for seven functional networks. For the DS group, we also examined associations between rsFC and other cognitive and genetic risk factors. In DS compared with TD, we observed higher levels of between-network connectivity in 6 out 21 network pairs but no differences in within-network connectivity. Participants with WS showed lower levels of within-network connectivity and no significant differences in between-network connectivity relative to DS. Finally, our comparison between WS and TD controls revealed lower within-network connectivity in multiple networks and higher between-network connectivity in one network pair relative to TD controls. While preliminary due to modest sample sizes, our findings suggest a global difference in between-network connectivity in individuals with neurodevelopmental disorders compared with controls and that such a difference is exacerbated across many brain regions in DS. However, this alteration in DS does not appear to extend to within-network connections, and therefore, the altered between-network connectivity must be interpreted within the framework of an intact intra-network pattern of activity. In contrast, WS shows markedly lower levels of within-network connectivity in the default mode network and somatomotor network relative to controls. These findings warrant further investigation using a task-based procedure that may help disentangle the relationship between brain function and cognitive performance across the spectrum of neurodevelopmental disorders.

Functional Connectivity Parcellation of the Human Thalamus by Independent Component Analysis.

PubMed

Zhang, Sheng; Li, Chiang-Shan R

2017-11-01

As a key structure to relay and integrate information, the thalamus supports multiple cognitive and affective functions through the connectivity between its subnuclei and cortical and subcortical regions. Although extant studies have largely described thalamic regional functions in anatomical terms, evidence accumulates to suggest a more complex picture of subareal activities and connectivities of the thalamus. In this study, we aimed to parcellate the thalamus and examine whole-brain connectivity of its functional clusters. With resting state functional magnetic resonance imaging data from 96 adults, we used independent component analysis (ICA) to parcellate the thalamus into 10 components. On the basis of the independence assumption, ICA helps to identify how subclusters overlap spatially. Whole brain functional connectivity of each subdivision was computed for independent component's time course (ICtc), which is a unique time series to represent an IC. For comparison, we computed seed-region-based functional connectivity using the averaged time course across all voxels within a thalamic subdivision. The results showed that, at p < 10 -6 , corrected, 49% of voxels on average overlapped among subdivisions. Compared with seed-region analysis, ICtc analysis revealed patterns of connectivity that were more distinguished between thalamic clusters. ICtc analysis demonstrated thalamic connectivity to the primary motor cortex, which has eluded the analysis as well as previous studies based on averaged time series, and clarified thalamic connectivity to the hippocampus, caudate nucleus, and precuneus. The new findings elucidate functional organization of the thalamus and suggest that ICA clustering in combination with ICtc rather than seed-region analysis better distinguishes whole-brain connectivities among functional clusters of a brain region.

Quantifying Individual Brain Connectivity with Functional Principal Component Analysis for Networks.

PubMed

Petersen, Alexander; Zhao, Jianyang; Carmichael, Owen; Müller, Hans-Georg

2016-09-01

In typical functional connectivity studies, connections between voxels or regions in the brain are represented as edges in a network. Networks for different subjects are constructed at a given graph density and are summarized by some network measure such as path length. Examining these summary measures for many density values yields samples of connectivity curves, one for each individual. This has led to the adoption of basic tools of functional data analysis, most commonly to compare control and disease groups through the average curves in each group. Such group differences, however, neglect the variability in the sample of connectivity curves. In this article, the use of functional principal component analysis (FPCA) is demonstrated to enrich functional connectivity studies by providing increased power and flexibility for statistical inference. Specifically, individual connectivity curves are related to individual characteristics such as age and measures of cognitive function, thus providing a tool to relate brain connectivity with these variables at the individual level. This individual level analysis opens a new perspective that goes beyond previous group level comparisons. Using a large data set of resting-state functional magnetic resonance imaging scans, relationships between connectivity and two measures of cognitive function-episodic memory and executive function-were investigated. The group-based approach was implemented by dichotomizing the continuous cognitive variable and testing for group differences, resulting in no statistically significant findings. To demonstrate the new approach, FPCA was implemented, followed by linear regression models with cognitive scores as responses, identifying significant associations of connectivity in the right middle temporal region with both cognitive scores.

Characterizing Variability of Modular Brain Connectivity with Constrained Principal Component Analysis

PubMed Central

Hirayama, Jun-ichiro; Hyvärinen, Aapo; Kiviniemi, Vesa; Kawanabe, Motoaki; Yamashita, Okito

2016-01-01

Characterizing the variability of resting-state functional brain connectivity across subjects and/or over time has recently attracted much attention. Principal component analysis (PCA) serves as a fundamental statistical technique for such analyses. However, performing PCA on high-dimensional connectivity matrices yields complicated “eigenconnectivity” patterns, for which systematic interpretation is a challenging issue. Here, we overcome this issue with a novel constrained PCA method for connectivity matrices by extending the idea of the previously proposed orthogonal connectivity factorization method. Our new method, modular connectivity factorization (MCF), explicitly introduces the modularity of brain networks as a parametric constraint on eigenconnectivity matrices. In particular, MCF analyzes the variability in both intra- and inter-module connectivities, simultaneously finding network modules in a principled, data-driven manner. The parametric constraint provides a compact module-based visualization scheme with which the result can be intuitively interpreted. We develop an optimization algorithm to solve the constrained PCA problem and validate our method in simulation studies and with a resting-state functional connectivity MRI dataset of 986 subjects. The results show that the proposed MCF method successfully reveals the underlying modular eigenconnectivity patterns in more general situations and is a promising alternative to existing methods. PMID:28002474

Investigation of Multiple Frequency Ranges Using Discrete Wavelet Decomposition of Resting-State Functional Connectivity in Mild Traumatic Brain Injury Patients

PubMed Central

Chen, Haoxing; Roys, Steven; Zhuo, Jiachen; Varshney, Amitabh; Gullapalli, Rao P.

2015-01-01

Abstract The aim of this study was to investigate if discrete wavelet decomposition provides additional insight into resting-state processes through the analysis of functional connectivity within specific frequency ranges within the default mode network (DMN) that may be affected by mild traumatic brain injury (mTBI). Participants included 32 mTBI patients (15 with postconcussive syndrome [PCS+] and 17 without [PCS−]). mTBI patients received resting-state functional magnetic resonance imaging (rs-fMRI) at acute (within 10 days of injury) and chronic (6 months postinjury) time points and were compared with 31 controls (healthy control [HC]). The wavelet decomposition divides the time series into multiple frequency ranges based on four scaling factors (SF1: 0.125–0.250 Hz, SF2: 0.060–0.125 Hz, SF3: 0.030–0.060 Hz, SF4: 0.015–0.030 Hz). Within each SF, wavelet connectivity matrices for nodes of the DMN were created for each group (HC, PCS+, PCS−), and bivariate measures of strength and diversity were calculated. The results demonstrate reduced strength of connectivity in PCS+ patients compared with PCS− patients within SF1 during both the acute and chronic stages of injury, as well as recovery of connectivity within SF1 across the two time points. Furthermore, the PCS− group demonstrated greater network strength compared with controls at both time points, suggesting a potential compensatory or protective mechanism in these patients. These findings stress the importance of investigating resting-state connectivity within multiple frequency ranges; however, many of our findings are within SF1, which may overlap with frequencies associated with cardiac and respiratory activities. PMID:25808612

Investigation of Multiple Frequency Ranges Using Discrete Wavelet Decomposition of Resting-State Functional Connectivity in Mild Traumatic Brain Injury Patients.

PubMed

Sours, Chandler; Chen, Haoxing; Roys, Steven; Zhuo, Jiachen; Varshney, Amitabh; Gullapalli, Rao P

2015-09-01

The aim of this study was to investigate if discrete wavelet decomposition provides additional insight into resting-state processes through the analysis of functional connectivity within specific frequency ranges within the default mode network (DMN) that may be affected by mild traumatic brain injury (mTBI). Participants included 32 mTBI patients (15 with postconcussive syndrome [PCS+] and 17 without [PCS-]). mTBI patients received resting-state functional magnetic resonance imaging (rs-fMRI) at acute (within 10 days of injury) and chronic (6 months postinjury) time points and were compared with 31 controls (healthy control [HC]). The wavelet decomposition divides the time series into multiple frequency ranges based on four scaling factors (SF1: 0.125-0.250 Hz, SF2: 0.060-0.125 Hz, SF3: 0.030-0.060 Hz, SF4: 0.015-0.030 Hz). Within each SF, wavelet connectivity matrices for nodes of the DMN were created for each group (HC, PCS+, PCS-), and bivariate measures of strength and diversity were calculated. The results demonstrate reduced strength of connectivity in PCS+ patients compared with PCS- patients within SF1 during both the acute and chronic stages of injury, as well as recovery of connectivity within SF1 across the two time points. Furthermore, the PCS- group demonstrated greater network strength compared with controls at both time points, suggesting a potential compensatory or protective mechanism in these patients. These findings stress the importance of investigating resting-state connectivity within multiple frequency ranges; however, many of our findings are within SF1, which may overlap with frequencies associated with cardiac and respiratory activities.

Effects of Cognitive-Behavioral Therapy (CBT) on Brain Connectivity Supporting Catastrophizing in Fibromyalgia.

PubMed

Lazaridou, Asimina; Kim, Jieun; Cahalan, Christine M; Loggia, Marco L; Franceschelli, Olivia; Berna, Chantal; Schur, Peter; Napadow, Vitaly; Edwards, Robert R

2017-03-01

Fibromyalgia (FM) is a chronic, common pain disorder characterized by hyperalgesia. A key mechanism by which cognitive-behavioral therapy (CBT) fosters improvement in pain outcomes is via reductions in hyperalgesia and pain-related catastrophizing, a dysfunctional set of cognitive-emotional processes. However, the neural underpinnings of these CBT effects are unclear. Our aim was to assess CBT's effects on the brain circuitry underlying hyperalgesia in FM patients, and to explore the role of treatment-associated reduction in catastrophizing as a contributor to normalization of pain-relevant brain circuitry and clinical improvement. In total, 16 high-catastrophizing FM patients were enrolled in the study and randomized to 4 weeks of individual treatment with either CBT or a Fibromyalgia Education (control) condition. Resting state functional magnetic resonance imaging scans evaluated functional connectivity between key pain-processing brain regions at baseline and posttreatment. Clinical outcomes were assessed at baseline, posttreatment, and 6-month follow-up. Catastrophizing correlated with increased resting state functional connectivity between S1 and anterior insula. The CBT group showed larger reductions (compared with the education group) in catastrophizing at posttreatment (P<0.05), and CBT produced significant reductions in both pain and catastrophizing at the 6-month follow-up (P<0.05). Patients in the CBT group also showed reduced resting state connectivity between S1 and anterior/medial insula at posttreatment; these reductions in resting state connectivity were associated with concurrent treatment-related reductions in catastrophizing. The results add to the growing support for the clinically important associations between S1-insula connectivity, clinical pain, and catastrophizing, and suggest that CBT may, in part via reductions in catastrophizing, help to normalize pain-related brain responses in FM.

Neuroimaging markers of glutamatergic and GABAergic systems in drug addiction: relationships to resting-state functional connectivity

PubMed Central

Moeller, Scott J.; London, Edythe D.; Northoff, Georg

2015-01-01

Drug addiction is characterized by widespread abnormalities in brain function and neurochemistry, including drug-associated effects on concentrations of the excitatory and inhibitory neurotransmitters glutamate and gamma-aminobutyric acid (GABA), respectively. In healthy individuals, these neurotransmitters drive the resting state, a default condition of brain function also disrupted in addiction. Here, our primary goal was to review in vivo magnetic resonance spectroscopy and positron emission tomography studies that examined markers of glutamate and GABA abnormalities in human drug addiction. Addicted individuals tended to show decreases in these markers compared with healthy controls, but findings also varied by individual characteristics (e.g., abstinence length). Interestingly, select corticolimbic brain regions showing glutamatergic and/or GABAergic abnormalities have been similarly implicated in resting-state functional connectivity deficits in drug addiction. Thus, our secondary goals were to provide a brief review of this resting-state literature, and an initial rationale for the hypothesis that abnormalities in glutamatergic and/or GABAergic neurotransmission may underlie resting-state functional deficits in drug addiction. In doing so, we suggest future research directions and possible treatment implications. PMID:26657968

Higher Dimensional Meta-State Analysis Reveals Reduced Resting fMRI Connectivity Dynamism in Schizophrenia Patients.

PubMed

Miller, Robyn L; Yaesoubi, Maziar; Turner, Jessica A; Mathalon, Daniel; Preda, Adrian; Pearlson, Godfrey; Adali, Tulay; Calhoun, Vince D

2016-01-01

Resting-state functional brain imaging studies of network connectivity have long assumed that functional connections are stationary on the timescale of a typical scan. Interest in moving beyond this simplifying assumption has emerged only recently. The great hope is that training the right lens on time-varying properties of whole-brain network connectivity will shed additional light on previously concealed brain activation patterns characteristic of serious neurological or psychiatric disorders. We present evidence that multiple explicitly dynamical properties of time-varying whole-brain network connectivity are strongly associated with schizophrenia, a complex mental illness whose symptomatic presentation can vary enormously across subjects. As with so much brain-imaging research, a central challenge for dynamic network connectivity lies in determining transformations of the data that both reduce its dimensionality and expose features that are strongly predictive of important population characteristics. Our paper introduces an elegant, simple method of reducing and organizing data around which a large constellation of mutually informative and intuitive dynamical analyses can be performed. This framework combines a discrete multidimensional data-driven representation of connectivity space with four core dynamism measures computed from large-scale properties of each subject's trajectory, ie., properties not identifiable with any specific moment in time and therefore reasonable to employ in settings lacking inter-subject time-alignment, such as resting-state functional imaging studies. Our analysis exposes pronounced differences between schizophrenia patients (Nsz = 151) and healthy controls (Nhc = 163). Time-varying whole-brain network connectivity patterns are found to be markedly less dynamically active in schizophrenia patients, an effect that is even more pronounced in patients with high levels of hallucinatory behavior. To the best of our knowledge this is the first demonstration that high-level dynamic properties of whole-brain connectivity, generic enough to be commensurable under many decompositions of time-varying connectivity data, exhibit robust and systematic differences between schizophrenia patients and healthy controls.

Higher Dimensional Meta-State Analysis Reveals Reduced Resting fMRI Connectivity Dynamism in Schizophrenia Patients

PubMed Central

Miller, Robyn L.; Yaesoubi, Maziar; Turner, Jessica A.; Mathalon, Daniel; Preda, Adrian; Pearlson, Godfrey; Adali, Tulay; Calhoun, Vince D.

2016-01-01

Resting-state functional brain imaging studies of network connectivity have long assumed that functional connections are stationary on the timescale of a typical scan. Interest in moving beyond this simplifying assumption has emerged only recently. The great hope is that training the right lens on time-varying properties of whole-brain network connectivity will shed additional light on previously concealed brain activation patterns characteristic of serious neurological or psychiatric disorders. We present evidence that multiple explicitly dynamical properties of time-varying whole-brain network connectivity are strongly associated with schizophrenia, a complex mental illness whose symptomatic presentation can vary enormously across subjects. As with so much brain-imaging research, a central challenge for dynamic network connectivity lies in determining transformations of the data that both reduce its dimensionality and expose features that are strongly predictive of important population characteristics. Our paper introduces an elegant, simple method of reducing and organizing data around which a large constellation of mutually informative and intuitive dynamical analyses can be performed. This framework combines a discrete multidimensional data-driven representation of connectivity space with four core dynamism measures computed from large-scale properties of each subject’s trajectory, ie., properties not identifiable with any specific moment in time and therefore reasonable to employ in settings lacking inter-subject time-alignment, such as resting-state functional imaging studies. Our analysis exposes pronounced differences between schizophrenia patients (Nsz = 151) and healthy controls (Nhc = 163). Time-varying whole-brain network connectivity patterns are found to be markedly less dynamically active in schizophrenia patients, an effect that is even more pronounced in patients with high levels of hallucinatory behavior. To the best of our knowledge this is the first demonstration that high-level dynamic properties of whole-brain connectivity, generic enough to be commensurable under many decompositions of time-varying connectivity data, exhibit robust and systematic differences between schizophrenia patients and healthy controls. PMID:26981625

Resting-state hemodynamics are spatiotemporally coupled to synchronized and symmetric neural activity in excitatory neurons.

PubMed

Ma, Ying; Shaik, Mohammed A; Kozberg, Mariel G; Kim, Sharon H; Portes, Jacob P; Timerman, Dmitriy; Hillman, Elizabeth M C

2016-12-27

Brain hemodynamics serve as a proxy for neural activity in a range of noninvasive neuroimaging techniques including functional magnetic resonance imaging (fMRI). In resting-state fMRI, hemodynamic fluctuations have been found to exhibit patterns of bilateral synchrony, with correlated regions inferred to have functional connectivity. However, the relationship between resting-state hemodynamics and underlying neural activity has not been well established, making the neural underpinnings of functional connectivity networks unclear. In this study, neural activity and hemodynamics were recorded simultaneously over the bilateral cortex of awake and anesthetized Thy1-GCaMP mice using wide-field optical mapping. Neural activity was visualized via selective expression of the calcium-sensitive fluorophore GCaMP in layer 2/3 and 5 excitatory neurons. Characteristic patterns of resting-state hemodynamics were accompanied by more rapidly changing bilateral patterns of resting-state neural activity. Spatiotemporal hemodynamics could be modeled by convolving this neural activity with hemodynamic response functions derived through both deconvolution and gamma-variate fitting. Simultaneous imaging and electrophysiology confirmed that Thy1-GCaMP signals are well-predicted by multiunit activity. Neurovascular coupling between resting-state neural activity and hemodynamics was robust and fast in awake animals, whereas coupling in urethane-anesthetized animals was slower, and in some cases included lower-frequency (<0.04 Hz) hemodynamic fluctuations that were not well-predicted by local Thy1-GCaMP recordings. These results support that resting-state hemodynamics in the awake and anesthetized brain are coupled to underlying patterns of excitatory neural activity. The patterns of bilaterally-symmetric spontaneous neural activity revealed by wide-field Thy1-GCaMP imaging may depict the neural foundation of functional connectivity networks detected in resting-state fMRI.

Resting-state hemodynamics are spatiotemporally coupled to synchronized and symmetric neural activity in excitatory neurons

PubMed Central

Ma, Ying; Shaik, Mohammed A.; Kozberg, Mariel G.; Portes, Jacob P.; Timerman, Dmitriy

2016-01-01

Brain hemodynamics serve as a proxy for neural activity in a range of noninvasive neuroimaging techniques including functional magnetic resonance imaging (fMRI). In resting-state fMRI, hemodynamic fluctuations have been found to exhibit patterns of bilateral synchrony, with correlated regions inferred to have functional connectivity. However, the relationship between resting-state hemodynamics and underlying neural activity has not been well established, making the neural underpinnings of functional connectivity networks unclear. In this study, neural activity and hemodynamics were recorded simultaneously over the bilateral cortex of awake and anesthetized Thy1-GCaMP mice using wide-field optical mapping. Neural activity was visualized via selective expression of the calcium-sensitive fluorophore GCaMP in layer 2/3 and 5 excitatory neurons. Characteristic patterns of resting-state hemodynamics were accompanied by more rapidly changing bilateral patterns of resting-state neural activity. Spatiotemporal hemodynamics could be modeled by convolving this neural activity with hemodynamic response functions derived through both deconvolution and gamma-variate fitting. Simultaneous imaging and electrophysiology confirmed that Thy1-GCaMP signals are well-predicted by multiunit activity. Neurovascular coupling between resting-state neural activity and hemodynamics was robust and fast in awake animals, whereas coupling in urethane-anesthetized animals was slower, and in some cases included lower-frequency (<0.04 Hz) hemodynamic fluctuations that were not well-predicted by local Thy1-GCaMP recordings. These results support that resting-state hemodynamics in the awake and anesthetized brain are coupled to underlying patterns of excitatory neural activity. The patterns of bilaterally-symmetric spontaneous neural activity revealed by wide-field Thy1-GCaMP imaging may depict the neural foundation of functional connectivity networks detected in resting-state fMRI. PMID:27974609

Task-Rest Modulation of Basal Ganglia Connectivity in Mild to Moderate Parkinson’s Disease

PubMed Central

Müller-Oehring, Eva M.; Sullivan, Edith V.; Pfefferbaum, Adolf; Huang, Neng C.; Poston, Kathleen L.; Bronte-Stewart, Helen M.; Schulte, Tilman

2014-01-01

Parkinson’s disease (PD) is associated with abnormal synchronization in basal ganglia-thalamo-cortical loops. We tested whether early PD patients without demonstrable cognitive impairment exhibit abnormal modulation of functional connectivity at rest, while engaged in a task, or both. PD and healthy controls underwent two functional MRI scans: a resting-state scan and a Stroop Match-to-Sample task scan. Rest-task modulation of basal ganglia (BG) connectivity was tested using seed-to-voxel connectivity analysis with task and rest time series as conditions. Despite substantial overlap of BG–cortical connectivity patterns in both groups, connectivity differences between groups had clinical and behavioral correlates. During rest, stronger putamen–medial parietal and pallidum–occipital connectivity in PD than controls was associated with worse task performance and more severe PD symptoms suggesting that abnormalities in resting-state connectivity denote neural network dedifferentiation. During the executive task, PD patients showed weaker BG-cortical connectivity than controls, i.e., between caudate–supramarginal gyrus and pallidum–inferior prefrontal regions, that was related to more severe PD symptoms and worse task performance. Yet, task processing also evoked stronger striatal–cortical connectivity, specifically between caudate–prefrontal, caudate–precuneus, and putamen–motor/premotor regions in PD relative to controls, which was related to less severe PD symptoms and better performance on the Stroop task. Thus, stronger task-evoked striatal connectivity in PD demonstrated compensatory neural network enhancement to meet task demands and improve performance levels. fMRI-based network analysis revealed that despite resting-state BG network compromise in PD, BG connectivity to prefrontal, premotor, and precuneus regions can be adequately invoked during executive control demands enabling near normal task performance. PMID:25280970

Modulating Intrinsic Connectivity: Adjacent Subregions within Supplementary Motor Cortex, Dorsolateral Prefrontal Cortex, and Parietal Cortex Connect to Separate Functional Networks during Task and Also Connect during Rest

PubMed Central

Roth, Jennifer K.; Johnson, Marcia K.; Tokoglu, Fuyuze; Murphy, Isabella; Constable, R. Todd

2014-01-01

Supplementary motor area (SMA), the inferior frontal junction (IFJ), superior frontal junction (SFJ) and parietal cortex are active in many cognitive tasks. In a previous study, we found that subregions of each of these major areas were differentially active in component processes of executive function during working memory tasks. In the present study, each of these subregions was used as a seed in a whole brain functional connectivity analysis of working memory and resting state data. These regions show functional connectivity to different networks, thus supporting the parcellation of these major regions into functional subregions. Many regions showing significant connectivity during the working memory residual data (with task events regressed from the data) were also significantly connected during rest suggesting that these network connections to subregions within major regions of cortex are intrinsic. For some of these connections, task demands modulate activity in these intrinsic networks. Approximately half of the connections significant during task were significant during rest, indicating that some of the connections are intrinsic while others are recruited only in the service of the task. Furthermore, the network connections to traditional ‘task positive’ and ‘task negative’ (a.k.a ‘default mode’) regions shift from positive connectivity to negative connectivity depending on task demands. These findings demonstrate that such task-identified subregions are part of distinct networks, and that these networks have different patterns of connectivity for task as they do during rest, engaging connections both to task positive and task negative regions. These results have implications for understanding the parcellation of commonly active regions into more specific functional networks. PMID:24637793

Dynamics of networks of excitatory and inhibitory neurons in response to time-dependent inputs.

PubMed

Ledoux, Erwan; Brunel, Nicolas

2011-01-01

We investigate the dynamics of recurrent networks of excitatory (E) and inhibitory (I) neurons in the presence of time-dependent inputs. The dynamics is characterized by the network dynamical transfer function, i.e., how the population firing rate is modulated by sinusoidal inputs at arbitrary frequencies. Two types of networks are studied and compared: (i) a Wilson-Cowan type firing rate model; and (ii) a fully connected network of leaky integrate-and-fire (LIF) neurons, in a strong noise regime. We first characterize the region of stability of the "asynchronous state" (a state in which population activity is constant in time when external inputs are constant) in the space of parameters characterizing the connectivity of the network. We then systematically characterize the qualitative behaviors of the dynamical transfer function, as a function of the connectivity. We find that the transfer function can be either low-pass, or with a single or double resonance, depending on the connection strengths and synaptic time constants. Resonances appear when the system is close to Hopf bifurcations, that can be induced by two separate mechanisms: the I-I connectivity and the E-I connectivity. Double resonances can appear when excitatory delays are larger than inhibitory delays, due to the fact that two distinct instabilities exist with a finite gap between the corresponding frequencies. In networks of LIF neurons, changes in external inputs and external noise are shown to be able to change qualitatively the network transfer function. Firing rate models are shown to exhibit the same diversity of transfer functions as the LIF network, provided delays are present. They can also exhibit input-dependent changes of the transfer function, provided a suitable static non-linearity is incorporated.

Brain functional connectivity changes in children that differ in impulsivity temperamental trait

PubMed Central

Inuggi, Alberto; Sanz-Arigita, Ernesto; González-Salinas, Carmen; Valero-García, Ana V.; García-Santos, Jose M.; Fuentes, Luis J.

2014-01-01

Impulsivity is a core personality trait forming part of normal behavior and contributing to adaptive functioning. However, in typically developing children, altered patterns of impulsivity constitute a risk factor for the development of behavioral problems. Since both pathological and non-pathological states are commonly characterized by continuous transitions, we used a correlative approach to investigate the potential link between personality and brain dynamics. We related brain functional connectivity of typically developing children, measured with magnetic resonance imaging at rest, with their impulsivity scores obtained from a questionnaire completed by their parents. We first looked for areas within the default mode network (DMN) whose functional connectivity might be modulated by trait impulsivity. Then, we calculated the functional connectivity among these regions and the rest of the brain in order to assess if impulsivity trait altered their relationships. We found two DMN clusters located at the posterior cingulate cortex and the right angular gyrus which were negatively correlated with impulsivity scores. The whole-brain correlation analysis revealed the classic network of correlating and anti-correlating areas with respect to the DMN. The impulsivity trait modulated such pattern showing that the canonical anti-phasic relation between DMN and action-related network was reduced in high impulsive children. These results represent the first evidence that the impulsivity, measured as personality trait assessed through parents' report, exerts a modulatory influence over the functional connectivity of resting state brain networks in typically developing children. The present study goes further to connect developmental approaches, mainly based on data collected through the use of questionnaires, and behavioral neuroscience, interested in how differences in brain structure and functions reflect in differences in behavior. PMID:24834038

Brain functional connectivity changes in children that differ in impulsivity temperamental trait.

PubMed

Inuggi, Alberto; Sanz-Arigita, Ernesto; González-Salinas, Carmen; Valero-García, Ana V; García-Santos, Jose M; Fuentes, Luis J

2014-01-01

Impulsivity is a core personality trait forming part of normal behavior and contributing to adaptive functioning. However, in typically developing children, altered patterns of impulsivity constitute a risk factor for the development of behavioral problems. Since both pathological and non-pathological states are commonly characterized by continuous transitions, we used a correlative approach to investigate the potential link between personality and brain dynamics. We related brain functional connectivity of typically developing children, measured with magnetic resonance imaging at rest, with their impulsivity scores obtained from a questionnaire completed by their parents. We first looked for areas within the default mode network (DMN) whose functional connectivity might be modulated by trait impulsivity. Then, we calculated the functional connectivity among these regions and the rest of the brain in order to assess if impulsivity trait altered their relationships. We found two DMN clusters located at the posterior cingulate cortex and the right angular gyrus which were negatively correlated with impulsivity scores. The whole-brain correlation analysis revealed the classic network of correlating and anti-correlating areas with respect to the DMN. The impulsivity trait modulated such pattern showing that the canonical anti-phasic relation between DMN and action-related network was reduced in high impulsive children. These results represent the first evidence that the impulsivity, measured as personality trait assessed through parents' report, exerts a modulatory influence over the functional connectivity of resting state brain networks in typically developing children. The present study goes further to connect developmental approaches, mainly based on data collected through the use of questionnaires, and behavioral neuroscience, interested in how differences in brain structure and functions reflect in differences in behavior.

Time-dependence of graph theory metrics in functional connectivity analysis

PubMed Central

Chiang, Sharon; Cassese, Alberto; Guindani, Michele; Vannucci, Marina; Yeh, Hsiang J.; Haneef, Zulfi; Stern, John M.

2016-01-01

Brain graphs provide a useful way to computationally model the network structure of the connectome, and this has led to increasing interest in the use of graph theory to quantitate and investigate the topological characteristics of the healthy brain and brain disorders on the network level. The majority of graph theory investigations of functional connectivity have relied on the assumption of temporal stationarity. However, recent evidence increasingly suggests that functional connectivity fluctuates over the length of the scan. In this study, we investigate the stationarity of brain network topology using a Bayesian hidden Markov model (HMM) approach that estimates the dynamic structure of graph theoretical measures of whole-brain functional connectivity. In addition to extracting the stationary distribution and transition probabilities of commonly employed graph theory measures, we propose two estimators of temporal stationarity: the S-index and N-index. These indexes can be used to quantify different aspects of the temporal stationarity of graph theory measures. We apply the method and proposed estimators to resting-state functional MRI data from healthy controls and patients with temporal lobe epilepsy. Our analysis shows that several graph theory measures, including small-world index, global integration measures, and betweenness centrality, may exhibit greater stationarity over time and therefore be more robust. Additionally, we demonstrate that accounting for subject-level differences in the level of temporal stationarity of network topology may increase discriminatory power in discriminating between disease states. Our results confirm and extend findings from other studies regarding the dynamic nature of functional connectivity, and suggest that using statistical models which explicitly account for the dynamic nature of functional connectivity in graph theory analyses may improve the sensitivity of investigations and consistency across investigations. PMID:26518632

Time-dependence of graph theory metrics in functional connectivity analysis.

PubMed

Chiang, Sharon; Cassese, Alberto; Guindani, Michele; Vannucci, Marina; Yeh, Hsiang J; Haneef, Zulfi; Stern, John M

2016-01-15

Brain graphs provide a useful way to computationally model the network structure of the connectome, and this has led to increasing interest in the use of graph theory to quantitate and investigate the topological characteristics of the healthy brain and brain disorders on the network level. The majority of graph theory investigations of functional connectivity have relied on the assumption of temporal stationarity. However, recent evidence increasingly suggests that functional connectivity fluctuates over the length of the scan. In this study, we investigate the stationarity of brain network topology using a Bayesian hidden Markov model (HMM) approach that estimates the dynamic structure of graph theoretical measures of whole-brain functional connectivity. In addition to extracting the stationary distribution and transition probabilities of commonly employed graph theory measures, we propose two estimators of temporal stationarity: the S-index and N-index. These indexes can be used to quantify different aspects of the temporal stationarity of graph theory measures. We apply the method and proposed estimators to resting-state functional MRI data from healthy controls and patients with temporal lobe epilepsy. Our analysis shows that several graph theory measures, including small-world index, global integration measures, and betweenness centrality, may exhibit greater stationarity over time and therefore be more robust. Additionally, we demonstrate that accounting for subject-level differences in the level of temporal stationarity of network topology may increase discriminatory power in discriminating between disease states. Our results confirm and extend findings from other studies regarding the dynamic nature of functional connectivity, and suggest that using statistical models which explicitly account for the dynamic nature of functional connectivity in graph theory analyses may improve the sensitivity of investigations and consistency across investigations. Copyright © 2015 Elsevier Inc. All rights reserved.

From structure to function, via dynamics

NASA Astrophysics Data System (ADS)

Stetter, O.; Soriano, J.; Geisel, T.; Battaglia, D.

2013-01-01

Neurons in the brain are wired into a synaptic network that spans multiple scales, from local circuits within cortical columns to fiber tracts interconnecting distant areas. However, brain function require the dynamic control of inter-circuit interactions on time-scales faster than synaptic changes. In particular, strength and direction of causal influences between neural populations (described by the so-called directed functional connectivity) must be reconfigurable even when the underlying structural connectivity is fixed. Such directed functional influences can be quantified resorting to causal analysis of time-series based on tools like Granger Causality or Transfer Entropy. The ability to quickly reorganize inter-areal interactions is a chief requirement for performance in a changing natural environment. But how can manifold functional networks stem "on demand" from an essentially fixed structure? We explore the hypothesis that the self-organization of neuronal synchronous activity underlies the control of brain functional connectivity. Based on simulated and real recordings of critical neuronal cultures in vitro, as well as on mean-field and spiking network models of interacting brain areas, we have found that "function follows dynamics", rather than structure. Different dynamic states of a same structural network, characterized by different synchronization properties, are indeed associated to different functional digraphs (functional multiplicity). We also highlight the crucial role of dynamics in establishing a structure-to-function link, by showing that whenever different structural topologies lead to similar dynamical states, than the associated functional connectivities are also very similar (structural degeneracy).

Electrophysiological Measures of Resting State Functional Connectivity and Their Relationship with Working Memory Capacity in Childhood

ERIC Educational Resources Information Center

Barnes, Jessica J.; Woolrich, Mark W.; Baker, Kate; Colclough, Giles L.; Astle, Duncan E.

2016-01-01

Functional connectivity is the statistical association of neuronal activity time courses across distinct brain regions, supporting specific cognitive processes. This coordination of activity is likely to be highly important for complex aspects of cognition, such as the communication of fluctuating task goals from higher-order control regions to…