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Sample records for abnormal functional connectivity

  1. Abnormal Functional Connectivity in Autism Spectrum Disorders during Face Processing

    ERIC Educational Resources Information Center

    Kleinhans, Natalia M.; Richards, Todd; Sterling, Lindsey; Stegbauer, Keith C.; Mahurin, Roderick; Johnson, L. Clark; Greenson, Jessica; Dawson, Geraldine; Aylward, Elizabeth

    2008-01-01

    Abnormalities in the interactions between functionally linked brain regions have been suggested to be associated with the clinical impairments observed in autism spectrum disorders (ASD). We investigated functional connectivity within the limbic system during face identification; a primary component of social cognition, in 19 high-functioning…

  2. Connectivity and functional profiling of abnormal brain structures in pedophilia

    PubMed Central

    Poeppl, Timm B.; Eickhoff, Simon B.; Fox, Peter T.; Laird, Angela R.; Rupprecht, Rainer; Langguth, Berthold; Bzdok, Danilo

    2015-01-01

    Despite its 0.5–1% lifetime prevalence in men and its general societal relevance, neuroimaging investigations in pedophilia are scarce. Preliminary findings indicate abnormal brain structure and function. However, no study has yet linked structural alterations in pedophiles to both connectional and functional properties of the aberrant hotspots. The relationship between morphological alterations and brain function in pedophilia as well as their contribution to its psychopathology thus remain unclear. First, we assessed bimodal connectivity of structurally altered candidate regions using meta-analytic connectivity modeling (MACM) and resting-state correlations employing openly accessible data. We compared the ensuing connectivity maps to the activation likelihood estimation (ALE) maps of a recent quantitative meta-analysis of brain activity during processing of sexual stimuli. Second, we functionally characterized the structurally altered regions employing meta-data of a large-scale neuroimaging database. Candidate regions were functionally connected to key areas for processing of sexual stimuli. Moreover, we found that the functional role of structurally altered brain regions in pedophilia relates to nonsexual emotional as well as neurocognitive and executive functions, previously reported to be impaired in pedophiles. Our results suggest that structural brain alterations affect neural networks for sexual processing by way of disrupted functional connectivity, which may entail abnormal sexual arousal patterns. The findings moreover indicate that structural alterations account for common affective and neurocognitive impairments in pedophilia. The present multi-modal integration of brain structure and function analyses links sexual and nonsexual psychopathology in pedophilia. PMID:25733379

  3. Connectivity and functional profiling of abnormal brain structures in pedophilia.

    PubMed

    Poeppl, Timm B; Eickhoff, Simon B; Fox, Peter T; Laird, Angela R; Rupprecht, Rainer; Langguth, Berthold; Bzdok, Danilo

    2015-06-01

    Despite its 0.5-1% lifetime prevalence in men and its general societal relevance, neuroimaging investigations in pedophilia are scarce. Preliminary findings indicate abnormal brain structure and function. However, no study has yet linked structural alterations in pedophiles to both connectional and functional properties of the aberrant hotspots. The relationship between morphological alterations and brain function in pedophilia as well as their contribution to its psychopathology thus remain unclear. First, we assessed bimodal connectivity of structurally altered candidate regions using meta-analytic connectivity modeling (MACM) and resting-state correlations employing openly accessible data. We compared the ensuing connectivity maps to the activation likelihood estimation (ALE) maps of a recent quantitative meta-analysis of brain activity during processing of sexual stimuli. Second, we functionally characterized the structurally altered regions employing meta-data of a large-scale neuroimaging database. Candidate regions were functionally connected to key areas for processing of sexual stimuli. Moreover, we found that the functional role of structurally altered brain regions in pedophilia relates to nonsexual emotional as well as neurocognitive and executive functions, previously reported to be impaired in pedophiles. Our results suggest that structural brain alterations affect neural networks for sexual processing by way of disrupted functional connectivity, which may entail abnormal sexual arousal patterns. The findings moreover indicate that structural alterations account for common affective and neurocognitive impairments in pedophilia. The present multimodal integration of brain structure and function analyses links sexual and nonsexual psychopathology in pedophilia. PMID:25733379

  4. Abnormal fronto-striatal functional connectivity in Parkinson's disease.

    PubMed

    Xu, Jinping; Zhang, Jiuquan; Wang, Jiaojian; Li, Guanglin; Hu, Qingmao; Zhang, Yuanchao

    2016-02-01

    Parkinson's disease (PD) is characterized by the relatively selective depletion of dopamine in the striatum, which consequently leads to dysfunctions in cortico-striatal-thalamic-cortical circuitries. It has been shown that the most common cognitive deficits in PD patients are related to the fronto-striatal circuits. In PD, most previous functional connectivity studies have been performed using seed-based methods to identify the brain regions that are abnormally connected to one or more seeds, but these cannot be used to quantify the interactions between one region and all other regions in a particular network. Functional connectivity degree, which is a measurement that can be used to quantify the functional or structural connectivity of a complex brain network, was adopted in this study to assess the interactions of the fronto-striatal network. Compared to healthy controls, PD patients had significantly decreased total functional connectivity degree for the left putamen and the right globus pallidum in fronto-striatal networks. Additionally, negative correlations between the fronto-pallial functional connectivity degree (i.e., the right globus pallidum with the left middle frontal gyrus, and with the right triangular part of inferior frontal gyrus) and disease duration were observed in PD patients. The results of this study demonstrate that fronto-striatal functional connectivity is abnormal in patients with PD and indicate that these deficits might be the result of motor and cognitive dysfunctions in PD patients. PMID:26724369

  5. Abnormal Functional Connectivity Density in Post-traumatic Stress Disorder.

    PubMed

    Zhang, Youxue; Xie, Bing; Chen, Heng; Li, Meiling; Liu, Feng; Chen, Huafu

    2016-05-01

    Post-traumatic stress disorder (PTSD) is a psychiatric disorder that occurs in individuals who have experienced life-threatening mental traumas. Previous neuroimaging studies have indicated that the pathology of PTSD may be associated with the abnormal functional integration among brain regions. In the current study, we used functional connectivity density (FCD) mapping, a novel voxel-wise data-driven approach based on graph theory, to explore aberrant FC through the resting-state functional magnetic resonance imaging of the PTSD. We calculated both short- and long-range FCD in PTSD patients and healthy controls (HCs). Compared with HCs, PTSD patients showed significantly increased long-range FCD in the left dorsolateral prefrontal cortex (DLPFC), but no abnormal short-range FCD was found in PTSD. Furthermore, seed-based FC analysis of the left DLPFC showed increased connectivity in the left superior parietal lobe and visual cortex of PTSD patients. The results suggested that PTSD patients experienced a disruption of intrinsic long-range functional connections in the fronto-parietal network and visual cortex, which are associated with attention control and visual information processing. PMID:26830769

  6. Abnormal functional connectivity during visuospatial processing is associated with disrupted organisation of white matter in autism

    PubMed Central

    McGrath, Jane; Johnson, Katherine; O'Hanlon, Erik; Garavan, Hugh; Leemans, Alexander; Gallagher, Louise

    2013-01-01

    Disruption of structural and functional neural connectivity has been widely reported in Autism Spectrum Disorder (ASD) but there is a striking lack of research attempting to integrate analysis of functional and structural connectivity in the same study population, an approach that may provide key insights into the specific neurobiological underpinnings of altered functional connectivity in autism. The aims of this study were (1) to determine whether functional connectivity abnormalities were associated with structural abnormalities of white matter (WM) in ASD and (2) to examine the relationships between aberrant neural connectivity and behavior in ASD. Twenty-two individuals with ASD and 22 age, IQ-matched controls completed a high-angular-resolution diffusion MRI scan. Structural connectivity was analysed using constrained spherical deconvolution (CSD) based tractography. Regions for tractography were generated from the results of a previous study, in which 10 pairs of brain regions showed abnormal functional connectivity during visuospatial processing in ASD. WM tracts directly connected 5 of the 10 region pairs that showed abnormal functional connectivity; linking a region in the left occipital lobe (left BA19) and five paired regions: left caudate head, left caudate body, left uncus, left thalamus, and left cuneus. Measures of WM microstructural organization were extracted from these tracts. Fractional anisotropy (FA) reductions in the ASD group relative to controls were significant for WM connecting left BA19 to left caudate head and left BA19 to left thalamus. Using a multimodal imaging approach, this study has revealed aberrant WM microstructure in tracts that directly connect brain regions that are abnormally functionally connected in ASD. These results provide novel evidence to suggest that structural brain pathology may contribute (1) to abnormal functional connectivity and (2) to atypical visuospatial processing in ASD. PMID:24133425

  7. Abnormal interhemispheric resting state functional connectivity of the insula in heroin users under methadone maintenance treatment.

    PubMed

    Wang, Peng-Wei; Lin, Huang-Chi; Liu, Gin-Chung; Yang, Yi-Hsin Connie; Ko, Chih-Hung; Yen, Cheng-Fang

    2016-09-30

    Abnormal interhemispheric functional connectivity is attracting more and more attention in the field of substance use. This study aimed to examine 1) the differences in interhemispheric functional connections of the insula with the contralateral insula and other brain regions between heroin users under methadone maintenance treatment (MMT) and healthy controls, and 2) the association between heroin users' interhemispheric insular functional connectivity using resting functional magnetic resonance imaging (fMRI) and the results of urine heroin analysis. Sixty male right-handed persons, including 30 with heroin dependence under MMT and 30 healthy controls, were recruited to this study. Resting fMRI experiments and urine heroin analysis were performed. Compared with the controls, the heroin users had a significantly lower interhemispheric insular functional connectivity. They also exhibited lower functional connectivity between insula and contralateral inferior orbital frontal lobe. After controlling for age, educational level and methadone dosage, less deviation of the interhemispheric insula functional connectivity was significantly associated with a lower risk of a positive urine heroin analysis result. Our findings demonstrated that the heroin users under MMT had abnormal long-range and interhemispheric resting functional connections. Those with a less dysfunctional interhemispheric insula functional connectivity had a lower risk of a positive urine heroin test. PMID:27497215

  8. Somatosensory cortex functional connectivity abnormalities in autism show opposite trends, depending on direction and spatial scale

    PubMed Central

    Khan, Sheraz; Michmizos, Konstantinos; Tommerdahl, Mark; Ganesan, Santosh; Kitzbichler, Manfred G.; Zetino, Manuel; Garel, Keri-Lee A.; Herbert, Martha R.; Hämäläinen, Matti S.

    2015-01-01

    Functional connectivity is abnormal in autism, but the nature of these abnormalities remains elusive. Different studies, mostly using functional magnetic resonance imaging, have found increased, decreased, or even mixed pattern functional connectivity abnormalities in autism, but no unifying framework has emerged to date. We measured functional connectivity in individuals with autism and in controls using magnetoencephalography, which allowed us to resolve both the directionality (feedforward versus feedback) and spatial scale (local or long-range) of functional connectivity. Specifically, we measured the cortical response and functional connectivity during a passive 25-Hz vibrotactile stimulation in the somatosensory cortex of 20 typically developing individuals and 15 individuals with autism, all males and right-handed, aged 8–18, and the mu-rhythm during resting state in a subset of these participants (12 per group, same age range). Two major significant group differences emerged in the response to the vibrotactile stimulus. First, the 50-Hz phase locking component of the cortical response, generated locally in the primary (S1) and secondary (S2) somatosensory cortex, was reduced in the autism group (P < 0.003, corrected). Second, feedforward functional connectivity between S1 and S2 was increased in the autism group (P < 0.004, corrected). During resting state, there was no group difference in the mu-α rhythm. In contrast, the mu-β rhythm, which has been associated with feedback connectivity, was significantly reduced in the autism group (P < 0.04, corrected). Furthermore, the strength of the mu-β was correlated to the relative strength of 50 Hz component of the response to the vibrotactile stimulus (r = 0.78, P < 0.00005), indicating a shared aetiology for these seemingly unrelated abnormalities. These magnetoencephalography-derived measures were correlated with two different behavioural sensory processing scores (P < 0.01 and P < 0.02 for the autism

  9. Abnormal striatal resting-state functional connectivity in adolescents with obsessive-compulsive disorder.

    PubMed

    Bernstein, Gail A; Mueller, Bryon A; Schreiner, Melinda Westlund; Campbell, Sarah M; Regan, Emily K; Nelson, Peter M; Houri, Alaa K; Lee, Susanne S; Zagoloff, Alexandra D; Lim, Kelvin O; Yacoub, Essa S; Cullen, Kathryn R

    2016-01-30

    Neuroimaging research has implicated abnormalities in cortico-striatal-thalamic-cortical (CSTC) circuitry in pediatric obsessive-compulsive disorder (OCD). In this study, resting-state functional magnetic resonance imaging (R-fMRI) was used to investigate functional connectivity in the CSTC circuitry in adolescents with OCD. Imaging was obtained with the Human Connectome Project (HCP) scanner using newly developed pulse sequences which allow for higher spatial and temporal resolution. Fifteen adolescents with OCD and 13 age- and gender-matched healthy controls (ages 12-19) underwent R-fMRI on the 3T HCP scanner. Twenty-four minutes of resting-state scans (two consecutive 12-min scans) were acquired. We investigated functional connectivity of the striatum using a seed-based, whole brain approach with anatomically-defined seeds placed in the bilateral caudate, putamen, and nucleus accumbens. Adolescents with OCD compared with controls exhibited significantly lower functional connectivity between the left putamen and a single cluster of right-sided cortical areas including parts of the orbitofrontal cortex, inferior frontal gyrus, insula, and operculum. Preliminary findings suggest that impaired striatal connectivity in adolescents with OCD in part falls within the predicted CSTC network, and also involves impaired connections between a key CSTC network region (i.e., putamen) and key regions in the salience network (i.e., insula/operculum). The relevance of impaired putamen-insula/operculum connectivity in OCD is discussed. PMID:26674413

  10. Resting state functional MRI reveals abnormal network connectivity in neurofibromatosis 1.

    PubMed

    Tomson, Steffie N; Schreiner, Matthew J; Narayan, Manjari; Rosser, Tena; Enrique, Nicole; Silva, Alcino J; Allen, Genevera I; Bookheimer, Susan Y; Bearden, Carrie E

    2015-11-01

    Neurofibromatosis type I (NF1) is a genetic disorder caused by mutations in the neurofibromin 1 gene at locus 17q11.2. Individuals with NF1 have an increased incidence of learning disabilities, attention deficits, and autism spectrum disorders. As a single-gene disorder, NF1 represents a valuable model for understanding gene-brain-behavior relationships. While mouse models have elucidated molecular and cellular mechanisms underlying learning deficits associated with this mutation, little is known about functional brain architecture in human subjects with NF1. To address this question, we used resting state functional connectivity magnetic resonance imaging (rs-fcMRI) to elucidate the intrinsic network structure of 30 NF1 participants compared with 30 healthy demographically matched controls during an eyes-open rs-fcMRI scan. Novel statistical methods were employed to quantify differences in local connectivity (edge strength) and modularity structure, in combination with traditional global graph theory applications. Our findings suggest that individuals with NF1 have reduced anterior-posterior connectivity, weaker bilateral edges, and altered modularity clustering relative to healthy controls. Further, edge strength and modular clustering indices were correlated with IQ and internalizing symptoms. These findings suggest that Ras signaling disruption may lead to abnormal functional brain connectivity; further investigation into the functional consequences of these alterations in both humans and in animal models is warranted. PMID:26304096

  11. Global functional connectivity abnormalities in children with Fetal Alcohol Spectrum Disorders (FASD)

    PubMed Central

    Wozniak, Jeffrey R.; Mueller, Bryon A.; Bell, Christopher J.; Muetzel, Ryan L.; Hoecker, Heather L.; Boys, Christopher J.; Lim, Kelvin O.

    2012-01-01

    Background Previous studies, including those employing Diffusion Tensor Imaging (DTI), have revealed significant disturbances in the white matter of individuals with Fetal Alcohol Spectrum Disorders (FASD). Both macrostructural and microstructural abnormalities have been observed across levels of FASD severity. Emerging evidence suggests that these white matter abnormalities are associated with functional deficits. This study used resting-state fMRI to evaluate the status of network functional connectivity in children with FASD compared to control subjects. Methods Participants included 24 children with FASD, ages 10–17, and 31 matched controls. Neurocognitive tests were administered including Wechsler Intelligence Scales, California Verbal Learning Test, and Behavior Rating Inventory of Executive Functioning. High resolution anatomical MRI data and six-minute resting-state fMRI data were collected. The resting-state fMRI data were subjected to a graph theory analysis and four global measures of cortical network connectivity were computed: characteristic path length, mean clustering coefficient, local efficiency, and global efficiency. Results Results revealed significantly altered network connectivity in those with FASD. The characteristic path length was 3.1% higher (p=.04, Cohen’s d=.47) and global efficiency was 1.9% lower (p=.04, d=.63) in children with FASD compared to controls, suggesting decreased network capacity that may have implications for integrative cognitive functioning. Global efficiency was significantly positively correlated with cortical thickness in frontal (r=.38, p=.005), temporal (r=.28, p=.043), and parietal (r=.36, p=.008) regions. No relationship between facial dysmorphology and functional connectivity was observed. Exploratory correlations suggested that global efficiency and characteristic path length are associated with capacity for immediate verbal memory on the CVLT (r=.41, p=.05 and r=.41, p=.01 respectively) among those with

  12. Abnormal prefrontal cortex resting state functional connectivity and severity of internet gaming disorder.

    PubMed

    Jin, Chenwang; Zhang, Ting; Cai, Chenxi; Bi, Yanzhi; Li, Yangding; Yu, Dahua; Zhang, Ming; Yuan, Kai

    2016-09-01

    Internet Gaming Disorder (IGD) among adolescents has become an important public concern and gained more and more attention internationally. Recent studies focused on IGD and revealed brain abnormalities in the IGD group, especially the prefrontal cortex (PFC). However, the role of PFC-striatal circuits in pathology of IGD remains unknown. Twenty-five adolescents with IGD and 21 age- and gender-matched healthy controls were recruited in our study. Voxel-based morphometric (VBM) and functional connectivity analysis were employed to investigate the abnormal structural and resting-state properties of several frontal regions in individuals with online gaming addiction. Relative to healthy comparison subjects, IGD subjects showed significant decreased gray matter volume in PFC regions including the bilateral dorsolateral prefrontal cortex (DLPFC), orbitofrontal cortex (OFC), anterior cingulate cortex (ACC) and the right supplementary motor area (SMA) after controlling for age and gender effects. We chose these regions as the seeding areas for the resting-state analysis and found that IGD subjects showed decreased functional connectivity between several cortical regions and our seeds, including the insula, and temporal and occipital cortices. Moreover, significant decreased functional connectivity between some important subcortical regions, i.e., dorsal striatum, pallidum, and thalamus, and our seeds were found in the IGD group and some of those changes were associated with the severity of IGD. Our results revealed the involvement of several PFC regions and related PFC-striatal circuits in the process of IGD and suggested IGD may share similar neural mechanisms with substance dependence at the circuit level. PMID:26311395

  13. Abnormal Functional Connectivity of Amygdala in Late-Onset Depression Was Associated with Cognitive Deficits

    PubMed Central

    Yue, Yingying; Yuan, Yonggui; Hou, Zhenghua; Jiang, Wenhao; Bai, Feng; Zhang, Zhijun

    2013-01-01

    Background Major depressive disorder (MDD) is associated with decreased function of cortico-limbic circuits, which play important roles in the pathogenesis of MDD. Abnormal functional connectivity (FC) with the amygdala, which is involved in cortico-limbic circuits, has also been observed in MDD. However, little is known about connectivity alterations in late-onset depression (LOD) or whether disrupted connectivity is correlated with cognitive impairment in LOD. Methods and Results A total of twenty-two LOD patients and twenty-two matched healthy controls (HC) underwent neuropsychological tests and resting state functional magnetic resonance imaging (rs-fMRI). Regional homogeneity (ReHo) and FC with bilateral amygdala seeds were used to analyze blood oxygen level-dependent fMRI data between two groups. Compared with HC, LOD patients showed decreased ReHo in the right middle frontal gyrus and left superior frontal gyrus. In the LOD group, the left amygdala had decreased FC with the right middle frontal gyrus and the left superior frontal gyrus in the amygdala positive network, and it had increased FC with the right post-central gyrus in the amygdala negative network. However, significantly reduced FC with the right amygdala was observed in the right middle occipital gyrus in the amygdala negative network. Further correlative analyses revealed that decreased FC between the amygdala and the right middle occipital gyrus was negatively correlated with the verbal fluency test (VFT, r = −0.485, P = 0.022) and the digit span test (DST, r = −0.561, P = 0.007). Conclusions Our findings of reduced activity of the prefrontal gyrus and abnormal FC with the bilateral amygdala may be key markers of cognitive dysfunction in LOD patients. PMID:24040385

  14. Abnormal functional global and local brain connectivity in female patients with anorexia nervosa

    PubMed Central

    Geisler, Daniel; Borchardt, Viola; Lord, Anton R.; Boehm, Ilka; Ritschel, Franziska; Zwipp, Johannes; Clas, Sabine; King, Joseph A.; Wolff-Stephan, Silvia; Roessner, Veit; Walter, Martin; Ehrlich, Stefan

    2016-01-01

    Background Previous resting-state functional connectivity studies in patients with anorexia nervosa used independent component analysis or seed-based connectivity analysis to probe specific brain networks. Instead, modelling the entire brain as a complex network allows determination of graph-theoretical metrics, which describe global and local properties of how brain networks are organized and how they interact. Methods To determine differences in network properties between female patients with acute anorexia nervosa and pairwise matched healthy controls, we used resting-state fMRI and computed well-established global and local graph metrics across a range of network densities. Results Our analyses included 35 patients and 35 controls. We found that the global functional network structure in patients with anorexia nervosa is characterized by increases in both characteristic path length (longer average routes between nodes) and assortativity (more nodes with a similar connectedness link together). Accordingly, we found locally decreased connectivity strength and increased path length in the posterior insula and thalamus. Limitations The present results may be limited to the methods applied during preprocessing and network construction. Conclusion We demonstrated anorexia nervosa–related changes in the network configuration for, to our knowledge, the first time using resting-state fMRI and graph-theoretical measures. Our findings revealed an altered global brain network architecture accompanied by local degradations indicating wide-scale disturbance in information flow across brain networks in patients with acute anorexia nervosa. Reduced local network efficiency in the thalamus and posterior insula may reflect a mechanism that helps explain the impaired integration of visuospatial and homeostatic signals in patients with this disorder, which is thought to be linked to abnormal representations of body size and hunger. PMID:26252451

  15. Abnormal resting-state functional connectivity of the nucleus accumbens in multi-year abstinent heroin addicts.

    PubMed

    Zou, Feng; Wu, Xinhuai; Zhai, Tianye; Lei, Yu; Shao, Yongcong; Jin, Xiao; Tan, Shuwen; Wu, Bing; Wang, Lubin; Yang, Zheng

    2015-11-01

    Functional neuroimaging studies suggest that abnormal brain functional connectivity may be the neural underpinning of addiction to illicit drugs and of relapse after successful cessation therapy. Aberrant brain networks have been demonstrated in addicted patients and in newly abstinent addicts. However, it is not known whether abnormal brain connectivity patterns persist after prolonged abstinence. In this cross-sectional study, whole-brain resting-state functional magnetic resonance images (8 min) were collected from 30 heroin-addicted individuals after a long period of abstinence (more than 3 years) and from 30 healthy controls. We first examined the group differences in the resting-state functional connectivity of the nucleus accumbens (NAc), a brain region implicated in relapse-related processes, including craving and reactivity to stress following acute and protracted withdrawal from heroin. We then examined the relation between the duration of abstinence and the altered NAc functional connectivity in the heroin group. We found that, compared with controls, heroin-dependent participants exhibited significantly greater functional connectivity between the right ventromedial prefrontal cortex and the NAc and weaker functional connectivity between the NAc and the left putamen, left precuneus, and supplementary motor area. However, with longer abstinence time, the strength of NAc functional connectivity with the left putamen increased. These results indicate that dysfunction of the NAc functional network is still present in long-term-abstinent heroin-dependent individuals. PMID:26280556

  16. Gray Matter Abnormalities in Temporal Lobe Epilepsy: Relationships with Resting-State Functional Connectivity and Episodic Memory Performance

    PubMed Central

    Doucet, Gaelle E.; He, Xiaosong; Sperling, Michael; Sharan, Ashwini; Tracy, Joseph I.

    2016-01-01

    Temporal lobe epilepsy (TLE) affects multiple brain regions through evidence from both structural (gray matter; GM) and functional connectivity (FC) studies. We tested whether these structural abnormalities were associated with FC abnormalities, and assessed the ability of these measures to explain episodic memory impairments in this population. A resting-state and T1 sequences were acquired on 94 (45 with mesial temporal pathology) TLE patients and 50 controls, using magnetic resonance imaging (MRI) technique. A voxel-based morphometry analysis was computed to determine the GM volume differences between groups (right, left TLE, controls). Resting-state FC between the abnormal GM volume regions was computed, and compared between groups. Finally, we investigated the relation between EM, GM and FC findings. Patients with and without temporal pathology were analyzed separately. The results revealed reduced GM volume in multiple regions in the patients relative to the controls. Using FC, we found the abnormal GM regions did not display abnormal functional connectivity. Lastly, we found in left TLE patients, verbal episodic memory was associated with abnormal left posterior hippocampus volume, while in right TLE, non-verbal episodic memory was better predicted by resting-state FC measures. This study investigated TLE abnormalities using a multi-modal approach combining GM, FC and neurocognitive measures. We did not find that the GM abnormalities were functionally or abnormally connected during an inter-ictal resting state, which may reflect a weak sensitivity of functional connectivity to the epileptic network. We provided evidence that verbal and non-verbal episodic memory in left and right TLE patients may have distinct relationships with structural and functional measures. Lastly, we provide data suggesting that in the setting of occult, non-lesional right TLE pathology, a coupling of structural and functional abnormalities in extra-temporal/non-ictal regions is

  17. Gray Matter Abnormalities in Temporal Lobe Epilepsy: Relationships with Resting-State Functional Connectivity and Episodic Memory Performance.

    PubMed

    Doucet, Gaelle E; He, Xiaosong; Sperling, Michael; Sharan, Ashwini; Tracy, Joseph I

    2016-01-01

    Temporal lobe epilepsy (TLE) affects multiple brain regions through evidence from both structural (gray matter; GM) and functional connectivity (FC) studies. We tested whether these structural abnormalities were associated with FC abnormalities, and assessed the ability of these measures to explain episodic memory impairments in this population. A resting-state and T1 sequences were acquired on 94 (45 with mesial temporal pathology) TLE patients and 50 controls, using magnetic resonance imaging (MRI) technique. A voxel-based morphometry analysis was computed to determine the GM volume differences between groups (right, left TLE, controls). Resting-state FC between the abnormal GM volume regions was computed, and compared between groups. Finally, we investigated the relation between EM, GM and FC findings. Patients with and without temporal pathology were analyzed separately. The results revealed reduced GM volume in multiple regions in the patients relative to the controls. Using FC, we found the abnormal GM regions did not display abnormal functional connectivity. Lastly, we found in left TLE patients, verbal episodic memory was associated with abnormal left posterior hippocampus volume, while in right TLE, non-verbal episodic memory was better predicted by resting-state FC measures. This study investigated TLE abnormalities using a multi-modal approach combining GM, FC and neurocognitive measures. We did not find that the GM abnormalities were functionally or abnormally connected during an inter-ictal resting state, which may reflect a weak sensitivity of functional connectivity to the epileptic network. We provided evidence that verbal and non-verbal episodic memory in left and right TLE patients may have distinct relationships with structural and functional measures. Lastly, we provide data suggesting that in the setting of occult, non-lesional right TLE pathology, a coupling of structural and functional abnormalities in extra-temporal/non-ictal regions is

  18. Abnormal resting-state functional connectivity of the left caudate nucleus in obsessive-compulsive disorder.

    PubMed

    Chen, Yunhui; Juhás, Michal; Greenshaw, Andrew J; Hu, Qiang; Meng, Xin; Cui, Hongsheng; Ding, Yongzhuo; Kang, Lu; Zhang, Yubo; Wang, Yuhua; Cui, Guangcheng; Li, Ping

    2016-06-01

    Altered brain activities in the cortico-striato-thalamocortical (CSTC) circuitry are implicated in the pathophysiology of obsessive-compulsive disorder (OCD). However, whether the underlying changes occur only within this circuitry or in large-scale networks is still not thoroughly understood. This study performed voxel-based functional connectivity analysis on resting-state functional magnetic resonance imaging (fMRI) data from thirty OCD patients and thirty healthy controls to investigate whole-brain intrinsic functional connectivity patterns in OCD. Relative to the healthy controls, OCD patients showed decreased functional connectivity within the CSTC circuitry but increased functional connectivity in other brain regions. Furthermore, decreased left caudate nucleus-thalamus connectivity within the CSTC circuitry was positively correlated with the illness duration of OCD. This study provides additional evidence that CSTC circuitry may play an essential role and alteration of large-scale brain networks may be involved in the pathophysiology of OCD. PMID:27143323

  19. Abnormal Functional Connectivity in Children with Attention-Deficit/Hyperactivity Disorder

    PubMed Central

    Tomasi, Dardo; Volkow, Nora D.

    2012-01-01

    Background Attention-deficit/hyperactivity disorder (ADHD) is typically characterized by symptoms of inattention and hyperactivity/impulsivity, but there is increased recognition of a motivation deficit too. This neuropathology may reflect dysfunction of both attention and reward-motivation networks. Methods To test this hypothesis, we compared the functional connectivity density between 247 ADHD and 304 typically developing control children from a public magnetic resonance imaging database. We quantified short- and long-range functional connectivity density in the brain using an ultrafast data-driven approach. Results Children with ADHD had lower connectivity (short- and long-range) in regions of the dorsal attention (superior parietal cortex) and default-mode (precuneus) networks and in cerebellum and higher connectivity (short-range) in reward-motivation regions (ventral striatum and orbitofrontal cortex) than control subjects. In ADHD children, the orbitofrontal cortex (region involved in salience attribution) had higher connectivity with reward-motivation regions (striatum and anterior cingulate) and lower connectivity with superior parietal cortex (region involved in attention processing). Conclusions The enhanced connectivity within reward-motivation regions and their decreased connectivity with regions from the default-mode and dorsal attention networks suggest impaired interactions between control and reward pathways in ADHD that might underlie attention and motivation deficits in ADHD. PMID:22153589

  20. Post mTBI fatigue is associated with abnormal brain functional connectivity

    PubMed Central

    Nordin, Love Engström; Möller, Marika Christina; Julin, Per; Bartfai, Aniko; Hashim, Farouk; Li, Tie-Qiang

    2016-01-01

    This study set out to investigate the behavioral correlates of changes in resting-state functional connectivity before and after performing a 20 minute continuous psychomotor vigilance task (PVT) for patients with chronic post-concussion syndrome. Ten patients in chronic phase after mild traumatic brain injury (mTBI) with persisting symptoms of fatigue and ten matched healthy controls participated in the study. We assessed the participants’ fatigue levels and conducted resting-state fMRI before and after a sustained PVT. We evaluated the changes in brain functional connectivity indices in relation to the subject’s fatigue behavior using a quantitative data-driven analysis approach. We found that the PVT invoked significant mental fatigue and specific functional connectivity changes in mTBI patients. Furthermore, we found a significant linear correlation between self-reported fatigue and functional connectivity in the thalamus and middle frontal cortex. Our findings indicate that resting-state fMRI measurements may be a useful indicator of performance potential and a marker of fatigue level in the neural attentional system. PMID:26878885

  1. Post mTBI fatigue is associated with abnormal brain functional connectivity.

    PubMed

    Nordin, Love Engström; Möller, Marika Christina; Julin, Per; Bartfai, Aniko; Hashim, Farouk; Li, Tie-Qiang

    2016-01-01

    This study set out to investigate the behavioral correlates of changes in resting-state functional connectivity before and after performing a 20 minute continuous psychomotor vigilance task (PVT) for patients with chronic post-concussion syndrome. Ten patients in chronic phase after mild traumatic brain injury (mTBI) with persisting symptoms of fatigue and ten matched healthy controls participated in the study. We assessed the participants' fatigue levels and conducted resting-state fMRI before and after a sustained PVT. We evaluated the changes in brain functional connectivity indices in relation to the subject's fatigue behavior using a quantitative data-driven analysis approach. We found that the PVT invoked significant mental fatigue and specific functional connectivity changes in mTBI patients. Furthermore, we found a significant linear correlation between self-reported fatigue and functional connectivity in the thalamus and middle frontal cortex. Our findings indicate that resting-state fMRI measurements may be a useful indicator of performance potential and a marker of fatigue level in the neural attentional system. PMID:26878885

  2. Abnormal gray matter volume and resting-state functional connectivity in former heroin-dependent individuals abstinent for multiple years.

    PubMed

    Wang, Lubin; Zou, Feng; Zhai, Tianye; Lei, Yu; Tan, Shuwen; Jin, Xiao; Ye, Enmao; Shao, Yongcong; Yang, Yihong; Yang, Zheng

    2016-05-01

    Previous studies have suggested that heroin addiction is associated with structural and functional brain abnormalities. However, it is largely unknown whether these characteristics of brain abnormalities would be persistent or restored after long periods of abstinence. Considering the very high rates of relapse, we hypothesized that there may exist some latent neural vulnerabilities in abstinent heroin users. In this study, structural and resting-state functional magnetic resonance imaging data were collected from 30 former heroin-dependent (FHD) subjects who were drug free for more than 3 years and 30 non-addicted control (CN) volunteers. Voxel-based morphometry was used to identify possible gray matter volume differences between the FHD and CN groups. Alterations in resting-state functional connectivity in FHD were examined using brain areas with gray matter deficits as seed regions. Significantly reduced gray matter volume was observed in FHD in an area surrounding the parieto-occipital sulcus, which included the precuneus and cuneus. Functional connectivity analyses revealed that the FHD subjects showed reduced positive correlation within the default mode network and visual network and decreased negative correlation between the default mode network, visual network and task positive network. Moreover, the altered functional connectivity was correlated with self-reported impulsivity scores in the FHD subjects. Our findings suggest that disruption of large-scale brain systems is present in former heroin users even after multi-year abstinence, which could serve as system-level neural underpinnings for behavioral dysfunctions associated with addiction. PMID:25727574

  3. Resting state functional MRI reveals abnormal network connectivity in orthostatic tremor.

    PubMed

    Benito-León, Julián; Louis, Elan D; Manzanedo, Eva; Hernández-Tamames, Juan Antonio; Álvarez-Linera, Juan; Molina-Arjona, José Antonio; Matarazzo, Michele; Romero, Juan Pablo; Domínguez-González, Cristina; Domingo-Santos, Ángela; Sánchez-Ferro, Álvaro

    2016-07-01

    Very little is known about the pathogenesis of orthostatic tremor (OT). We have observed that OT patients might have deficits in specific aspects of neuropsychological function, particularly those thought to rely on the integrity of the prefrontal cortex, which suggests a possible involvement of frontocerebellar circuits. We examined whether resting-state functional magnetic resonance imaging (fMRI) might provide further insights into the pathogenesis on OT. Resting-state fMRI data in 13 OT patients (11 women and 2 men) and 13 matched healthy controls were analyzed using independent component analysis, in combination with a "dual-regression" technique, to identify group differences in several resting-state networks (RSNs). All participants also underwent neuropsychological testing during the same session. Relative to healthy controls, OT patients showed increased connectivity in RSNs involved in cognitive processes (default mode network [DMN] and frontoparietal networks), and decreased connectivity in the cerebellum and sensorimotor networks. Changes in network integrity were associated not only with duration (DMN and medial visual network), but also with cognitive function. Moreover, in at least 2 networks (DMN and medial visual network), increased connectivity was associated with worse performance on different cognitive domains (attention, executive function, visuospatial ability, visual memory, and language). In this exploratory study, we observed selective impairments of RSNs in OT patients. This and other future resting-state fMRI studies might provide a novel method to understand the pathophysiological mechanisms of motor and nonmotor features of OT. PMID:27442678

  4. Abnormal functional connectivity density in patients with ischemic white matter lesions: An observational study.

    PubMed

    Ding, Ju-Rong; Ding, Xin; Hua, Bo; Xiong, Xingzhong; Wang, Qingsong; Chen, Huafu

    2016-09-01

    White matter lesions (WMLs) are frequently detected in elderly people. Previous structural and functional studies have demonstrated that WMLs are associated with cognitive and motor decline. However, the underlying mechanism of how WMLs lead to cognitive decline and motor disturbance remains unclear. We used functional connectivity density mapping (FCDM) to investigate changes in brain functional connectivity in 16 patients with ischemic WMLs and 13 controls. Both short- and long-range FCD maps were computed, and group comparisons were performed between the 2 groups. A correlation analysis was further performed between regions with altered FCD and cognitive test scores (Mini-Mental State Examination [MMSE] and Montreal Cognitive Assessment [MoCA]) in the patient group. We found that patients with ischemic WMLs showed reduced short-range FCD in the temporal cortex, primary motor cortex, and subcortical region, which may account for inadequate top-down attention, impaired motor, memory, and executive function associated with WMLs. The positive correlation between primary motor cortex and MoCA scores may provide evidence for the influences of cognitive function on behavioral performance. The inferior parietal cortex exhibited increased short-range FCD, reflecting a hyper bottom-up attention to compensate for the inadequate top-down attention for language comprehension and information retrieval in patients with WMLs. Moreover, the prefrontal and primary motor cortex showed increased long-range FCD and the former positively correlated with MoCA scores, which may suggest a strategy of cortical functional reorganization to compensate for motor and executive deficits. Our findings provide new insights into how WMLs cause cognitive and motor decline from cortical functional connectivity perspective. PMID:27603353

  5. Abnormal EEG Complexity and Functional Connectivity of Brain in Patients with Acute Thalamic Ischemic Stroke

    PubMed Central

    Liu, Shuang; Guo, Jie; Meng, Jiayuan; Wang, Zhijun; Yao, Yang; Yang, Jiajia; Qi, Hongzhi; Ming, Dong

    2016-01-01

    Ischemic thalamus stroke has become a serious cardiovascular and cerebral disease in recent years. To date the existing researches mostly concentrated on the power spectral density (PSD) in several frequency bands. In this paper, we investigated the nonlinear features of EEG and brain functional connectivity in patients with acute thalamic ischemic stroke and healthy subjects. Electroencephalography (EEG) in resting condition with eyes closed was recorded for 12 stroke patients and 11 healthy subjects as control group. Lempel-Ziv complexity (LZC), Sample Entropy (SampEn), and brain network using partial directed coherence (PDC) were calculated for feature extraction. Results showed that patients had increased mean LZC and SampEn than the controls, which implied the stroke group has higher EEG complexity. For the brain network, the stroke group displayed a trend of weaker cortical connectivity, which suggests a functional impairment of information transmission in cortical connections in stroke patients. These findings suggest that nonlinear analysis and brain network could provide essential information for better understanding the brain dysfunction in the stroke and assisting monitoring or prognostication of stroke evolution. PMID:27403202

  6. Abnormal interhemispheric connectivity in male psychopathic offenders

    PubMed Central

    Hoppenbrouwers, Sylco S.; De Jesus, Danilo R.; Sun, Yinming; Stirpe, Tania; Hofman, Dennis; McMaster, Jeff; Hughes, Ginny; Daskalakis, Zafiris J.; Schutter, Dennis J.L.G.

    2014-01-01

    Background Psychopathic offenders inevitably violate interpersonal norms and frequently resort to aggressive and criminal behaviour. The affective and cognitive deficits underlying these behaviours have been linked to abnormalities in functional interhemispheric connectivity. However, direct neurophysiological evidence for dysfunctional connectivity in psychopathic offenders is lacking. Methods We used transcranial magnetic stimulation combined with electroencephalography to examine interhemispheric connectivity in the dorsolateral and motor cortex in a sample of psychopathic offenders and healthy controls. We also measured intracortical inhibition and facilitation over the left and right motor cortex to investigate the effects of local cortical processes on interhemispheric connectivity. Results We enrolled 17 psychopathic offenders and 14 controls in our study. Global abnormalities in right to left functional connectivity were observed in psychopathic offenders compared with controls. Furthermore, in contrast to controls, psychopathic offenders showed increased intracortical inhibition in the right, but not the left, hemisphere. Limitations The relatively small sample size limited the sensitivity to show that the abnormalities in interhemispheric connectivity were specifically related to the dorsolateral prefrontal cortex in psychopathic offenders. Conclusion To our knowledge, this study provides the first neurophysiological evidence for abnormal interhemispheric connectivity in psychopathic offenders and may further our understanding of the disruptive antisocial behaviour of these offenders. PMID:23937798

  7. Abnormal functional connectivity of default mode sub-networks in autism spectrum disorder patients.

    PubMed

    Assaf, Michal; Jagannathan, Kanchana; Calhoun, Vince D; Miller, Laura; Stevens, Michael C; Sahl, Robert; O'Boyle, Jacqueline G; Schultz, Robert T; Pearlson, Godfrey D

    2010-10-15

    Autism spectrum disorders (ASDs) are characterized by deficits in social and communication processes. Recent data suggest that altered functional connectivity (FC), i.e. synchronous brain activity, might contribute to these deficits. Of specific interest is the FC integrity of the default mode network (DMN), a network active during passive resting states and cognitive processes related to social deficits seen in ASD, e.g. Theory of Mind. We investigated the role of altered FC of default mode sub-networks (DM-SNs) in 16 patients with high-functioning ASD compared to 16 matched healthy controls of short resting fMRI scans using independent component analysis (ICA). ICA is a multivariate data-driven approach that identifies temporally coherent networks, providing a natural measure of FC. Results show that compared to controls, patients showed decreased FC between the precuneus and medial prefrontal cortex/anterior cingulate cortex, DMN core areas, and other DM-SNs areas. FC magnitude in these regions inversely correlated with the severity of patients' social and communication deficits as measured by the Autism Diagnostic Observational Schedule and the Social Responsiveness Scale. Importantly, supplemental analyses suggest that these results were independent of treatment status. These results support the hypothesis that DM-SNs under-connectivity contributes to the core deficits seen in ASD. Moreover, these data provide further support for the use of data-driven analysis with resting-state data for illuminating neural systems that differ between groups. This approach seems especially well suited for populations where compliance with and performance of active tasks might be a challenge, as it requires minimal cooperation. PMID:20621638

  8. Abnormal functional connectivity of default mode sub-networks in autism spectrum disorder patients

    PubMed Central

    Assaf, Michal; Jagannathan, Kanchana; Calhoun, Vince D.; Miller, Laura; Stevens, Michael C.; Sahl, Robert; O'Boyle, Jacqueline G.; Schultz, Robert T.; Pearlson, Godfrey D.

    2011-01-01

    Autism spectrum disorders (ASDs) are characterized by deficits in social and communication processes. Recent data suggest that altered functional connectivity (FC), i.e. synchronous brain activity, might contribute to these deficits. Of specific interest is the FC integrity of the default mode network (DMN), a network active during passive resting states and cognitive processes related to social deficits seen in ASD, e.g. Theory of Mind. We investigated the role of altered FC of default mode sub-networks (DM-SNs) in 16 patients with high-functioning ASD compared to 16 matched healthy controls of short resting fMRI scans using independent component analysis (ICA). ICA is a multivariate data-driven approach that identifies temporally coherent networks, providing a natural measure of FC. Results show that compared to controls, patients showed decreased FC between the precuneus and medial prefrontal cortex/anterior cingulate cortex, DMN core areas, and other DM-SNs areas. FC magnitude in these regions inversely correlated with the severity of patients' social and communication deficits as measured by the Autism Diagnostic Observational Schedule and the Social Responsiveness Scale. Importantly, supplemental analyses suggest that these results were independent of treatment status. These results support the hypothesis that DM-SNs under-connectivity contributes to the core deficits seen in ASD. Moreover, these data provide further support for the use of data-driven analysis with resting-state data for illuminating neural systems that differ between groups. This approach seems especially well suited for populations where compliance with and performance of active tasks might be a challenge, as it requires minimal cooperation. PMID:20621638

  9. Abnormal Resting-State Functional Connectivity in Patients with Chronic Fatigue Syndrome: Results of Seed and Data-Driven Analyses.

    PubMed

    Gay, Charles W; Robinson, Michael E; Lai, Song; O'Shea, Andrew; Craggs, Jason G; Price, Donald D; Staud, Roland

    2016-02-01

    Although altered resting-state functional connectivity (FC) is a characteristic of many chronic pain conditions, it has not yet been evaluated in patients with chronic fatigue. Our objective was to investigate the association between fatigue and altered resting-state FC in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Thirty-six female subjects, 19 ME/CFS and 17 healthy controls, completed a fatigue inventory before undergoing functional magnetic resonance imaging. Two methods, (1) data driven and (2) model based, were used to estimate and compare the intraregional FC between both groups during the resting state (RS). The first approach using independent component analysis was applied to investigate five RS networks: the default mode network, salience network (SN), left frontoparietal networks (LFPN) and right frontoparietal networks, and the sensory motor network (SMN). The second approach used a priori selected seed regions demonstrating abnormal regional cerebral blood flow (rCBF) in ME/CFS patients at rest. In ME/CFS patients, Method-1 identified decreased intrinsic connectivity among regions within the LFPN. Furthermore, the FC of the left anterior midcingulate with the SMN and the connectivity of the left posterior cingulate cortex with the SN were significantly decreased. For Method-2, five distinct clusters within the right parahippocampus and occipital lobes, demonstrating significant rCBF reductions in ME/CFS patients, were used as seeds. The parahippocampal seed and three occipital lobe seeds showed altered FC with other brain regions. The degree of abnormal connectivity correlated with the level of self-reported fatigue. Our results confirm altered RS FC in patients with ME/CFS, which was significantly correlated with the severity of their chronic fatigue. PMID:26449441

  10. Abnormal resting-state functional connectivity within the default mode network subregions in male patients with obstructive sleep apnea

    PubMed Central

    Li, Hai-Jun; Nie, Xiao; Gong, Hong-Han; Zhang, Wei; Nie, Si; Peng, De-Chang

    2016-01-01

    Background and objective Abnormal resting-state functional connectivity (rs-FC) between the central executive network and the default mode network (DMN) in patients with obstructive sleep apnea (OSA) has been reported. However, the effect of OSA on rs-FC within the DMN subregions remains uncertain. This study was designed to investigate whether the rs-FC within the DMN subregions was disrupted and determine its relationship with clinical symptoms in patients with OSA. Methods Forty male patients newly diagnosed with severe OSA and 40 male education- and age-matched good sleepers (GSs) underwent functional magnetic resonance imaging (fMRI) examinations and clinical and neuropsychologic assessments. Seed-based region of interest rs-FC method was used to analyze the connectivity between each pair of subregions within the DMN, including the medial prefrontal cortex (MPFC), posterior cingulate cortex (PCC), hippocampus formation (HF), inferior parietal cortices (IPC), and medial temporal lobe (MTL). The abnormal rs-FC strength within the DMN subregions was correlated with clinical and neuropsychologic assessments using Pearson correlation analysis in patients with OSA. Results Compared with GSs, patients with OSA had significantly decreased rs-FC between the right HF and the PCC, MPFC, and left MTL. However, patients with OSA had significantly increased rs-FC between the MPFC and left and right IPC, and between the left IPC and right IPC. The rs-FC between the right HF and left MTL was positively correlated with rapid eye movement (r=0.335, P=0.035). The rs-FC between the PCC and right HF was negatively correlated with delayed memory (r=-0.338, P=0.033). Conclusion OSA selectively impairs the rs-FC between right HF and PCC, MPFC, and left MTL within the DMN subregions, and provides an imaging indicator for assessment of cognitive dysfunction in OSA patients. PMID:26855576

  11. Abnormal Resting-State Functional Connectivity Strength in Mild Cognitive Impairment and Its Conversion to Alzheimer's Disease

    PubMed Central

    Li, Yuxia; Wang, Xiaoni; Li, Yongqiu; Sun, Yu; Sheng, Can; Li, Hongyan; Li, Xuanyu; Yu, Yang; Chen, Guanqun; Hu, Xiaochen; Jing, Bin; Wang, Defeng; Li, Kuncheng; Jessen, Frank; Han, Ying

    2016-01-01

    Individuals diagnosed with mild cognitive impairment (MCI) are at high risk of transition to Alzheimer's disease (AD). However, little is known about functional characteristics of the conversion from MCI to AD. Resting-state functional magnetic resonance imaging was performed in 25 AD patients, 31 MCI patients, and 42 well-matched normal controls at baseline. Twenty-one of the 31 MCI patients converted to AD at approximately 24 months of follow-up. Functional connectivity strength (FCS) and seed-based functional connectivity analyses were used to assess the functional differences among the groups. Compared to controls, subjects with MCI and AD showed decreased FCS in the default-mode network and the occipital cortex. Importantly, the FCS of the left angular gyrus and middle occipital gyrus was significantly lower in MCI-converters as compared with MCI-nonconverters. Significantly decreased functional connectivity was found in MCI-converters compared to nonconverters between the left angular gyrus and bilateral inferior parietal lobules, dorsolateral prefrontal and lateral temporal cortices, and the left middle occipital gyrus and right middle occipital gyri. We demonstrated gradual but progressive functional changes during a median 2-year interval in patients converting from MCI to AD, which might serve as early indicators for the dysfunction and progression in the early stage of AD. PMID:26843991

  12. Cocaine addiction related reproducible brain regions of abnormal default-mode network functional connectivity: a group ICA study with different model orders.

    PubMed

    Ding, Xiaoyu; Lee, Seong-Whan

    2013-08-26

    Model order selection in group independent component analysis (ICA) has a significant effect on the obtained components. This study investigated the reproducible brain regions of abnormal default-mode network (DMN) functional connectivity related with cocaine addiction through different model order settings in group ICA. Resting-state fMRI data from 24 cocaine addicts and 24 healthy controls were temporally concatenated and processed by group ICA using model orders of 10, 20, 30, 40, and 50, respectively. For each model order, the group ICA approach was repeated 100 times using the ICASSO toolbox and after clustering the obtained components, centrotype-based anterior and posterior DMN components were selected for further analysis. Individual DMN components were obtained through back-reconstruction and converted to z-score maps. A whole brain mixed effects factorial ANOVA was performed to explore the differences in resting-state DMN functional connectivity between cocaine addicts and healthy controls. The hippocampus, which showed decreased functional connectivity in cocaine addicts for all the tested model orders, might be considered as a reproducible abnormal region in DMN associated with cocaine addiction. This finding suggests that using group ICA to examine the functional connectivity of the hippocampus in the resting-state DMN may provide an additional insight potentially relevant for cocaine-related diagnoses and treatments. PMID:23707901

  13. Abnormal functional connectivity density in first-episode, drug-naive adult patients with major depressive disorder.

    PubMed

    Zou, Ke; Gao, Qing; Long, Zhiliang; Xu, Fei; Sun, Xiao; Chen, Huafu; Sun, Xueli

    2016-04-01

    Previous studies have found evidence of brain functional connectivity (FC) changes with pre-selected region-of-interest (ROI) method in major depressive disorder (MDD). However, these studies could not completely exclude personal inequality when drawing ROIs manually and did not measure the total number of FC for each voxel. Here, we firstly applied functional connectivity density (FCD) mapping, a voxel-based analysis to locate the hubs with amount changes of FC between 22 first-episode, drug-naive adult MDD patients and 22 healthy control (HC) subjects. Both short-range (local) FCD and long-range (distal) FCD were measured. The relationships of FCD changes with Hamilton Depression Rating Scale (HAMD) scores and illness duration were also explored. Compared with the HC group, MDD patients showed significantly decreased short-range FCD in the left superior temporal gyrus (STG), the right orbital frontal cortex (OFC) and bilateral precuneus, while significantly decreased long-range FCD was found in bilateral middle occipital gyrus (MOG), superior occipital gyrus (SOG) and right calcarine. These results firstly demonstrated both local and distal alterations of connection amount at voxel level, and highlighted that the OFC, the precuneus, the STG and the visual cortex were important brain network hubs for first-episode, drug-naive adult MDD patients. Our findings were complementary for previous structural and functional studies in MDD patients, and provided new evidence of the dysfunction of connection hubs in the pathophysiology of MDD at voxel level. PMID:26826535

  14. Abnormal Functional Connectivity of the Amygdala-Based Network in Resting-State fMRI in Adolescents with Generalized Anxiety Disorder

    PubMed Central

    Liu, Wen-jing; Yin, Da-zhi; Cheng, Wen-hong; Fan, Ming-xia; You, Mei-na; Men, Wei-wei; Zang, Li-li; Shi, Dian-hong; Zhang, Fang

    2015-01-01

    Background We aimed to investigate the disruptions of functional connectivity of amygdala-based networks in adolescents with untreated generalized anxiety disorder (GAD). Material/Methods A total of 26 adolescents with first-episode GAD and 20 normal age-matched volunteers underwent resting-state and T1 functional magnetic resonance imaging (fMRI). We analyzed the correlation of fMRI signal fluctuation between the amygdala and other brain regions. The variation of amygdala-based functional connectivity and its correlation with anxiety severity were investigated. Results Decreased functional connectivity was found between the left amygdala and left dorsolateral prefrontal cortex. An increased right amygdala functional connectivity with right posterior and anterior lobes of the cerebellum, insula, superior temporal gyrus, putamen, and right amygdala were found in our study. Negative correlations between GAD scores and functional connectivity of the right amygdala with the cerebellum were also observed in the GAD adolescents. Conclusions Adolescents with GAD have abnormalities in brain regions associated with the emotional processing pathways. PMID:25673008

  15. Improvement of white matter and functional connectivity abnormalities by repetitive transcranial magnetic stimulation in crossed aphasia in dextral

    PubMed Central

    Lu, Haitao; Wu, Haiyan; Cheng, Hewei; Wei, Dongjie; Wang, Xiaoyan; Fan, Yong; Zhang, Hao; Zhang, Tong

    2014-01-01

    As a special aphasia, the occurrence of crossed aphasia in dextral (CAD) is unusual. This study aims to improve the language ability by applying 1 Hz repetitive transcranial magnetic stimulation (rTMS). We studied multiple modality imaging of structural connectivity (diffusion tensor imaging), functional connectivity (resting fMRI), PET, and neurolinguistic analysis on a patient with CAD. Furthermore, we applied rTMS of 1 Hz for 40 times and observed the language function improvement. The results indicated that a significantly reduced structural and function connectivity was found in DTI and fMRI data compared with the control. The PET imaging showed hypo-metabolism in right hemisphere and left cerebellum. In conclusion, one of the mechanisms of CAD is that right hemisphere is the language dominance. Stimulating left Wernicke area could improve auditory comprehension, stimulating left Broca’s area could enhance expression, and the results outlasted 6 months by 1 Hz rTMS balancing the excitability inter-hemisphere in CAD. PMID:25419415

  16. Functionally reduced sensorimotor connections form with normal specificity despite abnormal muscle spindle development: the role of spindle-derived NT3

    PubMed Central

    Shneider, Neil A.; Mentis, George Z.; Schustak, Joshua; O’Donovan, Michael J.

    2009-01-01

    Summary The mechanisms controlling the formation of synaptic connections between muscle spindle afferents and spinal motor neurons are believed to be regulated by factors originating from muscle spindles. Here, we find that the connections form with appropriate specificity in mice with abnormal spindle development caused by the conditional elimination of the neuregulin1 receptor ErbB2 from muscle precursors. However, despite a modest (~30%) decrease in the number of afferent terminals on motor neuron somata, the amplitude of afferent-evoked synaptic potentials recorded in motor neurons was reduced by ~80%, suggesting that many of the connections that form are functionally silent. The selective elimination of neurotrophin 3 (NT3) from muscle spindles had no effect on the amplitude of afferent-evoked ventral root potentials until the second postnatal week, revealing a late role for spindle-derived NT3 in the functional maintenance of the connections. These findings indicate that spindle-derived factors regulate the strength of the connections, but not their initial formation or their specificity. PMID:19369542

  17. Physiological consequences of abnormal connectivity in a developmental epilepsy

    PubMed Central

    Shafi, Mouhsin M.; Vernet, Marine; Klooster, Debby; Chu, Catherine J.; Boric, Katica; Barnard, Mollie E.; Romatoski, Kelsey; Westover, M. Brandon; Christodoulou, Joanna A.; Gabrieli, John D.E.; Whitfield-Gabrieli, Susan; Pascual-Leone, Alvaro; Chang, Bernard S.

    2015-01-01

    Objective Many forms of epilepsy are associated with aberrant neuronal connections, but the relationship between such pathological connectivity and the underlying physiological predisposition to seizures is unclear. We sought to characterize the cortical excitability profile of a developmental form of epilepsy known to have structural and functional connectivity abnormalities. Methods We employed transcranial magnetic stimulation (TMS) with simultaneous EEG recording in eight patients with epilepsy from periventricular nodular heterotopia (PNH) and matched healthy controls. We used connectivity imaging findings to guide TMS targeting and compared the evoked responses to single-pulse stimulation from different cortical regions. Results Heterotopia patients with active epilepsy demonstrated a relatively augmented late cortical response that was greater than that of matched controls. This abnormality was specific to cortical regions with connectivity to subcortical heterotopic gray matter. Topographic mapping of the late response differences showed distributed cortical networks that were not limited to the stimulation site, and source analysis in one subject revealed that the generator of abnormal TMS-evoked activity overlapped with the spike and seizure onset zone. Interpretation Our findings indicate that patients with epilepsy from gray matter heterotopia have altered cortical physiology consistent with hyperexcitability, and that this abnormality is specifically linked to the presence of aberrant connectivity. These results support the idea that TMS-EEG could be a useful biomarker in epilepsy in gray matter heterotopia, expand our understanding of circuit mechanisms of epileptogenesis, and have potential implications for therapeutic neuromodulation in similar epileptic conditions associated with deep lesions. PMID:25858773

  18. Abnormality on Liver Function Test

    PubMed Central

    2013-01-01

    Children with abnormal liver function can often be seen in outpatient clinics or inpatients wards. Most of them have respiratory disease, or gastroenteritis by virus infection, accompanying fever. Occasionally, hepatitis by the viruses causing systemic infection may occur, and screening tests are required. In patients with jaundice, the tests for differential diagnosis and appropriate treatment are important. In the case of a child with hepatitis B virus infection vertically from a hepatitis B surface antigen positive mother, the importance of the recognition of immune clearance can't be overstressed, for the decision of time to begin treatment. Early diagnosis changes the fate of a child with Wilson disease. So, screening test for the disease should not be omitted. Non-alcoholic fatty liver disease, which is mainly discovered in obese children, is a new strong candidate triggering abnormal liver function. Muscular dystrophy is a representative disease mimicking liver dysfunction. Although muscular dystrophy is a progressive disorder, and early diagnosis can't change the fate of patients, it will be better to avoid parent's blame for delayed diagnosis. PMID:24511518

  19. Abnormal cerebral effective connectivity during explicit emotional processing in adults with autism spectrum disorder

    PubMed Central

    Fonlupt, Pierre; Hubert, Bénédicte; Tardif, Carole; Gepner, Bruno; Deruelle, Christine

    2008-01-01

    Several recent studies suggest that autism may result from abnormal communication between brain regions. We directly assessed this hypothesis by testing the presence of abnormalities in a model of the functional cerebral network engaged during explicit emotion processing in adults with high functioning autism or Asperger syndrome. Comparison of structural equation models revealed abnormal patterns of effective connectivity, with the prefrontal cortex as a key site of dysfunction. These findings provide evidence that abnormal long-range connectivity between structures of the ‘social brain’ could explain the socio-emotional troubles that characterize the autistic pathology. PMID:19015104

  20. Abnormalities of Inter- and Intra-Hemispheric Functional Connectivity in Autism Spectrum Disorders: A Study Using the Autism Brain Imaging Data Exchange Database.

    PubMed

    Lee, Jung Min; Kyeong, Sunghyun; Kim, Eunjoo; Cheon, Keun-Ah

    2016-01-01

    Recently, the Autism Brain Imaging Data Exchange (ABIDE) project revealed decreased functional connectivity in individuals with Autism Spectrum Disorders (ASD) relative to the typically developing controls (TDCs). However, it is still questionable whether the source of functional under-connectivity in subjects with ASD is equally contributed by the ipsilateral and contralateral parts of the brain. In this study, we decomposed the inter- and intra-hemispheric regions and compared the functional connectivity density (FCD) between 458 subjects with ASD and 517 TDCs from the ABIDE database. We quantified the inter- and intra-hemispheric FCDs in the brain by counting the number of functional connectivity with all voxels in the opposite and same hemispheric brain regions, respectively. Relative to TDCs, both inter- and intra-hemispheric FCDs in the posterior cingulate cortex, lingual/parahippocampal gyrus, and postcentral gyrus were significantly decreased in subjects with ASD. Moreover, in the ASD group, the restricted and repetitive behavior subscore of the Autism Diagnostic Observation Schedule (ADOS-RRB) score showed significant negative correlations with the average inter-hemispheric FCD and contralateral FCD in the lingual/parahippocampal gyrus cluster. Also, the ADOS-RRB score showed significant negative correlations with the average contralateral FCD in the default mode network regions such as the posterior cingulate cortex and precuneus. Taken together, our findings imply that a deficit of non-social functioning processing in ASD such as restricted and repetitive behaviors and sensory hypersensitivity could be determined via both inter- and intra-hemispheric functional disconnections. PMID:27199653

  1. Abnormalities of Inter- and Intra-Hemispheric Functional Connectivity in Autism Spectrum Disorders: A Study Using the Autism Brain Imaging Data Exchange Database

    PubMed Central

    Lee, Jung Min; Kyeong, Sunghyun; Kim, Eunjoo; Cheon, Keun-Ah

    2016-01-01

    Recently, the Autism Brain Imaging Data Exchange (ABIDE) project revealed decreased functional connectivity in individuals with Autism Spectrum Disorders (ASD) relative to the typically developing controls (TDCs). However, it is still questionable whether the source of functional under-connectivity in subjects with ASD is equally contributed by the ipsilateral and contralateral parts of the brain. In this study, we decomposed the inter- and intra-hemispheric regions and compared the functional connectivity density (FCD) between 458 subjects with ASD and 517 TDCs from the ABIDE database. We quantified the inter- and intra-hemispheric FCDs in the brain by counting the number of functional connectivity with all voxels in the opposite and same hemispheric brain regions, respectively. Relative to TDCs, both inter- and intra-hemispheric FCDs in the posterior cingulate cortex, lingual/parahippocampal gyrus, and postcentral gyrus were significantly decreased in subjects with ASD. Moreover, in the ASD group, the restricted and repetitive behavior subscore of the Autism Diagnostic Observation Schedule (ADOS-RRB) score showed significant negative correlations with the average inter-hemispheric FCD and contralateral FCD in the lingual/parahippocampal gyrus cluster. Also, the ADOS-RRB score showed significant negative correlations with the average contralateral FCD in the default mode network regions such as the posterior cingulate cortex and precuneus. Taken together, our findings imply that a deficit of non-social functioning processing in ASD such as restricted and repetitive behaviors and sensory hypersensitivity could be determined via both inter- and intra-hemispheric functional disconnections. PMID:27199653

  2. Normal and abnormal human vestibular ocular function

    NASA Technical Reports Server (NTRS)

    Peterka, R. J.; Black, F. O.

    1986-01-01

    The major motivation of this research is to understand the role the vestibular system plays in sensorimotor interactions which result in spatial disorientation and motion sickness. A second goal was to explore the range of abnormality as it is reflected in quantitative measures of vestibular reflex responses. The results of a study of vestibular reflex measurements in normal subjects and preliminary results in abnormal subjects are presented in this report. Statistical methods were used to define the range of normal responses, and determine age related changes in function.

  3. Abnormal cortical thickness connectivity persists in childhood absence epilepsy

    PubMed Central

    Curwood, Evan K; Pedersen, Mangor; Carney, Patrick W; Berg, Anne T; Abbott, David F; Jackson, Graeme D

    2015-01-01

    Objective Childhood absence epilepsy (CAE) is a childhood-onset generalized epilepsy. Recent fMRI studies have suggested that frontal cortex activity occurs before thalamic involvement in epileptic discharges suggesting that frontal cortex may play an important role in childhood absence seizures. Neurocognitive deficits can persist after resolution of the epilepsy. We investigate whether structural connectivity changes are present in the brains of CAE patients in young adulthood. Methods Cortical thickness measurements were obtained for 30 subjects with CAE (mean age 21 ± 2 years) and 56 healthy controls (mean age 24 ± 4) and regressed for age, sex, and total intracranial volume (TIV). Structural connectivity was evaluated by measuring the correlation between average cortical thicknesses in 915 regions over the brain. Maps of connectivity strength were then obtained for both groups. Results When compared to controls, the CAE group shows overall increased “connectivity” with focal increased connection strength in anterior regions including; the anterior cingulate and the insula and superior temporal gyrus bilaterally; the right orbito-frontal and supramarginal regions; and the left entorhinal cortex. Decreased connection strength in the CAE group was found in the left occipital lobe, with a similar trend in right occipital lobe. Interpretation Brains in young adults whose CAE was resolved had abnormal structural connectivity. Our findings suggest that frontal regions correlate most with cortical thickness throughout the brain in CAE patients, whereas occipital regions correlate most in well matched normal controls. We interpret this as evidence of a developmental difference in CAE that emphasizes these frontal lobe regions, perhaps driven by frontal lobe epileptiform activity. PMID:26000319

  4. Evaluation of abnormal liver function tests.

    PubMed

    Agrawal, Swastik; Dhiman, Radha K; Limdi, Jimmy K

    2016-04-01

    Incidentally detected abnormality in liver function tests is a common situation encountered by physicians across all disciplines. Many of these patients do not have primary liver disease as most of the commonly performed markers are not specific for the liver and are affected by myriad factors unrelated to liver disease. Also, many of these tests like liver enzyme levels do not measure the function of the liver, but are markers of liver injury, which is broadly of two types: hepatocellular and cholestatic. A combination of a careful history and clinical examination along with interpretation of pattern of liver test abnormalities can often identify type and aetiology of liver disease, allowing for a targeted investigation approach. Severity of liver injury is best assessed by composite scores like the Model for End Stage Liver Disease rather than any single parameter. In this review, we discuss the interpretation of the routinely performed liver tests along with the indications and utility of quantitative tests. PMID:26842972

  5. Perceived functional impact of abnormal facial appearance.

    PubMed

    Rankin, Marlene; Borah, Gregory L

    2003-06-01

    Functional facial deformities are usually described as those that impair respiration, eating, hearing, or speech. Yet facial scars and cutaneous deformities have a significant negative effect on social functionality that has been poorly documented in the scientific literature. Insurance companies are declining payments for reconstructive surgical procedures for facial deformities caused by congenital disabilities and after cancer or trauma operations that do not affect mechanical facial activity. The purpose of this study was to establish a large, sample-based evaluation of the perceived social functioning, interpersonal characteristics, and employability indices for a range of facial appearances (normal and abnormal). Adult volunteer evaluators (n = 210) provided their subjective perceptions based on facial physical appearance, and an analysis of the consequences of facial deformity on parameters of preferential treatment was performed. A two-group comparative research design rated the differences among 10 examples of digitally altered facial photographs of actual patients among various age and ethnic groups with "normal" and "abnormal" congenital deformities or posttrauma scars. Photographs of adult patients with observable congenital and posttraumatic deformities (abnormal) were digitally retouched to eliminate the stigmatic defects (normal). The normal and abnormal photographs of identical patients were evaluated by the large sample study group on nine parameters of social functioning, such as honesty, employability, attractiveness, and effectiveness, using a visual analogue rating scale. Patients with abnormal facial characteristics were rated as significantly less honest (p = 0.007), less employable (p = 0.001), less trustworthy (p = 0.01), less optimistic (p = 0.001), less effective (p = 0.02), less capable (p = 0.002), less intelligent (p = 0.03), less popular (p = 0.001), and less attractive (p = 0.001) than were the same patients with normal facial

  6. Abnormal effective connectivity and psychopathological symptoms in the psychosis high-risk state

    PubMed Central

    Schmidt, André; Smieskova, Renata; Simon, Andor; Allen, Paul; Fusar-Poli, Paolo; McGuire, Philip K.; Bendfeldt, Kerstin; Aston, Jacqueline; Lang, Undine E.; Walter, Marc; Radue, Ernst-Wilhelm; Riecher-Rössler, Anita; Borgwardt, Stefan J.

    2014-01-01

    Background Recent evidence has revealed abnormal functional connectivity between the frontal and parietal brain regions during working memory processing in patients with schizophrenia and first-episode psychosis. However, it still remains unclear whether abnormal frontoparietal connectivity during working memory processing is already evident in the psychosis high-risk state and whether the connection strengths are related to psychopathological outcomes. Methods Healthy controls and antipsychotic-naive individuals with an at-risk mental state (ARMS) performed an n-back working memory task while undergoing functional magnetic resonance imaging. Effective connectivity between frontal and parietal brain regions during working memory processing were characterized using dynamic causal modelling. Results Our study included 19 controls and 27 individuals with an ARMS. In individuals with an ARMS, we found significantly lower task performances and reduced activity in the right superior parietal lobule and middle frontal gyrus than in controls. Furthermore, the working memory–induced modulation of the connectivity from the right middle frontal gyrus to the right superior parietal lobule was significantly reduced in individuals with an ARMS, while the extent of this connectivity was negatively related to the Brief Psychiatric Rating Scale total score. Limitations The modest sample size precludes a meaningful subgroup analysis for participants with a later transition to psychosis. Conclusion This study demonstrates that abnormal frontoparietal connectivity during working memory processing is already evident in individuals with an ARMS and is related to psychiatric symptoms. Thus, our results provide further insight into the pathophysiological mechanisms of the psychosis high-risk state by linking functional brain imaging, computational modelling and psychopathology. PMID:24506946

  7. Precentral gyrus functional connectivity signatures of autism

    PubMed Central

    Nebel, Mary Beth; Eloyan, Ani; Barber, Anita D.; Mostofsky, Stewart H.

    2014-01-01

    Motor impairments are prevalent in children with autism spectrum disorders (ASD) and are perhaps the earliest symptoms to develop. In addition, motor skills relate to the communicative/social deficits at the core of ASD diagnosis, and these behavioral deficits may reflect abnormal connectivity within brain networks underlying motor control and learning. Despite the fact that motor abnormalities in ASD are well-characterized, there remains a fundamental disconnect between the complexity of the clinical presentation of ASD and the underlying neurobiological mechanisms. In this study, we examined connectivity within and between functional subregions of a key component of the motor control network, the precentral gyrus, using resting state functional Magnetic Resonance Imaging data collected from a large, heterogeneous sample of individuals with ASD as well as neurotypical controls. We found that the strength of connectivity within and between distinct functional subregions of the precentral gyrus was related to ASD diagnosis and to the severity of ASD traits. In particular, connectivity involving the dorsomedial (lower limb/trunk) subregion was abnormal in ASD individuals as predicted by models using a dichotomous variable coding for the presence of ASD, as well as models using symptom severity ratings. These findings provide further support for a link between motor and social/communicative abilities in ASD. PMID:24860442

  8. Altered functional connectivity in persistent developmental stuttering.

    PubMed

    Yang, Yang; Jia, Fanlu; Siok, Wai Ting; Tan, Li Hai

    2016-01-01

    Persistent developmental stuttering (PDS) is a speech disorder that impairs communication skills. Despite extensive research, the core causes of PDS are elusive. Converging evidence from task-induced neuroimaging methods has demonstrated the contributions of the basal ganglia and the cerebellum to PDS, but such task-state neuroimaging findings are often confounded by behavioral performance differences between subjects who stutter and normal controls. Here, using resting-state functional magnetic resonance imaging, we investigated functional connectivity within cerebellar-cortical and basal ganglia-thalamocortical networks in 16 adults who stutter and 18 age-matched fluent speakers. Seed-to-voxel analysis demonstrated that, compared to controls, adults who stutter showed alternations in functional connectivity of cerebellum to motor cortex as well as connectivity among different locals within cerebellum. Additionally, we found that functional connectivity within cerebellar circuits was significantly correlated with severity of stuttering. The alternations of functional connectivity within basal ganglia-thalamocortical networks were identified as the reduced connectivity of the putamen to the superior temporal gyrus and inferior parietal lobules in adults who stutter. The abnormalities of resting state functional connectivity are assumed to affect language planning and motor execution critical for speaking fluently. Our findings may yield neurobiological cues to the biomarkers of PDS. PMID:26743821

  9. Altered functional connectivity in persistent developmental stuttering

    PubMed Central

    Yang, Yang; Jia, Fanlu; Siok, Wai Ting; Tan, Li Hai

    2016-01-01

    Persistent developmental stuttering (PDS) is a speech disorder that impairs communication skills. Despite extensive research, the core causes of PDS are elusive. Converging evidence from task-induced neuroimaging methods has demonstrated the contributions of the basal ganglia and the cerebellum to PDS, but such task-state neuroimaging findings are often confounded by behavioral performance differences between subjects who stutter and normal controls. Here, using resting-state functional magnetic resonance imaging, we investigated functional connectivity within cerebellar-cortical and basal ganglia-thalamocortical networks in 16 adults who stutter and 18 age-matched fluent speakers. Seed-to-voxel analysis demonstrated that, compared to controls, adults who stutter showed alternations in functional connectivity of cerebellum to motor cortex as well as connectivity among different locals within cerebellum. Additionally, we found that functional connectivity within cerebellar circuits was significantly correlated with severity of stuttering. The alternations of functional connectivity within basal ganglia-thalamocortical networks were identified as the reduced connectivity of the putamen to the superior temporal gyrus and inferior parietal lobules in adults who stutter. The abnormalities of resting state functional connectivity are assumed to affect language planning and motor execution critical for speaking fluently. Our findings may yield neurobiological cues to the biomarkers of PDS. PMID:26743821

  10. Functional connectivity hubs of the mouse brain.

    PubMed

    Liska, Adam; Galbusera, Alberto; Schwarz, Adam J; Gozzi, Alessandro

    2015-07-15

    Recent advances in functional connectivity methods have made it possible to identify brain hubs - a set of highly connected regions serving as integrators of distributed neuronal activity. The integrative role of hub nodes makes these areas points of high vulnerability to dysfunction in brain disorders, and abnormal hub connectivity profiles have been described for several neuropsychiatric disorders. The identification of analogous functional connectivity hubs in preclinical species like the mouse may provide critical insight into the elusive biological underpinnings of these connectional alterations. To spatially locate functional connectivity hubs in the mouse brain, here we applied a fully-weighted network analysis to map whole-brain intrinsic functional connectivity (i.e., the functional connectome) at a high-resolution voxel-scale. Analysis of a large resting-state functional magnetic resonance imaging (rsfMRI) dataset revealed the presence of six distinct functional modules related to known large-scale functional partitions of the brain, including a default-mode network (DMN). Consistent with human studies, highly-connected functional hubs were identified in several sub-regions of the DMN, including the anterior and posterior cingulate and prefrontal cortices, in the thalamus, and in small foci within well-known integrative cortical structures such as the insular and temporal association cortices. According to their integrative role, the identified hubs exhibited mutual preferential interconnections. These findings highlight the presence of evolutionarily-conserved, mutually-interconnected functional hubs in the mouse brain, and may guide future investigations of the biological foundations of aberrant rsfMRI hub connectivity associated with brain pathological states. PMID:25913701

  11. Dissociable cortico-striatal connectivity abnormalities in major depression in response to monetary gains and penalties

    PubMed Central

    Admon, Roee; Nickerson, Lisa D.; Dillon, Daniel G.; Holmes, Avram J.; Bogdan, Ryan; Kumar, Poornima; Dougherty, Darin D.; Iosifescu, Dan V.; Mischoulon, David; Fava, Maurizio; Pizzagalli, Diego A.

    2014-01-01

    Background Individuals with major depressive disorder (MDD) are characterized by maladaptive responses to both positive and negative outcomes, which have been linked to localized abnormal activations in cortical and striatal brain regions. However, the exact neural circuitry implicated in such abnormalities remains largely unexplored. Methods In this study 26 unmedicated adults with MDD and 29 matched healthy controls completed a monetary incentive delay task during functional magnetic resonance imaging (fMRI). Psycho-physiological interaction (PPI) analyses probed group differences in connectivity separately in response to positive and negative outcomes (i.e., monetary gains and penalties). Results Relative to controls, MDD subjects displayed decreased connectivity between the caudate and dorsal anterior cingulate cortex (dACC) in response to monetary gains, yet increased connectivity between the caudate and a different, more rostral, dACC sub-region in response to monetary penalties. Moreover, exploratory analyses of 14 MDD patients who completed a 12-week, double-blind, placebo-controlled clinical trial after the baseline fMRI scans indicated that a more normative pattern of cortico-striatal connectivity pre-treatment was associated with more symptoms improvement 12 weeks later. Conclusions These results identify the caudate as a region with dissociable incentive-dependent dACC connectivity abnormalities in MDD, and provide initial evidence that cortico-striatal circuitry may play a role in MDD treatment response. Given the role of cortico-striatal circuitry in encoding action-outcome contingencies, such dysregulated connectivity may relate to the prominent disruptions in goal-directed behavior that characterize MDD. PMID:25055809

  12. Abnormal Anatomical Connectivity between the Amygdala and Orbitofrontal Cortex in Conduct Disorder

    PubMed Central

    Passamonti, Luca; Fairchild, Graeme; Fornito, Alex; Goodyer, Ian M.; Nimmo-Smith, Ian; Hagan, Cindy C.; Calder, Andrew J.

    2012-01-01

    Objective Previous research suggested that structural and functional abnormalities within the amygdala and orbitofrontal cortex contribute to the pathophysiology of Conduct Disorder (CD). Here, we investigated whether the integrity of the white-matter pathways connecting these regions is abnormal and thus may represent a putative neurobiological marker for CD. Methods Diffusion Tensor Imaging (DTI) was used to investigate white-matter microstructural integrity in male adolescents with childhood-onset CD, compared with healthy controls matched in age, sex, intelligence, and socioeconomic status. Two approaches were employed to analyze DTI data: voxel-based morphometry of fractional anisotropy (FA), an index of white-matter integrity, and virtual dissection of white-matter pathways using tractography. Results Adolescents with CD displayed higher FA within the right external capsule relative to controls (T = 6.08, P<0.05, Family-Wise Error, whole-brain correction). Tractography analyses showed that FA values within the uncinate fascicle (connecting the amygdala and orbitofrontal cortex) were abnormally increased in individuals with CD relative to controls. This was in contrast with the inferior frontal-occipital fascicle, which showed no significant group differences in FA. The finding of increased FA in the uncinate fascicle remained significant when factoring out the contribution of attention-deficit/hyperactivity disorder symptoms. There were no group differences in the number of streamlines in either of these anatomical tracts. Conclusions These results provide evidence that CD is associated with white-matter microstructural abnormalities in the anatomical tract that connects the amygdala and orbitofrontal cortex, the uncinate fascicle. These results implicate abnormal maturation of white-matter pathways which are fundamental in the regulation of emotional behavior in CD. PMID:23144970

  13. Functional Neuroimaging Abnormalities in Psychosis Spectrum Youth

    PubMed Central

    Wolf, Daniel H.; Satterthwaite, Theodore D.; Calkins, Monica E.; Ruparel, Kosha; Elliott, Mark A.; Hopson, Ryan D.; Jackson, Chad; Prabhakaran, Karthik; Bilker, Warren B.; Hakonarson, Hakon; Gur, Ruben C.; Gur, Raquel E.

    2015-01-01

    Importance The continuum view of the psychosis spectrum (PS) implies that in population-based samples, PS symptoms should be associated with neural abnormalities similar to those found in help-seeking clinical-risk individuals and in schizophrenia. Functional neuroimaging has not previously been applied in large population-based PS samples, and can help understand the neural architecture of psychosis more broadly, and identify brain phenotypes beyond symptomatology that are associated with the extended psychosis phenotype. Objective To examine the categorical and dimensional relationships of PS symptoms to prefrontal hypoactivation during working memory and to amygdala hyperactivation during threat emotion processing. Design The Philadelphia Neurodevelopmental Cohort (PNC) is a genotyped prospectively accrued population-based sample of nearly 10,000 youths, who received a structured psychiatric evaluation and a computerized neurocognitive battery. A subsample of 1,445 subjects underwent neuroimaging including functional magnetic resonance imaging (fMRI) tasks examined here. Setting The PNC is a collaboration between The Children’s Hospital of Philadelphia and the Hospital of the University of Pennsylvania. Participants Youths ages 11–22 years identified through structured interview as having psychosis-spectrum features (PS, n=260), and typically developing comparison subjects without significant psychopathology (TD, n=220). Main Outcomes and Measures Two fMRI paradigms were utilized, a fractal n-back working memory task probing executive system function, and an emotion identification task probing amygdala responses to threatening faces. Results In the n-back task, PS showed reduced activation in executive control circuitry, which correlated with cognitive deficits. During emotion identification, PS demonstrated elevated amygdala responses to threatening facial expressions, which correlated with positive symptom severity. Conclusions and Relevance The pattern of

  14. Strengthening connections: functional connectivity and brain plasticity

    PubMed Central

    Kelly, Clare; Castellanos, F. Xavier

    2014-01-01

    The ascendancy of functional neuroimaging has facilitated the addition of network-based approaches to the neuropsychologist’s toolbox for evaluating the sequelae of brain insult. In particular, intrinsic functional connectivity (iFC) mapping of resting state fMRI (R-fMRI) data constitutes an ideal approach to measuring macro-scale networks in the human brain. Beyond the value of iFC mapping for charting how the functional topography of the brain is altered by insult and injury, iFC analyses can provide insights into effects of experience-dependent plasticity at the macro level of large-scale functional networks. Such insights are foundational to the design of training and remediation interventions that will best facilitate recovery of function. In this review, we consider what is currently known about the origin and function of iFC in the brain, and how this knowledge is informative in neuropsychological settings. We then summarize studies that have examined experience-driven plasticity of iFC in healthy control participants, and frame these findings in terms of a schema that may aid in the interpretation of results and the generation of hypothesis for rehabilitative studies. Finally, we outline some caveats to the R-fMRI approach, as well as some current developments that are likely to bolster the utility of the iFC paradigm for neuropsychology. PMID:24496903

  15. Executive function abnormalities in pathological gamblers

    PubMed Central

    2008-01-01

    Background Pathological gambling (PG) is an impulse control disorder characterized by persistent and maladaptive gambling behaviors with disruptive consequences for familial, occupational and social functions. The pathophysiology of PG is still unclear, but it is hypothesized that it might include environmental factors coupled with a genetic vulnerability and dysfunctions of different neurotransmitters and selected brain areas. Our study aimed to evaluate a group of patients suffering from PG by means of some neuropsychological tests in order to explore the brain areas related to the disorder. Methods Twenty outpatients (15 men, 5 women), with a diagnosis of PG according to DSM-IV criteria, were included in the study and evaluated with a battery of neuropsychological tests: the Wisconsin Card Sorting Test (WCST), the Wechsler Memory Scale revised (WMS-R) and the Verbal Associative Fluency Test (FAS). The results obtained in the patients were compared with normative values of matched healthy control subjects. Results The PG patients showed alterations at the WCST only, in particular they had a great difficulty in finding alternative methods of problem-solving and showed a decrease, rather than an increase, in efficiency, as they progressed through the consecutive phases of the test. The mean scores of the other tests were within the normal range. Conclusion Our findings showed that patients affected by PG, in spite of normal intellectual, linguistic and visual-spatial abilities, had abnormalities emerging from the WCST, in particular they could not learn from their mistakes and look for alternative solutions. Our results would seem to confirm an altered functioning of the prefrontal areas which might provoke a sort of cognitive "rigidity" that might predispose to the development of impulsive and/or compulsive behaviors, such as those typical of PG. PMID:18371193

  16. 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…

  17. Neuronal substrate and effective connectivity of abnormal movement sequencing in schizophrenia.

    PubMed

    Zemankova, Petra; Lungu, Ovidiu; Huttlova, Jitka; Kerkovsky, Milos; Zubor, Jozef; Lipova, Petra; Bares, Martin; Kasparek, Tomas

    2016-06-01

    Movement sequencing difficulties are part of the neurological soft signs (NSS), they have high clinical value because they are not always present in schizophrenia. We investigated the neuronal correlates of movement sequencing in 24 healthy controls and 24 schizophrenia patients, with (SZP SQ+) or without (SZP SQ-) sequencing difficulties. We characterized simultaneous and lagged functional connectivity between brain regions involved in movement sequencing using psychophysiological interaction (PPI) and the Granger causality modeling (GCM), respectively. Left premotor cortex (PMC) and superior parietal lobule (SPL) were specifically activated during sequential movements in all participants. Right PMC and precuneus, ipsilateral to the hand executing the task, activated during sequential movements only in healthy controls and SZP SQ-. SZP SQ+ showed hyperactivation in contralateral PMC, as compared to the other groups. PPI analysis revealed a deficit in inhibitory connections within this fronto-parietal network in SZP SQ+ during sequential task. GCM showed a significant lagged effective connectivity from right PMC to left SPL during task and rest periods in all groups and from right PMC to right precuneus in SZP SQ+ group only. Both SZP groups had a significant lagged connectivity from right to left PMC, during sequential task. Our results indicate that aberrant fronto-parietal network connectivity with cortical inhibition deficit and abnormal reliance on previous network activity are related to movement sequencing in SZP. The overactivation of motor cortex seems to be a good compensating strategy, the hyperactivation of parietal cortex is linked to motor deficit symptoms. PMID:26780603

  18. 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. PMID:27120982

  19. Dorsal Striatum and Its Limbic Connectivity Mediate Abnormal Anticipatory Reward Processing in Obesity

    PubMed Central

    Nummenmaa, Lauri; Hirvonen, Jussi; Hannukainen, Jarna C.; Immonen, Heidi; Lindroos, Markus M.; Salminen, Paulina; Nuutila, Pirjo

    2012-01-01

    Obesity is characterized by an imbalance in the brain circuits promoting reward seeking and those governing cognitive control. Here we show that the dorsal caudate nucleus and its connections with amygdala, insula and prefrontal cortex contribute to abnormal reward processing in obesity. We measured regional brain glucose uptake in morbidly obese (n = 19) and normal weighted (n = 16) subjects with 2-[18F]fluoro-2-deoxyglucose ([18F]FDG) positron emission tomography (PET) during euglycemic hyperinsulinemia and with functional magnetic resonance imaging (fMRI) while anticipatory food reward was induced by repeated presentations of appetizing and bland food pictures. First, we found that glucose uptake rate in the dorsal caudate nucleus was higher in obese than in normal-weight subjects. Second, obese subjects showed increased hemodynamic responses in the caudate nucleus while viewing appetizing versus bland foods in fMRI. The caudate also showed elevated task-related functional connectivity with amygdala and insula in the obese versus normal-weight subjects. Finally, obese subjects had smaller responses to appetizing versus bland foods in the dorsolateral and orbitofrontal cortices than did normal-weight subjects, and failure to activate the dorsolateral prefrontal cortex was correlated with high glucose metabolism in the dorsal caudate nucleus. These findings suggest that enhanced sensitivity to external food cues in obesity may involve abnormal stimulus-response learning and incentive motivation subserved by the dorsal caudate nucleus, which in turn may be due to abnormally high input from the amygdala and insula and dysfunctional inhibitory control by the frontal cortical regions. These functional changes in the responsiveness and interconnectivity of the reward circuit could be a critical mechanism to explain overeating in obesity. PMID:22319604

  20. Abnormalities in Hippocampal Functioning with Persistent Pain

    PubMed Central

    Mutso, Amelia A.; Radzicki, Daniel; Baliki, Marwan N.; Huang, Lejian; Banisadr, Ghazal; Centeno, Maria Virginia; Radulovic, Jelena; Martina, Marco; Miller, Richard J.; Apkarian, A. Vania

    2012-01-01

    Chronic pain patients exhibit increased anxiety, depression, and deficits in learning and memory. Yet how persistent pain affects the key brain area regulating these behaviors, the hippocampus, has remained minimally explored. In this study we investigated the impact of spared nerve injury (SNI) neuropathic pain in mice on hippocampal-dependent behavior and underlying cellular and molecular changes. In parallel, we measured the hippocampal volume of three groups of chronic pain patients. We found that SNI animals were unable to extinguish to contextual fear and showed increased anxiety-like behavior. Additionally, SNI mice in comparison to sham animals exhibited hippocampal 1) reduced extracellular signal-regulated kinase (ERK) expression and phosphorylation, 2) decreased neurogenesis and 3) altered short-term synaptic plasticity. In order to relate the observed hippocampal abnormalities with human chronic pain, we measured the volume of human hippocampus in chronic back pain (CBP), complex regional pain syndrome (CRPS), and osteoarthritis patients (OA). Compared to controls, CBP and CRPS, but not OA, had significantly less bilateral hippocampal volume. These results indicate that hippocampus-mediated behavior, synaptic plasticity and neurogenesis are abnormal in neuropathic rodents. The changes may be related to the reduction in hippocampal volume we see in chronic pain patients, and these abnormalities may underlie learning and emotional deficits commonly observed in such patients. PMID:22539837

  1. Altered resting state functional network connectivity in children absence epilepsy.

    PubMed

    Li, Qifu; Cao, Weifang; Liao, Xiaoping; Chen, Zhibin; Yang, Tianhua; Gong, Qiyong; Zhou, Dong; Luo, Cheng; Yao, Dezhong

    2015-07-15

    Altered functional connectivity has been associated with the influence of epileptic activity. Abnormalities in connectivity, particularly in dorsal attention (DAN), salience (SN) and default mode (DMN) networks, might contribute to the loss of consciousness during seizures and cognitive deficits in patients with children absence epilepsy (CAE). The objective of the present study was to identify whether the functional network connectivity (FNC) is changed between patients with CAE and healthy controls. Using independent component analysis, twelve resting state networks (RSNs) were identified in resting state functional magnetic resonance imaging data sets in eighteen CAE patients and twenty-one healthy controls. Analyses of the group differences in FNC strength were conducted, controlling for age and gender effects. The findings showed that some functional networks were clustered into two subgroups, correlated within subgroups and antagonized with each other. Compared with the controls, patients with CAE demonstrated abnormal FNC strength among three networks: DMN, DAN and SN. In addition, the antagonism of two subgroups was altered. These results might reflect the underlying neuronal functional impairment or altered integration among these RSNs in CAE, suggesting that the abnormal functional connectivity is likely to imply the pathological mechanism associated with the accumulative influence of epileptic activity. These findings contribute to the understanding of the behavior abnormality in CAE, such as disturbed executive and attentional functions and the loss of consciousness during absence seizures. PMID:25982500

  2. Myelodysplastic syndromes: pathogenesis, functional abnormalities, and clinical implications.

    PubMed Central

    Jacobs, A

    1985-01-01

    The myelodysplastic syndromes represent a preleukaemic state in which a clonal abnormality of haemopoietic stem cell is characterised by a variety of phenotypic manifestations with varying degrees of ineffective haemopoiesis. This state probably develops as a sequence of events in which the earliest stages may be difficult to detect by conventional pathological techniques. The process is characterised by genetic changes leading to abnormal control of cell proliferation and differentiation. Expansion of an abnormal clone may be related to independence from normal growth factors, insensitivity to normal inhibitory factors, suppression of normal clonal growth, or changes in the immunological or nutritional condition of the host. The haematological picture is of peripheral blood cytopenias: a cellular bone marrow, and functional abnormalities of erythroid, myeloid, and megakaryocytic cells. In most cases marrow cells have an abnormal DNA content, often with disturbances of the cell cycle: an abnormal karyotype is common in premalignant clones. Growth abnormalities of erythroid or granulocyte-macrophage progenitors are common in marrow cultures, and lineage specific surface membrane markers indicate aberrations of differentiation. Progression of the disorder may occur through clonal expansion or through clonal evolution with a greater degree of malignancy. Current attempts to influence abnormal growth and differentiation have had only limited success. Clinical recognition of the syndrome depends on an acute awareness of the signs combined with the identification of clonal and functional abnormalities. PMID:2999194

  3. Abnormal Connectional Fingerprint in Schizophrenia: A Novel Network Analysis of Diffusion Tensor Imaging Data.

    PubMed

    Edwin Thanarajah, Sharmili; Han, Cheol E; Rotarska-Jagiela, Anna; Singer, Wolf; Deichmann, Ralf; Maurer, Konrad; Kaiser, Marcus; Uhlhaas, Peter J

    2016-01-01

    The graph theoretical analysis of structural magnetic resonance imaging (MRI) data has received a great deal of interest in recent years to characterize the organizational principles of brain networks and their alterations in psychiatric disorders, such as schizophrenia. However, the characterization of networks in clinical populations can be challenging, since the comparison of connectivity between groups is influenced by several factors, such as the overall number of connections and the structural abnormalities of the seed regions. To overcome these limitations, the current study employed the whole-brain analysis of connectional fingerprints in diffusion tensor imaging data obtained at 3 T of chronic schizophrenia patients (n = 16) and healthy, age-matched control participants (n = 17). Probabilistic tractography was performed to quantify the connectivity of 110 brain areas. The connectional fingerprint of a brain area represents the set of relative connection probabilities to all its target areas and is, hence, less affected by overall white and gray matter changes than absolute connectivity measures. After detecting brain regions with abnormal connectional fingerprints through similarity measures, we tested each of its relative connection probability between groups. We found altered connectional fingerprints in schizophrenia patients consistent with a dysconnectivity syndrome. While the medial frontal gyrus showed only reduced connectivity, the connectional fingerprints of the inferior frontal gyrus and the putamen mainly contained relatively increased connection probabilities to areas in the frontal, limbic, and subcortical areas. These findings are in line with previous studies that reported abnormalities in striatal-frontal circuits in the pathophysiology of schizophrenia, highlighting the potential utility of connectional fingerprints for the analysis of anatomical networks in the disorder. PMID:27445870

  4. Abnormal Connectional Fingerprint in Schizophrenia: A Novel Network Analysis of Diffusion Tensor Imaging Data

    PubMed Central

    Edwin Thanarajah, Sharmili; Han, Cheol E.; Rotarska-Jagiela, Anna; Singer, Wolf; Deichmann, Ralf; Maurer, Konrad; Kaiser, Marcus; Uhlhaas, Peter J.

    2016-01-01

    The graph theoretical analysis of structural magnetic resonance imaging (MRI) data has received a great deal of interest in recent years to characterize the organizational principles of brain networks and their alterations in psychiatric disorders, such as schizophrenia. However, the characterization of networks in clinical populations can be challenging, since the comparison of connectivity between groups is influenced by several factors, such as the overall number of connections and the structural abnormalities of the seed regions. To overcome these limitations, the current study employed the whole-brain analysis of connectional fingerprints in diffusion tensor imaging data obtained at 3 T of chronic schizophrenia patients (n = 16) and healthy, age-matched control participants (n = 17). Probabilistic tractography was performed to quantify the connectivity of 110 brain areas. The connectional fingerprint of a brain area represents the set of relative connection probabilities to all its target areas and is, hence, less affected by overall white and gray matter changes than absolute connectivity measures. After detecting brain regions with abnormal connectional fingerprints through similarity measures, we tested each of its relative connection probability between groups. We found altered connectional fingerprints in schizophrenia patients consistent with a dysconnectivity syndrome. While the medial frontal gyrus showed only reduced connectivity, the connectional fingerprints of the inferior frontal gyrus and the putamen mainly contained relatively increased connection probabilities to areas in the frontal, limbic, and subcortical areas. These findings are in line with previous studies that reported abnormalities in striatal–frontal circuits in the pathophysiology of schizophrenia, highlighting the potential utility of connectional fingerprints for the analysis of anatomical networks in the disorder. PMID:27445870

  5. Largely Typical Patterns of Resting-State Functional Connectivity in High-Functioning Adults with Autism

    PubMed Central

    Tyszka, J. Michael; Kennedy, Daniel P.; Paul, Lynn K.; Adolphs, Ralph

    2014-01-01

    A leading hypothesis for the neural basis of autism postulates globally abnormal brain connectivity, yet the majority of studies report effects that are either very weak, inconsistent across studies, or explain results incompletely. Here we apply multiple analytical approaches to resting-state BOLD-fMRI data at the whole-brain level. Neurotypical and high-functioning adults with autism displayed very similar patterns and strengths of resting-state connectivity. We found only limited evidence in autism for abnormal resting-state connectivity at the regional level and no evidence for altered connectivity at the whole-brain level. Regional abnormalities in functional connectivity in autism spectrum disorder were primarily in the frontal and temporal cortices. Within these regions, functional connectivity with other brain regions was almost exclusively lower in the autism group. Further examination showed that even small amounts of head motion during scanning have large effects on functional connectivity measures and must be controlled carefully. Consequently, we suggest caution in the interpretation of apparent positive findings until all possible confounding effects can be ruled out. Additionally, we do not rule out the possibility that abnormal connectivity in autism is evident at the microstructural synaptic level, which may not be reflected sensitively in hemodynamic changes measured with BOLD-fMRI. PMID:23425893

  6. Abnormally Malicious Autonomous Systems and their Internet Connectivity

    SciTech Connect

    Shue, Craig A; Kalafut, Prof. Andrew; Gupta, Prof. Minaxi

    2011-01-01

    While many attacks are distributed across botnets, investigators and network operators have recently targeted malicious networks through high profile autonomous system (AS) de-peerings and network shut-downs. In this paper, we explore whether some ASes indeed are safe havens for malicious activity. We look for ISPs and ASes that exhibit disproportionately high malicious behavior using ten popular blacklists, plus local spam data, and extensive DNS resolutions based on the contents of the blacklists. We find that some ASes have over 80% of their routable IP address space blacklisted. Yet others account for large fractions of blacklisted IP addresses. Several ASes regularly peer with ASes associated with significant malicious activity. We also find that malicious ASes as a whole differ from benign ones in other properties not obviously related to their malicious activities, such as more frequent connectivity changes with their BGP peers. Overall, we conclude that examining malicious activity at AS granularity can unearth networks with lax security or those that harbor cybercrime.

  7. The circuitry of abulia: Insights from functional connectivity MRI

    PubMed Central

    Siegel, J.S.; Snyder, A.Z.; Metcalf, N.V.; Fucetola, R.P.; Hacker, C.D.; Shimony, J.S.; Shulman, G.L.; Corbetta, M.

    2014-01-01

    Background Functional imaging and lesion studies have associated willed behavior with the anterior cingulate cortex (ACC). Abulia is a syndrome characterized by apathy and deficiency of motivated behavior. Abulia is most frequently associated with ACC damage, but also occurs following damage to subcortical nuclei (striatum, globus pallidus, thalamic nuclei). We present resting state functional connectivity MRI (fcMRI) data from an individual who suffered a stroke leading to abulia. We hypothesized that, although structural imaging revealed no damage to the patient's ACC, fcMRI would uncover aberrant function in this region and in the relevant cortical networks. Methods Resting state correlations in the patient's gray matter were compared to those of age-matched controls. Using a novel method to identify abnormal patterns of functional connectivity in single subjects, we identified areas and networks with aberrant connectivity. Results Networks associated with memory (default mode network) and executive function (cingulo-opercular network) were abnormal. The patient's anterior cingulate was among the areas showing aberrant functional connectivity. In a rescan 3 years later, deficits remained stable and fcMRI findings were replicated. Conclusions These findings suggest that the aberrant functional connectivity mapping approach described may be useful for linking stroke symptoms to disrupted network connectivity. PMID:25379445

  8. Diverticular Disease of the Colon: Neuromuscular Function Abnormalities.

    PubMed

    Bassotti, Gabrio; Villanacci, Vincenzo; Bernardini, Nunzia; Dore, Maria P

    2016-10-01

    Colonic diverticular disease is a frequent finding in daily clinical practice. However, its pathophysiological mechanisms are largely unknown. This condition is likely the result of several concomitant factors occurring together to cause anatomic and functional abnormalities, leading as a result to the outpouching of the colonic mucosa. A pivotal role seems to be played by an abnormal colonic neuromuscular function, as shown repeatedly in these patients, and by an altered visceral perception. There is recent evidence that these abnormalities might be related to the derangement of the enteric innervation, to an abnormal distribution of mucosal neuropeptides, and to low-grade mucosal inflammation. The latter might be responsible for the development of visceral hypersensitivity, often causing abdominal pain in a subset of these patients. PMID:27622368

  9. Abnormalities in large scale functional networks in unmedicated patients with schizophrenia and effects of risperidone

    PubMed Central

    Kraguljac, Nina Vanessa; White, David Matthew; Hadley, Jennifer Ann; Visscher, Kristina; Knight, David; ver Hoef, Lawrence; Falola, Blessing; Lahti, Adrienne Carol

    2015-01-01

    Objective To describe abnormalities in large scale functional networks in unmedicated patients with schizophrenia and to examine effects of risperidone on networks. Material and methods 34 unmedicated patients with schizophrenia and 34 matched healthy controls were enrolled in this longitudinal study. We collected resting state functional MRI data with a 3T scanner at baseline and six weeks after they were started on risperidone. In addition, a group of 19 healthy controls were scanned twice six weeks apart. Four large scale networks, the dorsal attention network, executive control network, salience network, and default mode network were identified with seed based functional connectivity analyses. Group differences in connectivity, as well as changes in connectivity over time, were assessed on the group's participant level functional connectivity maps. Results In unmedicated patients with schizophrenia we found resting state connectivity to be increased in the dorsal attention network, executive control network, and salience network relative to control participants, but not the default mode network. Dysconnectivity was attenuated after six weeks of treatment only in the dorsal attention network. Baseline connectivity in this network was also related to clinical response at six weeks of treatment with risperidone. Conclusions Our results demonstrate abnormalities in large scale functional networks in patients with schizophrenia that are modulated by risperidone only to a certain extent, underscoring the dire need for development of novel antipsychotic medications that have the ability to alleviate symptoms through attenuation of dysconnectivity. PMID:26793436

  10. Brief Report: Brain Mechanisms in Autism: Functional and Structural Abnormalities.

    ERIC Educational Resources Information Center

    Minshew, Nancy J.

    1996-01-01

    This paper summarizes results of research on functional and structural abnormalities of the brain in autism. The current concept of causation is seen to involve multiple biologic levels. A consistent profile of brain function and dysfunction across methods has been found and specific neuropathologic findings have been found; but some research…

  11. Determination of effective brain connectivity from functional connectivity with application to resting state connectivities.

    PubMed

    Robinson, P A; Sarkar, S; Pandejee, Grishma Mehta; Henderson, J A

    2014-07-01

    Neural field theory insights are used to derive effective brain connectivity matrices from the functional connectivity matrix defined by activity covariances. The symmetric case is exactly solved for a resting state system driven by white noise, in which strengths of connections, often termed effective connectivities, are inferred from functional data; these include strengths of connections that are underestimated or not detected by anatomical imaging. Proximity to criticality is calculated and found to be consistent with estimates obtainable from other methods. Links between anatomical, effective, and functional connectivity and resting state activity are quantified, with applicability to other complex networks. Proof-of-principle results are illustrated using published experimental data on anatomical connectivity and resting state functional connectivity. In particular, it is shown that functional connection matrices can be used to uncover the existence and strength of connections that are missed from anatomical connection matrices, including interhemispheric connections that are difficult to track with techniques such as diffusion spectrum imaging. PMID:25122335

  12. Dissociated functional connectivity profiles for motor and attention deficits in acute right-hemisphere stroke.

    PubMed

    Baldassarre, Antonello; Ramsey, Lenny; Rengachary, Jennifer; Zinn, Kristi; Siegel, Joshua S; Metcalf, Nicholas V; Strube, Michael J; Snyder, Abraham Z; Corbetta, Maurizio; Shulman, Gordon L

    2016-07-01

    Strokes often cause multiple behavioural deficits that are correlated at the population level. Here, we show that motor and attention deficits are selectively associated with abnormal patterns of resting state functional connectivity in the dorsal attention and motor networks. We measured attention and motor deficits in 44 right hemisphere-damaged patients with a first-time stroke at 1-2 weeks post-onset. The motor battery included tests that evaluated deficits in both upper and lower extremities. The attention battery assessed both spatial and non-spatial attention deficits. Summary measures for motor and attention deficits were identified through principal component analyses on the raw behavioural scores. Functional connectivity in structurally normal cortex was estimated based on the temporal correlation of blood oxygenation level-dependent signals measured at rest with functional magnetic resonance imaging. Any correlation between motor and attention deficits and between functional connectivity in the dorsal attention network and motor networks that might spuriously affect the relationship between each deficit and functional connectivity was statistically removed. We report a double dissociation between abnormal functional connectivity patterns and attention and motor deficits, respectively. Attention deficits were significantly more correlated with abnormal interhemispheric functional connectivity within the dorsal attention network than motor networks, while motor deficits were significantly more correlated with abnormal interhemispheric functional connectivity patterns within the motor networks than dorsal attention network. These findings indicate that functional connectivity patterns in structurally normal cortex following a stroke link abnormal physiology in brain networks to the corresponding behavioural deficits. PMID:27225794

  13. Abnormalities of autonomic function in the Lambert Eaton myasthenic syndrome.

    PubMed Central

    Heath, J P; Ewing, D J; Cull, R E

    1988-01-01

    Two cases of Lambert Eaton syndrome unassociated with an underlying malignancy are described. Both had mild autonomic symptoms but markedly abnormal autonomic function tests. These results are suggestive of a widespread defect in cholinergic transmission in addition to that at the skeletal neuromuscular junction. Images PMID:3361337

  14. Cognition and resting-state functional connectivity in schizophrenia.

    PubMed

    Sheffield, Julia M; Barch, Deanna M

    2016-02-01

    Individuals with schizophrenia consistently display deficits in a multitude of cognitive domains, but the neurobiological source of these cognitive impairments remains unclear. By analyzing the functional connectivity of resting-state functional magnetic resonance imaging (rs-fcMRI) data in clinical populations like schizophrenia, research groups have begun elucidating abnormalities in the intrinsic communication between specific brain regions, and assessing relationships between these abnormalities and cognitive performance in schizophrenia. Here we review studies that have reported analysis of these brain-behavior relationships. Through this systematic review we found that patients with schizophrenia display abnormalities within and between regions comprising (1) the cortico-cerebellar-striatal-thalamic loop and (2) task-positive and task-negative cortical networks. Importantly, we did not observe unique relationships between specific functional connectivity abnormalities and distinct cognitive domains, suggesting that the observed functional systems may underlie mechanisms that are shared across cognitive abilities, the disturbance of which could contribute to the "generalized" cognitive deficit found in schizophrenia. We also note several areas of methodological change that we believe will strengthen this literature. PMID:26698018

  15. A small number of abnormal brain connections predicts adult autism spectrum disorder

    PubMed Central

    Yahata, Noriaki; Morimoto, Jun; Hashimoto, Ryuichiro; Lisi, Giuseppe; Shibata, Kazuhisa; Kawakubo, Yuki; Kuwabara, Hitoshi; Kuroda, Miho; Yamada, Takashi; Megumi, Fukuda; Imamizu, Hiroshi; Náñez Sr, José E.; Takahashi, Hidehiko; Okamoto, Yasumasa; Kasai, Kiyoto; Kato, Nobumasa; Sasaki, Yuka; Watanabe, Takeo; Kawato, Mitsuo

    2016-01-01

    Although autism spectrum disorder (ASD) is a serious lifelong condition, its underlying neural mechanism remains unclear. Recently, neuroimaging-based classifiers for ASD and typically developed (TD) individuals were developed to identify the abnormality of functional connections (FCs). Due to over-fitting and interferential effects of varying measurement conditions and demographic distributions, no classifiers have been strictly validated for independent cohorts. Here we overcome these difficulties by developing a novel machine-learning algorithm that identifies a small number of FCs that separates ASD versus TD. The classifier achieves high accuracy for a Japanese discovery cohort and demonstrates a remarkable degree of generalization for two independent validation cohorts in the USA and Japan. The developed ASD classifier does not distinguish individuals with major depressive disorder and attention-deficit hyperactivity disorder from their controls but moderately distinguishes patients with schizophrenia from their controls. The results leave open the viable possibility of exploring neuroimaging-based dimensions quantifying the multiple-disorder spectrum. PMID:27075704

  16. A small number of abnormal brain connections predicts adult autism spectrum disorder.

    PubMed

    Yahata, Noriaki; Morimoto, Jun; Hashimoto, Ryuichiro; Lisi, Giuseppe; Shibata, Kazuhisa; Kawakubo, Yuki; Kuwabara, Hitoshi; Kuroda, Miho; Yamada, Takashi; Megumi, Fukuda; Imamizu, Hiroshi; Náñez, José E; Takahashi, Hidehiko; Okamoto, Yasumasa; Kasai, Kiyoto; Kato, Nobumasa; Sasaki, Yuka; Watanabe, Takeo; Kawato, Mitsuo

    2016-01-01

    Although autism spectrum disorder (ASD) is a serious lifelong condition, its underlying neural mechanism remains unclear. Recently, neuroimaging-based classifiers for ASD and typically developed (TD) individuals were developed to identify the abnormality of functional connections (FCs). Due to over-fitting and interferential effects of varying measurement conditions and demographic distributions, no classifiers have been strictly validated for independent cohorts. Here we overcome these difficulties by developing a novel machine-learning algorithm that identifies a small number of FCs that separates ASD versus TD. The classifier achieves high accuracy for a Japanese discovery cohort and demonstrates a remarkable degree of generalization for two independent validation cohorts in the USA and Japan. The developed ASD classifier does not distinguish individuals with major depressive disorder and attention-deficit hyperactivity disorder from their controls but moderately distinguishes patients with schizophrenia from their controls. The results leave open the viable possibility of exploring neuroimaging-based dimensions quantifying the multiple-disorder spectrum. PMID:27075704

  17. Reduced Functional Connectivity during Working Memory in Turner Syndrome

    PubMed Central

    Dunkin, Bria; Hong, David S.; Reiss, Allan L.

    2011-01-01

    Turner syndrome (TS) is a genetic disorder affecting females, resulting from the complete or partial absence of an X chromosome. The cognitive profile of TS shows relative strengths in the verbal domain and weaknesses in the procedural domain, including working memory. Neuroimaging studies have identified differences in the morphology of the parietal lobes, and white matter pathways linking frontal and parietal regions, as well as abnormal activation in dorsal frontal and parietal regions. Taken together these findings suggest that abnormal functional connectivity between frontal and parietal regions may be related to working memory impairments in TS, a hypothesis we tested in the present study. We scanned TS and typically developing participants with functional magnetic resonance imaging while they performed visuospatial and phonological working memory tasks. We generated a seed region in parietal cortex based on structural differences in TS and found that functional connectivity with dorsal frontal regions was reduced during working memory in TS. Finally, we found that connectivity was correlated with task performance in TS. These findings suggest that structural brain abnormalities in TS affect not only regional activity but also the functional interactions between regions and that this has important consequences for behavior. PMID:21441396

  18. Abnormal functional architecture of amygdala-centered networks in adolescent posttraumatic stress disorder.

    PubMed

    Aghajani, Moji; Veer, Ilya M; van Hoof, Marie-José; Rombouts, Serge A R B; van der Wee, Nic J; Vermeiren, Robert R J M

    2016-03-01

    Posttraumatic stress disorder (PTSD) is a prevalent, debilitating, and difficult to treat psychiatric disorder. Very little is known of how PTSD affects neuroplasticity in the developing adolescent brain. Whereas multiple lines of research implicate amygdala-centered network dysfunction in the pathophysiology of adult PTSD, no study has yet examined the functional architecture of amygdala subregional networks in adolescent PTSD. Using intrinsic functional connectivity analysis, we investigated functional connectivity of the basolateral (BLA) and centromedial (CMA) amygdala in 19 sexually abused adolescents with PTSD relative to 23 matched controls. Additionally, we examined whether altered amygdala subregional connectivity coincides with abnormal grey matter volume of the amygdaloid complex. Our analysis revealed abnormal amygdalar connectivity and morphology in adolescent PTSD patients. More specifically, PTSD patients showed diminished right BLA connectivity with a cluster including dorsal and ventral portions of the anterior cingulate and medial prefrontal cortices (p < 0.05, corrected). In contrast, PTSD patients showed increased left CMA connectivity with a cluster including the orbitofrontal and subcallosal cortices (p < 0.05, corrected). Critically, these connectivity changes coincided with diminished grey matter volume within BLA and CMA subnuclei (p < 0.05, corrected), with CMA connectivity shifts additionally relating to more severe symptoms of PTSD. These findings provide unique insights into how perturbations in major amygdalar circuits could hamper fear regulation and drive excessive acquisition and expression of fear in PTSD. As such, they represent an important step toward characterizing the neurocircuitry of adolescent PTSD, thereby informing the development of reliable biomarkers and potential therapeutic targets. PMID:26859310

  19. The abnormal electrostatic discharge of a no-connect metal cover in a ceramic packaging device

    NASA Astrophysics Data System (ADS)

    Song, Li; Chuanbin, Zeng; Jiajun, Luo; Zhengsheng, Han

    2013-08-01

    The human body model (HBM) stress of a no-connect metal cover is tested to obtain the characteristics of abnormal electrostatic discharge, including current waveforms and peak current under varied stress voltage and device failure voltage. A new discharge model called the "sparkover-induced model" is proposed based on the results. Then, failure mechanism analysis and model simulation are performed to prove that the transient peak current caused by a sparkover of low arc impedance will result in the devices' premature damage when the potential difference between the no-connect metal cover and the chip exceeds the threshold voltage of sparkover.

  20. Random geometric graphs with general connection functions

    NASA Astrophysics Data System (ADS)

    Dettmann, Carl P.; Georgiou, Orestis

    2016-03-01

    In the original (1961) Gilbert model of random geometric graphs, nodes are placed according to a Poisson point process, and links formed between those within a fixed range. Motivated by wireless ad hoc networks "soft" or "probabilistic" connection models have recently been introduced, involving a "connection function" H (r ) that gives the probability that two nodes at distance r are linked (directly connect). In many applications (not only wireless networks), it is desirable that the graph is connected; that is, every node is linked to every other node in a multihop fashion. Here the connection probability of a dense network in a convex domain in two or three dimensions is expressed in terms of contributions from boundary components for a very general class of connection functions. It turns out that only a few quantities such as moments of the connection function appear. Good agreement is found with special cases from previous studies and with numerical simulations.

  1. Structural and functional connectivity in traumatic brain injury

    PubMed Central

    Xiao, Hui; Yang, Yang; Xi, Ji-hui; Chen, Zi-qian

    2015-01-01

    Traumatic brain injury survivors often experience cognitive deficits and neuropsychiatric symptoms. However, the neurobiological mechanisms underlying specific impairments are not fully understood. Advances in neuroimaging techniques (such as diffusion tensor imaging and functional MRI) have given us new insights on structural and functional connectivity patterns of the human brain in both health and disease. The connectome derived from connectivity maps reflects the entire constellation of distributed brain networks. Using these powerful neuroimaging approaches, changes at the microstructural level can be detected through regional and global properties of neuronal networks. Here we will review recent developments in the study of brain network abnormalities in traumatic brain injury, mainly focusing on structural and functional connectivity. Some connectomic studies have provided interesting insights into the neurological dysfunction that occurs following traumatic brain injury. These techniques could eventually be helpful in developing imaging biomarkers of cognitive and neurobehavioral sequelae, as well as predicting outcome and prognosis. PMID:26889200

  2. Left-Hemispheric Microstructural Abnormalities in Children With High Functioning Autism Spectrum Disorder

    PubMed Central

    Peterson, Daniel; Mahajan, Rajneesh; Crocetti, Deana; Mejia, Amanda; Mostofsky, Stewart

    2014-01-01

    Current theories of the neurobiological basis of Autism Spectrum Disorder (ASD) posit an altered pattern of connectivity in large-scale brain networks. Here we used Diffusion Tensor Imaging to investigate the microstructural properties of the white matter that mediates inter-regional connectivity in 36 high-functioning children with ASD (HF-ASD), as compared to 37 controls. By employing an atlas-based analysis using LDDMM registration, a widespread, but left-lateralized pattern of abnormalities was revealed. The Mean Diffusivity (MD) of water in the white matter of HF-ASD children was significantly elevated throughout the left hemisphere, particularly in the outer-zone cortical white matter. Across diagnostic groups there was a significant effect of age on left hemisphere MD, with a similar reduction in MD during childhood in both TD and HF-ASD children. The increased MD in children with HF-ASD suggests hypomyelination, and may reflect increased short-range cortico-cortical connections subsequent to early white matter overgrowth. These findings also highlight left hemispheric connectivity as relevant to the pathophysiology of ASD, and indicate that the spatial distribution of microstructural abnormalities in HF-ASD is widespread, and left-lateralized. This altered left-hemispheric connectivity may contribute to deficits in communication and praxis observed in ASD. PMID:25256103

  3. Abnormal thyroid function tests in children on ethionamide treatment.

    PubMed

    Thee, S; Zöllner, E W; Willemse, M; Hesseling, A C; Magdorf, K; Schaaf, H S

    2011-09-01

    Ethionamide (ETH) treatment may cause hypothyroidism. Clinical data, serum thyroid stimulating hormone (TSH) and free thyroxine (fT4) levels were retrospectively assessed in 137 children receiving anti-tuberculosis treatment including ETH. Abnormal thyroid function tests (TFTs) were recorded in 79 (58%) children: elevated serum TSH and suppressed fT4 (n = 30), isolated elevated serum TSH (n = 20), isolated low serum fT4 (n = 28) and isolated low TSH (n = 1). The risk for biochemical hypothyroidism was higher for children on regimens including para-aminosalicylic acid and in human immunodeficiency virus infected children. TFT abnormalities are frequent in children on ETH and are mainly due to primary hypothyroidism or euthyroid sick syndrome. PMID:21943844

  4. Associations between Kidney Function and Subclinical Cardiac Abnormalities in CKD

    PubMed Central

    Hsu, Chi-yuan; Li, Yongmei; Mishra, Rakesh K.; Keane, Martin; Rosas, Sylvia E.; Dries, Daniel; Xie, Dawei; Chen, Jing; He, Jiang; Anderson, Amanda; Go, Alan S.; Shlipak, Michael G.

    2012-01-01

    Heart failure is a common consequence of CKD, and it portends high risk for mortality. However, among patients without known heart failure, the associations of different stages of estimated GFR (eGFR) with changes in cardiac structure and function are not well described. Here, we performed a cross-sectional analysis to study these associations among 3487 participants of the Chronic Renal Insufficiency Cohort Study. We estimated GFR using cystatin C. The prevalence of left ventricular hypertrophy (LVH) assessed by echocardiography was 32%, 48%, 57%, and 75% for eGFR categories ≥60, 45–59, 30–44, and <30 ml/min per 1.73 m2, respectively. In fully adjusted multivariable analyses, subjects with eGFR levels of <30 ml/min per 1.73 m2 had twofold higher odds of LVH (OR=2.20, 95% CI=1.40–3.40; P<0.001) relative to subjects with eGFR≥60 ml/min per 1.73 m2. This reduction in kidney function also significantly associated with abnormal LV geometry but not diastolic or systolic dysfunction. An eGFR of 30–44 ml/min per 1.73 m2 also significantly associated with LVH and abnormal LV geometry compared with eGFR≥60 ml/min per 1.73 m2. In summary, in this large CKD cohort, reduced kidney function associated with abnormal cardiac structure. We did not detect significant associations between kidney function and systolic or diastolic function after adjusting for potential confounding variables. PMID:22935481

  5. A Preliminary Study of Functional Connectivity in Comorbid Adolescent Depression

    PubMed Central

    Cullen, Kathryn R.; Gee, Dylan G.; Klimes-Dougan, Bonnie; Gabbay, Vilma; Hulvershorn, Leslie; Mueller, Bryon A.; Camchong, Jazmin; Bell, Christopher J.; Houri, Alaa; Kumra, Sanjiv; Lim, Kelvin O.; Castellanos, F. Xavier; Milham, Michael P.

    2009-01-01

    Major Depressive Disorder (MDD) begins frequently in adolescence and is associated with severe outcomes, but the developmental neurobiology of MDD is not well understood. Research in adults has implicated fronto-limbic neural networks in the pathophysiology of MDD, particularly in relation to the subgenual anterior cingulate cortex (ACC). Developmental changes in brain networks during adolescence highlight the need to examine MDD-related circuitry in teens separately from adults. Using resting state functional magnetic resonance imaging (fMRI), this study examined functional connectivity in adolescents with MDD (n=12) and healthy adolescents (n=14). Seed-based connectivity analysis revealed that adolescents with MDD have decreased functional connectivity in a subgenual ACC-based neural network that includes the supragenual ACC (BA 32), the right medial frontal cortex (BA 10), the left inferior (BA 47) and superior frontal cortex (BA 22), superior temporal gyrus (BA 22), and the insular cortex (BA 13). These preliminary data suggest that MDD in adolescence is associated with abnormal connectivity within neural circuits that mediate emotion processing. Future research in larger, un-medicated samples will be necessary to confirm this finding. We conclude that hypothesis-driven, seed-based analyses of resting state fMRI data hold promise for advancing our current understanding of abnormal development of neural circuitry in adolescents with MDD. PMID:19446602

  6. Energetic cost of brain functional connectivity

    PubMed Central

    Tomasi, Dardo; Wang, Gene-Jack; Volkow, Nora D.

    2013-01-01

    The brain's functional connectivity is complex, has high energetic cost, and requires efficient use of glucose, the brain's main energy source. It has been proposed that regions with a high degree of functional connectivity are energy efficient and can minimize consumption of glucose. However, the relationship between functional connectivity and energy consumption in the brain is poorly understood. To address this neglect, here we propose a simple model for the energy demands of brain functional connectivity, which we tested with positron emission tomography and MRI in 54 healthy volunteers at rest. Higher glucose metabolism was associated with proportionally larger MRI signal amplitudes, and a higher degree of connectivity was associated with nonlinear increases in metabolism, supporting our hypothesis for the energy efficiency of the connectivity hubs. Basal metabolism (in the absence of connectivity) accounted for 30% of brain glucose utilization, which suggests that the spontaneous brain activity accounts for 70% of the energy consumed by the brain. The energy efficiency of the connectivity hubs was higher for ventral precuneus, cerebellum, and subcortical hubs than for cortical hubs. The higher energy demands of brain communication that hinges upon higher connectivity could render brain hubs more vulnerable to deficits in energy delivery or utilization and help explain their sensitivity to neurodegenerative conditions, such as Alzheimer’s disease. PMID:23898179

  7. Altered Immune Function Associated with Disordered Neural Connectivity and Executive Dysfunctions: A Neurophysiological Study on Children with Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Han, Yvonne M. Y.; Chan, Agnes S.; Sze, Sophia L.; Cheung, Mei-Chun; Wong, Chun-kwok; Lam, Joseph M. K.; Poon, Priscilla M. K.

    2013-01-01

    Previous studies have shown that children with autism spectrum disorders (ASDs) have impaired executive function, disordered neural connectivity, and abnormal immunologic function. The present study examined whether these abnormalities were associated. Seventeen high-functioning (HFA) and 17 low-functioning (LFA) children with ASD, aged 8-17…

  8. Abnormalities of vascular structure and function in pediatric hypertension.

    PubMed

    Urbina, Elaine M

    2016-07-01

    Hypertension is associated with adverse cardiovascular (CV) events in adults. Measures of vascular structure and function, including increased carotid intima-media thickness (cIMT) and elevated arterial stiffness predict hard CV events in adulthood. Newer data suggest that abnormalities in target organ damage are occurring in adolescents and young adults with high blood pressure. In this review, we discuss the techniques for measuring vascular dysfunction in young people and the evidence linking blood pressure levels to this type of target organ damage. PMID:26275663

  9. Abnormal subendocardial function in restrictive left ventricular disease.

    PubMed Central

    Henein, M Y; Gibson, D G

    1994-01-01

    OBJECTIVE--To study possible disturbances in left ventricular long axis function in patients with a restrictive filling pattern. DESIGN--Prospective examination of the left ventricular transverse and longitudinal axes, transmitral flow, and the apexcardiogram. SETTING--A tertiary referral centre for cardiac diseases. SUBJECTS--21 normal subjects, age (SD) 51(11); 30 patients of similar age with a restrictive left ventricular filling pattern, defined as short early diastolic deceleration time less than the lower 95% confidence limit of the normal value (120 ms). 20 patients had a normal and 10 had an increased left ventricular end diastolic cavity size. RESULTS--Mitral Doppler echocardiography: E wave velocity was high only in patients with a normal cavity size. A wave velocity was greatly reduced in the two groups (P < 0.001) so that the E/A ratio was abnormally high. The relative A wave amplitude on the apexcardiogram was greatly increased in the two groups: 46(15)% (mean (SD)) and 54(4)% v 15(5)%. Minor axis: Fractional shortening was reduced from 30(10)% to 17(7)% in patients with normal cavity size and to 13(4.2)% in those with a dilated cavity (P < 0.001), as was the posterior wall thickening fraction from 100(30)% to 42(20)% and 50(25)% respectively (P < 0.001). Total systolic epicardial motion was normal and isovolumic relaxation time was short in the two groups. Long axis: Left ventricular abnormalities included reduced total amplitude of motion and its component during atrial systole (P < 0.001 for the two groups at both sites). Peak long axis shortening and lengthening were decreased at both left ventricular sites (P < 0.001). The time intervals from q wave of the electrocardiogram and A2 (aortic valve closure) to the onset of shortening and lengthening respectively were increased (both P < 0.001). Right ventricular long axis function was similarly affected but to a lesser extent. CONCLUSION--Left ventricular long axis function is consistently abnormal in

  10. Anatomical and functional brain abnormalities in unmedicated major depressive disorder

    PubMed Central

    Yang, Xiao; Ma, Xiaojuan; Li, Mingli; Liu, Ye; Zhang, Jian; Huang, Bin; Zhao, Liansheng; Deng, Wei; Li, Tao; Ma, Xiaohong

    2015-01-01

    Background Using magnetic resonance imaging (MRI) and resting-state functional magnetic resonance imaging (rsfMRI) to explore the mechanism of brain structure and function in unmedicated patients with major depressive disorder (MDD). Patients and methods Fifty patients with MDD and 50 matched healthy control participants free of psychotropic medication underwent high-resolution structural and rsfMRI scanning. Optimized diffeomorphic anatomical registration through exponentiated lie algebra and the Data Processing Assistant for rsfMRI were used to find potential differences in gray-matter volume (GMV) and regional homogeneity (ReHo) between the two groups. A Pearson correlation model was used to analyze associations of morphometric and functional changes with clinical symptoms. Results Compared to healthy controls, patients with MDD showed significant GMV increase in the left posterior cingulate gyrus and GMV decrease in the left lingual gyrus (P<0.001, uncorrected). In ReHo analysis, values were significantly increased in the left precuneus and decreased in the left putamen (P<0.001, uncorrected) in patients with MDD compared to healthy controls. There was no overlap between anatomical and functional changes. Linear correlation suggested no significant correlation between mean GMV values within regions with anatomical abnormality and ReHo values in regions with functional abnormality in the patient group. These changes were not significantly correlated with symptom severity. Conclusion Our study suggests a dissociation pattern of brain regions with anatomical and functional alterations in unmedicated patients with MDD, especially with regard to GMV and ReHo. PMID:26425096

  11. Cannabinoid Modulation of Functional Connectivity within Regions Processing Attentional Salience

    PubMed Central

    Bhattacharyya, Sagnik; Falkenberg, Irina; Martin-Santos, Rocio; Atakan, Zerrin; Crippa, Jose A; Giampietro, Vincent; Brammer, Mick; McGuire, Philip

    2015-01-01

    There is now considerable evidence to support the hypothesis that psychotic symptoms are the result of abnormal salience attribution, and that the attribution of salience is largely mediated through the prefrontal cortex, the striatum, and the hippocampus. Although these areas show differential activation under the influence of delta-9-tetrahydrocannabinol (delta-9-THC) and cannabidiol (CBD), the two major derivatives of cannabis sativa, little is known about the effects of these cannabinoids on the functional connectivity between these regions. We investigated this in healthy occasional cannabis users by employing event-related functional magnetic resonance imaging (fMRI) following oral administration of delta-9-THC, CBD, or a placebo capsule. Employing a seed cluster-based functional connectivity analysis that involved using the average time series from each seed cluster for a whole-brain correlational analysis, we investigated the effect of drug condition on functional connectivity between the seed clusters and the rest of the brain during an oddball salience processing task. Relative to the placebo condition, delta-9-THC and CBD had opposite effects on the functional connectivity between the dorsal striatum, the prefrontal cortex, and the hippocampus. Delta-9-THC reduced fronto-striatal connectivity, which was related to its effect on task performance, whereas this connection was enhanced by CBD. Conversely, mediotemporal-prefrontal connectivity was enhanced by delta-9-THC and reduced by CBD. Our results suggest that the functional integration of brain regions involved in salience processing is differentially modulated by single doses of delta-9-THC and CBD and that this relates to the processing of salient stimuli. PMID:25249057

  12. Cannabinoid modulation of functional connectivity within regions processing attentional salience.

    PubMed

    Bhattacharyya, Sagnik; Falkenberg, Irina; Martin-Santos, Rocio; Atakan, Zerrin; Crippa, Jose A; Giampietro, Vincent; Brammer, Mick; McGuire, Philip

    2015-05-01

    There is now considerable evidence to support the hypothesis that psychotic symptoms are the result of abnormal salience attribution, and that the attribution of salience is largely mediated through the prefrontal cortex, the striatum, and the hippocampus. Although these areas show differential activation under the influence of delta-9-tetrahydrocannabinol (delta-9-THC) and cannabidiol (CBD), the two major derivatives of cannabis sativa, little is known about the effects of these cannabinoids on the functional connectivity between these regions. We investigated this in healthy occasional cannabis users by employing event-related functional magnetic resonance imaging (fMRI) following oral administration of delta-9-THC, CBD, or a placebo capsule. Employing a seed cluster-based functional connectivity analysis that involved using the average time series from each seed cluster for a whole-brain correlational analysis, we investigated the effect of drug condition on functional connectivity between the seed clusters and the rest of the brain during an oddball salience processing task. Relative to the placebo condition, delta-9-THC and CBD had opposite effects on the functional connectivity between the dorsal striatum, the prefrontal cortex, and the hippocampus. Delta-9-THC reduced fronto-striatal connectivity, which was related to its effect on task performance, whereas this connection was enhanced by CBD. Conversely, mediotemporal-prefrontal connectivity was enhanced by delta-9-THC and reduced by CBD. Our results suggest that the functional integration of brain regions involved in salience processing is differentially modulated by single doses of delta-9-THC and CBD and that this relates to the processing of salient stimuli. PMID:25249057

  13. Abnormal Default System Functioning in Depression: Implications for Emotion Regulation.

    PubMed

    Messina, Irene; Bianco, Francesca; Cusinato, Maria; Calvo, Vincenzo; Sambin, Marco

    2016-01-01

    Depression is widely seen as the result of difficulties in regulating emotions. Based on neuroimaging studies on voluntary emotion regulation, neurobiological models have focused on the concept of cognitive control, considering emotion regulation as a shift toward involving controlled processes associated with activation of the prefrontal and parietal executive areas, instead of responding automatically to emotional stimuli. According to such models, the weaker executive area activation observed in depressed patients is attributable to a lack of cognitive control over negative emotions. Going beyond the concept of cognitive control, psychodynamic models describe the development of individuals' capacity to regulate their emotional states in mother-infant interactions during childhood, through the construction of the representation of the self, others, and relationships. In this mini-review, we link these psychodynamic models with recent findings regarding the abnormal functioning of the default system in depression. Consistently with psychodynamic models, psychological functions associated with the default system include self-related processing, semantic processes, and implicit forms of emotion regulation. The abnormal activation of the default system observed in depression may explain the dysfunctional aspects of emotion regulation typical of the condition, such as an exaggerated negative self-focus and rumination on self-esteem issues. We also discuss the clinical implications of these findings with reference to the therapeutic relationship as a key tool for revisiting impaired or distorted representations of the self and relational objects. PMID:27375536

  14. Abnormal Default System Functioning in Depression: Implications for Emotion Regulation

    PubMed Central

    Messina, Irene; Bianco, Francesca; Cusinato, Maria; Calvo, Vincenzo; Sambin, Marco

    2016-01-01

    Depression is widely seen as the result of difficulties in regulating emotions. Based on neuroimaging studies on voluntary emotion regulation, neurobiological models have focused on the concept of cognitive control, considering emotion regulation as a shift toward involving controlled processes associated with activation of the prefrontal and parietal executive areas, instead of responding automatically to emotional stimuli. According to such models, the weaker executive area activation observed in depressed patients is attributable to a lack of cognitive control over negative emotions. Going beyond the concept of cognitive control, psychodynamic models describe the development of individuals’ capacity to regulate their emotional states in mother-infant interactions during childhood, through the construction of the representation of the self, others, and relationships. In this mini-review, we link these psychodynamic models with recent findings regarding the abnormal functioning of the default system in depression. Consistently with psychodynamic models, psychological functions associated with the default system include self-related processing, semantic processes, and implicit forms of emotion regulation. The abnormal activation of the default system observed in depression may explain the dysfunctional aspects of emotion regulation typical of the condition, such as an exaggerated negative self-focus and rumination on self-esteem issues. We also discuss the clinical implications of these findings with reference to the therapeutic relationship as a key tool for revisiting impaired or distorted representations of the self and relational objects. PMID:27375536

  15. Abnormalities of hippocampal-cortical connectivity in temporal lobe epilepsy patients with hippocampal sclerosis

    NASA Astrophysics Data System (ADS)

    Li, Wenjing; He, Huiguang; Lu, Jingjing; Wang, Chunheng; Li, Meng; Lv, Bin; Jin, Zhengyu

    2011-03-01

    Hippocampal sclerosis (HS) is the most common damage seen in the patients with temporal lobe epilepsy (TLE). In the present study, the hippocampal-cortical connectivity was defined as the correlation between the hippocampal volume and cortical thickness at each vertex throughout the whole brain. We aimed to investigate the differences of ipsilateral hippocampal-cortical connectivity between the unilateral TLE-HS patients and the normal controls. In our study, the bilateral hippocampal volumes were first measured in each subject, and we found that the ipsilateral hippocampal volume significantly decreased in the left TLE-HS patients. Then, group analysis showed significant thinner average cortical thickness of the whole brain in the left TLE-HS patients compared with the normal controls. We found significantly increased ipsilateral hippocampal-cortical connectivity in the bilateral superior temporal gyrus, the right cingulate gyrus and the left parahippocampal gyrus of the left TLE-HS patients, which indicated structural vulnerability related to the hippocampus atrophy in the patient group. However, for the right TLE-HS patients, no significant differences were found between the patients and the normal controls, regardless of the ipsilateral hippocampal volume, the average cortical thickness or the patterns of hippocampal-cortical connectivity, which might be related to less atrophies observed in the MRI scans. Our study provided more evidence for the structural abnormalities in the unilateral TLE-HS patients.

  16. Disrupted resting-state insular subregions functional connectivity in post-traumatic stress disorder.

    PubMed

    Zhang, Youxue; Xie, Bing; Chen, Heng; Li, Meiling; Guo, Xiaonan; Chen, Huafu

    2016-07-01

    Post-traumatic stress disorder (PTSD) is suggested to be a structural and functional abnormality in the insula. The insula, which consists of distinct subregions with various patterns of connectivity, displays complex and diverse functions. However, whether these insular subregions have different patterns of connectivity in PTSD remains unclear. Investigating the abnormal functional connectivity of the insular subregions is crucial to reveal its potential effect on diseases specifically PTSD. This study uses a seed-based method to investigate the altered resting-state functional connectivity of insular subregions in PTSD. We found that patients with PTSD showed reduced functional connectivity compared with healthy controls (HCs) between the left ventral anterior insula and the anterior cingulate cortex. The patients with PTSD also exhibited decreased functional connectivity between the right posterior insula and left inferior parietal lobe, and the postcentral gyrus relative to HCs. These results suggest the involvement of altered functional connectivity of insular subregions in the abnormal regulation of emotion and processing of somatosensory information in patients with PTSD. Such impairments in functional connectivity patterns of the insular subregions may advance our understanding of the pathophysiological basis underlying PTSD. PMID:27399097

  17. Functional connectivity magnetic resonance imaging classification of autism.

    PubMed

    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

    2011-12-01

    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 whether functional connectivity is sufficiently robust to be used as a diagnostic or prognostic metric in individual patients with autism. We obtained pairwise functional connectivity measurements from a lattice of 7266 regions of interest covering the entire grey matter (26.4 million connections) in a well-characterized set of 40 male adolescents and young adults with autism and 40 age-, sex- and IQ-matched typically developing subjects. A single resting state blood oxygen level-dependent scan of 8 min was used for the classification in each subject. A leave-one-out classifier successfully distinguished autism from control subjects with 83% sensitivity and 75% specificity for a total accuracy of 79% (P = 1.1 × 10(-7)). In subjects <20 years of age, the classifier performed at 89% accuracy (P = 5.4 × 10(-7)). In a replication dataset consisting of 21 individuals from six families with both affected and unaffected siblings, the classifier performed at 71% accuracy (91% accuracy for subjects <20 years of age). Classification scores in subjects with autism were significantly correlated with the Social Responsiveness Scale (P = 0.05), verbal IQ (P = 0.02) and the Autism Diagnostic Observation Schedule-Generic's combined social and communication subscores (P = 0.05). An analysis of informative connections demonstrated that region of interest pairs with strongest correlation values were most abnormal in autism. Negatively correlated region of interest pairs showed higher correlation in autism (less anticorrelation), possibly representing weaker inhibitory connections, particularly for long connections (Euclidean distance >10 cm

  18. Variability of structurally constrained and unconstrained functional connectivity in schizophrenia

    PubMed Central

    Yao, Ye; Liddle, Peter; Zhang, Jie; Francis, Susan

    2015-01-01

    Abstract Spatial variation in connectivity is an integral aspect of the brain's architecture. In the absence of this variability, the brain may act as a single homogenous entity without regional specialization. In this study, we investigate the variability in functional links categorized on the basis of the presence of direct structural paths (primary) or indirect paths mediated by one (secondary) or more (tertiary) brain regions ascertained by diffusion tensor imaging. We quantified the variability in functional connectivity using an unbiased estimate of unpredictability (functional connectivity entropy) in a neuropsychiatric disorder where structure‐function relationship is considered to be abnormal; 34 patients with schizophrenia and 32 healthy controls underwent DTI and resting state functional MRI scans. Less than one‐third (27.4% in patients, 27.85% in controls) of functional links between brain regions were regarded as direct primary links on the basis of DTI tractography, while the rest were secondary or tertiary. The most significant changes in the distribution of functional connectivity in schizophrenia occur in indirect tertiary paths with no direct axonal linkage in both early (P = 0.0002, d = 1.46) and late (P = 1 × 10−17, d = 4.66) stages of schizophrenia, and are not altered by the severity of symptoms, suggesting that this is an invariant feature of this illness. Unlike those with early stage illness, patients with chronic illness show some additional reduction in the distribution of connectivity among functional links that have direct structural paths (P = 0.08, d = 0.44). Our findings address a critical gap in the literature linking structure and function in schizophrenia, and demonstrate for the first time that the abnormal state of functional connectivity preferentially affects structurally unconstrained links in schizophrenia. It also raises the question of a continuum of dysconnectivity ranging from less direct

  19. Abnormal structural connectivity in the brain networks of children with hydrocephalus

    PubMed Central

    Yuan, Weihong; Holland, Scott K.; Shimony, Joshua S.; Altaye, Mekibib; Mangano, Francesco T.; Limbrick, David D.; Jones, Blaise V.; Nash, Tiffany; Rajagopal, Akila; Simpson, Sarah; Ragan, Dustin; McKinstry, Robert C.

    2015-01-01

    Increased intracranial pressure and ventriculomegaly in children with hydrocephalus are known to have adverse effects on white matter structure. This study seeks to investigate the impact of hydrocephalus on topological features of brain networks in children. The goal was to investigate structural network connectivity, at both global and regional levels, in the brains in children with hydrocephalus using graph theory analysis and diffusion tensor tractography. Three groups of children were included in the study (29 normally developing controls, 9 preoperative hydrocephalus patients, and 17 postoperative hydrocephalus patients). Graph theory analysis was applied to calculate the global network measures including small-worldness, normalized clustering coefficients, normalized characteristic path length, global efficiency, and modularity. Abnormalities in regional network parameters, including nodal degree, local efficiency, clustering coefficient, and betweenness centrality, were also compared between the two patients groups (separately) and the controls using two tailed t-test at significance level of p < 0.05 (corrected for multiple comparison). Children with hydrocephalus in both the preoperative and postoperative groups were found to have significantly lower small-worldness and lower normalized clustering coefficient than controls. Children with hydrocephalus in the postoperative group were also found to have significantly lower normalized characteristic path length and lower modularity. At regional level, significant group differences (or differences at trend level) in regional network measures were found between hydrocephalus patients and the controls in a series of brain regions including the medial occipital gyrus, medial frontal gyrus, thalamus, cingulate gyrus, lingual gyrus, rectal gyrus, caudate, cuneus, and insular. Our data showed that structural connectivity analysis using graph theory and diffusion tensor tractography is sensitive to detect

  20. Abnormal structural connectivity in the brain networks of children with hydrocephalus.

    PubMed

    Yuan, Weihong; Holland, Scott K; Shimony, Joshua S; Altaye, Mekibib; Mangano, Francesco T; Limbrick, David D; Jones, Blaise V; Nash, Tiffany; Rajagopal, Akila; Simpson, Sarah; Ragan, Dustin; McKinstry, Robert C

    2015-01-01

    Increased intracranial pressure and ventriculomegaly in children with hydrocephalus are known to have adverse effects on white matter structure. This study seeks to investigate the impact of hydrocephalus on topological features of brain networks in children. The goal was to investigate structural network connectivity, at both global and regional levels, in the brains in children with hydrocephalus using graph theory analysis and diffusion tensor tractography. Three groups of children were included in the study (29 normally developing controls, 9 preoperative hydrocephalus patients, and 17 postoperative hydrocephalus patients). Graph theory analysis was applied to calculate the global network measures including small-worldness, normalized clustering coefficients, normalized characteristic path length, global efficiency, and modularity. Abnormalities in regional network parameters, including nodal degree, local efficiency, clustering coefficient, and betweenness centrality, were also compared between the two patients groups (separately) and the controls using two tailed t-test at significance level of p < 0.05 (corrected for multiple comparison). Children with hydrocephalus in both the preoperative and postoperative groups were found to have significantly lower small-worldness and lower normalized clustering coefficient than controls. Children with hydrocephalus in the postoperative group were also found to have significantly lower normalized characteristic path length and lower modularity. At regional level, significant group differences (or differences at trend level) in regional network measures were found between hydrocephalus patients and the controls in a series of brain regions including the medial occipital gyrus, medial frontal gyrus, thalamus, cingulate gyrus, lingual gyrus, rectal gyrus, caudate, cuneus, and insular. Our data showed that structural connectivity analysis using graph theory and diffusion tensor tractography is sensitive to detect

  1. Functional connectivity homogeneity correlates with duration of temporal lobe epilepsy.

    PubMed

    Haneef, Zulfi; Chiang, Sharon; Yeh, Hsiang J; Engel, Jerome; Stern, John M

    2015-05-01

    Temporal lobe epilepsy (TLE) is often associated with progressive changes to seizures, memory, and mood during its clinical course. However, the cerebral changes related to this progression are not well understood. Because the changes may be related to changes in brain networks, we used functional connectivity MRI (fcMRI) to determine whether brain network parameters relate to the duration of TLE. Graph theory-based analysis of the sites of reported regions of TLE abnormality was performed on resting-state fMRI data in 48 subjects: 24 controls, 13 patients with left TLE, and 11 patients with right TLE. Various network parameters were analyzed including betweenness centrality (BC), clustering coefficient (CC), path length (PL), small-world index (SWI), global efficiency (GE), connectivity strength (CS), and connectivity diversity (CD). These were compared for patients with TLE as a group, compared to controls, and for patients with left and right TLE separately. The association of changes in network parameters with epilepsy duration was also evaluated. We found that CC, CS, and CD decreased in subjects with TLE compared to control subjects. Analyzed according to epilepsy duration, patients with TLE showed a progressive reduction in CD. In conclusion, we found that several network parameters decreased in patients with TLE compared to controls, which suggested reduced connectivity in TLE. Reduction in CD associated with epilepsy duration suggests a homogenization of connections over time in TLE, indicating a reduction of the normal repertoire of stronger and weaker connections to other brain regions. PMID:25873437

  2. Functional Connectivity Homogeneity Correlates with Duration of Temporal Lobe Epilepsy

    PubMed Central

    Haneef, Zulfi; Chiang, Sharon; Yeh, Hsiang J.; Engel, Jerome; Stern, John M.

    2015-01-01

    Temporal lobe epilepsy (TLE) often is associated with progressive changes to seizures, memory, and mood during its clinical course. However, the cerebral changes related to this progression are not well understood. Because the changes may be related to changes in brain networks, we used functional connectivity MRI (fcMRI) to determine whether brain network parameters relate to the duration of TLE. Graph theory based analysis of the sites of reported regions of TLE abnormality, was performed on resting state fMRI data in 48 subjects: 24 controls, 13 patients with left TLE, and 11 patients with right TLE. Various network parameters were analyzed including betweenness centrality (BC), clustering coefficient (CC), path length (PL), small-world index (SWI), global efficiency (GE), connectivity strength (CS), and connectivity diversity (CD). These were compared for TLE as a group, compared to controls, and for left and right TLE separately. Association of changes in network parameters with epilepsy duration was also evaluated. We found that CC, CS and CD were decreased in TLE, compared to control subjects. Analyzed according to epilepsy duration, TLE showed a progressive reduction in CD. In conclusion, we found that several network parameters were decreased in TLE compared to controls, which suggested reduced connectivity in TLE. Reduction in CD associated with epilepsy duration suggests a homogenization of connections over time in TLE, indicating a reduction of the normal repertoire of stronger and weaker connections to other brain regions. PMID:25873437

  3. Multimodal Imaging of Dynamic Functional Connectivity

    PubMed Central

    Tagliazucchi, Enzo; Laufs, Helmut

    2015-01-01

    The study of large-scale functional interactions in the human brain with functional magnetic resonance imaging (fMRI) extends almost to the first applications of this technology. Due to historical reasons and preconceptions about the limitations of this brain imaging method, most studies have focused on assessing connectivity over extended periods of time. It is now clear that fMRI can resolve the temporal dynamics of functional connectivity, like other faster imaging techniques such as electroencephalography and magnetoencephalography (albeit on a different temporal scale). However, the indirect nature of fMRI measurements can hinder the interpretability of the results. After briefly summarizing recent advances in the field, we discuss how the simultaneous combination of fMRI with electrophysiological activity measurements can contribute to a better understanding of dynamic functional connectivity in humans both during rest and task, wakefulness, and other brain states. PMID:25762977

  4. Abnormal synchrony and effective connectivity in patients with schizophrenia and auditory hallucinations

    PubMed Central

    de la Iglesia-Vaya, Maria; Escartí, Maria José; Molina-Mateo, Jose; Martí-Bonmatí, Luis; Gadea, Marien; Castellanos, Francisco Xavier; Aguilar García-Iturrospe, Eduardo J.; Robles, Montserrat; Biswal, Bharat B.; Sanjuan, Julio

    2014-01-01

    Auditory hallucinations (AH) are the most frequent positive symptoms in patients with schizophrenia. Hallucinations have been related to emotional processing disturbances, altered functional connectivity and effective connectivity deficits. Previously, we observed that, compared to healthy controls, the limbic network responses of patients with auditory hallucinations differed when the subjects were listening to emotionally charged words. We aimed to compare the synchrony patterns and effective connectivity of task-related networks between schizophrenia patients with and without AH and healthy controls. Schizophrenia patients with AH (n = 27) and without AH (n = 14) were compared with healthy participants (n = 31). We examined functional connectivity by analyzing correlations and cross-correlations among previously detected independent component analysis time courses. Granger causality was used to infer the information flow direction in the brain regions. The results demonstrate that the patterns of cortico-cortical functional synchrony differentiated the patients with AH from the patients without AH and from the healthy participants. Additionally, Granger-causal relationships between the networks clearly differentiated the groups. In the patients with AH, the principal causal source was an occipital–cerebellar component, versus a temporal component in the patients without AH and the healthy controls. These data indicate that an anomalous process of neural connectivity exists when patients with AH process emotional auditory stimuli. Additionally, a central role is suggested for the cerebellum in processing emotional stimuli in patients with persistent AH. PMID:25379429

  5. Abnormal synchrony and effective connectivity in patients with schizophrenia and auditory hallucinations.

    PubMed

    de la Iglesia-Vaya, Maria; Escartí, Maria José; Molina-Mateo, Jose; Martí-Bonmatí, Luis; Gadea, Marien; Castellanos, Francisco Xavier; Aguilar García-Iturrospe, Eduardo J; Robles, Montserrat; Biswal, Bharat B; Sanjuan, Julio

    2014-01-01

    Auditory hallucinations (AH) are the most frequent positive symptoms in patients with schizophrenia. Hallucinations have been related to emotional processing disturbances, altered functional connectivity and effective connectivity deficits. Previously, we observed that, compared to healthy controls, the limbic network responses of patients with auditory hallucinations differed when the subjects were listening to emotionally charged words. We aimed to compare the synchrony patterns and effective connectivity of task-related networks between schizophrenia patients with and without AH and healthy controls. Schizophrenia patients with AH (n = 27) and without AH (n = 14) were compared with healthy participants (n = 31). We examined functional connectivity by analyzing correlations and cross-correlations among previously detected independent component analysis time courses. Granger causality was used to infer the information flow direction in the brain regions. The results demonstrate that the patterns of cortico-cortical functional synchrony differentiated the patients with AH from the patients without AH and from the healthy participants. Additionally, Granger-causal relationships between the networks clearly differentiated the groups. In the patients with AH, the principal causal source was an occipital-cerebellar component, versus a temporal component in the patients without AH and the healthy controls. These data indicate that an anomalous process of neural connectivity exists when patients with AH process emotional auditory stimuli. Additionally, a central role is suggested for the cerebellum in processing emotional stimuli in patients with persistent AH. PMID:25379429

  6. Interpreting the effects of altered brain anatomical connectivity on fMRI functional connectivity: a role for computational neural modeling

    PubMed Central

    Horwitz, Barry; Hwang, Chuhern; Alstott, Jeff

    2013-01-01

    Recently, there have been a large number of studies using resting state fMRI to characterize abnormal brain connectivity in patients with a variety of neurological, psychiatric, and developmental disorders. However, interpreting what the differences in resting state fMRI functional connectivity (rsfMRI-FC) actually reflect in terms of the underlying neural pathology has proved to be elusive because of the complexity of brain anatomical connectivity. The same is the case for task-based fMRI studies. In the last few years, several groups have used large-scale neural modeling to help provide some insight into the relationship between brain anatomical connectivity and the corresponding patterns of fMRI-FC. In this paper we review several efforts at using large-scale neural modeling to investigate the relationship between structural connectivity and functional/effective connectivity to determine how alterations in structural connectivity are manifested in altered patterns of functional/effective connectivity. Because the alterations made in the anatomical connectivity between specific brain regions in the model are known in detail, one can use the results of these simulations to determine the corresponding alterations in rsfMRI-FC. Many of these simulation studies found that structural connectivity changes do not necessarily result in matching changes in functional/effective connectivity in the areas of structural modification. Often, it was observed that increases in functional/effective connectivity in the altered brain did not necessarily correspond to increases in the strength of the anatomical connection weights. Note that increases in rsfMRI-FC in patients have been interpreted in some cases as resulting from neural plasticity. These results suggest that this interpretation can be mistaken. The relevance of these simulation findings to the use of functional/effective fMRI connectivity as biomarkers for brain disorders is also discussed. PMID:24273500

  7. Resting state functional connectivity in anorexia nervosa.

    PubMed

    Phillipou, Andrea; Abel, Larry Allen; Castle, David Jonathan; Hughes, Matthew Edward; Nibbs, Richard Grant; Gurvich, Caroline; Rossell, Susan Lee

    2016-05-30

    Anorexia Nervosa (AN) is a serious psychiatric illness characterised by a disturbance in body image, a fear of weight gain and significantly low body weight. The factors involved in the genesis and maintenance of AN are unclear, though the potential neurobiological underpinnings of the condition are of increasing interest. Through the investigation of functional connectivity of the brain at rest, information relating to neuronal communication and integration of information that may relate to behaviours and cognitive symptoms can be explored. The aim of this study was to investigate functional connectivity of the default mode network, and sensorimotor and visual networks in AN. 26 females with AN and 27 healthy control participants matched for age, gender and premorbid intelligence underwent a resting state functional magnetic resonance imaging scan. Default mode network functional connectivity did not differ between groups. AN participants displayed reduced functional connectivity between the sensorimotor and visual networks, in comparison to healthy controls. This finding is discussed in terms of differences in visuospatial processing in AN and the distortion of body image experienced by these individuals. Overall, the findings suggest that sensorimotor and visual network connectivity may be related to visuospatial processing in AN, though, further research is required. PMID:27111812

  8. A systematic framework for functional connectivity measures

    PubMed Central

    Wang, Huifang E.; Bénar, Christian G.; Quilichini, Pascale P.; Friston, Karl J.; Jirsa, Viktor K.; Bernard, Christophe

    2014-01-01

    Various methods have been proposed to characterize the functional connectivity between nodes in a network measured with different modalities (electrophysiology, functional magnetic resonance imaging etc.). Since different measures of functional connectivity yield different results for the same dataset, it is important to assess when and how they can be used. In this work, we provide a systematic framework for evaluating the performance of a large range of functional connectivity measures—based upon a comprehensive portfolio of models generating measurable responses. Specifically, we benchmarked 42 methods using 10,000 simulated datasets from 5 different types of generative models with different connectivity structures. Since all functional connectivity methods require the setting of some parameters (window size and number, model order etc.), we first optimized these parameters using performance criteria based upon (threshold free) ROC analysis. We then evaluated the performance of the methods on data simulated with different types of models. Finally, we assessed the performance of the methods against different levels of signal-to-noise ratios and network configurations. A MATLAB toolbox is provided to perform such analyses using other methods and simulated datasets. PMID:25538556

  9. Hypercatabolism of normal IgG; an unexplained immunoglobulin abnormality in the connective tissue diseases

    PubMed Central

    Wochner, R. Dean

    1970-01-01

    The metabolism of radioiodinated IgG was studied in a series of 42 patients with connective tissue diseases (16 systemic lupus erythematosus, nine rheumatoid arthritis, five polymyositis, five vasculitis, and seven miscellaneous diagnoses). Fractional catabolic rates were increased and survival half-lives were shortened in all diagnostic categories indicating hypercatabolism of IgG. This hypercatabolism was masked by increased IgG synthesis, resulting in elevated serum concentrations of IgG in patients with systemic lupus erythematosus and rheumatoid arthritis and in generally normal concentrations in the others. The metabolism of iodinated IgM was also studied in eight patients with systemic lupus erythematosus, in seven with rheumatoid arthritis, and in 12 controls. The fractional catabolic rates were normal in both groups of patients. Serum concentrations of both IgM and IgA were moderately elevated in all diagnostic categories. Serum albumin metabolism was entirely normal in the nine subjects studied who were not receiving corticosteroids; in three who were receiving them, moderate hypercatabolism was observed. The hypercatabolism of IgG could not be accounted for by factors previously known to alter IgG metabolism. It was not observed in 15 patients with other chronic, inflammatory diseases and was not explained by concomitant administration of adrenal corticosteroids to some patients. Identical results were obtained whether the IgG was obtained from a patient himself or from a normal donor, demonstrating that the hypercatabolism is a host defect and not an abnormality of the protein. Thus, patients with connective tissue disease of several different diagnostic categories have been shown to have an unexplained immunoglobulin abnormality: they catabolize normal IgG at an accelerated rate. PMID:5415673

  10. Decreased coherence and functional connectivity of electroencephalograph in Alzheimer's disease

    NASA Astrophysics Data System (ADS)

    Wang, Ruofan; Wang, Jiang; Yu, Haitao; Wei, Xile; Yang, Chen; Deng, Bin

    2014-09-01

    In this paper, we investigate the abnormalities of electroencephalograph (EEG) signals in the Alzheimer's disease (AD) by analyzing 16-scalp electrodes EEG signals and make a comparison with the normal controls. Coherence is introduced to measure the pair-wise normalized linear synchrony and functional correlations between two EEG signals in different frequency domains, and graph analysis is further used to investigate the influence of AD on the functional connectivity of human brain. Data analysis results show that, compared with the control group, the pair-wise coherence of AD group is significantly decreased, especially for the theta and alpha frequency bands in the frontal and parieto-occipital regions. Furthermore, functional connectivity among different brain regions is reconstructed based on EEG, which exhibit obvious small-world properties. Graph analysis demonstrates that the local functional connections between regions for AD decrease. In addition, it is found that small-world properties of AD networks are largely weakened, by calculating its average path lengths, clustering coefficients, global efficiency, local efficiency, and small-worldness. The obtained results show that both pair-wise coherence and functional network can be taken as effective measures to distinguish AD patients from the normal, which may benefit our understanding of the disease.

  11. Altered Functional Connectivity between Emotional and Cognitive Resting State Networks in Euthymic Bipolar I Disorder Patients

    PubMed Central

    Lois, Giannis; Linke, Julia; Wessa, Michèle

    2014-01-01

    Bipolar disorder is characterized by a functional imbalance between hyperactive ventral/limbic areas and hypoactive dorsal/cognitive brain regions potentially contributing to affective and cognitive symptoms. Resting-state studies in bipolar disorder have identified abnormal functional connectivity between these brain regions. However, most of these studies used a seed-based approach, thus restricting the number of regions that were analyzed. Using data-driven approaches, researchers identified resting state networks whose spatial maps overlap with frontolimbic areas such as the default mode network, the frontoparietal networks, the salient network, and the meso/paralimbic network. These networks are specifically engaged during affective and cognitive tasks and preliminary evidence suggests that functional connectivity within and between some of these networks is impaired in bipolar disorder. The present study used independent component analysis and functional network connectivity approaches to investigate functional connectivity within and between these resting state networks in bipolar disorder. We compared 30 euthymic bipolar I disorder patients and 35 age- and gender-matched healthy controls. Inter-network connectivity analysis revealed increased functional connectivity between the meso/paralimbic and the right frontoparietal network in bipolar disorder. This abnormal connectivity pattern did not correlate with variables related to the clinical course of the disease. The present finding may reflect abnormal integration of affective and cognitive information in ventral-emotional and dorsal-cognitive networks in euthymic bipolar patients. Furthermore, the results provide novel insights into the role of the meso/paralimbic network in bipolar disorder. PMID:25343370

  12. Abnormalities of functional brain networks in pathological gambling: a graph-theoretical approach

    PubMed Central

    Tschernegg, Melanie; Crone, Julia S.; Eigenberger, Tina; Schwartenbeck, Philipp; Fauth-Bühler, Mira; Lemènager, Tagrid; Mann, Karl; Thon, Natasha; Wurst, Friedrich M.; Kronbichler, Martin

    2013-01-01

    Functional neuroimaging studies of pathological gambling (PG) demonstrate alterations in frontal and subcortical regions of the mesolimbic reward system. However, most investigations were performed using tasks involving reward processing or executive functions. Little is known about brain network abnormalities during task-free resting state in PG. In the present study, graph-theoretical methods were used to investigate network properties of resting state functional magnetic resonance imaging data in PG. We compared 19 patients with PG to 19 healthy controls (HCs) using the Graph Analysis Toolbox (GAT). None of the examined global metrics differed between groups. At the nodal level, pathological gambler showed a reduced clustering coefficient in the left paracingulate cortex and the left juxtapositional lobe (supplementary motor area, SMA), reduced local efficiency in the left SMA, as well as an increased node betweenness for the left and right paracingulate cortex and the left SMA. At an uncorrected threshold level, the node betweenness in the left inferior frontal gyrus was decreased and increased in the caudate. Additionally, increased functional connectivity between fronto-striatal regions and within frontal regions has also been found for the gambling patients. These findings suggest that regions associated with the reward system demonstrate reduced segregation but enhanced integration while regions associated with executive functions demonstrate reduced integration. The present study makes evident that PG is also associated with abnormalities in the topological network structure of the brain during rest. Since alterations in PG cannot be explained by direct effects of abused substances on the brain, these findings will be of relevance for understanding functional connectivity in other addictive disorders. PMID:24098282

  13. Modeling the Relationship among Gray Matter Atrophy, Abnormalities in Connecting White Matter, and Cognitive Performance in Early Multiple Sclerosis

    PubMed Central

    Kuceyeski, A.F.; Vargas, W.; Dayan, M.; Monohan, E.; Blackwell, C.; Raj, A.; Fujimoto, K.; Gauthier, S.A.

    2016-01-01

    Background and Purpose Quantitative assessment of clinical and pathologic consequences of white matter abnormalities in multiple sclerosis is critical in understanding the pathways of disease. This study aimed to test whether gray matter atrophy was related to abnormalities in connecting white matter and to identify patterns of imaging biomarker abnormalities that were related to patient processing speed. Materials and Methods Image data and Symbol Digit Modalities Test scores were collected from a cohort of patients with early multiple sclerosis. The Network Modification Tool was used to estimate connectivity irregularities by projecting white matter abnormalities onto connecting gray matter regions. Partial least-squares regression quantified the relationship between imaging biomarkers and processing speed as measured by the Symbol Digit Modalities Test. Results Atrophy in deep gray matter structures of the thalami and putamen had moderate and significant correlations with abnormalities in connecting white matter (r = 0.39–0.41, P < .05 corrected). The 2 models of processing speed, 1 for each of the WM imaging biomarkers, had goodness-of-fit (R2) values of 0.42 and 0.30. A measure of the impact of white matter lesions on the connectivity of occipital and parietal areas had significant nonzero regression coefficients. Conclusions We concluded that deep gray matter regions may be susceptible to inflammation and/or demyelination in white matter, possibly having a higher sensitivity to remote degeneration, and that lesions affecting visual processing pathways were related to processing speed. The Network Modification Tool may be used to quantify the impact of early white matter abnormalities on both connecting gray matter structures and processing speed. PMID:25414004

  14. The Developmental Cognitive Neuroscience of Functional Connectivity

    ERIC Educational Resources Information Center

    Stevens, Michael C.

    2009-01-01

    Developmental cognitive neuroscience is a rapidly growing field that examines the relationships between biological development and cognitive ability. In the past decade, there has been ongoing refinement of concepts and methodology related to the study of "functional connectivity" among distributed brain regions believed to underlie cognition and…

  15. Biochemical and functional abnormalities in hypercholesterolemic rabbit platelets

    SciTech Connect

    Dalal, K.B.; Ebbe, S.; Mazoyer, E.; Carpenter, D.; Yee, T. )

    1990-02-01

    This study was designed to elucidate changes in rabbit platelet lipids induced by a cholesterol rich diet and to explore the possible correlation of these lipid changes with platelet abnormalities. Pronounced biochemical alterations were observed when serum cholesterol levels of 700-1000 mg% were reached. Hypercholesterolemic (HC) platelets contained 37% more neutral lipids and 16% less phospholipids than the controls. Lysolecithin, cholesterol esters and phosphatidylinositol (PI) levels were increased in HC platelets, and the levels of phosphatidylcholine (PC) were decreased. The cholesterol/phospholipid molar ratio of lipidemic platelets increased from 0.55 +/- 0.011 to 0.89 +/- 0.016 (P less than 0.01) in eight weeks. HC platelets had 90% more arachidonic acid (AA) in the PI than normal platelets. No significant changes in AA of PC were observed. Platelet function was monitored by the uptake and release of (14C)serotonin in platelet rich plasma (PRP), using varying concentrations of collagen as an aggregating agent. The uptake of (14C)serotonin in HC and normal platelets ranged from 78-94%. The percent of (14C)serotonin released from normal and HC platelets was proportional to the concentration of collagen. However, lipidemic platelets were hyperreactive to low concentrations of collagen. Incorporation of 50 microM acetylsalicylic acid into the aggregating medium suppressed the release of (14C)serotonin in normal PRP by more than 90%, but had only a partial effect on lipidemic PRP.

  16. Impact of Autocorrelation on Functional Connectivity

    PubMed Central

    Arbabshirani, Mohammad R.; Damaraju, Eswar; Phlypo, Ronald; Plis, Sergey; Allen, Elena; Ma, Sai; Mathalon, Daniel; Preda, Adrian; Vaidya, Jatin G.; Adali, Tülay; Calhoun, Vince D.

    2014-01-01

    Although the impact of serial correlation (autocorrelation) in residuals of general linear models for fMRI time-series has been studied extensively, the effect of autocorrelation on functional connectivity studies has been largely neglected until recently. Some recent studies based on results from economics have questioned the conventional estimation of functional connectivity and argue that not correcting for autocorrelation in fMRI time-series results in “spurious” correlation coefficients. In this paper, first we assess the effect of autocorrelation on Pearson correlation coefficient through theoretical approximation and simulation. Then we present this effect on real fMRI data. To our knowledge this is the first work comprehensively investigating the effect of autocorrelation on functional connectivity estimates. Our results show that although FC values are altered, even following correction for autocorrelation, results of hypothesis testing on FC values remain very similar to those before correction. In real data we show this is true for main effects and also for group difference testing between healthy controls and schizophrenia patients. We further discuss model order selection in the context of autoregressive processes, effects of frequency filtering and propose a preprocessing pipeline for connectivity studies. PMID:25072392

  17. Dynamic Resting-State Functional Connectivity in Major Depression.

    PubMed

    Kaiser, Roselinde H; Whitfield-Gabrieli, Susan; Dillon, Daniel G; Goer, Franziska; Beltzer, Miranda; Minkel, Jared; Smoski, Moria; Dichter, Gabriel; Pizzagalli, Diego A

    2016-06-01

    Major depressive disorder (MDD) is characterized by abnormal resting-state functional connectivity (RSFC), especially in medial prefrontal cortical (MPFC) regions of the default network. However, prior research in MDD has not examined dynamic changes in functional connectivity as networks form, interact, and dissolve over time. We compared unmedicated individuals with MDD (n=100) to control participants (n=109) on dynamic RSFC (operationalized as SD in RSFC over a series of sliding windows) of an MPFC seed region during a resting-state functional magnetic resonance imaging scan. Among participants with MDD, we also investigated the relationship between symptom severity and RSFC. Secondary analyses probed the association between dynamic RSFC and rumination. Results showed that individuals with MDD were characterized by decreased dynamic (less variable) RSFC between MPFC and regions of parahippocampal gyrus within the default network, a pattern related to sustained positive connectivity between these regions across sliding windows. In contrast, the MDD group exhibited increased dynamic (more variable) RSFC between MPFC and regions of insula, and higher severity of depression was related to increased dynamic RSFC between MPFC and dorsolateral prefrontal cortex. These patterns of highly variable RSFC were related to greater frequency of strong positive and negative correlations in activity across sliding windows. Secondary analyses indicated that increased dynamic RSFC between MPFC and insula was related to higher levels of recent rumination. These findings provide initial evidence that depression, and ruminative thinking in depression, are related to abnormal patterns of fluctuating communication among brain systems involved in regulating attention and self-referential thinking. PMID:26632990

  18. Abnormalities of endothelial function in patients with predialysis renal failure

    PubMed Central

    Thambyrajah, J; Landray, M; McGlynn, F; Jones, H; Wheeler, D; Townend, J

    2000-01-01

    BACKGROUND—Endothelial dysfunction plays an important role in the development of atherosclerotic vascular disease, which is the leading cause of mortality in patients with chronic renal failure.
OBJECTIVE—To examine the relation between predialysis renal failure and endothelial function.
DESIGN—Two groups were studied: 80 patients with non-diabetic chronic renal failure and 26 healthy controls, with similar age and sex distributions. Two indices of endothelial function were assessed: high resolution ultrasonography to measure flow mediated endothelium dependent dilatation of the brachial artery following reactive hyperaemia, and plasma concentration of von Willebrand factor. Endothelium independent dilatation was also assessed following sublingual glyceryl trinitrate. The patients were divided into those with and without overt atherosclerotic vascular disease.
RESULTS—Although patients with chronic renal failure had significantly impaired endothelium dependent dilatation compared with controls (median (interquartile range), 2.6% (0.7% to 4.8%) v 6.5% (4.8% to 8.3%); p < 0.001) and increased von Willebrand factor (254 (207 to 294) v 106 (87 to 138) iu/dl; p < 0.001), there was no difference between renal failure patients with and without atherosclerotic vascular disease. Within the chronic renal failure group, endothelium dependent dilatation and von Willebrand factor were similar in patients in the upper and lower quartiles of glomerular filtration rate (2.7% (0.7% to 6.7%) v 2.8% (1.1% to 5.0%); and 255 (205 to 291) v 254 (209 to 292) iu/dl, respectively). Endothelium independent dilatation did not differ between the renal failure or control groups and was also similar in patients with renal failure irrespective of the degree of renal failure or the presence of atherosclerotic vascular disease.
CONCLUSIONS—Endothelial function is abnormal in chronic renal failure, even in patients with mild renal insufficiency and those without

  19. Pattern Genes Suggest Functional Connectivity of Organs.

    PubMed

    Qin, Yangmei; Pan, Jianbo; Cai, Meichun; Yao, Lixia; Ji, Zhiliang

    2016-01-01

    Human organ, as the basic structural and functional unit in human body, is made of a large community of different cell types that organically bound together. Each organ usually exerts highly specified physiological function; while several related organs work smartly together to perform complicated body functions. In this study, we present a computational effort to understand the roles of genes in building functional connection between organs. More specifically, we mined multiple transcriptome datasets sampled from 36 human organs and tissues, and quantitatively identified 3,149 genes whose expressions showed consensus modularly patterns: specific to one organ/tissue, selectively expressed in several functionally related tissues and ubiquitously expressed. These pattern genes imply intrinsic connections between organs. According to the expression abundance of the 766 selective genes, we consistently cluster the 36 human organs/tissues into seven functional groups: adipose &gland, brain, muscle, immune, metabolism, mucoid and nerve conduction. The organs and tissues in each group either work together to form organ systems or coordinate to perform particular body functions. The particular roles of specific genes and selective genes suggest that they could not only be used to mechanistically explore organ functions, but also be designed for selective biomarkers and therapeutic targets. PMID:27225987

  20. Pattern Genes Suggest Functional Connectivity of Organs

    PubMed Central

    Qin, Yangmei; Pan, Jianbo; Cai, Meichun; Yao, Lixia; Ji, Zhiliang

    2016-01-01

    Human organ, as the basic structural and functional unit in human body, is made of a large community of different cell types that organically bound together. Each organ usually exerts highly specified physiological function; while several related organs work smartly together to perform complicated body functions. In this study, we present a computational effort to understand the roles of genes in building functional connection between organs. More specifically, we mined multiple transcriptome datasets sampled from 36 human organs and tissues, and quantitatively identified 3,149 genes whose expressions showed consensus modularly patterns: specific to one organ/tissue, selectively expressed in several functionally related tissues and ubiquitously expressed. These pattern genes imply intrinsic connections between organs. According to the expression abundance of the 766 selective genes, we consistently cluster the 36 human organs/tissues into seven functional groups: adipose & gland, brain, muscle, immune, metabolism, mucoid and nerve conduction. The organs and tissues in each group either work together to form organ systems or coordinate to perform particular body functions. The particular roles of specific genes and selective genes suggest that they could not only be used to mechanistically explore organ functions, but also be designed for selective biomarkers and therapeutic targets. PMID:27225987

  1. Pattern Genes Suggest Functional Connectivity of Organs

    NASA Astrophysics Data System (ADS)

    Qin, Yangmei; Pan, Jianbo; Cai, Meichun; Yao, Lixia; Ji, Zhiliang

    2016-05-01

    Human organ, as the basic structural and functional unit in human body, is made of a large community of different cell types that organically bound together. Each organ usually exerts highly specified physiological function; while several related organs work smartly together to perform complicated body functions. In this study, we present a computational effort to understand the roles of genes in building functional connection between organs. More specifically, we mined multiple transcriptome datasets sampled from 36 human organs and tissues, and quantitatively identified 3,149 genes whose expressions showed consensus modularly patterns: specific to one organ/tissue, selectively expressed in several functionally related tissues and ubiquitously expressed. These pattern genes imply intrinsic connections between organs. According to the expression abundance of the 766 selective genes, we consistently cluster the 36 human organs/tissues into seven functional groups: adipose & gland, brain, muscle, immune, metabolism, mucoid and nerve conduction. The organs and tissues in each group either work together to form organ systems or coordinate to perform particular body functions. The particular roles of specific genes and selective genes suggest that they could not only be used to mechanistically explore organ functions, but also be designed for selective biomarkers and therapeutic targets.

  2. Dynamic Functional Brain Connectivity for Face Perception

    PubMed Central

    Yang, Yuan; Qiu, Yihong; Schouten, Alfred C.

    2015-01-01

    Face perception is mediated by a distributed brain network comprised of the core system at occipito-temporal areas and the extended system at other relevant brain areas involving bilateral hemispheres. In this study we explored how the brain connectivity changes over the time for face-sensitive processing. We investigated the dynamic functional connectivity in face perception by analyzing time-dependent EEG phase synchronization in four different frequency bands: theta (4–7 Hz), alpha (8–14 Hz), beta (15–24 Hz), and gamma (25–45 Hz) bands in the early stages of face processing from 30 to 300 ms. High-density EEG were recorded from subjects who were passively viewing faces, buildings, and chairs. The dynamic connectivity within the core system and between the extended system were investigated. Significant differences between faces and non-faces mainly appear in theta band connectivity: (1) at the time segment of 90–120 ms between parietal area and occipito-temporal area in the right hemisphere, and (2) at the time segment of 150–180 ms between bilateral occipito-temporal areas. These results indicate (1) the importance of theta-band connectivity in the face-sensitive processing, and (2) that different parts of network are involved for the initial stage of face categorization and the stage of face structural encoding. PMID:26696870

  3. Morphological and functional platelet abnormalities in Berkeley sickle cell mice.

    PubMed

    Shet, Arun S; Hoffmann, Thomas J; Jirouskova, Marketa; Janczak, Christin A; Stevens, Jacqueline R M; Adamson, Adewole; Mohandas, Narla; Manci, Elizabeth A; Cynober, Therese; Coller, Barry S

    2008-01-01

    Berkeley sickle cell mice are used as animal models of human sickle cell disease but there are no reports of platelet studies in this model. Since humans with sickle cell disease have platelet abnormalities, we studied platelet morphology and function in Berkeley mice (SS). We observed elevated mean platelet forward angle light scatter (FSC) values (an indirect measure of platelet volume) in SS compared to wild type (WT) (37+/-3.2 vs. 27+/-1.4, mean+/-SD; p<0.001), in association with moderate thrombocytopenia (505+/-49 x 10(3)/microl vs. 1151+/-162 x 10(3)/microl; p<0.001). Despite having marked splenomegaly, SS mice had elevated levels of Howell-Jolly bodies and "pocked" erythrocytes (p<0.001 for both) suggesting splenic dysfunction. SS mice also had elevated numbers of thiazole orange positive platelets (5+/-1% vs. 1+/-1%; p<0.001), normal to low plasma thrombopoietin levels, normal plasma glycocalicin levels, normal levels of platelet recovery, and near normal platelet life spans. Platelets from SS mice bound more fibrinogen and antibody to P-selectin following activation with a threshold concentration of a protease activated receptor (PAR)-4 peptide compared to WT mice. Enlarged platelets are associated with a predisposition to arterial thrombosis in humans and some humans with SCD have been reported to have large platelets. Thus, additional studies are needed to assess whether large platelets contribute either to pulmonary hypertension or the large vessel arterial occlusion that produces stroke in some children with sickle cell disease. PMID:18374611

  4. Functional Connectivity Modulation by Acupuncture in Patients with Bell's Palsy

    PubMed Central

    He, Xiaoxuan; Hu, Sheng; Li, Chuanfu; Xu, Chunsheng; Kan, Hongxing; Xue, Qiuju; Qiu, Bensheng

    2016-01-01

    Bell's palsy (BP), an acute unilateral facial paralysis, is frequently treated with acupuncture in many countries. However, the mechanism of treatment is not clear so far. In order to explore the potential mechanism, 22 healthy volunteers and 17 BP patients with different clinical duration were recruited. The resting-state functional magnetic resonance imaging scans were conducted before and after acupuncture at LI4 (Hegu), respectively. By comparing BP-induced functional connectivity (FC) changes with acupuncture-induced FC changes in the patients, the abnormal increased FC that could be reduced by acupuncture was selected. The FC strength of the selected FC at various stages was analyzed subsequently. Our results show that FC modulation of acupuncture is specific and consistent with the tendency of recovery. Therefore, we propose that FC modulation by acupuncture may be beneficial to recovery from the disease. PMID:27293461

  5. Connection formulas for thermal density functional theory

    NASA Astrophysics Data System (ADS)

    Pribram-Jones, A.; Burke, K.

    2016-05-01

    The adiabatic connection formula of ground-state density functional theory relates the correlation energy to a coupling-constant integral over a purely potential contribution, and is widely used to understand and improve approximations. The corresponding formula for thermal density functional theory is cast as an integral over temperatures instead, ranging upward from the system's physical temperature. We also show how to relate different correlation components to each other, either in terms of temperature or coupling-constant integrations. We illustrate our results on the uniform electron gas.

  6. Increased functional connectivity in intrinsic neural networks in individuals with aniridia

    PubMed Central

    Pierce, Jordan E.; Krafft, Cynthia E.; Rodrigue, Amanda L.; Bobilev, Anastasia M.; Lauderdale, James D.; McDowell, Jennifer E.

    2014-01-01

    Mutations affecting the PAX6 gene result in aniridia, a condition characterized by the lack of an iris and other panocular defects. Among humans with aniridia, structural abnormalities also have been reported within the brain. The current study examined the functional implications of these deficits through “resting state” or task-free functional magnetic resonance imaging (fMRI) in 12 individuals with aniridia and 12 healthy age- and gender-matched controls. Using independent components analysis (ICA) and dual regression, individual patterns of functional connectivity associated with three intrinsic connectivity networks (ICNs; executive control, primary visual, and default mode) were compared across groups. In all three analyses, the aniridia group exhibited regions of greater connectivity correlated with the network, while the controls did not show any such regions. These differences suggest that individuals with aniridia recruit additional neural regions to supplement function in critical intrinsic networks, possibly due to inherent structural or sensory abnormalities related to the disorder. PMID:25566032

  7. The Therapeutic Function of the Instructor in Abnormal Psychology.

    ERIC Educational Resources Information Center

    Halgin, Richard P.

    1982-01-01

    Describes three main types of therapeutic problems which college instructors of abnormal psychology courses may encounter with their students. Students may seek the instructor's assistance in helping a relative or acquaintance or for self-help. Often a student may not seek help but may display pathological behavior. (AM)

  8. Connectivity disruptions in resting-state functional brain networks in children with temporal lobe epilepsy.

    PubMed

    Mankinen, Katariina; Jalovaara, Paula; Paakki, Jyri-Johan; Harila, Marika; Rytky, Seppo; Tervonen, Osmo; Nikkinen, Juha; Starck, Tuomo; Remes, Jukka; Rantala, Heikki; Kiviniemi, Vesa

    2012-06-01

    Functional resting-state connectivity has been shown to be altered in certain adult epilepsy populations, but few connectivity studies have been performed on pediatric epilepsy patients. Here functional connectivity was measured in pediatric, non-lesional temporal lobe epilepsy patients with normal intelligence and compared with that in age and gender-matched healthy controls using the independent component analysis method. We hypothesized that children with non-lesional temporal lobe epilepsy have disrupted functional connectivity within resting-state networks. Significant differences were demonstrated between the two groups, pointing to a decrease in connectivity. When the results were analyzed according to the interictal electroencephalogram findings, however, the connectivity disruptions were seen in different networks. In addition, increased connectivity and abnormally anti-correlated thalamic activity was detected only in the patients with abnormal electroencephalograms. In summary, connectivity disruptions are already to be seen at an early stage of epilepsy, and epileptiform activity seems to affect connectivity differently. The results indicate that interictal epileptiform activity may lead to reorganization of the resting-state brain networks, but further studies would be needed in order to understand the pathophysiology behind this phenomenon. PMID:22418271

  9. Is Abnormal Urine Protein/Osmolality Ratio Associated with Abnormal Renal Function in Patients Receiving Tenofovir Disoproxil Fumarate?

    PubMed Central

    Marcelin, Jasmine R.; Berg, Melody L.; Tan, Eugene M.; Amer, Hatem; Cummins, Nathan W.; Rizza, Stacey A.

    2016-01-01

    Background Risk factors for and optimal surveillance of renal dysfunction in patients on tenofovir disoproxil fumarate (TDF) remain unclear. We investigated whether a urine protein-osmolality (P/O) ratio would be associated with renal dysfunction in HIV-infected persons on TDF. Methods This retrospective, single-center study investigated the relationship between parameters of renal function (estimated glomerular filtration rate (eGFR) and P/O-ratio) and risk factors for development of kidney dysfunction. Subjects were HIV-infected adults receiving TDF with at least one urinalysis and serum creatinine performed between 2010 and 2013. Regression analyses were used to analyze risk factors associated with abnormal P/O-ratio and abnormal eGFR during TDF therapy. Results Patients were predominately male (81%); (65%) were Caucasian. Mean age was 45.1(±11.8) years; median [IQR] TDF duration was 3.3 years. [1.5–7.6]. Median CD4+ T cell count and HIV viral load were 451 cells/μL [267.5–721.5] and 62 copies/mL [0–40,150], respectively. Abnormal P/O-ratio was not associated with low eGFR. 68% of subjects had an abnormal P/O-ratio and 9% had low eGFR. Duration of TDF use, age, diabetes and hypertension were associated with renal dysfunction in this study. After adjustment for age, subjects on TDF > 5 years had almost a four-fold increased likelihood of having an abnormal P/O-ratio than subjects on TDF for < 1yr (OR 3.9; 95% CI 1.2–14.0; p = 0.024). Conclusion Abnormal P/O-ratio is common in HIV-infected patients on TDF but was not significantly associated with low eGFR, suggesting that abnormal P/O-ratio may be a very early biomarker of decreased renal function in HIV infected patients. PMID:26872144

  10. Multiscale fingerprinting of neuronal functional connectivity.

    PubMed

    Song, Gang; Tin, Chung; Poon, Chi-Sang

    2015-09-01

    Current cellular-based connectomics approaches aim to delineate the functional or structural organizations of mammalian brain circuits through neuronal activity mapping and/or axonal tracing. To discern possible connectivity between functionally identified neurons in widely distributed brain circuits, reliable and efficient network-based approaches of cross-registering or cross-correlating such functional-structural data are essential. Here, a novel cross-correlation approach that exploits multiple timing-specific, response-specific, and cell-specific neuronal characteristics as coincident fingerprint markers at the systems, network, and cellular levels is proposed. Application of this multiscale temporal-cellular coincident fingerprinting assay to the respiratory central pattern generator network in rats revealed a descending excitatory pathway with characteristic activity pattern and projecting from a distinct neuronal population in pons to its counterparts in medulla that control the post-inspiratory phase of the respiratory rhythm important for normal breathing, airway protection, and respiratory-vocalization coordination. This enabling neurotracing approach may prove valuable for functional connectivity mapping of other brain circuits. PMID:25056933

  11. Dynamic functional network connectivity using distance correlation

    NASA Astrophysics Data System (ADS)

    Rudas, Jorge; Guaje, Javier; Demertzi, Athena; Heine, Lizette; Tshibanda, Luaba; Soddu, Andrea; Laureys, Steven; Gómez, Francisco

    2015-01-01

    Investigations about the intrinsic brain organization in resting-state are critical for the understanding of healthy, pathological and pharmacological cerebral states. Recent studies on fMRI suggest that resting state activity is organized on large scale networks of coordinated activity, in the so called, Resting State Networks (RSNs). The assessment of the interactions among these functional networks plays an important role for the understanding of different brain pathologies. Current methods to quantify these interactions commonly assume that the underlying coordination mechanisms are stationary and linear through the whole recording of the resting state phenomena. Nevertheless, recent evidence suggests that rather than stationary, these mechanisms may exhibit a rich set of time-varying repertoires. In addition, these approaches do not consider possible non-linear relationships maybe linked to feed-back communication mechanisms between RSNs. In this work, we introduce a novel approach for dynamical functional network connectivity for functional magnetic resonance imaging (fMRI) resting activity, which accounts for non-linear dynamic relationships between RSNs. The proposed method is based on a windowed distance correlations computed on resting state time-courses extracted at single subject level. We showed that this strategy is complementary to the current approaches for dynamic functional connectivity and will help to enhance the discrimination capacity of patients with disorder of consciousness.

  12. A Connection Formula for the q-Confluent Hypergeometric Function

    NASA Astrophysics Data System (ADS)

    Morita, Takeshi

    2013-07-01

    We show a connection formula for the q-confluent hypergeometric functions {}_2ϕ_1(a,b;0;q,x). Combining our connection formula with Zhang's connection formula for {}_2ϕ_0(a,b;-;q,x), we obtain the connection formula for the q-confluent hypergeometric equation in the matrix form. Also we obtain the connection formula of Kummer's confluent hypergeometric functions by taking the limit qto 1^{-} of our connection formula.

  13. Altered striatal intrinsic functional connectivity in pediatric anxiety.

    PubMed

    Dorfman, Julia; Benson, Brenda; Farber, Madeline; Pine, Daniel; Ernst, Monique

    2016-05-01

    Anxiety disorders are among the most common psychiatric disorders of adolescence. Behavioral and task-based imaging studies implicate altered reward system function, including striatal dysfunction, in adolescent anxiety. However, no study has yet examined alterations of the striatal intrinsic functional connectivity in adolescent anxiety disorders. The current study examines striatal intrinsic functional connectivity (iFC), using six bilateral striatal seeds, among 35 adolescents with anxiety disorders and 36 healthy comparisons. Anxiety is associated with abnormally low iFC within the striatum (e.g., between nucleus accumbens and caudate nucleus), and between the striatum and prefrontal regions, including subgenual anterior cingulate cortex, posterior insula and supplementary motor area. The current findings extend prior behavioral and task-based imaging research, and provide novel data implicating decreased striatal iFC in adolescent anxiety. Alterations of striatal neurocircuitry identified in this study may contribute to the perturbations in the processing of motivational, emotional, interoceptive, and motor information seen in pediatric anxiety disorders. This pattern of the striatal iFC perturbations can guide future research on specific mechanisms underlying anxiety. PMID:27004799

  14. Abnormalities of the executive control network in multiple sclerosis phenotypes: An fMRI effective connectivity study.

    PubMed

    Dobryakova, Ekaterina; Rocca, Maria Assunta; Valsasina, Paola; Ghezzi, Angelo; Colombo, Bruno; Martinelli, Vittorio; Comi, Giancarlo; DeLuca, John; Filippi, Massimo

    2016-06-01

    The Stroop interference task is a cognitively demanding task of executive control, a cognitive ability that is often impaired in patients with multiple sclerosis (MS). The aim of this study was to compare effective connectivity patterns within a network of brain regions involved in the Stroop task performance between MS patients with three disease clinical phenotypes [relapsing-remitting (RRMS), benign (BMS), and secondary progressive (SPMS)] and healthy subjects. Effective connectivity analysis was performed on Stroop task data using a novel method based on causal Bayes networks. Compared with controls, MS phenotypes were slower at performing the task and had reduced performance accuracy during incongruent trials that required increased cognitive control. MS phenotypes also exhibited connectivity abnormalities reflected as weaker shared connections, presence of extra connections (i.e., connections absent in the HC connectivity pattern), connection reversal, and loss. In SPMS and the BMS groups but not in the RRMS group, extra connections were associated with deficits in the Stroop task performance. In the BMS group, the response time associated with correct responses during the congruent condition showed a positive correlation with the left posterior parietal → dorsal anterior cingulate connection. In the SPMS group, performance accuracy during the congruent condition showed a negative correlation with the right insula → left insula connection. No associations between extra connections and behavioral performance measures were observed in the RRMS group. These results suggest that, depending on the phenotype, patients with MS use different strategies when cognitive control demands are high and rely on different network connections. Hum Brain Mapp, 37:2293-2304, 2016. © 2016 Wiley Periodicals, Inc. PMID:26956182

  15. Dynamic functional connectivity: Promise, issues, and interpretations

    PubMed Central

    Hutchison, R. Matthew; Womelsdorf, Thilo; Allen, Elena A.; Bandettini, Peter A.; Calhoun, Vince D.; Corbetta, Maurizio; Penna, Stefania Della; Duyn, Jeff H.; Glover, Gary H.; Gonzalez-Castillo, Javier; Handwerker, Daniel A.; Keilholz, Shella; Kiviniemi, Vesa; Leopold, David A.; de Pasquale, Francesco; Sporns, Olaf; Walter, Martin; Chang, Catie

    2013-01-01

    The brain must dynamically integrate, coordinate, and respond to internal and external stimuli across multiple time scales. Non-invasive measurements of brain activity with fMRI have greatly advanced our understanding of the large-scale functional organization supporting these fundamental features of brain function. Conclusions from previous resting-state fMRI investigations were based upon static descriptions of functional connectivity (FC), and only recently studies have begun to capitalize on the wealth of information contained within the temporal features of spontaneous BOLD FC. Emerging evidence suggests that dynamic FC metrics may index changes in macroscopic neural activity patterns underlying critical aspects of cognition and behavior, though limitations with regard to analysis and interpretation remain. Here, we review recent findings, methodological considerations, neural and behavioral correlates, and future directions in the emerging field of dynamic FC investigations. PMID:23707587

  16. CSF proteins and resting-state functional connectivity in Parkinson disease

    PubMed Central

    Koller, Jonathan M.; Snyder, Abraham Z.; Buddhala, Chandana; Kotzbauer, Paul T.; Perlmutter, Joel S.

    2015-01-01

    Objective: The purpose of this study was to investigate the relationship between disruption of MRI-measured resting-state functional connectivity (rs-fcMRI) brain networks and CSF levels of potentially pathogenic proteins that reflect brain pathology in Parkinson disease (PD). Methods: PD participants without dementia (n = 43) and age-matched controls (n = 22) had lumbar punctures to measure CSF protein levels, Pittsburgh compound B (PiB)–PET imaging, and rs-fcMRI while off medication. Imaging analyses focused on 5 major resting-state networks as well as the striatum. Results: Participants with PD had significantly reduced sensorimotor functional connectivity, which correlated with reduced CSF levels of α-synuclein. The PD group also had significantly stronger default mode network functional connectivity that did not correlate with CSF β-amyloid (Aβ)42 or PiB uptake. In contrast, default mode network functional connectivity in the control group did correlate with CSF Aβ42 levels. Functional connectivity was similar between groups in the dorsal attention, control, and salience networks. Conclusion: These results suggest that abnormal α-synuclein accumulation, but not Aβ, contributes to the disruption of motor-related functional connectivity in PD. Furthermore, correlating CSF protein measures with the strength of resting-state networks provides a direct link between abnormal α-synuclein metabolism and disrupted brain function in PD. PMID:25979701

  17. Abnormal ventilation scans in middle-aged smokers. Comparison with tests of overall lung function

    SciTech Connect

    Barter, S.J.; Cunningham, D.A.; Lavender, J.P.; Gibellino, F.; Connellan, S.J.; Pride, N.B.

    1985-07-01

    The uniformity of regional ventilation during tidal breathing has been assessed using continuous inhalation of krypton-81m in 43 male, lifelong nonsmokers and 46 male, current cigarette smokers (mean daily consumption 24.1 cigarettes/day) between 44 and 61 yr of age and with mild or no respiratory symptoms. All subjects had normal chest radiographs. The results of the ventilation scans were compared with tests of overall lung function (spirometry, maximal expiratory flow-volume curves, and single-breath N2 test). Diffuse abnormalities of the ventilation scan were found in 19 (41%) of the 46 smokers but in none of the nonsmokers. Focal abnormalities were found in 7 smokers and 3 nonsmokers. Smokers showed the expected abnormalities in overall lung function (reduced FEV1 and VC, increased single-breath N2 slope, and closing volume), but in individual smokers there was only a weak relation between the severity of abnormality of overall lung function and an abnormal ventilation scan. Abnormal scans could be found when overall lung function was normal and were not invariably found when significant abnormalities in FEV1/VC or N2 slope were present. There was no relation between the presence of chronic expectoration and an abnormal scan. The prognostic significance of an abnormal ventilation scan in such smokers remains to be established.

  18. 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. PMID:20941370

  19. Global network influences on local functional connectivity

    PubMed Central

    Snyder, Adam C.; Morais, Michael J.; Willis, Cory M.; Smith, Matthew A.

    2015-01-01

    A central neuroscientific pursuit is understanding neuronal interactions that support computations underlying cognition and behavior. Although neurons interact across disparate scales – from cortical columns to whole-brain networks – research has been restricted to one scale at a time. We measured local interactions through multi-neuronal recordings while accessing global networks using scalp EEG in rhesus macaques. We measured spike count correlation, an index of functional connectivity with computational relevance, and EEG oscillations, which have been linked to various cognitive functions. We found a surprising non-monotonic relationship between EEG oscillation amplitude and spike count correlation, contrary to the intuitive expectation of a direct relationship. With a widely-used network model we replicated these findings by incorporating a private signal targeting inhibitory neurons, a common mechanism proposed for gain modulation. Finally, we report that spike count correlation explains nonlinearities in the relationship between EEG oscillations and response time in a spatial selective attention task. PMID:25799040

  20. Resting-State Network Disruption and APOE Genotype in Alzheimer's Disease: A lagged Functional Connectivity Study

    PubMed Central

    Canuet, Leonides; Tellado, Ivan; Couceiro, Veronica; Fraile, Carmen; Fernandez-Novoa, Lucia; Ishii, Ryouhei; Takeda, Masatoshi; Cacabelos, Ramon

    2012-01-01

    Background The apolipoprotein E epsilon 4 (APOE-4) is associated with a genetic vulnerability to Alzheimer's disease (AD) and with AD-related abnormalities in cortical rhythms. However, it is unclear whether APOE-4 is linked to a specific pattern of intrinsic functional disintegration of the brain after the development of the disease or during its different stages. This study aimed at identifying spatial patterns and effects of APOE genotype on resting-state oscillations and functional connectivity in patients with AD, using a physiological connectivity index called “lagged phase synchronization”. Methodology/Principal Findings Resting EEG was recorded during awake, eyes-closed state in 125 patients with AD and 60 elderly controls. Source current density and functional connectivity were determined using eLORETA. Patients with AD exhibited reduced parieto-occipital alpha oscillations compared with controls, and those carrying the APOE-4 allele had reduced alpha activity in the left inferior parietal and temporo-occipital cortex relative to noncarriers. There was a decreased alpha2 connectivity pattern in AD, involving the left temporal and bilateral parietal cortex. Several brain regions exhibited increased lagged phase synchronization in low frequencies, specifically in the theta band, across and within hemispheres, where temporal lobe connections were particularly compromised. Areas with abnormal theta connectivity correlated with cognitive scores. In patients with early AD, we found an APOE-4-related decrease in interhemispheric alpha connectivity in frontal and parieto-temporal regions. Conclusions/Significance In addition to regional cortical dysfunction, as indicated by abnormal alpha oscillations, there are patterns of functional network disruption affecting theta and alpha bands in AD that associate with the level of cognitive disturbance or with the APOE genotype. These functional patterns of nonlinear connectivity may potentially represent

  1. Decreased Resting Functional Connectivity after Traumatic Brain Injury in the Rat

    PubMed Central

    Mishra, Asht Mangal; Bai, Xiaoxiao; Sanganahalli, Basavaraju G.; Waxman, Stephen G.; Shatillo, Olena; Grohn, Olli; Hyder, Fahmeed; Pitkänen, Asla; Blumenfeld, Hal

    2014-01-01

    Traumatic brain injury (TBI) contributes to about 10% of acquired epilepsy. Even though the mechanisms of post-traumatic epileptogenesis are poorly known, a disruption of neuronal networks predisposing to altered neuronal synchrony remains a viable candidate mechanism. We tested a hypothesis that resting state BOLD-fMRI functional connectivity can reveal network abnormalities in brain regions that are connected to the lesioned cortex, and that these changes associate with functional impairment, particularly epileptogenesis. TBI was induced using lateral fluid-percussion injury in seven adult male Sprague-Dawley rats followed by functional imaging at 9.4T 4 months later. As controls we used six sham-operated animals that underwent all surgical operations but were not injured. Electroencephalogram (EEG)-functional magnetic resonance imaging (fMRI) was performed to measure resting functional connectivity. A week after functional imaging, rats were implanted with bipolar skull electrodes. After recovery, rats underwent pentyleneterazol (PTZ) seizure-susceptibility test under EEG. For image analysis, four pairs of regions of interests were analyzed in each hemisphere: ipsilateral and contralateral frontal and parietal cortex, hippocampus, and thalamus. High-pass and low-pass filters were applied to functional imaging data. Group statistics comparing injured and sham-operated rats and correlations over time between each region were calculated. In the end, rats were perfused for histology. None of the rats had epileptiform discharges during functional imaging. PTZ-test, however revealed increased seizure susceptibility in injured rats as compared to controls. Group statistics revealed decreased connectivity between the ipsilateral and contralateral parietal cortex and between the parietal cortex and hippocampus on the side of injury as compared to sham-operated animals. Injured animals also had abnormal negative connectivity between the ipsilateral and contralateral

  2. Abnormal fusiform activation during emotional-face encoding assessed with functional magnetic resonance imaging.

    PubMed

    Adleman, Nancy E; Kayser, Reilly R; Olsavsky, Aviva K; Bones, Brian L; Muhrer, Eli J; Fromm, Stephen J; Pine, Daniel S; Zarate, Carlos; Leibenluft, Ellen; Brotman, Melissa A

    2013-05-30

    This functional magnetic resonance imaging study shows that children and adults with bipolar disorder (BD), compared with healthy subjects, exhibit impaired memory for emotional faces and abnormal fusiform activation during encoding. Fusiform activation abnormalities in BD were correlated with mania severity and may therefore represent a trait and state BD biomarker. PMID:23541333

  3. Altered resting-state functional connectivity of the amygdala in Chinese earthquake survivors.

    PubMed

    Zhang, Xiaoyu; Zhang, Jianxin; Wang, Li; Li, Rui; Zhang, Wencai

    2016-02-01

    Posttraumatic stress disorder (PTSD) is linked to abnormal amygdala activities. This study measured amygdala functional connectivity using DSM-5 criteria. There were 33 participants in the PTSD group and 33 participants in a trauma-exposed control (TEC) group, who did not have PTSD according to the PTSD checklist of the DSM-5 (PCL-5). Our findings are as follows: (1) In the PTSD group, the amygdala had increased positive connectivity with the medial prefrontal cortex (mPFC) and hippocampus, and decreased positive connectivity with the inferior mPFC and insula. The amygdala had increased negative connectivity with the orbital prefrontal cortex and decreased negative connectivity with the insula in comparison with TEC group. (2) PCL of all participants was correlated with the connectivity between the amygdala and the mPFC, hippocampus, and insula. These regions overlapped with those identified in the between-group comparisons. However, there was no association between PCL of the PTSD group and connectivity in these regions. Abnormal functional connectivity between the amygdala and mPFC subdivisions, hippocampus, and insula reveals their importance in PTSD pathogenesis. PMID:26476339

  4. Alterations in interhemispheric functional and anatomical connectivity are associated with tobacco smoking in humans.

    PubMed

    Viswanath, Humsini; Velasquez, Kenia M; Thompson-Lake, Daisy Gemma Yan; Savjani, Ricky; Carter, Asasia Q; Eagleman, David; Baldwin, Philip R; De La Garza, Richard; Salas, Ramiro

    2015-01-01

    Abnormal interhemispheric functional connectivity correlates with several neurologic and psychiatric conditions, including depression, obsessive-compulsive disorder, schizophrenia, and stroke. Abnormal interhemispheric functional connectivity also correlates with abuse of cannabis and cocaine. In the current report, we evaluated whether tobacco abuse (i.e., cigarette smoking) is associated with altered interhemispheric connectivity. To that end, we examined resting state functional connectivity (RSFC) using magnetic resonance imaging (MRI) in short term tobacco deprived and smoking as usual tobacco smokers, and in non-smoker controls. Additionally, we compared diffusion tensor imaging (DTI) in the same subjects to study differences in white matter. The data reveal a significant increase in interhemispheric functional connectivity in sated tobacco smokers when compared to controls. This difference was larger in frontal regions, and was positively correlated with the average number of cigarettes smoked per day. In addition, we found a negative correlation between the number of DTI streamlines in the genual corpus callosum and the number of cigarettes smoked per day. Taken together, our results implicate changes in interhemispheric functional and anatomical connectivity in current cigarette smokers. PMID:25805986

  5. Cognitive Behavioral Therapy Normalizes Functional Connectivity for Social Threat in Psychosis.

    PubMed

    Mason, Liam; Peters, Emmanuelle R; Dima, Danai; Williams, Steven C; Kumari, Veena

    2016-05-01

    Psychosis is often characterized by paranoia and poor social functioning. Neurally, there is evidence of functional dysconnectivity including abnormalities when processing facial affect. We sought to establish whether these abnormalities are resolved by cognitive behavioral therapy for psychosis (CBTp). The study involved 38 outpatients with one or more persistent positive psychotic symptoms, and 20 healthy participants. All participants completed an implicit facial affect processing task during functional magnetic resonance imaging (fMRI). Subsequently, patients either continued to receive standard care only (SCO,n= 16) or received CBTp on top of standard care (+CBTp,n= 22), with fMRI repeated 6-8 months later. To examine the mechanisms underlying CBTp-led changes in threat processing and appraisal, functional connectivity during the social threat (angry faces) condition was assessed separately from left amygdala and right dorsolateral prefrontal cortex (DLPFC) seeds. At baseline, patients, compared with healthy participants, showed greater amygdala connectivity with the insula and visual areas, but less connectivity with somatosensory areas. These differences normalized following CBTp and, compared with the SCO group, the +CBTp group showed greater increases in amygdala connectivity with DLPFC and inferior parietal lobule, with the latter correlating with improvement in positive symptoms. From the DLPFC seed, the +CBTp (compared with SCO) group showed significantly greater increase in DLPFC connectivity with other prefrontal regions including dorsal anterior cingulate and ventromedial prefrontal cortex. These findings indicate that CBTp strengthens connectivity between higher-order cognitive systems and those involved in threat and salience, potentially facilitating reappraisal. PMID:26508777

  6. Impaired long distance functional connectivity and weighted network architecture in Alzheimer's disease.

    PubMed

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

    2014-06-01

    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

  7. Reduced Interhemispheric Resting State Functional Connectivity in Cocaine Addiction

    PubMed Central

    Kelly, Clare; Zuo, Xi-Nian; Gotimer, Kristin; Cox, Christine; Lynch, Lauren; Brock, Dylan; Imperati, Davide; Garavan, Hugh; Rotrosen, John; Castellanos, F. Xavier; Milham, Michael

    2010-01-01

    Background Models of cocaine addiction emphasize the role of disrupted frontal circuitry supporting cognitive control processes. Yet, addiction-related alterations in functional interactions among brain regions, especially between the cerebral hemispheres, are rarely examined directly. Resting state fMRI approaches, which reveal patterns of coherent spontaneous fluctuations in the fMRI signal, offer a means to directly quantify functional interactions between the hemispheres. We examined interhemispheric resting state functional connectivity (RSFC) in cocaine dependence using a recently validated approach named “voxel-mirrored homotopic connectivity.” Methods We compared interhemispheric RSFC between 25 adults (aged 35.0±8.8) meeting DSM-IV criteria for cocaine dependence within the past 12 months, but currently abstaining (>2 weeks) from cocaine, and 24 healthy comparisons (35.1±7.5), group-matched on age, sex, education and employment status. Results We observed reduced prefrontal interhemispheric RSFC in cocaine dependent participants relative to controls. Further analyses demonstrated a striking cocaine-dependence-related reduction in interhemispheric RSFC among nodes of the dorsal attention network (DAN), comprising bilateral lateral frontal, medial premotor and posterior parietal areas. Further, within the cocaine-dependent group, RSFC within the DAN was associated with self-reported lapses of attention. Conclusions Our findings provide further evidence of an association between chronic exposure to cocaine and disruptions within large-scale brain circuitry supporting cognitive control. We did not detect group differences in DTI measures, suggesting that alterations in the brain’s functional architecture associated with cocaine exposure can be observed in the absence of detectable abnormalities in the white matter microstructure supporting that architecture. PMID:21251646

  8. LANDSCAPE CONNECTIVITY: DIFFERENT FUNCTIONS AT DIFFERENT SCALES

    EPA Science Inventory

    Connectivity is more than corridors, and corridors are more than linear strips of habitat. ather, connectivity involves linkages of habitats, species, communities, and ecological processes at spatial scales ranging from fencerows to biomes, and at temporal scales ranging from dai...

  9. Reorganization of functionally connected brain subnetworks in high-functioning autism.

    PubMed

    Glerean, Enrico; Pan, Raj K; Salmi, Juha; Kujala, Rainer; Lahnakoski, Juha M; Roine, Ulrika; Nummenmaa, Lauri; Leppämäki, Sami; Nieminen-von Wendt, Taina; Tani, Pekka; Saramäki, Jari; Sams, Mikko; Jääskeläinen, Iiro P

    2016-03-01

    Previous functional connectivity studies have found both hypo- and hyper-connectivity in brains of individuals having autism spectrum disorder (ASD). Here we studied abnormalities in functional brain subnetworks in high-functioning individuals with ASD during free viewing of a movie containing social cues and interactions. Twenty-six subjects (13 with ASD) watched a 68-min movie during functional magnetic resonance imaging. For each subject, we computed Pearson's correlation between haemodynamic time-courses of each pair of 6-mm isotropic voxels. From the whole-brain functional networks, we derived individual and group-level subnetworks using graph theory. Scaled inclusivity was then calculated between all subject pairs to estimate intersubject similarity of connectivity structure of each subnetwork. Additional 54 individuals (27 with ASD) from the ABIDE resting-state database were included to test the reproducibility of the results. Between-group differences were observed in the composition of default-mode and ventro-temporal-limbic (VTL) subnetworks. The VTL subnetwork included amygdala, striatum, thalamus, parahippocampal, fusiform, and inferior temporal gyri. Further, VTL subnetwork similarity between subject pairs correlated significantly with similarity of symptom gravity measured with autism quotient. This correlation was observed also within the controls, and in the reproducibility dataset with ADI-R and ADOS scores. Our results highlight how the reorganization of functional subnetworks in individuals with ASD clarifies the mixture of hypo- and hyper-connectivity findings. Importantly, only the functional organization of the VTL subnetwork emerges as a marker of inter-individual similarities that co-vary with behavioral measures across all participants. These findings suggest a pivotal role of ventro-temporal and limbic systems in autism. PMID:26686668

  10. Abnormal brain activation and connectivity to standardized disorder-related visual scenes in social anxiety disorder.

    PubMed

    Heitmann, Carina Yvonne; Feldker, Katharina; Neumeister, Paula; Zepp, Britta Maria; Peterburs, Jutta; Zwitserlood, Pienie; Straube, Thomas

    2016-04-01

    Our understanding of altered emotional processing in social anxiety disorder (SAD) is hampered by a heterogeneity of findings, which is probably due to the vastly different methods and materials used so far. This is why the present functional magnetic resonance imaging (fMRI) study investigated immediate disorder-related threat processing in 30 SAD patients and 30 healthy controls (HC) with a novel, standardized set of highly ecologically valid, disorder-related complex visual scenes. SAD patients rated disorder-related as compared with neutral scenes as more unpleasant, arousing and anxiety-inducing than HC. On the neural level, disorder-related as compared with neutral scenes evoked differential responses in SAD patients in a widespread emotion processing network including (para-)limbic structures (e.g. amygdala, insula, thalamus, globus pallidus) and cortical regions (e.g. dorsomedial prefrontal cortex (dmPFC), posterior cingulate cortex (PCC), and precuneus). Functional connectivity analysis yielded an altered interplay between PCC/precuneus and paralimbic (insula) as well as cortical regions (dmPFC, precuneus) in SAD patients, which emphasizes a central role for PCC/precuneus in disorder-related scene processing. Hyperconnectivity of globus pallidus with amygdala, anterior cingulate cortex (ACC) and medial prefrontal cortex (mPFC) additionally underlines the relevance of this region in socially anxious threat processing. Our findings stress the importance of specific disorder-related stimuli for the investigation of altered emotion processing in SAD. Disorder-related threat processing in SAD reveals anomalies at multiple stages of emotion processing which may be linked to increased anxiety and to dysfunctionally elevated levels of self-referential processing reported in previous studies. PMID:26806013

  11. Abnormal Liver Function Tests in an Anorexia Nervosa Patient and an Atypical Manifestation of Refeeding Syndrome

    PubMed Central

    Vootla, Vamshidhar R.; Daniel, Myrta

    2015-01-01

    Refeeding syndrome is defined as electrolyte and fluid abnormalities that occur in significantly malnourished patients when they are refed orally, enterally, or parenterally. The principal manifestations include hypophosphatemia, hypokalemia, vitamin deficiencies, volume overload and edema. This can affect multiple organ systems, such as the cardiovascular, pulmonary, or neurological systems, secondary to the above-mentioned abnormalities. Rarely, patients may develop gastrointestinal symptoms and show abnormal liver function test results. We report the case of a 52-year-old woman with anorexia nervosa who developed refeeding syndrome and simultaneous elevations of liver function test results, which normalized upon the resolution of the refeeding syndrome. PMID:26351414

  12. Cytoarchitectural and functional abnormalities of the inferior colliculus in sudden unexplained perinatal death.

    PubMed

    Lavezzi, Anna M; Pusiol, Teresa; Matturri, Luigi

    2015-02-01

    The inferior colliculus is a mesencephalic structure endowed with serotonergic fibers that plays an important role in the processing of acoustic information. The implication of the neuromodulator serotonin also in the aetiology of sudden unexplained fetal and infant death syndromes and the demonstration in these pathologies of developmental alterations of the superior olivary complex (SOC), a group of pontine nuclei likewise involved in hearing, prompted us to investigate whether the inferior colliculus may somehow contribute to the pathogenetic mechanism of unexplained perinatal death. Therefore, we performed in a wide set of fetuses and infants, aged from 33 gestational weeks to 7 postnatal months and died of both known and unknown cause, an in-depth anatomopathological analysis of the brainstem, particularly of the midbrain. Peculiar neuroanatomical and functional abnormalities of the inferior colliculus, such as hypoplasia/structural disarrangement and immunonegativity or poor positivity of serotonin, were exclusively found in sudden death victims, and not in controls. In addition, these alterations were frequently related to dysgenesis of connected structures, precisely the raphé nuclei and the superior olivary complex, and to nicotine absorption in pregnancy. We propose, on the basis of these results, the involvement of the inferior colliculus in more important functions than those related to hearing, as breathing and, more extensively, all the vital activities, and then in pathological conditions underlying a sudden death in vulnerable periods of the autonomic nervous system development, particularly associated to harmful risk factors as cigarette smoking. PMID:25674737

  13. 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. PMID:26660886

  14. Aberrant Functional Connectivity and Structural Atrophy in Subcortical Vascular Cognitive Impairment: Relationship with Cognitive Impairments

    PubMed Central

    Zhou, Xia; Hu, Xiaopeng; Zhang, Chao; Wang, Haibao; Zhu, Xiaoqun; Xu, Liyan; Sun, Zhongwu; Yu, Yongqiang

    2016-01-01

    Abnormal structures in the cortical and subcortical regions have been identified in subcortical vascular cognition impairment (SVCI). However, little is known about the functional alterations in SVCI, and no study refers to the functional connectivity in the prefrontal and subcortical regions in this context. The medial prefrontal cortex (MPFC) is an important region of the executive network and default mode network, and the subcortical thalamus plays vital roles in mediating or modulating these two networks. To investigate both thalamus- and MPFC-related functional connectivity as well as its relationship with cognition in SVCI, 32 SVCI patients and 23 control individuals were administered neuropsychological assessments. They also underwent structural and functional magnetic resonance imaging scans. Voxel-based morphometry and functional connectivity analysis were performed to detect gray matter (GM) atrophy and to characterize the functional alterations in the thalamus and the MPFC. For structural data, we observed that GM atrophy was distributed in both cortical regions and subcortical areas. For functional data, we observed that the thalamus functional connectivity in SVCI was significantly decreased in several cortical regions [i.e., the orbitofrontal lobe (OFL)], which are mainly involved in executive function and memory function. However, connectivity was increased in several frontal regions (i.e., the inferior frontal gyrus), which may be induced by the compensatory recruitment of the decreased functional connectivity. The MPFC functional connectivity was also decreased in executive- and memory-related regions (i.e., the anterior cingulate cortex) along with a motor region (i.e., the supplementary motor area). In addition, the cognitive performance was closely correlated with functional connectivity between the left thalamus and the left OFL in SVCI. The present study, thus, provides evidence for an association between structural and functional alterations

  15. 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

  16. Pheochromocytoma with Markedly Abnormal Liver Function Tests and Severe Leukocytosis

    PubMed Central

    Eun, Chai Ryoung; Ahn, Jae Hee; Seo, Ji A

    2014-01-01

    Pheochromocytoma is a rare neuroendocrine tumor arising from the medulla of the adrenal glands, which causes an overproduction of catecholamines. The common symptoms are headache, palpitations, and sweating; however, various other clinical manifestations might also be present. Accurate diagnosis of pheochromocytoma is important because surgical treatment is usually successful, and associated clinical problems are reversible if treated early. A 49-year-old man with a history of uncontrolled hypertension and diabetes mellitus presented with chest pain, fever, and sweating. His liver function tests and white blood cell counts were markedly increased and his echocardiography results suggested stress-induced cardiomyopathy. His abdominal computed tomography showed a 5×5-cm-sized tumor in the left adrenal gland, and laboratory tests confirmed catecholamine overproduction. After surgical resection of the left adrenal gland, his liver function tests and white blood cell counts normalized, and echocardiography showed normal cardiac function. Moreover, his previous antihypertensive regimen was deescalated, and his previously uncontrolled blood glucose levels normalized without medication. PMID:24741459

  17. The connection between rhythmicity and brain function.

    PubMed

    Thaut, M H; Kenyon, G P; Schauer, M L; McIntosh, G C

    1999-01-01

    Although rhythm and music are not entirely synonymous terms, rhythm constitutes one of the most essential structural and organizational elements of music. When considering the effect of music on human adaptation, the profound effect of rhythm on the motor system strongly suggests that the time structure of music is the essential element relating music specifically to motor behavior. Why the motor system appears so sensitive to auditory priming and timing stimulation can only be partially answered so far. The high-performance function of the auditory system regarding processing of time information makes good functional sense within the constraints of auditory sensory processing. Thus, the motor system sensitivity to auditory entrainment may simply be an evolutionary useful function of taking advantage of the specific and unique aspects of auditory information processing for enhanced control and organization of motor behavior; e.g, in the time domain. Unlike processes in the motor system, many other physiological processes cannot be effectively entrained by external sensory stimuli. For example, there is probably a very good protective reason why other cyclical physiological processes (e.g., autonomic processes such as heart rate) have only very limited entrainment capacity to external rhythmic cues. Some of the basic auditory-motor arousal connections may also have their basis in adaptive evolutionary processes related to survival behavior; e.g., in fight or flight reactions. Much of the "why" in auditory-motor interactions, however, remains unknown heuristically. In the absence of this knowledge, great care should be taken to not compensate for this lack of understanding of specific cause and effect processes by assigning anthropomorphic descriptions to the behavior of biological and physical systems. The unraveling of the perceptual, physiological, and neuroanatomical basis of the interaction between rhythm and movement has been, and continues to be, a fascinating

  18. Diagnostic classification of intrinsic functional connectivity highlights somatosensory, default mode, and visual regions in autism

    PubMed Central

    Chen, Colleen P.; Keown, Christopher L.; Jahedi, Afrooz; Nair, Aarti; Pflieger, Mark E.; Bailey, Barbara A.; Müller, Ralph-Axel

    2015-01-01

    Despite consensus on the neurological nature of autism spectrum disorders (ASD), brain biomarkers remain unknown and diagnosis continues to be based on behavioral criteria. Growing evidence suggests that brain abnormalities in ASD occur at the level of interconnected networks; however, previous attempts using functional connectivity data for diagnostic classification have reached only moderate accuracy. We selected 252 low-motion resting-state functional MRI (rs-fMRI) scans from the Autism Brain Imaging Data Exchange (ABIDE) including typically developing (TD) and ASD participants (n = 126 each), matched for age, non-verbal IQ, and head motion. A matrix of functional connectivities between 220 functionally defined regions of interest was used for diagnostic classification, implementing several machine learning tools. While support vector machines in combination with particle swarm optimization and recursive feature elimination performed modestly (with accuracies for validation datasets <70%), diagnostic classification reached a high accuracy of 91% with random forest (RF), a nonparametric ensemble learning method. Among the 100 most informative features (connectivities), for which this peak accuracy was achieved, participation of somatosensory, default mode, visual, and subcortical regions stood out. Whereas some of these findings were expected, given previous findings of default mode abnormalities and atypical visual functioning in ASD, the prominent role of somatosensory regions was remarkable. The finding of peak accuracy for 100 interregional functional connectivities further suggests that brain biomarkers of ASD may be regionally complex and distributed, rather than localized. PMID:26106547

  19. Connecting Functions in Geometry and Algebra

    ERIC Educational Resources Information Center

    Steketee, Scott; Scher, Daniel

    2016-01-01

    One goal of a mathematics education is that students make significant connections among different branches of mathematics. Connections--such as those between arithmetic and algebra, between two-dimensional and three-dimensional geometry, between compass-and-straight-edge constructions and transformations, and between calculus and analytic…

  20. Abnormal systolic and diastolic myocardial function in obese asymptomatic adolescents.

    PubMed

    Batalli-Këpuska, Arbnora; Bajraktari, Gani; Zejnullahu, Murat; Azemi, Mehmedali; Shala, Mujë; Batalli, Arlind; Ibrahimi, Pranvera; Jashari, Fisnik; Henein, Michael Y

    2013-10-01

    Structural and functional cardiac changes are known in obese adults. We aimed to assess the relationship between body mass index (BMI) and cardiac function in overweight and obese asymptomatic adolescents. Ninety three healthy adolescents, aged 12.6 ± 1.2 years, received weight, height, BMI, waist, hips, waist/hips ratio assessment, hematology and biochemistry tests and an echocardiogram. Based on BMI, subjects were divided into: lean (L, n=32), overweight (Ov, n=33) and obese (Ob, n=32). Interventricular septal and LV posterior wall thickness were increased parallel to the BMI (L: 0.84 ± 0.1cm, Ov: 0.88 ± 0.1cm, Ob: 0.96 ± 0.1cm, p<0.001, and L: 0.78 ± 0.1cm, Ov: 0.8 ± 0.1cm, Ob: 0.94 ± 0.1cm, p<0.001, respectively) as were relative wall thickness (RWT) and mass index (LVMI) (L: 0.34 ± 0.05, Ov: 0.34 ± 0.05, Ob: 0.40 ± 0.04, p<0.001, and L: 47.7 ± 8.4 g/m(2), Ov: 51.9 ± 8.3g/m(2), Ob: 65.2 ± 13.3g/m(2), p=0<001, respectively). LV early diastolic (E') lateral and septal velocities (L: 15.3 ± 3.9 cm/s, Ov: 13.6 ± 4 cm/s, Ob: 10.5 ± 3.4 cm/s, p<0.001, and L: 12.2 ± 2.3 cm/s, Ov: 11.1 ± 2.4 cm/s, Ob: 9.8 ± 3.1cm/s, p=0.003, respectively), and systolic (S') velocities (L: 9.2 ± 1.4 cm/s, Ov: 9.3 ± 2.3 cm/s, Ob: 8.04 ± 1.5 cm/s, p=0.018, and L: 9.05 ± 2.3 cm/s, Ov: 9 ± 2.4 cm/s, Ob: 7.6 ± 1.1cm/s, p=0.014, respectively) were all reduced, only in obese adolescents. LV lateral E' (r=-0.44, p<0.001) and S' (r=-0.29, p=0.005) correlated with BMI. In asymptomatic adolescents, LV wall is thicker and diastolic function impaired and correlate with BMI. These findings demonstrate early cardiac functional disturbances which might explain the known obesity risk for cardiac disease. PMID:23416017

  1. HFE gene: Structure, function, mutations, and associated iron abnormalities.

    PubMed

    Barton, James C; Edwards, Corwin Q; Acton, Ronald T

    2015-12-15

    The hemochromatosis gene HFE was discovered in 1996, more than a century after clinical and pathologic manifestations of hemochromatosis were reported. Linked to the major histocompatibility complex (MHC) on chromosome 6p, HFE encodes the MHC class I-like protein HFE that binds beta-2 microglobulin. HFE influences iron absorption by modulating the expression of hepcidin, the main controller of iron metabolism. Common HFE mutations account for ~90% of hemochromatosis phenotypes in whites of western European descent. We review HFE mapping and cloning, structure, promoters and controllers, and coding region mutations, HFE protein structure, cell and tissue expression and function, mouse Hfe knockouts and knockins, and HFE mutations in other mammals with iron overload. We describe the pertinence of HFE and HFE to mechanisms of iron homeostasis, the origin and fixation of HFE polymorphisms in European and other populations, and the genetic and biochemical basis of HFE hemochromatosis and iron overload. PMID:26456104

  2. Resting-State EEG Source Localization and Functional Connectivity in Schizophrenia-Like Psychosis of Epilepsy

    PubMed Central

    Canuet, Leonides; Ishii, Ryouhei; Pascual-Marqui, Roberto D.; Iwase, Masao; Kurimoto, Ryu; Aoki, Yasunori; Ikeda, Shunichiro; Takahashi, Hidetoshi; Nakahachi, Takayuki; Takeda, Masatoshi

    2011-01-01

    Background It is unclear whether, like in schizophrenia, psychosis-related disruption in connectivity between certain regions, as an index of intrinsic functional disintegration, occurs in schizophrenia-like psychosis of epilepsy (SLPE). In this study, we sought to determine abnormal patterns of resting-state EEG oscillations and functional connectivity in patients with SLPE, compared with nonpsychotic epilepsy patients, and to assess correlations with psychopathological deficits. Methodology/Principal Findings Resting EEG was recorded in 21 patients with focal epilepsy and SLPE and in 21 clinically-matched non-psychotic epilepsy controls. Source current density and functional connectivity were determined using eLORETA software. For connectivity analysis, a novel nonlinear connectivity measure called “lagged phase synchronization” was used. We found increased theta oscillations in regions involved in the default mode network (DMN), namely the medial and lateral parietal cortex bilaterally in the psychotic patients relative to their nonpsychotic counterparts. In addition, patients with psychosis had increased beta temporo-prefrontal connectivity in the hemisphere with predominant seizure focus. This functional connectivity in temporo-prefrontal circuits correlated with positive symptoms. Additionally, there was increased interhemispheric phase synchronization between the auditory cortex of the affected temporal lobe and the Broca's area correlating with auditory hallucination scores. Conclusions/Significance In addition to dysfunction of parietal regions that are part of the DMN, resting-state disrupted connectivity of the medial temporal cortex with prefrontal areas that are either involved in the DMN or implicated in psychopathological dysfunction may be critical to schizophrenia-like psychosis, especially in individuals with temporal lobe epilepsy. This suggests that DMN deficits might be a core neurobiological feature of the disorder, and that abnormalities

  3. Abnormal tracheal smooth muscle function in the CF mouse

    PubMed Central

    Wallace, Helen L; Southern, Kevin W; Connell, Marilyn G; Wray, Susan; Burdyga, Theodor

    2013-01-01

    Increased airway smooth muscle (ASM) contractility is thought to underlie symptoms of airway hyperresponsiveness (AHR). In the cystic fibrosis (CF) airway, ASM anomalies have been reported, but have not been fully characterized and the underlying mechanisms are largely unknown. We examined ASM in an adult CF mouse tracheal ring preparation, and determined whether changes in contractility were associated with altered ASM morphology. We looked for inherent changes in the cellular pathways involved in contractility, and characterized trachea morphology in the adult trachea and in an embryonic lung culture model during development. Results showed that that there was a reduction in tracheal caliber in CF mice as indicated by a reduction in the number of cartilage rings; proximal cross-sectional areas of cftr−/− tracheas and luminal areas were significantly smaller, but there was no difference in the area or distribution of smooth muscle. Morphological differences observed in adult trachea were not evident in the embryonic lung at 11.5 days gestation or after 72 h in culture. Functional data showed a significant reduction in the amplitude and duration of contraction in response to carbachol (CCh) in Ca-free conditions. The reduction in contraction was agonist specific, and occurred throughout the length of the trachea. These data show that there is a loss in the contractile capacity of the CF mouse trachea due to downregulation of the pathway specific to acetylcholine (ACh) activation. This reduction in contraction is not associated with changes in the area or distribution of ASM. PMID:24400140

  4. Alternations of functional connectivity in amblyopia patients: a resting-state fMRI study

    NASA Astrophysics Data System (ADS)

    Wang, Jieqiong; Hu, Ling; Li, Wenjing; Xian, Junfang; Ai, Likun; He, Huiguang

    2014-03-01

    Amblyopia is a common yet hard-to-cure disease in children and results in poor or blurred vision. Some efforts such as voxel-based analysis, cortical thickness analysis have been tried to reveal the pathogenesis of amblyopia. However, few studies focused on alterations of the functional connectivity (FC) in amblyopia. In this study, we analyzed the abnormalities of amblyopia patients by both the seed-based FC with the left/right primary visual cortex and the network constructed throughout the whole brain. Experiments showed the following results: (1)As for the seed-based FC analysis, FC between superior occipital gyrus and the primary visual cortex was found to significantly decrease in both sides. The abnormalities were also found in lingual gyrus. The results may reflect functional deficits both in dorsal stream and ventral stream. (2)Two increased functional connectivities and 64 decreased functional connectivities were found in the whole brain network analysis. The decreased functional connectivities most concentrate in the temporal cortex. The results suggest that amblyopia may be caused by the deficits in the visual information transmission.

  5. Alterations in Brain Structure and Functional Connectivity in Alcohol Dependent Patients and Possible Association with Impulsivity

    PubMed Central

    Dong, Yue; Ma, Mengying; Ma, Yi; Dong, Yuru; Niu, Yajuan; Jiang, Yin; Wang, Hong; Wang, Zhiyan; Wu, Liuzhen; Sun, Hongqiang; Cui, Cailian

    2016-01-01

    Background Previous studies have documented that heightened impulsivity likely contributes to the development and maintenance of alcohol use disorders. However, there is still a lack of studies that comprehensively detected the brain changes associated with abnormal impulsivity in alcohol addicts. This study was designed to investigate the alterations in brain structure and functional connectivity associated with abnormal impulsivity in alcohol dependent patients. Methods Brain structural and functional magnetic resonance imaging data as well as impulsive behavior data were collected from 20 alcohol dependent patients and 20 age- and sex-matched healthy controls respectively. Voxel-based morphometry was used to investigate the differences of grey matter volume, and tract-based spatial statistics was used to detect abnormal white matter regions between alcohol dependent patients and healthy controls. The alterations in resting-state functional connectivity in alcohol dependent patients were examined using selected brain areas with gray matter deficits as seed regions. Results Compared with healthy controls, alcohol dependent patients had significantly reduced gray matter volume in the mesocorticolimbic system including the dorsal posterior cingulate cortex, the dorsal anterior cingulate cortex, the medial prefrontal cortex, the orbitofrontal cortex and the putamen, decreased fractional anisotropy in the regions connecting the damaged grey matter areas driven by higher radial diffusivity value in the same areas and decreased resting-state functional connectivity within the reward network. Moreover, the gray matter volume of the left medial prefrontal cortex exhibited negative correlations with various impulse indices. Conclusions These findings suggest that chronic alcohol dependence could cause a complex neural changes linked to abnormal impulsivity. PMID:27575491

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

    PubMed

    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

    2016-08-01

    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

  7. Abnormal degree centrality in Alzheimer's disease patients with depression: A resting-state functional magnetic resonance imaging study.

    PubMed

    Guo, Zhongwei; Liu, Xiaozheng; Hou, Hongtao; Wei, Fuquan; Liu, Jian; Chen, Xingli

    2016-06-15

    Depression is common in Alzheimer's disease (AD) and occurs in AD patients with a prevalence of up to 40%. It reduces cognitive function and increases the burden on caregivers. Currently, there are very few medications that are useful for treating depression in AD patients. Therefore, understanding the brain abnormalities in AD patients with depression (D-AD) is crucial for developing effective interventions. The aim of this study was to investigate the intrinsic dysconnectivity pattern of whole-brain functional networks at the voxel level in D-AD patients based on degree centrality (DC) as measured by resting-state functional magnetic resonance imaging (R-fMRI). Our study included 32 AD patients. All patients were evaluated using the Neuropsychiatric Inventory and Hamilton Depression Rating Scale and further divided into two groups: 15 D-AD patients and 17 non-depressed AD (nD-AD) patients. R-fMRI datasets were acquired from these D-AD and nD-AD patients. First, we performed a DC analysis to identify voxels that showed altered whole brain functional connectivity (FC) with other voxels. We then further investigated FC using the abnormal DC regions to examine in more detail the connectivity patterns of the identified DC changes. D-AD patients had lower DC values in the right middle frontal, precentral, and postcentral gyrus than nD-AD patients. Seed-based analysis revealed decreased connectivity between the precentral and postcentral gyrus to the supplementary motor area and middle cingulum. FC also decreased in the right middle frontal, precentral, and postcentral gyrus. Thus, AD patients with depression fit a 'network dysfunction model' distinct from major depressive disorder and AD. PMID:27079332

  8. Using computational models to relate structural and functional brain connectivity

    PubMed Central

    Hlinka, Jaroslav; Coombes, Stephen

    2012-01-01

    Modern imaging methods allow a non-invasive assessment of both structural and functional brain connectivity. This has lead to the identification of disease-related alterations affecting functional connectivity. The mechanism of how such alterations in functional connectivity arise in a structured network of interacting neural populations is as yet poorly understood. Here we use a modeling approach to explore the way in which this can arise and to highlight the important role that local population dynamics can have in shaping emergent spatial functional connectivity patterns. The local dynamics for a neural population is taken to be of the Wilson–Cowan type, whilst the structural connectivity patterns used, describing long-range anatomical connections, cover both realistic scenarios (from the CoComac database) and idealized ones that allow for more detailed theoretical study. We have calculated graph–theoretic measures of functional network topology from numerical simulations of model networks. The effect of the form of local dynamics on the observed network state is quantified by examining the correlation between structural and functional connectivity. We document a profound and systematic dependence of the simulated functional connectivity patterns on the parameters controlling the dynamics. Importantly, we show that a weakly coupled oscillator theory explaining these correlations and their variation across parameter space can be developed. This theoretical development provides a novel way to characterize the mechanisms for the breakdown of functional connectivity in diseases through changes in local dynamics. PMID:22805059

  9. Changes in brain functional network connectivity after stroke

    PubMed Central

    Li, Wei; Li, Yapeng; Zhu, Wenzhen; Chen, Xi

    2014-01-01

    Studies have shown that functional network connection models can be used to study brain network changes in patients with schizophrenia. In this study, we inferred that these models could also be used to explore functional network connectivity changes in stroke patients. We used independent component analysis to find the motor areas of stroke patients, which is a novel way to determine these areas. In this study, we collected functional magnetic resonance imaging datasets from healthy controls and right-handed stroke patients following their first ever stroke. Using independent component analysis, six spatially independent components highly correlated to the experimental paradigm were extracted. Then, the functional network connectivity of both patients and controls was established to observe the differences between them. The results showed that there were 11 connections in the model in the stroke patients, while there were only four connections in the healthy controls. Further analysis found that some damaged connections may be compensated for by new indirect connections or circuits produced after stroke. These connections may have a direct correlation with the degree of stroke rehabilitation. Our findings suggest that functional network connectivity in stroke patients is more complex than that in hea-lthy controls, and that there is a compensation loop in the functional network following stroke. This implies that functional network reorganization plays a very important role in the process of rehabilitation after stroke. PMID:25206743

  10. Alterations of functional and structural connectivity of freezing of gait in Parkinson's disease.

    PubMed

    Wang, Min; Jiang, Siming; Yuan, Yongsheng; Zhang, Li; Ding, Jian; Wang, Jianwei; Zhang, Jiejin; Zhang, Kezhong; Wang, Jie

    2016-08-01

    This study assessed the patterns of functional and structural connectivity abnormalities in patients with Parkinson's disease with freezing of gait (PD FOG+) compared with those without freezing (PD FOG-) and healthy controls (HCs). Resting state functional MRI (rs-fMRI) and diffusion tensor imaging (DTI) scans were obtained from 14 PD FOG+, 16 PD FOG- and 16HCs. Between-group difference in pedunculopontine nucleus (PPN) functional connectivity (FC) was performed to assess FC dysfunction. Tract-based spatial statistics (TBSS) was applied to compare white matter (WM) impairment across the whole brain between groups. PD FOG+ patients exhibited abnormal PPN FC, compared with HCs and with PD FOG-, mainly in the corticopontine-cerebellar pathways (in the bilateral cerebellum and in the pons), as well as the visual temporal areas (in the right middle temporal gyrus and in the right inferior temporal gyrus). Moreover, PD FOG+ patients, showed more pronounced WM abnormalities, relative to controls, including the interhemispheric connections of corpus callosum, the cortico-cortical WM tracts of the cingulum, the superior longitudinal fasciculus and inferior fronto-occipital fasciculus, the corticofugal tract (cerebral peduncles, internal capsule, corona radiata), as well as tracts connecting the thalamus (thalamic radiation). This study suggests that FOG in PD is associated with abnormal PPN FC network, mainly affecting the corticopontine-cerebellar pathways as well as visual temporal areas involved in visual processing, and with diffuse WM deficits extending to motor, sensory and cognitive regions. Combining rs-fMRI and DTI method, our study should advance the understanding of neural mechanisms underlying FOG in PD. PMID:27230857

  11. Effects of chronic and acute stimulants on brain functional connectivity hubs.

    PubMed

    Konova, Anna B; Moeller, Scott J; Tomasi, Dardo; Goldstein, Rita Z

    2015-12-01

    The spatial distribution and strength of information processing 'hubs' are essential features of the brain׳s network topology, and may thus be particularly susceptible to neuropsychiatric disease. Despite growing evidence that drug addiction alters functioning and connectivity of discrete brain regions, little is known about whether chronic drug use is associated with abnormalities in this network-level organization, and if such abnormalities could be targeted for intervention. We used functional connectivity density (FCD) mapping to evaluate how chronic and acute stimulants affect brain hubs (i.e., regions with many short-range or long-range functional connections). Nineteen individuals with cocaine use disorders (CUD) and 15 healthy controls completed resting-state fMRI scans following a randomly assigned dose of methylphenidate (MPH; 20mg) or placebo. Short-range and long-range FCD maps were computed for each participant and medication condition. CUD participants had increased short-range and long-range FCD in the ventromedial prefrontal cortex, posterior cingulate/precuneus, and putamen/amygdala, which in areas of the default mode network correlated with years of use. Across participants, MPH decreased short-range FCD in the thalamus/putamen, and decreased long-range FCD in the supplementary motor area and postcentral gyrus. Increased density of short-range and long-range functional connections to default mode hubs in CUD suggests an overrepresentation of these resource-expensive hubs. While the effects of MPH on FCD were only partly overlapping with those of CUD, MPH-induced reduction in the density of short-range connections to the putamen/thalamus, a network of core relevance to habit formation and addiction, suggests that some FCD abnormalities could be targeted for intervention. PMID:25721787

  12. Three Systems of Insular Functional Connectivity Identified with Cluster Analysis

    PubMed Central

    Pitskel, Naomi B.; Pelphrey, Kevin A.

    2011-01-01

    Despite much research on the function of the insular cortex, few studies have investigated functional subdivisions of the insula in humans. The present study used resting-state functional connectivity magnetic resonance imaging (MRI) to parcellate the human insular lobe based on clustering of functional connectivity patterns. Connectivity maps were computed for each voxel in the insula based on resting-state functional MRI (fMRI) data and segregated using cluster analysis. We identified 3 insular subregions with distinct patterns of connectivity: a posterior region, functionally connected with primary and secondary somatomotor cortices; a dorsal anterior to middle region, connected with dorsal anterior cingulate cortex, along with other regions of a previously described control network; and a ventral anterior region, primarily connected with pregenual anterior cingulate cortex. Applying these regions to a separate task data set, we found that dorsal and ventral anterior insula responded selectively to disgusting images, while posterior insula did not. These results demonstrate that clustering of connectivity patterns can be used to subdivide cerebral cortex into anatomically and functionally meaningful subregions; the insular regions identified here should be useful in future investigations on the function of the insula. PMID:21097516

  13. BASCO: a toolbox for task-related functional connectivity

    PubMed Central

    Göttlich, Martin; Beyer, Frederike; Krämer, Ulrike M.

    2015-01-01

    BASCO (BetA Series COrrelation) is a user-friendly MATLAB toolbox with a graphical user interface (GUI) which allows investigating functional connectivity in event-related functional magnetic resonance imaging (fMRI) data. Connectivity analyses extend and compliment univariate activation analyses since the actual interaction between brain regions involved in a task can be explored. BASCO supports seed-based functional connectivity as well as brain network analyses. Although there are a multitude of advanced toolboxes for investigating resting-state functional connectivity, BASCO is the first toolbox for evaluating task-related whole-brain functional connectivity employing a large number of network nodes. Thus, BASCO allows investigating task-specific rather than resting-state networks. Here, we summarize the main features of the toolbox and describe the methods and algorithms. PMID:26441558

  14. Liver Function Test Abnormalities in Patients with Inflammatory Bowel Diseases: A Hospital-based Survey

    PubMed Central

    Cappello, Maria; Randazzo, Claudia; Bravatà, Ivana; Licata, Anna; Peralta, Sergio; Craxì, Antonio; Almasio, Piero Luigi

    2014-01-01

    BACKGROUND AND AIMS Inflammatory bowel diseases (IBD) are frequently associated with altered liver function tests (LFTs). The causal relationship between abnormal LFTs and IBD is unclear. The aim of our study was to evaluate the prevalence and etiology of LFTs abnormalities and their association with clinical variables in a cohort of IBD patients followed up in a single center. MATERIALS AND METHODS A retrospective review was undertaken of all consecutive IBD in- and outpatients routinely followed up at a single referral center. Clinical and demographic parameters were recorded. Subjects were excluded if they had a previous diagnosis of chronic liver disease. LFT abnormality was defined as an increase in aspartate aminotransferase, (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), or total bilirubin. RESULTS A cohort of 335 patients (179 males, mean age 46.0 ± 15.6 years) was analyzed. Abnormal LFTs were detected in 70 patients (20.9%). In most cases, the alterations were mild and spontaneously returned to normal values in about 60% of patients. Patients with abnormal LFTs were less frequently on treatment with aminosalicylates (22.8 vs. 36.6%, P = 0.04). The most frequent cause for transient abnormal LFTs was drug-induced cholestasis (34.1%), whereas fatty liver was the most frequent cause of persistent liver damage (65.4%). A cholestatic pattern was found in 60.0% of patients and was mainly related to older age, longer duration of disease, and hypertension. CONCLUSIONS The prevalence of LFT abnormalities is relatively high in IBD patients, but the development of severe liver injury is exceptional. Moreover, most alterations of LFTs are mild and spontaneously return to normal values. Drug-induced hepatotoxicity and fatty liver are the most relevant causes of abnormal LFTs in patients with IBD. PMID:24966712

  15. Reversible cold-induced abnormalities in myocardial perfusion and function in systemic sclerosis

    SciTech Connect

    Alexander, E.L.; Firestein, G.S.; Weiss, J.L.; Heuser, R.R.; Leitl, G.; Wagner, H.N. Jr.; Brinker, J.A.; Ciuffo, A.A.; Becker, L.C.

    1986-11-01

    The effects of peripheral cold exposure on myocardial perfusion and function were studied in 13 patients with scleroderma without clinically evident myocardial disease. Ten patients had at least one transient, cold-induced, myocardial perfusion defect visualized by thallium-201 scintigraphy, and 12 had reversible, cold-induced, segmental left ventricular hypokinesis by two-dimensional echocardiography. The 10 patients with transient perfusion defects all had anatomically corresponding ventricular wall motion abnormalities. No one in either of two control groups (9 normal volunteers and 7 patients with chest pain and normal coronary arteriograms) had cold-induced abnormalities. This study is the first to show the simultaneous occurrence of cold-induced abnormalities in myocardial perfusion and function in patients with scleroderma. The results suggest that cold exposure in such patients may elicit transient reflex coronary vasoconstriction resulting in reversible myocardial ischemia and dysfunction. Chronic recurrent episodes of coronary spasm may lead to focal myocardial fibrosis.

  16. Efficiency of weak brain connections support general cognitive functioning.

    PubMed

    Santarnecchi, Emiliano; Galli, Giulia; Polizzotto, Nicola Riccardo; Rossi, Alessandro; Rossi, Simone

    2014-09-01

    Brain network topology provides valuable information on healthy and pathological brain functioning. Novel approaches for brain network analysis have shown an association between topological properties and cognitive functioning. Under the assumption that "stronger is better", the exploration of brain properties has generally focused on the connectivity patterns of the most strongly correlated regions, whereas the role of weaker brain connections has remained obscure for years. Here, we assessed whether the different strength of connections between brain regions may explain individual differences in intelligence. We analyzed-functional connectivity at rest in ninety-eight healthy individuals of different age, and correlated several connectivity measures with full scale, verbal, and performance Intelligent Quotients (IQs). Our results showed that the variance in IQ levels was mostly explained by the distributed communication efficiency of brain networks built using moderately weak, long-distance connections, with only a smaller contribution of stronger connections. The variability in individual IQs was associated with the global efficiency of a pool of regions in the prefrontal lobes, hippocampus, temporal pole, and postcentral gyrus. These findings challenge the traditional view of a prominent role of strong functional brain connections in brain topology, and highlight the importance of both strong and weak connections in determining the functional architecture responsible for human intelligence variability. PMID:24585433

  17. Abnormal Parietal Brain Function in ADHD: Replication and Extension of Previous EEG Beta Asymmetry Findings

    PubMed Central

    Hale, T. Sigi; Kane, Andrea M.; Tung, Kelly L.; Kaminsky, Olivia; McGough, James J.; Hanada, Grant; Loo, Sandra K.

    2014-01-01

    Background: Abundant work indicates ADHD abnormal posterior brain structure and function, including abnormal structural and functional asymmetries and reduced corpus callosum size. However, this literature has attracted considerably less research interest than fronto-striatal findings. Objective: To help address this imbalance, the current study replicates and extends our previous work showing abnormal parietal brain function in ADHD adults during the Conner’s Continuous Performance Test (CPT). Method: Our previous study found that ADHD adults had increased rightward EEG beta (16–21 Hz) asymmetry in inferior parietal brain regions during the CPT (p = 0.00001), and that this metric exhibited a lack of normal correlation (i.e., observed in controls) with beta asymmetry at temporal–parietal regions. We re-tested these effects in a new ADHD sample and with both new and old samples combined. We additionally examined: (a) EEG asymmetry in multiple frequency bands, (b) unilateral effects for all asymmetry findings, and (c) the association between EEG asymmetry and a battery of cognitive tests. Results: We replicated our original findings by demonstrating abnormal rightward inferior parietal beta asymmetry in adults with ADHD during the CPT, and again this metric exhibited abnormal reduced correlation to temporal–parietal beta asymmetry. Novel analyses also demonstrated a broader pattern of rightward beta and theta asymmetry across inferior, superior, and temporal–parietal brain regions, and showed that rightward parietal asymmetry in ADHD was atypically associated with multiple cognitive tests. Conclusion: Abnormal increased rightward parietal EEG beta asymmetry is an important feature of ADHD. We speculate that this phenotype may occur with any form of impaired capacity for top-down task-directed control over sensory encoding functions, and that it may reflect associated increase of attentional shifting and compensatory sustained/selective attention. PMID

  18. 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

  19. GPU accelerated dynamic functional connectivity analysis for functional MRI data.

    PubMed

    Akgün, Devrim; Sakoğlu, Ünal; Esquivel, Johnny; Adinoff, Bryon; Mete, Mutlu

    2015-07-01

    Recent advances in multi-core processors and graphics card based computational technologies have paved the way for an improved and dynamic utilization of parallel computing techniques. Numerous applications have been implemented for the acceleration of computationally-intensive problems in various computational science fields including bioinformatics, in which big data problems are prevalent. In neuroimaging, dynamic functional connectivity (DFC) analysis is a computationally demanding method used to investigate dynamic functional interactions among different brain regions or networks identified with functional magnetic resonance imaging (fMRI) data. In this study, we implemented and analyzed a parallel DFC algorithm based on thread-based and block-based approaches. The thread-based approach was designed to parallelize DFC computations and was implemented in both Open Multi-Processing (OpenMP) and Compute Unified Device Architecture (CUDA) programming platforms. Another approach developed in this study to better utilize CUDA architecture is the block-based approach, where parallelization involves smaller parts of fMRI time-courses obtained by sliding-windows. Experimental results showed that the proposed parallel design solutions enabled by the GPUs significantly reduce the computation time for DFC analysis. Multicore implementation using OpenMP on 8-core processor provides up to 7.7× speed-up. GPU implementation using CUDA yielded substantial accelerations ranging from 18.5× to 157× speed-up once thread-based and block-based approaches were combined in the analysis. Proposed parallel programming solutions showed that multi-core processor and CUDA-supported GPU implementations accelerated the DFC analyses significantly. Developed algorithms make the DFC analyses more practical for multi-subject studies with more dynamic analyses. PMID:25805449

  20. Functional Brain Network Abnormalities during Verbal Working Memory Performance in Adolescents and Young Adults with Dyslexia

    ERIC Educational Resources Information Center

    Wolf, Robert Christian; Sambataro, Fabio; Lohr, Christina; Steinbrink, Claudia; Martin, Claudia; Vasic, Nenad

    2010-01-01

    Behavioral and functional neuroimaging studies indicate deficits in verbal working memory (WM) and frontoparietal dysfunction in individuals with dyslexia. Additionally, structural brain abnormalities in dyslexics suggest a dysconnectivity of brain regions associated with phonological processing. However, little is known about the functional…

  1. 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.

  2. Detecting Functional Connectivity During Audiovisual Integration with MEG: A Comparison of Connectivity Metrics

    PubMed Central

    Carver, Frederick W.; Holroyd, Tom; Horwitz, Barry; Coppola, Richard

    2015-01-01

    Abstract In typical magnetoencephalography and/or electroencephalography functional connectivity analysis, researchers select one of several methods that measure a relationship between regions to determine connectivity, such as coherence, power correlations, and others. However, it is largely unknown if some are more suited than others for various types of investigations. In this study, the authors investigate seven connectivity metrics to evaluate which, if any, are sensitive to audiovisual integration by contrasting connectivity when tracking an audiovisual object versus connectivity when tracking a visual object uncorrelated with the auditory stimulus. The authors are able to assess the metrics' performances at detecting audiovisual integration by investigating connectivity between auditory and visual areas. Critically, the authors perform their investigation on a whole-cortex all-to-all mapping, avoiding confounds introduced in seed selection. The authors find that amplitude-based connectivity measures in the beta band detect strong connections between visual and auditory areas during audiovisual integration, specifically between V4/V5 and auditory cortices in the right hemisphere. Conversely, phase-based connectivity measures in the beta band as well as phase and power measures in alpha, gamma, and theta do not show connectivity between audiovisual areas. The authors postulate that while beta power correlations detect audiovisual integration in the current experimental context, it may not always be the best measure to detect connectivity. Instead, it is likely that the brain utilizes a variety of mechanisms in neuronal communication that may produce differential types of temporal relationships. PMID:25599264

  3. Detecting Functional Connectivity During Audiovisual Integration with MEG: A Comparison of Connectivity Metrics.

    PubMed

    Ard, Tyler; Carver, Frederick W; Holroyd, Tom; Horwitz, Barry; Coppola, Richard

    2015-08-01

    In typical magnetoencephalography and/or electroencephalography functional connectivity analysis, researchers select one of several methods that measure a relationship between regions to determine connectivity, such as coherence, power correlations, and others. However, it is largely unknown if some are more suited than others for various types of investigations. In this study, the authors investigate seven connectivity metrics to evaluate which, if any, are sensitive to audiovisual integration by contrasting connectivity when tracking an audiovisual object versus connectivity when tracking a visual object uncorrelated with the auditory stimulus. The authors are able to assess the metrics' performances at detecting audiovisual integration by investigating connectivity between auditory and visual areas. Critically, the authors perform their investigation on a whole-cortex all-to-all mapping, avoiding confounds introduced in seed selection. The authors find that amplitude-based connectivity measures in the beta band detect strong connections between visual and auditory areas during audiovisual integration, specifically between V4/V5 and auditory cortices in the right hemisphere. Conversely, phase-based connectivity measures in the beta band as well as phase and power measures in alpha, gamma, and theta do not show connectivity between audiovisual areas. The authors postulate that while beta power correlations detect audiovisual integration in the current experimental context, it may not always be the best measure to detect connectivity. Instead, it is likely that the brain utilizes a variety of mechanisms in neuronal communication that may produce differential types of temporal relationships. PMID:25599264

  4. Sex Differences in the Development of Neuroanatomical Functional Connectivity underlying Intelligence found using Bayesian Connectivity Analysis

    PubMed Central

    Schmithorst, Vincent J.; Holland, Scott K.

    2007-01-01

    A Bayesian method for functional connectivity analysis was adapted to investigate between-group differences. This method was applied in a large cohort of almost 300 children to investigate differences in boys and girls in the relationship between intelligence and functional connectivity for the task of narrative comprehension. For boys, a greater association was shown between intelligence and the functional connectivity linking Broca’s area to auditory processing areas, including Wernicke’s areas and the right posterior superior temporal gyrus. For girls, a greater association was shown between intelligence and the functional connectivity linking the left posterior superior temporal gyrus to Wernicke’s areas bilaterally. A developmental effect was also seen, with girls displaying a positive correlation with age in the association between intelligence and the functional connectivity linking the right posterior superior temporal gyrus to Wernicke’s areas bilaterally. Our results demonstrate a sexual dimorphism in the relationship of functional connectivity to intelligence in children and an increasing reliance on inter-hemispheric connectivity in girls with age. PMID:17223578

  5. Sex differences in the development of neuroanatomical functional connectivity underlying intelligence found using Bayesian connectivity analysis.

    PubMed

    Schmithorst, Vincent J; Holland, Scott K

    2007-03-01

    A Bayesian method for functional connectivity analysis was adapted to investigate between-group differences. This method was applied in a large cohort of almost 300 children to investigate differences in boys and girls in the relationship between intelligence and functional connectivity for the task of narrative comprehension. For boys, a greater association was shown between intelligence and the functional connectivity linking Broca's area to auditory processing areas, including Wernicke's areas and the right posterior superior temporal gyrus. For girls, a greater association was shown between intelligence and the functional connectivity linking the left posterior superior temporal gyrus to Wernicke's areas bilaterally. A developmental effect was also seen, with girls displaying a positive correlation with age in the association between intelligence and the functional connectivity linking the right posterior superior temporal gyrus to Wernicke's areas bilaterally. Our results demonstrate a sexual dimorphism in the relationship of functional connectivity to intelligence in children and an increasing reliance on inter-hemispheric connectivity in girls with age. PMID:17223578

  6. Ongoing dynamics in large-scale functional connectivity predict perception

    PubMed Central

    Sadaghiani, Sepideh; Poline, Jean-Baptiste; Kleinschmidt, Andreas; D’Esposito, Mark

    2015-01-01

    Most brain activity occurs in an ongoing manner not directly locked to external events or stimuli. Regional ongoing activity fluctuates in unison with some brain regions but not others, and the degree of long-range coupling is called functional connectivity, often measured with correlation. Strength and spatial distributions of functional connectivity dynamically change in an ongoing manner over seconds to minutes, even when the external environment is held constant. Direct evidence for any behavioral relevance of these continuous large-scale dynamics has been limited. Here, we investigated whether ongoing changes in baseline functional connectivity correlate with perception. In a continuous auditory detection task, participants perceived the target sound in roughly one-half of the trials. Very long (22–40 s) interstimulus intervals permitted investigation of baseline connectivity unaffected by preceding evoked responses. Using multivariate classification, we observed that functional connectivity before the target predicted whether it was heard or missed. Using graph theoretical measures, we characterized the difference in functional connectivity between states that lead to hits vs. misses. Before misses compared with hits and task-free rest, connectivity showed reduced modularity, a measure of integrity of modular network structure. This effect was strongest in the default mode and visual networks and caused by both reduced within-network connectivity and enhanced across-network connections before misses. The relation of behavior to prestimulus connectivity was dissociable from that of prestimulus activity amplitudes. In conclusion, moment to moment dynamic changes in baseline functional connectivity may shape subsequent behavioral performance. A highly modular network structure seems beneficial to perceptual efficiency. PMID:26106164

  7. Neural correlates of substance abuse: Reduced functional connectivity between areas underlying reward and cognitive control

    PubMed Central

    Motzkin, Julian C.; Baskin-Sommers, Arielle; Newman, Joseph P.; Kiehl, Kent A.; Koenigs, Michael

    2014-01-01

    Substance use disorders (SUD) have been associated with dysfunction in reward processing, habit formation, and cognitive-behavioral control. Accordingly, neurocircuitry models of addiction highlight roles for nucleus accumbens, dorsal striatum, and prefrontal/anterior cingulate cortex. However, the precise nature of the disrupted interactions between these brain regions in SUD, and the psychological correlates thereof, remain unclear. Here we used magnetic resonance imaging to measure rest-state functional connectivity of three key striatal nuclei (nucleus accumbens, dorsal caudate, dorsal putamen) in a sample of 40 adult male prison inmates (n=22 diagnosed with SUD; n=18 without SUD). Relative to the non-SUD group, the SUD group exhibited significantly lower functional connectivity between the nucleus accumbens and a network of frontal cortical regions involved in cognitive control (dorsal anterior cingulate cortex, dorsolateral prefrontal cortex, and frontal operculum). There were no group differences in functional connectivity for the dorsal caudate or dorsal putamen. Moreover, the SUD group exhibited impairments in laboratory measures of cognitive-behavioral control, and individual differences in functional connectivity between nucleus accumbens and the frontal cortical regions were related to individual differences in measures of cognitive-behavioral control across groups. The strength of the relationship between functional connectivity and cognitive control did not differ between groups. These results indicate that SUD is associated with abnormal interactions between subcortical areas that process reward (nucleus accumbens) and cortical areas that govern cognitive-behavioral control. PMID:24510765

  8. Perfusion deficits and functional connectivity alterations in patients with post-traumatic stress disorder

    NASA Astrophysics Data System (ADS)

    Liu, Yang; Li, Baojuan; Zhang, Xi; Zhang, Linchuan; Li, Liang; Lu, Hongbing

    2016-03-01

    To explore the alteration in cerebral blood flow (CBF) and functional connectivity between survivors with recent onset post-traumatic stress disorder (PTSD) and without PTSD, survived from the same coal mine flood disaster. In this study, a processing pipeline using arterial spin labeling (ASL) sequence was proposed. Considering low spatial resolution of ASL sequence, a linear regression method was firstly used to correct the partial volume (PV) effect for better CBF estimation. Then the alterations of CBF between two groups were analyzed using both uncorrected and PV-corrected CBF maps. Based on altered CBF regions detected from the CBF analysis as seed regions, the functional connectivity abnormities in PTSD patients was investigated. The CBF analysis using PV-corrected maps indicates CBF deficits in the bilateral frontal lobe, right superior frontal gyrus and right corpus callosum of PTSD patients, while only right corpus callosum was identified in uncorrected CBF analysis. Furthermore, the regional CBF of the right superior frontal gyrus exhibits significantly negative correlation with the symptom severity in PTSD patients. The resting-state functional connectivity indicates increased connectivity between left frontal lobe and right parietal lobe. These results indicate that PV-corrected CBF exhibits more subtle perfusion changes and may benefit further perfusion and connectivity analysis. The symptom-specific perfusion deficits and aberrant connectivity in above memory-related regions may be putative biomarkers for recent onset PTSD induced by a single prolonged trauma exposure and help predict the severity of PTSD.

  9. Joint brain connectivity estimation from diffusion and functional MRI data

    NASA Astrophysics Data System (ADS)

    Chu, Shu-Hsien; Lenglet, Christophe; Parhi, Keshab K.

    2015-03-01

    Estimating brain wiring patterns is critical to better understand the brain organization and function. Anatomical brain connectivity models axonal pathways, while the functional brain connectivity characterizes the statistical dependencies and correlation between the activities of various brain regions. The synchronization of brain activity can be inferred through the variation of blood-oxygen-level dependent (BOLD) signal from functional MRI (fMRI) and the neural connections can be estimated using tractography from diffusion MRI (dMRI). Functional connections between brain regions are supported by anatomical connections, and the synchronization of brain activities arises through sharing of information in the form of electro-chemical signals on axon pathways. Jointly modeling fMRI and dMRI data may improve the accuracy in constructing anatomical connectivity as well as functional connectivity. Such an approach may lead to novel multimodal biomarkers potentially able to better capture functional and anatomical connectivity variations. We present a novel brain network model which jointly models the dMRI and fMRI data to improve the anatomical connectivity estimation and extract the anatomical subnetworks associated with specific functional modes by constraining the anatomical connections as structural supports to the functional connections. The key idea is similar to a multi-commodity flow optimization problem that minimizes the cost or maximizes the efficiency for flow configuration and simultaneously fulfills the supply-demand constraint for each commodity. In the proposed network, the nodes represent the grey matter (GM) regions providing brain functionality, and the links represent white matter (WM) fiber bundles connecting those regions and delivering information. The commodities can be thought of as the information corresponding to brain activity patterns as obtained for instance by independent component analysis (ICA) of fMRI data. The concept of information

  10. Joint brain connectivity estimation from diffusion and functional MRI data

    NASA Astrophysics Data System (ADS)

    Chu, Shu-Hsien; Lenglet, Christophe; Parhi, Keshab K.

    2015-03-01

    Estimating brain wiring patterns is critical to better understand the brain organization and function. Anatomical brain connectivity models axonal pathways, while the functional brain connectivity characterizes the statistical dependencies and correlation between the activities of various brain regions. The synchronization of brain activity can be inferred through the variation of blood-oxygen-level dependent (BOLD) signal from functional MRI (fMRI) and the neural connections can be estimated using tractography from diffusion MRI (dMRI). Functional connections between brain regions are supported by anatomical connections, and the synchronization of brain activities arises through sharing of information in the form of electro-chemical signals on axon pathways. Jointly modeling fMRI and dMRI data may improve the accuracy in constructing anatomical connectivity as well as functional connectivity. Such an approach may lead to novel multimodal biomarkers potentially able to better capture functional and anatomical connectivity variations. We present a novel brain network model which jointly models the dMRI and fMRI data to improve the anatomical connectivity estimation and extract the anatomical subnetworks associated with specific functional modes by constraining the anatomical connections as structural supports to the functional connections. The key idea is similar to a multi-commodity flow optimization problem that minimizes the cost or maximizes the efficiency for flow configuration and simultaneously fulfills the supply-demand constraint for each commodity. In the proposed network, the nodes represent the grey matter (GM) regions providing brain functionality, and the links represent white matter (WM) fiber bundles connecting those regions and delivering information. The commodities can be thought of as the information corresponding to brain activity patterns as obtained for instance by independent component analysis (ICA) of fMRI data. The concept of information

  11. Motor Network Plasticity and Low-Frequency Oscillations Abnormalities in Patients with Brain Gliomas: A Functional MRI Study

    PubMed Central

    Niu, Chen; Zhang, Ming; Min, Zhigang; Rana, Netra; Zhang, Qiuli; Liu, Xin; Li, Min; Lin, Pan

    2014-01-01

    Brain plasticity is often associated with the process of slow-growing tumor formation, which remodels neural organization and optimizes brain network function. In this study, we aimed to investigate whether motor function plasticity would display deficits in patients with slow-growing brain tumors located in or near motor areas, but who were without motor neurological deficits. We used resting-state functional magnetic resonance imaging to probe motor networks in 15 patients with histopathologically confirmed brain gliomas and 15 age-matched healthy controls. All subjects performed a motor task to help identify individual motor activity in the bilateral primary motor cortex (PMC) and supplementary motor area (SMA). Frequency-based analysis at three different frequencies was then used to investigate possible alterations in the power spectral density (PSD) of low-frequency oscillations. For each group, the average PSD was determined for each brain region and a nonparametric test was performed to determine the difference in power between the two groups. Significantly reduced inter-hemispheric functional connectivity between the left and right PMC was observed in patients compared with controls (P<0.05). We also found significantly decreased PSD in patients compared to that in controls, in all three frequency bands (low: 0.01–0.02 Hz; middle: 0.02–0.06 Hz; and high: 0.06–0.1 Hz), at three key motor regions. These findings suggest that in asymptomatic patients with brain tumors located in eloquent regions, inter-hemispheric connection may be more vulnerable. A comparison of the two approaches indicated that power spectral analysis is more sensitive than functional connectivity analysis for identifying the neurological abnormalities underlying motor function plasticity induced by slow-growing tumors. PMID:24806463

  12. Co-localisation of abnormal brain structure and function in specific language impairment

    PubMed Central

    Badcock, Nicholas A.; Bishop, Dorothy V.M.; Hardiman, Mervyn J.; Barry, Johanna G.; Watkins, Kate E.

    2012-01-01

    We assessed the relationship between brain structure and function in 10 individuals with specific language impairment (SLI), compared to six unaffected siblings, and 16 unrelated control participants with typical language. Voxel-based morphometry indicated that grey matter in the SLI group, relative to controls, was increased in the left inferior frontal cortex and decreased in the right caudate nucleus and superior temporal cortex bilaterally. The unaffected siblings also showed reduced grey matter in the caudate nucleus relative to controls. In an auditory covert naming task, the SLI group showed reduced activation in the left inferior frontal cortex, right putamen, and in the superior temporal cortex bilaterally. Despite spatially coincident structural and functional abnormalities in frontal and temporal areas, the relationships between structure and function in these regions were different. These findings suggest multiple structural and functional abnormalities in SLI that are differently associated with receptive and expressive language processing. PMID:22137677

  13. Abnormal Amygdalar Activation and Connectivity in Adolescents with Attention-Deficit/Hyperactivity Disorder

    ERIC Educational Resources Information Center

    Posner, Jonathan; Nagel, Bonnie J.; Maia, Tiago V.; Mechling, Anna; Oh, Milim; Wang, Zhishun; Peterson, Bradley S.

    2011-01-01

    Objective: Emotional reactivity is one of the most disabling symptoms associated with attention-deficit/hyperactivity disorder (ADHD). We aimed to identify neural substrates associated with emotional reactivity and to assess the effects of stimulants on those substrates. Method: We used functional magnetic resonance imaging (fMRI) to assess neural…

  14. Aberrant structural and functional connectivity in the salience network and central executive network circuit in schizophrenia.

    PubMed

    Chen, Quan; Chen, Xingui; He, Xiaoxuan; Wang, Lu; Wang, Kai; Qiu, Bensheng

    2016-08-01

    Consistent structural and functional abnormities have been detected in the salience network (SN) and the central-executive network (CEN) in schizophrenia. SN, known for its critical role in switching CEN and default-mode network (DMN) during cognitively demanding tasks, is proved to show aberrant regulation on the interaction between DMN and CEN in schizophrenia. However, it has not been elucidated whether there is a direct alteration of structural and functional connectivity between SN and CEN. 22 schizophrenia patients and 21 healthy controls were recruited for functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) in present study. The results show that schizophrenia patients had lower fractional anisotropy (FA) in right inferior long fasciculus (ILF), left inferior fronto-occipital fasciculus (IFOF) and callosal body than healthy controls. Significantly reduced functional connectivity was also found between right fronto-insular cortex (rFIC) and right posterior parietal cortex (rPPC). FA in right ILF was positively correlated with the functional connectivity of rFIC-rPPC. Therefore, we proposed a disruption of structural and functional connectivity and a positive anatomo-functional relationship in SN-CEN circuit, which might account for a core feature of schizophrenia. PMID:27233217

  15. Functional specificity of local synaptic connections in neocortical networks

    PubMed Central

    Ko, Ho; Hofer, Sonja B.; Pichler, Bruno; Buchanan, Kate; Sjöström, P. Jesper; Mrsic-Flogel, Thomas D.

    2011-01-01

    Neuronal connectivity is fundamental to information processing in the brain. Understanding the mechanisms of sensory processing, therefore, requires uncovering how connection patterns between neurons relate to their function. On a coarse scale long range projections can preferentially link cortical regions with similar responses to sensory stimuli1-4. But on the local scale, where dendrites and axons overlap substantially, the functional specificity of connections remains unknown. Here we determine synaptic connectivity between nearby layer 2/3 pyramidal neurons in vitro whose response properties were first characterized in mouse visual cortex in vivo. We found that connection probability was related to the similarity of visually driven neuronal activity. Neurons with the same preference for oriented stimuli connected at twice the rate of neurons with orthogonal orientation preferences. Neurons responding similarly to naturalistic stimuli formed connections at much higher rates than those with uncorrelated responses. Bidirectional synaptic connections were found more frequently between neuronal pairs with strongly correlated visual responses. Our results reveal the deg of functional specificity of local synaptic connections in visual cortex, and point to the existence of fine-scale subnetworks dedicated to processing related sensory information. PMID:21478872

  16. Disrupted Functional Connectivity with Dopaminergic Midbrain in Cocaine Abusers

    SciTech Connect

    Tomasi, D.; Tomasi, D.; Volkow, N.D.; Wang, R.; Carrillo, J.; Maloney, T.; Alia-Klein, N.; Woicik, P.A.; Telang, F.; Goldstein, R.Z.

    2010-06-01

    Chronic cocaine use is associated with disrupted dopaminergic neurotransmission but how this disruption affects overall brain function (other than reward/motivation) is yet to be fully investigated. Here we test the hypothesis that cocaine addicted subjects will have disrupted functional connectivity between the midbrain (where dopamine neurons are located) and cortical and subcortical brain regions during the performance of a sustained attention task. We measured brain activation and functional connectivity with fMRI in 20 cocaine abusers and 20 matched controls. When compared to controls, cocaine abusers had lower positive functional connectivity of midbrain with thalamus, cerebellum, and rostral cingulate, and this was associated with decreased activation in thalamus and cerebellum and enhanced deactivation in rostral cingulate. These findings suggest that decreased functional connectivity of the midbrain interferes with the activation and deactivation signals associated with sustained attention in cocaine addicts.

  17. Abnormal hippocampal structure and function in clinical anxiety and comorbid depression.

    PubMed

    Cha, Jiook; Greenberg, Tsafrir; Song, Inkyung; Blair Simpson, Helen; Posner, Jonathan; Mujica-Parodi, Lilianne R

    2016-05-01

    Given the high prevalence rates of comorbidity of anxiety and depressive disorders, identifying a common neural pathway to both disorders is important not only for better diagnosis and treatment, but also for a more complete conceptualization of each disease. Hippocampal abnormalities have been implicated in anxiety and depression, separately; however, it remains unknown whether these abnormalities are also implicated in their comorbidity. Here we address this question by testing 32 adults with generalized anxiety disorder (15 GAD only and 17 comorbid MDD) and 25 healthy controls (HC) using multimodal MRI (structure, diffusion and functional) and automated hippocampal segmentation. We demonstrate that (i) abnormal microstructure of the CA1 and CA2-3 is associated with GAD/MDD comorbidity and (ii) decreased anterior hippocampal reactivity in response to repetition of the threat cue is associated with GAD (with or without MDD comorbidity). In addition, mediation-structural equation modeling (SEM) reveals that our hippocampal and dimensional symptom data are best explained by a model describing a significant influence of abnormal hippocampal microstructure on both anxiety and depression-mediated through its impact on abnormal hippocampal threat processing. Collectively, our findings show a strong association between changes in hippocampal microstructure and threat processing, which together may present a common neural pathway to comorbidity of anxiety and depression. © 2016 Wiley Periodicals, Inc. PMID:26743454

  18. 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

  19. Abnormal Vascular Function and Hypertension in Mice Deficient in Estrogen Receptor β

    NASA Astrophysics Data System (ADS)

    Zhu, Yan; Bian, Zhao; Lu, Ping; Karas, Richard H.; Bao, Lin; Cox, Daniel; Hodgin, Jeffrey; Shaul, Philip W.; Thorén, Peter; Smithies, Oliver; Gustafsson, Jan-Åke; Mendelsohn, Michael E.

    2002-01-01

    Blood vessels express estrogen receptors, but their role in cardiovascular physiology is not well understood. We show that vascular smooth muscle cells and blood vessels from estrogen receptor β (ERβ)-deficient mice exhibit multiple functional abnormalities. In wild-type mouse blood vessels, estrogen attenuates vasoconstriction by an ERβ-mediated increase in inducible nitric oxide synthase expression. In contrast, estrogen augments vasoconstriction in blood vessels from ERβ-deficient mice. Vascular smooth muscle cells isolated from ERβ-deficient mice show multiple abnormalities of ion channel function. Furthermore, ERβ-deficient mice develop sustained systolic and diastolic hypertension as they age. These data support an essential role for ERβ in the regulation of vascular function and blood pressure.

  20. Modulatory Interactions of Resting-State Brain Functional Connectivity

    PubMed Central

    Di, Xin; Biswal, Bharat B.

    2013-01-01

    The functional brain connectivity studies are generally based on the synchronization of the resting-state functional magnetic resonance imaging (fMRI) signals. Functional connectivity measures usually assume a stable relationship over time; however, accumulating studies have reported time-varying properties of strength and spatial distribution of functional connectivity. The present study explored the modulation of functional connectivity between two regions by a third region using the physiophysiological interaction (PPI) technique. We first identified eight brain networks and two regions of interest (ROIs) representing each of the networks using a spatial independent component analysis. A voxel-wise analysis was conducted to identify regions that showed modulatory interactions (PPI) with the two ROIs of each network. Mostly, positive modulatory interactions were observed within regions involved in the same system. For example, the two regions of the dorsal attention network revealed modulatory interactions with the regions related to attention, while the two regions of the extrastriate network revealed modulatory interactions with the regions in the visual cortex. In contrast, the two regions of the default mode network (DMN) revealed negative modulatory interactions with the regions in the executive network, and vice versa, suggesting that the activities of one network may be associated with smaller within network connectivity of the competing network. These results validate the use of PPI analysis to study modulation of resting-state functional connectivity by a third region. The modulatory effects may provide a better understanding of complex brain functions. PMID:24023609

  1. 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

  2. Altered functional brain network connectivity and glutamate system function in transgenic mice expressing truncated Disrupted-in-Schizophrenia 1.

    PubMed

    Dawson, N; Kurihara, M; Thomson, D M; Winchester, C L; McVie, A; Hedde, J R; Randall, A D; Shen, S; Seymour, P A; Hughes, Z A; Dunlop, J; Brown, J T; Brandon, N J; Morris, B J; Pratt, J A

    2015-01-01

    Considerable evidence implicates DISC1 as a susceptibility gene for multiple psychiatric diseases. DISC1 has been intensively studied at the molecular, cellular and behavioral level, but its role in regulating brain connectivity and brain network function remains unknown. Here, we utilize a set of complementary approaches to assess the functional brain network abnormalities present in mice expressing a truncated Disc1 gene (Disc1tr Hemi mice). Disc1tr Hemi mice exhibited hypometabolism in the prefrontal cortex (PFC) and reticular thalamus along with a reorganization of functional brain network connectivity that included compromised hippocampal-PFC connectivity. Altered hippocampal-PFC connectivity in Disc1tr Hemi mice was confirmed by electrophysiological analysis, with Disc1tr Hemi mice showing a reduced probability of presynaptic neurotransmitter release in the monosynaptic glutamatergic hippocampal CA1-PFC projection. Glutamate system dysfunction in Disc1tr Hemi mice was further supported by the attenuated cerebral metabolic response to the NMDA receptor (NMDAR) antagonist ketamine and decreased hippocampal expression of NMDAR subunits 2A and 2B in these animals. These data show that the Disc1 truncation in Disc1tr Hemi mice induces a range of translationally relevant endophenotypes underpinned by glutamate system dysfunction and altered brain connectivity. PMID:25989143

  3. Lower gray matter density and functional connectivity in the anterior insula in smokers compared with never smokers.

    PubMed

    Stoeckel, Luke E; Chai, Xiaoqian J; Zhang, Jiahe; Whitfield-Gabrieli, Susan; Evins, A Eden

    2016-07-01

    Although nicotine addiction is characterized by both structural and functional abnormalities in brain networks involved in salience and cognitive control, few studies have integrated these data to understand how these abnormalities may support addiction. This study aimed to (1) evaluate gray matter density and functional connectivity of the anterior insula in cigarette smokers and never smokers and (2) characterize how differences in these measures were related to smoking behavior. We compared structural magnetic resonance imaging (MRI) (gray matter density via voxel-based morphometry) and seed-based functional connectivity MRI data in 16 minimally deprived smokers and 16 matched never smokers. Compared with controls, smokers had lower gray matter density in left anterior insula extending into inferior frontal and temporal cortex. Gray matter density in this region was inversely correlated with cigarettes smoked per day. Smokers exhibited negative functional connectivity (anti-correlation) between the anterior insula and regions involved in cognitive control (left lPFC) and semantic processing/emotion regulation (lateral temporal cortex), whereas controls exhibited positive connectivity between these regions. There were differences in the anterior insula, a central region in the brain's salience network, when comparing both volumetric and functional connectivity data between cigarette smokers and never smokers. Volumetric data, but not the functional connectivity data, were also associated with an aspect of smoking behavior (daily cigarettes smoked). PMID:25990865

  4. The Functional Connectivity Landscape of the Human Brain

    PubMed Central

    Fatima, Zainab; Jonides, John; McIntosh, Anthony R.

    2014-01-01

    Functional brain networks emerge and dissipate over a primarily static anatomical foundation. The dynamic basis of these networks is inter-regional communication involving local and distal regions. It is assumed that inter-regional distances play a pivotal role in modulating network dynamics. Using three different neuroimaging modalities, 6 datasets were evaluated to determine whether experimental manipulations asymmetrically affect functional relationships based on the distance between brain regions in human participants. Contrary to previous assumptions, here we show that short- and long-range connections are equally likely to strengthen or weaken in response to task demands. Additionally, connections between homotopic areas are the most stable and less likely to change compared to any other type of connection. Our results point to a functional connectivity landscape characterized by fluid transitions between local specialization and global integration. This ability to mediate functional properties irrespective of spatial distance may engender a diverse repertoire of cognitive processes when faced with a dynamic environment. PMID:25350370

  5. Altered Fronto-Temporal Functional Connectivity in Individuals at Ultra-High-Risk of Developing Psychosis

    PubMed Central

    Jung, Wi Hoon; Cho, Kang Ik K.; Kim, Sung Nyun; Lee, Tae Young; Park, Hye Yoon; Kwon, Jun Soo

    2015-01-01

    Background The superior temporal gyrus (STG) is one of the key regions implicated in psychosis, given that abnormalities in this region are associated with an increased risk of conversion from an at-risk mental state to psychosis. However, inconsistent results regarding the functional connectivity strength of the STG have been reported, and the regional heterogeneous characteristics of the STG should be considered. Methods To investigate the distinctive functional connection of each subregion in the STG, we parcellated the STG of each hemisphere into three regions: the planum temporale, Heschl’s gyrus, and planum polare. Resting-state functional magnetic resonance imaging was obtained from 22 first-episode psychosis (FEP) patients, 41 individuals at ultra-high-risk for psychosis (UHR), and 47 demographically matched healthy controls. Results Significant group differences (in seed-based connectivity) were demonstrated in the left planum temporale and from both the right and left Heschl’s gyrus seeds. From the left planum temporale seed, the FEP and UHR groups exhibited increased connectivity to the bilateral dorsolateral prefrontal cortex. In contrast, the FEP and UHR groups demonstrated decreased connectivity from the bilateral Heschl’s gyrus seeds to the dorsal anterior cingulate cortex. The enhanced connectivity between the left planum temporale and right dorsolateral prefrontal cortex was positively correlated with positive symptom severity in individuals at UHR (r = .34, p = .03). Conclusions These findings corroborate the fronto-temporal connectivity disruption hypothesis in schizophrenia by providing evidence supporting the altered fronto-temporal intrinsic functional connection at earlier stages of psychosis. Our data indicate that subregion-specific aberrant fronto-temporal interactions exist in the STG at the early stage of psychosis, thus suggesting that these aberrancies are the neural underpinning of proneness to psychosis. PMID:26267069

  6. Sleep spindles and hippocampal functional connectivity in human NREM sleep.

    PubMed

    Andrade, Kátia C; Spoormaker, Victor I; Dresler, Martin; Wehrle, Renate; Holsboer, Florian; Sämann, Philipp G; Czisch, Michael

    2011-07-13

    We investigated human hippocampal functional connectivity in wakefulness and throughout non-rapid eye movement sleep. Young healthy subjects underwent simultaneous EEG and functional magnetic resonance imaging (fMRI) measurements at 1.5 T under resting conditions in the descent to deep sleep. Continuous 5 min epochs representing a unique sleep stage (i.e., wakefulness, sleep stages 1 and 2, or slow-wave sleep) were extracted. fMRI time series of subregions of the hippocampal formation (HF) (cornu ammonis, dentate gyrus, and subiculum) were extracted based on cytoarchitectonical probability maps. We observed sleep stage-dependent changes in HF functional coupling. The HF was integrated to variable strength in the default mode network (DMN) in wakefulness and light sleep stages but not in slow-wave sleep. The strongest functional connectivity between the HF and neocortex was observed in sleep stage 2 (compared with both slow-wave sleep and wakefulness). We observed a strong interaction of sleep spindle occurrence and HF functional connectivity in sleep stage 2, with increased HF/neocortical connectivity during spindles. Moreover, the cornu ammonis exhibited strongest functional connectivity with the DMN during wakefulness, while the subiculum dominated hippocampal functional connectivity to frontal brain regions during sleep stage 2. Increased connectivity between HF and neocortical regions in sleep stage 2 suggests an increased capacity for possible global information transfer, while connectivity in slow-wave sleep is reflecting a functional system optimal for segregated information reprocessing. Our data may be relevant to differentiating sleep stage-specific contributions to neural plasticity as proposed in sleep-dependent memory consolidation. PMID:21753010

  7. Functional connectivity in obesity during reward processing.

    PubMed

    García-García, I; Jurado, M A; Garolera, M; Segura, B; Marqués-Iturria, I; Pueyo, R; Vernet-Vernet, M; Sender-Palacios, M J; Sala-Llonch, R; Ariza, M; Narberhaus, A; Junqué, C

    2013-02-01

    Obesity is a health problem that has become a major focus of attention in recent years. There is growing evidence of an association between obesity and differences in reward processing. However, it is not known at present whether these differences are linked exclusively to food, or whether they can be detected in other rewarding stimuli. We compared responses to food, rewarding non-food and neutral pictures in 18 young adults with obesity and 19 normal-weight subjects using independent component analysis. Both groups modulated task-related activity in a plausible way. However, in response to both food and non-food rewarding stimuli, participants with obesity showed weaker connectivity in a network involving activation of frontal and occipital areas and deactivation of the posterior part of the default mode network. In addition, obesity was related with weaker activation of the default mode network and deactivation of frontal and occipital areas while viewing neutral stimuli. Together, our findings suggest that obesity is related to a different allocation of cognitive resources in a fronto-occipital network and in the default mode network. PMID:23103690

  8. Integration, Continuity and a Connection with Probability Density Functions

    ERIC Educational Resources Information Center

    Samuels, M.

    2006-01-01

    This note considers functions of two variables which are continuous on a possibly unbounded closed region in [vertical bar]R[squared], and the functions of one variable obtained by integrating out the other variable over this region. The question of continuity of these functions is investigated, as are connections with joint density and marginal…

  9. The structure of Airy's stress function in multiply connected regions

    NASA Technical Reports Server (NTRS)

    Grioli, Giusippe

    1951-01-01

    In solving two-dimensional problems using Airy's stress function for multiply connected regions, the form of the function depends on the dislocations and boundary forces present. The structure of Airy's function is shown to consist of a part expressible in terms of boundary forces and a part expressible in the manner of Poincare. Meanings of the constants occurring in Poincare's expression are discussed.

  10. Functional connectivity of paired default mode network subregions in primary insomnia

    PubMed Central

    Nie, Xiao; Shao, Yi; Liu, Si-yu; Li, Hai-jun; Wan, Ai-lan; Nie, Si; Peng, De-chang; Dai, Xi-jian

    2015-01-01

    Objective The aim of this study is to explore the resting-state functional connectivity (FC) differences between the paired default mode network (DMN) subregions in patients with primary insomnia (PIs). Methods Forty-two PIs and forty-two age- and sex-matched good sleepers (GSs) were recruited. All subjects underwent the resting-state functional magnetic resonance imaging scans. The seed-based region-to-region FC method was used to evaluate the abnormal connectivity within the DMN subregions between the PIs and the GSs. Pearson correlation analysis was used to investigate the relationships between the abnormal FC strength within the paired DMN subregions and the clinical features in PIs. Results Compared with the GSs, the PIs showed higher Pittsburgh Sleep Quality Index score, Hamilton Anxiety Rating Scale score, Hamilton Depression Rating Scale score, Self-Rating Depression Scale score, Self Rating Anxiety Scale score, Self-Rating Scale of Sleep score, and Profile of Mood States score (P<0.001). Compared with the GSs, the PIs showed significant decreased region-to-region FC between the medial prefrontal cortex and the right medial temporal lobe (t=−2.275, P=0.026), and between the left medial temporal lobe and the left inferior parietal cortices (t=−3.32, P=0.001). The abnormal FC strengths between the DMN subregions did not correlate with the clinical features. Conclusion PIs showed disrupted FC within the DMN subregions. PMID:26719693

  11. Estimation of dynamic functional connectivity using Multiplication of Temporal Derivatives.

    PubMed

    Shine, James M; Koyejo, Oluwasanmi; Bell, Peter T; Gorgolewski, Krzysztof J; Gilat, Moran; Poldrack, Russell A

    2015-11-15

    Functional connectivity provides an informative and powerful framework for exploring brain organization. Despite this, few statistical methods are available for the accurate estimation of dynamic changes in functional network architecture. To date, the majority of existing statistical techniques have assumed that connectivity structure is stationary, which is in direct contrast to emerging data that suggests that the strength of connectivity between regions is variable over time. Therefore, the development of statistical methods that enable exploration of dynamic changes in functional connectivity is currently of great importance to the neuroscience community. In this paper, we introduce the 'Multiplication of Temporal Derivatives' (MTD) and then demonstrate the utility of this metric to: (i) detect dynamic changes in connectivity using data from a novel state-switching simulation; (ii) accurately estimate graph structure in a previously-described 'ground-truth' simulated dataset; and (iii) identify task-driven alterations in functional connectivity. We show that the MTD is more sensitive than existing sliding-window methods in detecting dynamic alterations in connectivity structure across a range of correlation strengths and window lengths in simulated data. In addition to the temporal precision offered by MTD, we demonstrate that the metric is also able to accurately estimate stationary network structure in both simulated and real task-based data, suggesting that the method may be used to identify dynamic changes in network structure as they evolve through time. PMID:26231247

  12. Structural and Functional Small Fiber Abnormalities in the Neuropathic Postural Tachycardia Syndrome

    PubMed Central

    Gibbons, Christopher H.; Bonyhay, Istvan; Benson, Adam; Wang, Ningshan; Freeman, Roy

    2013-01-01

    Objective To define the neuropathology, clinical phenotype, autonomic physiology and differentiating features in individuals with neuropathic and non-neuropathic postural tachycardia syndrome (POTS). Methods Twenty-four subjects with POTS and 10 healthy control subjects had skin biopsy analysis of intra-epidermal nerve fiber density (IENFD), quantitative sensory testing (QST) and autonomic testing. Subjects completed quality of life, fatigue and disability questionnaires. Subjects were divided into neuropathic and non-neuropathic POTS, defined by abnormal IENFD and abnormal small fiber and sudomotor function. Results Nine of 24 subjects had neuropathic POTS and had significantly lower resting and tilted heart rates; reduced parasympathetic function; and lower phase 4 valsalva maneuver overshoot compared with those with non-neuropathic POTS (P<0.05). Neuropathic POTS subjects also had less anxiety and depression and greater overall self-perceived health-related quality of life scores than non-neuropathic POTS subjects. A sub-group of POTS patients (cholinergic POTS) had abnormal proximal sudomotor function and symptoms that suggest gastrointestinal and genitourinary parasympathetic nervous system dysfunction. Conclusions and Relevance POTS subtypes may be distinguished using small fiber and autonomic structural and functional criteria. Patients with non-neuropathic POTS have greater anxiety, greater depression and lower health-related quality of life scores compared to those with neuropathic POTS. These findings suggest different pathophysiological processes underlie the postural tachycardia in neuropathic and non-neuropathic POTS patients. The findings have implications for the therapeutic interventions to treat this disorder. PMID:24386408

  13. Assessing Thalamocortical Functional Connectivity with Granger Causality

    PubMed Central

    Israel, David; Thakor, Nitish V.; Jia, Xiaofeng

    2014-01-01

    Assessment of network connectivity across multiple brain regions is critical to understanding the mechanisms underlying various neurological disorders. Conventional methods for assessing dynamic interactions include cross-correlation and coherence analysis. However, these methods do not reveal the direction of information flow, which is important for studying the highly directional neurological system. Granger causality (GC) analysis can characterize the directional influences between two systems. We tested GC analysis for its capability to capture directional interactions within both simulated and in-vivo neural networks. The simulated networks consisted of Hindmarsh-Rose neurons; GC analysis was used to estimate the causal influences between two model networks. Our analysis successfully detected asymmetrical interactions between these networks (p<10−10, t-test). Next, we characterized the relationship between the “electrical synaptic strength” in the model networks and interactions estimated by GC analysis. We demonstrated the novel application of GC to monitor interactions between thalamic and cortical neurons following ischemia induced brain injury in a rat model of cardiac arrest (CA). We observed that during the post-CA acute period the GC interactions from the thalamus to the cortex were consistently higher than those from the cortex to the thalamus (1.983±0.278 times higher, p=0.021). In addition, the dynamics of GC interactions between the thalamus and the cortex were frequency dependent. Our study demonstrated the feasibility of GC to monitor the dynamics of thalamocortical interactions after a global nervous system injury such as CA-induced ischemia, and offers preferred alternative applications in characterizing other inter-regional interactions in an injured brain. PMID:23864221

  14. Atypically diffuse functional connectivity between caudate nuclei and cerebral cortex in autism

    PubMed Central

    Turner, Katherine C; Frost, Leonard; Linsenbardt, David; McIlroy, John R; Müller, Ralph-Axel

    2006-01-01

    Background Autism is a neurodevelopmental disorder affecting sociocommunicative behavior, but also sensorimotor skill learning, oculomotor control, and executive functioning. Some of these impairments may be related to abnormalities of the caudate nuclei, which have been reported for autism. Methods Our sample was comprised of 8 high-functioning males with autism and 8 handedness, sex, and age-matched controls. Subjects underwent functional MRI scanning during performance on simple visuomotor coordination tasks. Functional connectivity MRI (fcMRI) effects were identified as interregional blood oxygenation level dependent (BOLD) signal cross-correlation, using the caudate nuclei as seed volumes. Results In the control group, fcMRI effects were found in circuits with known participation of the caudate nuclei (associative, orbitofrontal, oculomotor, motor circuits). Although in the autism group fcMRI effects within these circuits were less pronounced or absent, autistic subjects showed diffusely increased connectivity mostly in pericentral regions, but also in brain areas outside expected anatomical circuits (such as visual cortex). Conclusion These atypical connectivity patterns may be linked to developmental brain growth disturbances recently reported in autism and suggest inefficiently organized functional connectivity between caudate nuclei and cerebral cortex, potentially accounting for stereotypic behaviors and executive impairments. PMID:17042953

  15. ToolConnect: A Functional Connectivity Toolbox for In vitro Networks.

    PubMed

    Pastore, Vito Paolo; Poli, Daniele; Godjoski, Aleksandar; Martinoia, Sergio; Massobrio, Paolo

    2016-01-01

    Nowadays, the use of in vitro reduced models of neuronal networks to investigate the interplay between structural-functional connectivity and the emerging collective dynamics is a widely accepted approach. In this respect, a relevant advance for this kind of studies has been given by the recent introduction of high-density large-scale Micro-Electrode Arrays (MEAs) which have favored the mapping of functional connections and the recordings of the neuronal electrical activity. Although, several toolboxes have been implemented to characterize network dynamics and derive functional links, no specifically dedicated software for the management of huge amount of data and direct estimation of functional connectivity maps has been developed. toolconnect offers the implementation of up to date algorithms and a user-friendly Graphical User Interface (GUI) to analyze recorded data from large scale networks. It has been specifically conceived as a computationally efficient open-source software tailored to infer functional connectivity by analyzing the spike trains acquired from in vitro networks coupled to MEAs. In the current version, toolconnect implements correlation- (cross-correlation, partial-correlation) and information theory (joint entropy, transfer entropy) based core algorithms, as well as useful and practical add-ons to visualize functional connectivity graphs and extract some topological features. In this work, we present the software, its main features and capabilities together with some demonstrative applications on hippocampal recordings. PMID:27065841

  16. ToolConnect: A Functional Connectivity Toolbox for In vitro Networks

    PubMed Central

    Pastore, Vito Paolo; Poli, Daniele; Godjoski, Aleksandar; Martinoia, Sergio; Massobrio, Paolo

    2016-01-01

    Nowadays, the use of in vitro reduced models of neuronal networks to investigate the interplay between structural-functional connectivity and the emerging collective dynamics is a widely accepted approach. In this respect, a relevant advance for this kind of studies has been given by the recent introduction of high-density large-scale Micro-Electrode Arrays (MEAs) which have favored the mapping of functional connections and the recordings of the neuronal electrical activity. Although, several toolboxes have been implemented to characterize network dynamics and derive functional links, no specifically dedicated software for the management of huge amount of data and direct estimation of functional connectivity maps has been developed. toolconnect offers the implementation of up to date algorithms and a user-friendly Graphical User Interface (GUI) to analyze recorded data from large scale networks. It has been specifically conceived as a computationally efficient open-source software tailored to infer functional connectivity by analyzing the spike trains acquired from in vitro networks coupled to MEAs. In the current version, toolconnect implements correlation- (cross-correlation, partial-correlation) and information theory (joint entropy, transfer entropy) based core algorithms, as well as useful and practical add-ons to visualize functional connectivity graphs and extract some topological features. In this work, we present the software, its main features and capabilities together with some demonstrative applications on hippocampal recordings. PMID:27065841

  17. Measuring functional connectivity using MEG: Methodology and comparison with fcMRI

    PubMed Central

    Brookes, Matthew J.; Hale, Joanne R.; Zumer, Johanna M.; Stevenson, Claire M.; Francis, Susan T.; Barnes, Gareth R.; Owen, Julia P.; Morris, Peter G.; Nagarajan, Srikantan S.

    2011-01-01

    Functional connectivity (FC) between brain regions is thought to be central to the way in which the brain processes information. Abnormal connectivity is thought to be implicated in a number of diseases. The ability to study FC is therefore a key goal for neuroimaging. Functional connectivity (fc) MRI has become a popular tool to make connectivity measurements but the technique is limited by its indirect nature. A multimodal approach is therefore an attractive means to investigate the electrodynamic mechanisms underlying hemodynamic connectivity. In this paper, we investigate resting state FC using fcMRI and magnetoencephalography (MEG). In fcMRI, we exploit the advantages afforded by ultra high magnetic field. In MEG we apply envelope correlation and coherence techniques to source space projected MEG signals. We show that beamforming provides an excellent means to measure FC in source space using MEG data. However, care must be taken when interpreting these measurements since cross talk between voxels in source space can potentially lead to spurious connectivity and this must be taken into account in all studies of this type. We show good spatial agreement between FC measured independently using MEG and fcMRI; FC between sensorimotor cortices was observed using both modalities, with the best spatial agreement when MEG data are filtered into the β band. This finding helps to reduce the potential confounds associated with each modality alone: while it helps reduce the uncertainties in spatial patterns generated by MEG (brought about by the ill posed inverse problem), addition of electrodynamic metric confirms the neural basis of fcMRI measurements. Finally, we show that multiple MEG based FC metrics allow the potential to move beyond what is possible using fcMRI, and investigate the nature of electrodynamic connectivity. Our results extend those from previous studies and add weight to the argument that neural oscillations are intimately related to functional

  18. Multisite functional connectivity MRI classification of autism: ABIDE results

    PubMed Central

    Nielsen, Jared A.; Zielinski, Brandon A.; Fletcher, P. Thomas; Alexander, Andrew L.; Lange, Nicholas; Bigler, Erin D.; Lainhart, Janet E.; Anderson, Jeffrey S.

    2013-01-01

    Background: Systematic differences in functional connectivity MRI metrics have been consistently observed in autism, with predominantly decreased cortico-cortical connectivity. Previous attempts at single subject classification in high-functioning autism using whole brain point-to-point functional connectivity have yielded about 80% accurate classification of autism vs. control subjects across a wide age range. We attempted to replicate the method and results using the Autism Brain Imaging Data Exchange (ABIDE) including resting state fMRI data obtained from 964 subjects and 16 separate international sites. Methods: For each of 964 subjects, we obtained pairwise functional connectivity measurements from a lattice of 7266 regions of interest covering the gray matter (26.4 million “connections”) after preprocessing that included motion and slice timing correction, coregistration to an anatomic image, normalization to standard space, and voxelwise removal by regression of motion parameters, soft tissue, CSF, and white matter signals. Connections were grouped into multiple bins, and a leave-one-out classifier was evaluated on connections comprising each set of bins. Age, age-squared, gender, handedness, and site were included as covariates for the classifier. Results: Classification accuracy significantly outperformed chance but was much lower for multisite prediction than for previous single site results. As high as 60% accuracy was obtained for whole brain classification, with the best accuracy from connections involving regions of the default mode network, parahippocampaland fusiform gyri, insula, Wernicke Area, and intraparietal sulcus. The classifier score was related to symptom severity, social function, daily living skills, and verbal IQ. Classification accuracy was significantly higher for sites with longer BOLD imaging times. Conclusions: Multisite functional connectivity classification of autism outperformed chance using a simple leave-one-out classifier

  19. fMRI functional connectivity applied to adolescent neurodevelopment.

    PubMed

    Ernst, Monique; Torrisi, Salvatore; Balderston, Nicholas; Grillon, Christian; Hale, Elizabeth A

    2015-01-01

    The exponential rise in the number of functional brain connectivity studies, particularly those examining intrinsic functional connectivity (iFC) at rest, and the promises of this work for unraveling the ontogeny of functional neural systems motivate this review. Shortly before this explosion in functional connectivity research, developmental neuroscientists had proposed theories based on neural systems models to explain behavioral changes, particularly in adolescence. The current review presents recent advances in imaging in brain connectivity research, which provides a unique tool for the study of neural systems. Understanding the potential of neuroimaging for refining neurodevelopmental models of brain function requires a description of various functional connectivity approaches. In this review, we describe task-based and resting-state functional magnetic resonance imaging (fMRI) analytic strategies, but we focus on iFC findings from resting-state data to describe general developmental trajectories of brain network organization. Finally, we use the example of drug addiction to frame a discussion of psychopathology that emerges in adolescence. PMID:25581237

  20. Prevalence and Determinants of True Thyroid Dysfunction Among Pediatric Referrals for Abnormal Thyroid Function Tests

    PubMed Central

    Lahoti, Amit; Klein, Jason; Schumaker, Tiffany; Vuguin, Patricia; Frank, Graeme

    2016-01-01

    Background/Aims. Abnormalities in thyroid function tests (TFTs) are a common referral reason for pediatric endocrine evaluation. However, a sizable proportion of these laboratory abnormalities do not warrant therapy or endocrine follow-up. The objectives of this study were (a) to evaluate the prevalence of true thyroid dysfunction among pediatric endocrinology referrals for abnormal TFTs; (b) to identify the historical, clinical, and laboratory characteristics that predict decision to treat. Methods. This was a retrospective chart review of patients evaluated in pediatric endocrinology office during a weekly clinic designated for new referrals for abnormal TFTs in 2010. Results. A total of 230 patients were included in the study. Median age at referral was 12 years (range = 2-18); 56% were females. Routine screening was cited as the reason for performing TFTs by 33% patients. Majority was evaluated for hypothyroidism (n = 206). Elevated thyroid-stimulating hormone was the most common referral reason (n = 140). A total of 41 out of 206 patients were treated for hypothyroidism. Conclusions. Prevalence of hypothyroidism was 20%. Thyroid follow-up was not recommended for nearly one third of the patients. Among all the factors analyzed, an elevated thyroid-stimulating hormone level and antithyroglobulin antibodies strongly correlated with the decision to treat (P < .005). PMID:27336020

  1. Functional connectivity in in vitro neuronal assemblies

    PubMed Central

    Poli, Daniele; Pastore, Vito P.; Massobrio, Paolo

    2015-01-01

    Complex network topologies represent the necessary substrate to support complex brain functions. In this work, we reviewed in vitro neuronal networks coupled to Micro-Electrode Arrays (MEAs) as biological substrate. Networks of dissociated neurons developing in vitro and coupled to MEAs, represent a valid experimental model for studying the mechanisms governing the formation, organization and conservation of neuronal cell assemblies. In this review, we present some examples of the use of statistical Cluster Coefficients and Small World indices to infer topological rules underlying the dynamics exhibited by homogeneous and engineered neuronal networks. PMID:26500505

  2. 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. PMID:26662457

  3. Auditory connections and functions of prefrontal cortex

    PubMed Central

    Plakke, Bethany; Romanski, Lizabeth M.

    2014-01-01

    The functional auditory system extends from the ears to the frontal lobes with successively more complex functions occurring as one ascends the hierarchy of the nervous system. Several areas of the frontal lobe receive afferents from both early and late auditory processing regions within the temporal lobe. Afferents from the early part of the cortical auditory system, the auditory belt cortex, which are presumed to carry information regarding auditory features of sounds, project to only a few prefrontal regions and are most dense in the ventrolateral prefrontal cortex (VLPFC). In contrast, projections from the parabelt and the rostral superior temporal gyrus (STG) most likely convey more complex information and target a larger, widespread region of the prefrontal cortex. Neuronal responses reflect these anatomical projections as some prefrontal neurons exhibit responses to features in acoustic stimuli, while other neurons display task-related responses. For example, recording studies in non-human primates indicate that VLPFC is responsive to complex sounds including vocalizations and that VLPFC neurons in area 12/47 respond to sounds with similar acoustic morphology. In contrast, neuronal responses during auditory working memory involve a wider region of the prefrontal cortex. In humans, the frontal lobe is involved in auditory detection, discrimination, and working memory. Past research suggests that dorsal and ventral subregions of the prefrontal cortex process different types of information with dorsal cortex processing spatial/visual information and ventral cortex processing non-spatial/auditory information. While this is apparent in the non-human primate and in some neuroimaging studies, most research in humans indicates that specific task conditions, stimuli or previous experience may bias the recruitment of specific prefrontal regions, suggesting a more flexible role for the frontal lobe during auditory cognition. PMID:25100931

  4. Hyper-connectivity of functional networks for brain disease diagnosis.

    PubMed

    Jie, Biao; Wee, Chong-Yaw; Shen, Dinggang; Zhang, Daoqiang

    2016-08-01

    Exploring structural and functional interactions among various brain regions enables better understanding of pathological underpinnings of neurological disorders. Brain connectivity network, as a simplified representation of those structural and functional interactions, has been widely used for diagnosis and classification of neurodegenerative diseases, especially for Alzheimer's disease (AD) and its early stage - mild cognitive impairment (MCI). However, the conventional functional connectivity network is usually constructed based on the pairwise correlation among different brain regions and thus ignores their higher-order relationships. Such loss of high-order information could be important for disease diagnosis, since neurologically a brain region predominantly interacts with more than one other brain regions. Accordingly, in this paper, we propose a novel framework for estimating the hyper-connectivity network of brain functions and then use this hyper-network for brain disease diagnosis. Here, the functional connectivity hyper-network denotes a network where each of its edges representing the interactions among multiple brain regions (i.e., an edge can connect with more than two brain regions), which can be naturally represented by a hyper-graph. Specifically, we first construct connectivity hyper-networks from the resting-state fMRI (R-fMRI) time series by using sparse representation. Then, we extract three sets of brain-region specific features from the connectivity hyper-networks, and further exploit a manifold regularized multi-task feature selection method to jointly select the most discriminative features. Finally, we use multi-kernel support vector machine (SVM) for classification. The experimental results on both MCI dataset and attention deficit hyperactivity disorder (ADHD) dataset demonstrate that, compared with the conventional connectivity network-based methods, the proposed method can not only improve the classification performance, but also help

  5. Online detection of low-frequency functional connectivity

    NASA Astrophysics Data System (ADS)

    Peltier, Scott J.; LaConte, Stephen M.; Hu, Xiaoping

    2004-04-01

    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 pontential 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 (such as cocaine injection). Thus, detection of these functional connectivity patterns may help to serve as a guage of normal brain activity. Currently, functional connectivity detection is applied only in offline post-processing analysis. Online detection methods have been applied to detect task activation in functional MRI. This allows real-time analysis of fMRI results, and could be important in detecting short-term changes in functional states. In this work, we develop an outline algorithm to detect low frequency resting state functional connectivity in real time. This will extend connectivity analysis to allow online detection of changes in "resting state" brain networks.

  6. Functional Connectivity of the Dorsal Striatum in Female Musicians.

    PubMed

    Tanaka, Shoji; Kirino, Eiji

    2016-01-01

    The dorsal striatum (caudate/putamen) is a node of the cortico-striato-pallido-thalamo-cortical (CSPTC) motor circuit, which plays a central role in skilled motor learning, a critical feature of musical performance. The dorsal striatum receives input from a large part of the cerebral cortex, forming a hub in the cortical-subcortical network. This study sought to examine how the functional network of the dorsal striatum differs between musicians and nonmusicians. Resting state functional magnetic resonance imaging (fMRI) data were acquired from female university students majoring in music and nonmusic disciplines. The data were subjected to functional connectivity analysis and graph theoretical analysis. The functional connectivity analysis indicated that compared with nonmusicians, musicians had significantly decreased connectivity between the left putamen and bilateral frontal operculum (FO) and between the left caudate nucleus and cerebellum. The graph theoretical analysis of the entire brain revealed that the degrees, which represent the numbers of connections, of the bilateral putamen were significantly lower in musicians than in nonmusicians. In conclusion, compared with nonmusicians, female musicians have a smaller functional network of the dorsal striatum with decreased connectivity. These data are consistent with previous anatomical studies reporting a reduced volume of the dorsal striatum in musicians and ballet dancers, suggesting that long-term musical training reshapes the functional network of the dorsal striatum to be less extensive or selective. PMID:27148025

  7. Functional Connectivity of the Dorsal Striatum in Female Musicians

    PubMed Central

    Tanaka, Shoji; Kirino, Eiji

    2016-01-01

    The dorsal striatum (caudate/putamen) is a node of the cortico-striato-pallido-thalamo-cortical (CSPTC) motor circuit, which plays a central role in skilled motor learning, a critical feature of musical performance. The dorsal striatum receives input from a large part of the cerebral cortex, forming a hub in the cortical-subcortical network. This study sought to examine how the functional network of the dorsal striatum differs between musicians and nonmusicians. Resting state functional magnetic resonance imaging (fMRI) data were acquired from female university students majoring in music and nonmusic disciplines. The data were subjected to functional connectivity analysis and graph theoretical analysis. The functional connectivity analysis indicated that compared with nonmusicians, musicians had significantly decreased connectivity between the left putamen and bilateral frontal operculum (FO) and between the left caudate nucleus and cerebellum. The graph theoretical analysis of the entire brain revealed that the degrees, which represent the numbers of connections, of the bilateral putamen were significantly lower in musicians than in nonmusicians. In conclusion, compared with nonmusicians, female musicians have a smaller functional network of the dorsal striatum with decreased connectivity. These data are consistent with previous anatomical studies reporting a reduced volume of the dorsal striatum in musicians and ballet dancers, suggesting that long-term musical training reshapes the functional network of the dorsal striatum to be less extensive or selective. PMID:27148025

  8. 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

  9. Microheterogeneity of antithrombin III: effect of single amino acid substitutions and relationship with functional abnormalities.

    PubMed

    De Stefano, V; Leone, G; Mastrangelo, S; Lane, D A; Girolami, A; de Moerloose, P; Sas, G; Abildgaard, U; Blajchman, M; Rodeghiero, F

    1994-02-01

    Microheterogeneity of antithrombin III (AT-III) was investigated by crossed immunoelectrofocusing (CIEF) on eleven molecular variants. A normal pattern was found in five variants while two different abnormal CIEF patterns were found in the other four and two variants, respectively. Point mutations causing a major pI change (exceeding 4.0) of the amino acid substituted lead to alterations in the overall microheterogeneity. The variants thus substituted share a first type of abnormal CIEF pattern with alterations throughout the pH range, regardless of the location of the mutation (reactive site and adjacent regions or heparin binding region). Minor amino acid pI changes in these regions do not alter the AT-III overall microheterogeneity, whatever the resulting functional defect. However, if the mutation is placed in the region around positions 404 or 429, then even minor changes of the amino acid pI seem able to alter the overall charge, leading to a second type of abnormal CIEF pattern with the main alteration at pH 4.8-4.6. Neuraminidase treatment leads to disappearance of microheterogeneity except for the variants with the Arg393 to Cys substitution. Addition of thrombin induces CIEF modifications specifically related to the functional defect. A normal formation of thrombin-antithrombin complexes induces a shift towards the more acid pH range, whereas in the variants substituted at the reactive site the CIEF pattern is substantially unaffected by thrombin; variants substituted at positions 382-384 show a maximal thrombin-induced increase of the isoforms at pI 4.8-4.6. Therefore mutant antithrombins with different functional abnormalities but sharing a common CIEF pattern were well distinguished.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8180341

  10. Linking Functional Connectivity and Structural Connectivity Quantitatively: A Comparison of Methods.

    PubMed

    Huang, Haiqing; Ding, Mingzhou

    2016-03-01

    Structural connectivity in the brain is the basis of functional connectivity. Quantitatively linking the two, however, remains a challenge. For a pair of regions of interest (ROIs), anatomical connections derived from diffusion-weighted imaging are often quantified by fractional anisotropy (FA) or edge weight, whereas functional connections, derived from resting-state functional magnetic resonance imaging, can be characterized by non-time-series measures such as zero-lag cross correlation and partial correlation, as well as by time-series measures such as coherence and Granger causality. In this study, we addressed the question of linking structural connectivity and functional connectivity quantitatively by considering two pairs of ROIs, one from the default mode network (DMN) and the other from the central executive network (CEN), using two different data sets. Selecting (1) posterior cingulate cortex and medial prefrontal cortex of the DMN as the first pair of ROIs and (2) left dorsal lateral prefrontal cortex and left inferior parietal lobule of the CEN as the second pair of ROIs, we show that (1) zero-lag cross correlation, partial correlation, and pairwise Granger causality were not significantly correlated with either mean FA or edge weight and (2) conditional Granger causality (CGC) was significantly correlated with edge weight but not with mean FA. These results suggest that (1) edge weight may be a more appropriate measure to quantify the strength of the anatomical connection between ROIs and (2) CGC, which statistically removes common input and the indirect influences between a given ROI pair, may be a more appropriate measure to quantify the strength of the functional interaction enabled by the fibers linking the two ROIs. PMID:26598788

  11. Connecting leptin signaling to biological function

    PubMed Central

    Allison, Margaret B.; Myers, Martin G.

    2014-01-01

    Hypothalamic leptin action promotes negative energy balance and modulates glucose homeostasis, as well as serving as a permissive signal to the neuroendocrine axes that control growth and reproduction. Since the initial discovery of leptin 20 years ago, we have learned a great deal about the molecular mechanisms of leptin action. An important aspect of this has been the dissection of the cellular mechanisms of leptin signaling, and how specific leptin signals influence physiology. Leptin acts via the long form of the leptin receptor, LepRb. LepRb activation and subsequent tyrosine phosphorylation recruits and activates multiple signaling pathways, including STAT transcription factors, SHP2 and ERK signaling, the IRS-protein/PI3Kinase pathway, and SH2B1. Each of these pathways controls specific aspects of leptin action and physiology. Important inhibitory pathways mediated by suppressor of cytokine signaling (SOCS) proteins and protein tyrosine phosphatases (PTPases) also limit physiologic leptin action. This review summarizes the signaling pathways engaged by LepRb and their effects on energy balance, glucose homeostasis, and reproduction. Particular emphasis is given to the multiple mouse models which have been used to elucidate these functions in vivo. PMID:25232147

  12. Functional connectivity dynamics among cortical neurons: a dependence analysis.

    PubMed

    Li, Lin; Park, Il Memming; Seth, Sohan; Sanchez, Justin C; Principe, José C

    2012-01-01

    This paper quantifies and comparatively validates functional connectivity between neurons by measuring the statistical dependence between their firing rates. Based on statistical analysis of the pairwise functional connectivity, we estimate, exclusively from neural data, the neural assembly functional connectivity given a behavior task, which provides a quantifiable representation of the dynamic nature during the behavioral task. Because of the time scale of behavior (100-1000 ms), a statistical method that yields robust estimators for this small sample size is desirable. In this work, the temporal resolutions of four estimators of functional connectivity are compared on both simulated data and real neural ensemble recordings. The comparison highlights how the properties and assumptions of statistical-based and phase-based metrics affect the interpretation of connectivity. Simulation results show that mean square contingency (MSC) and mutual information (MI) create more robust quantification of functional connectivity under identical conditions than cross correlation (CC) and phase synchronization (PhS) when the sample size is 1 s. The results of the simulated analysis are extended to real neuronal recordings to assess the functional connectivity in monkey's cortex corresponding to three movement states in a food reaching task and construct the assembly graph given a movement state and the activation degree of a state-related assembly over time using the statistical test exclusively from neural data dependencies. The activation degree of a given state-related assembly reaches the peak repeatedly when the specific movement states occur, which also reveals the network of interactions among the neurons are key for the operation of a specific behavior. PMID:22194249

  13. Prenatal stress alters amygdala functional connectivity in preterm neonates.

    PubMed

    Scheinost, Dustin; Kwon, Soo Hyun; Lacadie, Cheryl; Sze, Gordon; Sinha, Rajita; Constable, R Todd; Ment, Laura R

    2016-01-01

    Exposure to prenatal and early-life stress results in alterations in neural connectivity and an increased risk for neuropsychiatric disorders. In particular, alterations in amygdala connectivity have emerged as a common effect across several recent studies. However, the impact of prenatal stress exposure on the functional organization of the amygdala has yet to be explored in the prematurely-born, a population at high risk for neuropsychiatric disorders. We test the hypothesis that preterm birth and prenatal exposure to maternal stress alter functional connectivity of the amygdala using two independent cohorts. The first cohort is used to establish the effects of preterm birth and consists of 12 very preterm neonates and 25 term controls, all without prenatal stress exposure. The second is analyzed to establish the effects of prenatal stress exposure and consists of 16 extremely preterm neonates with prenatal stress exposure and 10 extremely preterm neonates with no known prenatal stress exposure. Standard resting-state functional magnetic resonance imaging and seed connectivity methods are used. When compared to term controls, very preterm neonates show significantly reduced connectivity between the amygdala and the thalamus, the hypothalamus, the brainstem, and the insula (p < 0.05). Similarly, when compared to extremely preterm neonates without exposure to prenatal stress, extremely preterm neonates with exposure to prenatal stress show significantly less connectivity between the left amygdala and the thalamus, the hypothalamus, and the peristriate cortex (p < 0.05). Exploratory analysis of the combined cohorts suggests additive effects of prenatal stress on alterations in amygdala connectivity associated with preterm birth. Functional connectivity from the amygdala to other subcortical regions is decreased in preterm neonates compared to term controls. In addition, these data, for the first time, suggest that prenatal stress exposure amplifies these

  14. BOLD signal and functional connectivity associated with loving kindness meditation.

    PubMed

    Garrison, Kathleen A; Scheinost, Dustin; Constable, R Todd; Brewer, Judson A

    2014-05-01

    Loving kindness is a form of meditation involving directed well-wishing, typically supported by the silent repetition of phrases such as "may all beings be happy," to foster a feeling of selfless love. Here we used functional magnetic resonance imaging to assess the neural substrate of loving kindness meditation in experienced meditators and novices. We first assessed group differences in blood oxygen level-dependent (BOLD) signal during loving kindness meditation. We next used a relatively novel approach, the intrinsic connectivity distribution of functional connectivity, to identify regions that differ in intrinsic connectivity between groups, and then used a data-driven approach to seed-based connectivity analysis to identify which connections differ between groups. Our findings suggest group differences in brain regions involved in self-related processing and mind wandering, emotional processing, inner speech, and memory. Meditators showed overall reduced BOLD signal and intrinsic connectivity during loving kindness as compared to novices, more specifically in the posterior cingulate cortex/precuneus (PCC/PCu), a finding that is consistent with our prior work and other recent neuroimaging studies of meditation. Furthermore, meditators showed greater functional connectivity during loving kindness between the PCC/PCu and the left inferior frontal gyrus, whereas novices showed greater functional connectivity during loving kindness between the PCC/PCu and other cortical midline regions of the default mode network, the bilateral posterior insula lobe, and the bilateral parahippocampus/hippocampus. These novel findings suggest that loving kindness meditation involves a present-centered, selfless focus for meditators as compared to novices. PMID:24944863

  15. Abnormalities in personal space and parietal-frontal function in schizophrenia.

    PubMed

    Holt, Daphne J; Boeke, Emily A; Coombs, Garth; DeCross, Stephanie N; Cassidy, Brittany S; Stufflebeam, Steven; Rauch, Scott L; Tootell, Roger B H

    2015-01-01

    Schizophrenia is associated with subtle abnormalities in day-to-day social behaviors, including a tendency in some patients to "keep their distance" from others in physical space. The neural basis of this abnormality, and related changes in social functioning, is unknown. Here we examined, in schizophrenic patients and healthy control subjects, the functioning of a parietal-frontal network involved in monitoring the space immediately surrounding the body ("personal space"). Using fMRI, we found that one region of this network, the dorsal intraparietal sulcus (DIPS), was hyper-responsive in schizophrenic patients to face stimuli appearing to move towards the subjects, intruding into personal space. This hyper-responsivity was predicted both by the size of personal space (which was abnormally elevated in the schizophrenia group) and the severity of negative symptoms. In contrast, in a second study, the activity of two lower-level visual areas that send information to DIPS (the fusiform face area and middle temporal area) was normal in schizophrenia. Together, these findings suggest that changes in parietal-frontal networks that support the sensory-guided initiation of behavior, including actions occurring in the space surrounding the body, contribute to social dysfunction and negative symptoms in schizophrenia. PMID:26484048

  16. Abnormalities in personal space and parietal–frontal function in schizophrenia

    PubMed Central

    Holt, Daphne J.; Boeke, Emily A.; Coombs, Garth; DeCross, Stephanie N.; Cassidy, Brittany S.; Stufflebeam, Steven; Rauch, Scott L.; Tootell, Roger B.H.

    2015-01-01

    Schizophrenia is associated with subtle abnormalities in day-to-day social behaviors, including a tendency in some patients to “keep their distance” from others in physical space. The neural basis of this abnormality, and related changes in social functioning, is unknown. Here we examined, in schizophrenic patients and healthy control subjects, the functioning of a parietal–frontal network involved in monitoring the space immediately surrounding the body (“personal space”). Using fMRI, we found that one region of this network, the dorsal intraparietal sulcus (DIPS), was hyper-responsive in schizophrenic patients to face stimuli appearing to move towards the subjects, intruding into personal space. This hyper-responsivity was predicted both by the size of personal space (which was abnormally elevated in the schizophrenia group) and the severity of negative symptoms. In contrast, in a second study, the activity of two lower-level visual areas that send information to DIPS (the fusiform face area and middle temporal area) was normal in schizophrenia. Together, these findings suggest that changes in parietal–frontal networks that support the sensory-guided initiation of behavior, including actions occurring in the space surrounding the body, contribute to social dysfunction and negative symptoms in schizophrenia. PMID:26484048

  17. Large-scale functional connectivity networks in the rodent brain.

    PubMed

    Gozzi, Alessandro; Schwarz, Adam J

    2016-02-15

    Resting-state functional Magnetic Resonance Imaging (rsfMRI) of the human brain has revealed multiple large-scale neural networks within a hierarchical and complex structure of coordinated functional activity. These distributed neuroanatomical systems provide a sensitive window on brain function and its disruption in a variety of neuropathological conditions. The study of macroscale intrinsic connectivity networks in preclinical species, where genetic and environmental conditions can be controlled and manipulated with high specificity, offers the opportunity to elucidate the biological determinants of these alterations. While rsfMRI methods are now widely used in human connectivity research, these approaches have only relatively recently been back-translated into laboratory animals. Here we review recent progress in the study of functional connectivity in rodent species, emphasising the ability of this approach to resolve large-scale brain networks that recapitulate neuroanatomical features of known functional systems in the human brain. These include, but are not limited to, a distributed set of regions identified in rats and mice that may represent a putative evolutionary precursor of the human default mode network (DMN). The impact and control of potential experimental and methodological confounds are also critically discussed. Finally, we highlight the enormous potential and some initial application of connectivity mapping in transgenic models as a tool to investigate the neuropathological underpinnings of the large-scale connectional alterations associated with human neuropsychiatric and neurological conditions. We conclude by discussing the translational potential of these methods in basic and applied neuroscience. PMID:26706448

  18. [The impact of mood on the intrinsic functional connectivity].

    PubMed

    Wang, Zicong; Song, Sen; Wang, Lihong

    2014-04-01

    Although a great number of studies have investigated the changes of resting-state functional connectivity (rsFC) in patients with mental disorders, such as depression and schizophrenia etc, little is known how stable the changes are, and whether temporal sad or happy mood can modulate the intrinsic rsFC. In our experiments, happy and sad video clips were used to induce temporally happy and sad mood states in 20 healthy young adults. We collected functional magnetic resonance imaging (fMRI) data while participants were watching happy or sad video clips, which were administrated in two consecutive days. Seed-based functional connectivity analyses were conducted using the anterior cingulate cortex (ACC), dorsolateral prefrontal cortex (DLPFC), and amygdala as seeds to investigate neural network related to executive function, attention, and emotion. We also investigated the association of the rsFC changes with emotional arousability level to understand individual differences. There is significantly stronger functional connectivity between the left DLPFC and posterior cingulate cortex (PCC) under sad mood than that under happy mood. The increased connectivity strength was positively correlated with subjects' emotional arousability. The increased positive correlation between the left DLPFC and PCC under sad relative to happy mood might reflect an increased processing of negative emotion-relevant stimuli. The easier one was induced by strong negative emotion (higher emotional arousability), the greater the left DLPFC-PCC connectivity was indicated, the greater the instability of the intrinsic rsFC was shown. PMID:25039124

  19. Aberrant regional neural fluctuations and functional connectivity in generalized anxiety disorder revealed by resting-state functional magnetic resonance imaging.

    PubMed

    Wang, Wei; Hou, Jingming; Qian, Shaowen; Liu, Kai; Li, Bo; Li, Min; Peng, Zhaohui; Xin, Kuolin; Sun, Gang

    2016-06-15

    The purpose of this study was to investigate the neural activity and functional connectivity in generalized anxiety disorder (GAD) during resting state, and how these alterations correlate to patients' symptoms. Twenty-eight GAD patients and 28 matched healthy controls underwent resting-state functional magnetic resonance (fMRI) scans. Amplitude of low-frequency fluctuation (ALFF) and seed-based resting-state functional connectivity (RSFC) were computed to explore regional activity and functional integration, and were compared between the two groups using the voxel-based two-sample t test. Pearson's correlation analyses were performed to examine the neural relationships with demographics and clinical symptoms scores. Compared to controls, GAD patients showed functional abnormalities: higher ALFF in the bilateral dorsomedial prefrontal cortex, bilateral dorsolateral prefrontal cortex and left precuneus/posterior cingulate cortex; lower connectivity in prefrontal gyrus; lower in prefrontal-limbic and cingulate RSFC and higher prefrontal-hippocampus RSFC were correlated with clinical symptoms severity, but these associations were unable to withstand correction for multiple testing. These findings may help facilitate further understanding of the potential neural substrate of GAD. PMID:27163197

  20. Habenula functional resting-state connectivity in pediatric CRPS

    PubMed Central

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

    2013-01-01

    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. PMID:24155006

  1. Limbic Metabolic Abnormalities in Remote Traumatic Brain Injury and Correlation With Psychiatric Morbidity and Social Functioning

    PubMed Central

    Capizzano, Arístides A.; Jorge, Ricardo E.; Robinson, Robert G.

    2013-01-01

    The aim of this study was to investigate limbic metabolic abnormalities in remote traumatic brain injury (TBI) and their psychiatric correlates. Twenty patients and 13 age-matched comparison subjects received complete psychiatric evaluation and brain MRI and MR spectroscopy at 3 Tesla. Patients had reduced NAA to creatine ratio in the left hippocampus relative to comparison subjects (mean=1.3 [SD=0.21] compared with mean=1.55 [SD=0.21]; F=10.73, df=1, 30, p=0.003), which correlated with the Social Functioning Examination scores (rs=−0.502, p=0.034). Furthermore, patients with mood disorders had reduced NAA to creatine ratio in the left cingulate relative to patients without mood disorders (1.47 compared with 1.68; F=3.393, df=3, 19, p=0.044). Remote TBI displays limbic metabolic abnormalities, which correlate to social outcome and psychiatric status. PMID:21037120

  2. 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

  3. Parcellation of left parietal tool representations by functional connectivity

    PubMed Central

    Garcea, Frank E.; Z. Mahon, Bradford

    2014-01-01

    Manipulating a tool according to its function requires the integration of visual, conceptual, and motor information, a process subserved in part by left parietal cortex. How these different types of information are integrated and how their integration is reflected in neural responses in the parietal lobule remains an open question. Here, participants viewed images of tools and animals during functional magnetic resonance imaging (fMRI). K-means clustering over time series data was used to parcellate left parietal cortex into subregions based on functional connectivity to a whole brain network of regions involved in tool processing. One cluster, in the inferior parietal cortex, expressed privileged functional connectivity to the left ventral premotor cortex. A second cluster, in the vicinity of the anterior intraparietal sulcus, expressed privileged functional connectivity with the left medial fusiform gyrus. A third cluster in the superior parietal lobe expressed privileged functional connectivity with dorsal occipital cortex. Control analyses using Monte Carlo style permutation tests demonstrated that the clustering solutions were outside the range of what would be observed based on chance ‘lumpiness’ in random data, or mere anatomical proximity. Finally, hierarchical clustering analyses were used to formally relate the resulting parcellation scheme of left parietal tool representations to previous work that has parcellated the left parietal lobule on purely anatomical grounds. These findings demonstrate significant heterogeneity in the functional organization of manipulable object representations in left parietal cortex, and outline a framework that generates novel predictions about the causes of some forms of upper limb apraxia. PMID:24892224

  4. Retrospective analysis of lung function abnormalities of Bhopal gas tragedy affected population

    PubMed Central

    De, Sajal

    2012-01-01

    Background & objectives: A large numbers of subjects were exposed to the aerosol of methyl isocyanate (MIC) during Bhopal gas disaster and lung was one of the most commonly affected organs. The aim of the present study was to analyze retrospectively the lung function abnormalities among the surviving MIC exposed population (gas victims) and to compare it with the non-MIC exposed (non gas exposed) population. Methods: The spirometry data of both gas victims and non gas exposed population who attended the Bhopal Memorial Hospital & Research Centre for evaluation of their respiratory complaints from August 2001 to December 2009, were retrospectively evaluated and compared. Results: A total 4782 gas victims and 1190 non gas exposed individuals performed spirometry during the study period. Among the gas victims, obstructive pattern was the commonest (50.8%) spirometric abnormality followed by restrictive pattern (13.3%). The increased relative risk of developing restrictive abnormality among gas victims was observed in 20-29 yr age group only (adjusted relative risk: 2.94, P<0.001). Male gas victims were more affected by severe airflow obstruction than females and the overall increased relative risk (1.33 to 1.45, P<0.001) of developing obstructive pattern among gas victims was observed. Interpretation & conclusions: The present study showed that the relative risk for pulmonary function abnormalities in gas victims was significantly more among those who were young at the time of disaster. Increased smoking habit among gas victims might have played an additive effect on predominance of obstructive pattern in spirometry. PMID:22446861

  5. Altered resting-state functional connectivity of the insula in young adults with Internet gaming disorder.

    PubMed

    Zhang, Jin-Tao; Yao, Yuan-Wei; Li, Chiang-Shan R; Zang, Yu-Feng; Shen, Zi-Jiao; Liu, Lu; Wang, Ling-Jiao; Liu, Ben; Fang, Xiao-Yi

    2016-05-01

    The insula has been implicated in salience processing, craving, and interoception, all of which are critical to the clinical manifestations of drug and behavioral addiction. In this functional magnetic resonance imaging (fMRI) study, we examined resting-state functional connectivity (rsFC) of the insula and its association with Internet gaming characteristics in 74 young adults with Internet gaming disorder (IGD) and 41 age- and gender-matched healthy control subjects (HCs). In comparison with HCs, IGD subjects (IGDs) exhibited enhanced rsFC between the anterior insula and a network of regions including anterior cingulate cortex (ACC), putamen, angular gyrus, and precuneous, which are involved in salience, craving, self-monitoring, and attention. IGDs also demonstrated significantly stronger rsFC between the posterior insula and postcentral gyrus, precentral gyrus, supplemental motor area, and superior temporal gyrus (STG), which are involved in interoception, movement control, and auditory processing. Furthermore, IGD severity was positively associated with connectivity between the anterior insula and angular gyrus, and STG, and with connectivity between the posterior insula and STG. Duration of Internet gaming was positively associated with connectivity between the anterior insula and ACC. These findings highlight a key role of the insula in manifestation of the core symptoms of IGD and the importance to examine functional abnormalities of the anterior and posterior insula separately in IGDs. PMID:25899520

  6. Functional Connectivity Disruption in Neonates with Prenatal Marijuana Exposure

    PubMed Central

    Grewen, Karen; Salzwedel, Andrew P.; Gao, Wei

    2015-01-01

    Prenatal marijuana exposure (PME) is linked to neurobehavioral and cognitive impairments; however, findings in childhood and adolescence are inconsistent. Type-1 cannabinoid receptors (CB1R) modulate fetal neurodevelopment, mediating PME effects on growth of functional circuitry sub-serving behaviors critical for academic and social success. The purpose of this study was to investigate the effects of prenatal marijuana on development of early brain functional circuitry prior to prolonged postnatal environmental influences. We measured resting state functional connectivity during unsedated sleep in infants at 2–6 weeks (+MJ: 20 with PME in combination with nicotine, alcohol, opiates, and/or selective serotonin reuptake inhibitors; −MJ: 23 exposed to the same other drugs without marijuana, CTR: 20 drug-free controls). Connectivity of subcortical seed regions with high fetal CB1R expression was examined. Marijuana-specific differences were observed in insula and three striatal connections: anterior insula–cerebellum, right caudate–cerebellum, right caudate–right fusiform gyrus/inferior occipital, left caudate–cerebellum. +MJ neonates had hypo-connectivity in all clusters compared with −MJ and CTR groups. Altered striatal connectivity to areas involved in visual spatial and motor learning, attention, and in fine-tuning of motor outputs involved in movement and language production may contribute to neurobehavioral deficits reported in this at-risk group. Disrupted anterior insula connectivity may contribute to altered integration of interoceptive signals with salience estimates, motivation, decision-making, and later drug use. Compared with CTRs, both +MJ and −MJ groups demonstrated hyper-connectivity of left amygdala seed with orbital frontal cortex and hypo-connectivity of posterior thalamus seed with hippocampus, suggesting vulnerability to multiple drugs in these circuits. PMID:26582983

  7. Cocaine dependence and thalamic functional connectivity: a multivariate pattern analysis.

    PubMed

    Zhang, Sheng; Hu, Sien; Sinha, Rajita; Potenza, Marc N; Malison, Robert T; Li, Chiang-Shan R

    2016-01-01

    Cocaine dependence is associated with deficits in cognitive control. Previous studies demonstrated that chronic cocaine use affects the activity and functional connectivity of the thalamus, a subcortical structure critical for cognitive functioning. However, the thalamus contains nuclei heterogeneous in functions, and it is not known how thalamic subregions contribute to cognitive dysfunctions in cocaine dependence. To address this issue, we used multivariate pattern analysis (MVPA) to examine how functional connectivity of the thalamus distinguishes 100 cocaine-dependent participants (CD) from 100 demographically matched healthy control individuals (HC). We characterized six task-related networks with independent component analysis of fMRI data of a stop signal task and employed MVPA to distinguish CD from HC on the basis of voxel-wise thalamic connectivity to the six independent components. In an unbiased model of distinct training and testing data, the analysis correctly classified 72% of subjects with leave-one-out cross-validation (p < 0.001), superior to comparison brain regions with similar voxel counts (p < 0.004, two-sample t test). Thalamic voxels that form the basis of classification aggregate in distinct subclusters, suggesting that connectivities of thalamic subnuclei distinguish CD from HC. Further, linear regressions provided suggestive evidence for a correlation of the thalamic connectivities with clinical variables and performance measures on the stop signal task. Together, these findings support thalamic circuit dysfunction in cognitive control as an important neural marker of cocaine dependence. PMID:27556009

  8. Correlations and Functional Connections in a Population of Grid Cells

    PubMed Central

    Roudi, Yasser

    2015-01-01

    We study the statistics of spike trains of simultaneously recorded grid cells in freely behaving rats. We evaluate pairwise correlations between these cells and, using a maximum entropy kinetic pairwise model (kinetic Ising model), study their functional connectivity. Even when we account for the covariations in firing rates due to overlapping fields, both the pairwise correlations and functional connections decay as a function of the shortest distance between the vertices of the spatial firing pattern of pairs of grid cells, i.e. their phase difference. They take positive values between cells with nearby phases and approach zero or negative values for larger phase differences. We find similar results also when, in addition to correlations due to overlapping fields, we account for correlations due to theta oscillations and head directional inputs. The inferred connections between neurons in the same module and those from different modules can be both negative and positive, with a mean close to zero, but with the strongest inferred connections found between cells of the same module. Taken together, our results suggest that grid cells in the same module do indeed form a local network of interconnected neurons with a functional connectivity that supports a role for attractor dynamics in the generation of grid pattern. PMID:25714908

  9. Magnetoencephalographic signatures of insular epileptic spikes based on functional connectivity.

    PubMed

    Zerouali, Younes; Pouliot, Philippe; Robert, Manon; Mohamed, Ismail; Bouthillier, Alain; Lesage, Frédéric; Nguyen, Dang K

    2016-09-01

    Failure to recognize insular cortex seizures has recently been identified as a cause of epilepsy surgeries targeting the temporal, parietal, or frontal lobe. Such failures are partly due to the fact that current noninvasive localization techniques fare poorly in recognizing insular epileptic foci. Our group recently demonstrated that magnetoencephalography (MEG) is sensitive to epileptiform spikes generated by the insula. In this study, we assessed the potential of distributed source imaging and functional connectivity analyses to distinguish insular networks underlying the generation of spikes. Nineteen patients with operculo-insular epilepsy were investigated. Each patient underwent MEG as well as T1-weighted magnetic resonance imaging (MRI) as part of their standard presurgical evaluation. Cortical sources of MEG spikes were reconstructed with the maximum entropy on the mean algorithm, and their time courses served to analyze source functional connectivity. The results indicate that the anterior and posterior subregions of the insula have specific patterns of functional connectivity mainly involving frontal and parietal regions, respectively. In addition, while their connectivity patterns are qualitatively similar during rest and during spikes, couplings within these networks are much stronger during spikes. These results show that MEG can establish functional connectivity-based signatures that could help in the diagnosis of different subtypes of insular cortex epilepsy. Hum Brain Mapp 37:3250-3261, 2016. © 2016 Wiley Periodicals, Inc. PMID:27220112

  10. Resting-state functional connectivity associated with mild cognitive impairment in Parkinson's disease.

    PubMed

    Amboni, Marianna; Tessitore, Alessandro; Esposito, Fabrizio; Santangelo, Gabriella; Picillo, Marina; Vitale, Carmine; Giordano, Alfonso; Erro, Roberto; de Micco, Rosa; Corbo, Daniele; Tedeschi, Gioacchino; Barone, Paolo

    2015-02-01

    Cognitive impairment is common in PD, even in early stages. The construct of mild cognitive impairment has been used to identify clinically evident cognitive impairment without functional decline in PD patients (PD-MCI). The aim of the present study was to investigate brain connectivity associated with PD-MCI through RS-fMRI. RS-fMRI at 3T was collected in 42 PD patients and 20 matched healthy controls. Among PD patients, 21 were classified as having MCI (PD-MCI) and 21 as cognitively unimpaired (PD-nMCI) based on criteria for possible PD-MCI (level I category). Single-subject and group-level ICA was used to investigate the integrity of brain networks related to cognition in PD patients with and without MCI. Image data processing and statistical analysis were performed in BrainVoyager QX. In addition, we used VBM to test whether functional connectivity differences were related to structural abnormalities. PD-nMCI and PD-MCI patients compared with controls showed decreased DMN connectivity. PD-MCI patients, but not PD-nMCI, compared with controls, showed decreased functional connectivity of bilateral prefrontal cortex within the frontoparietal network. The decreased prefrontal cortex connectivity correlated with cognitive parameters but not with clinical variables. VBM analysis did not reveal any difference in local gray matter between patients and controls. Our findings suggest that an altered DMN connectivity characterizes PD patients, regardless of cognitive status, whereas a functional disconnection of the frontoparietal network could be associated with MCI in PD in the absence of detectable structural changes. PMID:25428532

  11. Assessing functional connectivity of neural ensembles using directed information

    NASA Astrophysics Data System (ADS)

    So, Kelvin; Koralek, Aaron C.; Ganguly, Karunesh; Gastpar, Michael C.; Carmena, Jose M.

    2012-04-01

    Neurons in the brain form highly complex networks through synaptic connections. Traditionally, functional connectivity between neurons has been explored using methods such as correlations, which do not contain any notion of directionality. Recently, an information-theoretic approach based on directed information theory has been proposed as a way to infer the direction of influence. However, it is still unclear whether this new approach provides any additional insight beyond conventional correlation analyses. In this paper, we present a modified procedure for estimating directed information and provide a comparison of results obtained using correlation analyses on both simulated and experimental data. Using physiologically realistic simulations, we demonstrate that directed information can outperform correlation in determining connections between neural spike trains while also providing directionality of the relationship, which cannot be assessed using correlation. Secondly, applying our method to rodent and primate data sets, we demonstrate that directed information can accurately estimate the conduction delay in connections between different brain structures. Moreover, directed information reveals connectivity structures that are not captured by correlations. Hence, directed information provides accurate and novel insights into the functional connectivity of neural ensembles that are applicable to data from neurophysiological studies in awake behaving animals.

  12. Linked Sex Differences in Cognition and Functional Connectivity in Youth.

    PubMed

    Satterthwaite, Theodore D; Wolf, Daniel H; Roalf, David R; Ruparel, Kosha; Erus, Guray; Vandekar, Simon; Gennatas, Efstathios D; Elliott, Mark A; Smith, Alex; Hakonarson, Hakon; Verma, Ragini; Davatzikos, Christos; Gur, Raquel E; Gur, Ruben C

    2015-09-01

    Sex differences in human cognition are marked, but little is known regarding their neural origins. Here, in a sample of 674 human participants ages 9-22, we demonstrate that sex differences in cognitive profiles are related to multivariate patterns of resting-state functional connectivity MRI (rsfc-MRI). Males outperformed females on motor and spatial cognitive tasks; females were faster in tasks of emotion identification and nonverbal reasoning. Sex differences were also prominent in the rsfc-MRI data at multiple scales of analysis, with males displaying more between-module connectivity, while females demonstrated more within-module connectivity. Multivariate pattern analysis using support vector machines classified subject sex on the basis of their cognitive profile with 63% accuracy (P < 0.001), but was more accurate using functional connectivity data (71% accuracy; P < 0.001). Moreover, the degree to which a given participant's cognitive profile was "male" or "female" was significantly related to the masculinity or femininity of their pattern of brain connectivity (P = 2.3 × 10(-7)). This relationship was present even when considering males and female separately. Taken together, these results demonstrate for the first time that sex differences in patterns of cognition are in part represented on a neural level through divergent patterns of brain connectivity. PMID:24646613

  13. Altered functional and effective connectivity in anticorrelated intrinsic networks in children with benign childhood epilepsy with centrotemporal spikes

    PubMed Central

    Luo, Cheng; Yang, Fei; Deng, Jiayan; Zhang, Yaodan; Hou, Changyue; Huang, Yue; Cao, Weifang; Wang, Jianjun; Xiao, Ruhui; Zeng, Nanlin; Wang, Xiaoming; Yao, Dezhong

    2016-01-01

    Abstract There are 2 intrinsic networks in the human brain: the task positive network (TPN) and task negative network (alternately termed the default mode network, DMN) in which inverse correlations have been observed during resting state and event-related functional magnetic resonance imaging (fMRI). The antagonism between the 2 networks might indicate a dynamic interaction in the brain that is associated with development. To evaluate the alterations in the relations of the 2 networks in children with benign childhood epilepsy with centrotemporal spikes (BECTS), resting state fMRI was performed in 17 patients with BECTS and 17 healthy controls. The functional and effective connectivities of 29 nodes in the TPN and DMN were analyzed. Positive functional connectivity (FC) within the networks and negative FC between the 2 networks were observed in both groups. The patients exhibited increased FC within both networks, particularly in the frontoparietal nodes such as the left superior frontal cortex, and enhanced antagonism between the 2 networks, suggesting abnormal functional integration of the nodes of the 2 networks in the patients. Granger causality analysis revealed a significant difference in the degree of outflow to inflow in the left superior frontal cortex and the left ventral occipital lobe. The alterations observed in the combined functional and effective connectivity analyses might indicate an association of an abnormal ability to integrate information between the DMN and TPN and the epileptic neuropathology of BECTS and provide preliminary evidence supporting the occurrence of abnormal development in children with BECTS. PMID:27310959

  14. Abnormal function of the corpus luteum in some ewes with phyto-oestrogenic infertility.

    PubMed

    Adams, N R; Hearnshaw, H; Oldham, C M

    1981-01-01

    Ewes with permanent phyto-estrogenic infertility show oestrus less regularly than normal ewes, and the present study examines the extent to which this results from abnormal ovarian function. Forty-nine affected ewes and 53 controls were run with rams fitted with marking crayons and harnesses, and crayon marks were recorded and laparoscopy performed at weekly intervals for 3 weeks. Fewer affected ewes showed oestrus accompanied by ovulation (28 v. 49, P less than 0.001), and four of these affected ewes had a second ovulation during the experiment. More of the ovulations observed in affected ewes were unaccompanied by behavioural oestrus than in controls (8 out of 38 v. 2 out of 50; P less than 0.05). Six affected ewes had no corpus luteum or oestrus, and five of these had adhesions over the genitalia. Hydrops uteri in five other affected ewes was accompanied by prolonged maintenance of the corpus luteum. Some other abnormalities were also observed. In a second study, plasma progesterone concentrations were measured twice daily in 12 affected ewes which were run with rams. Five ewes had oestrous cycles of abnormal duration (two of more than 23 days, two of 21 days, and one of 11 days), and these were accompanied by plasma progesterone patterns different from those of the ewes with an oestrous cycle duration of 16-18 days. It is concluded that the irregular oestrous cycles in affected ewes are due mainly to abnormal life span and progesterone secretion by the corpus luteum, which in turn largely result from changes in the uterus. PMID:7196218

  15. Functional organization of the fusiform gyrus revealed with connectivity profiles.

    PubMed

    Zhang, Wen; Wang, Jiaojian; Fan, Lingzhong; Zhang, Yuanchao; Fox, Peter T; Eickhoff, Simon B; Yu, Chunshui; Jiang, Tianzi

    2016-08-01

    Within the object recognition-related ventral visual stream, the human fusiform gyrus (FG), which topographically connects the striate cortex to the inferior temporal lobe, plays a pivotal role in high-level visual/cognitive functions. However, though there are many previous investigations of distinct functional modules within the FG, the functional organization of the whole FG in its full functional heterogeneity has not yet been established. In the current study, a replicable functional organization of the FG based on distinct anatomical connectivity patterns was identified. The FG was parcellated into medial (FGm), lateral (FGl), and anterior (FGa) regions using diffusion tensor imaging. We validated the reasonability of such an organizational scheme from the perspective of resting-state whole brain functional connectivity patterns and the involvement of functional subnetworks. We found corroborating support for these three distinct modules, and suggest that the FGm serves as a transition region that combines multiple stimuli, the FGl is responsible for categorical recognition, and the FGa is involved in semantic understanding. These findings support two organizational functional transitions of the ventral temporal gyrus, a posterior/anterior direction of visual/semantic processing, and a media/lateral direction of high-level visual processing. Our results may facilitate a more detailed study of the human FG in the future. Hum Brain Mapp 37:3003-3016, 2016. © 2016 Wiley Periodicals, Inc. PMID:27132874

  16. A Multivariate Granger Causality Concept towards Full Brain Functional Connectivity

    PubMed Central

    Schmid-Hertel, Nicole; Witte, Herbert; Wismüller, Axel; Leistritz, Lutz

    2016-01-01

    Detecting changes of spatially high-resolution functional connectivity patterns in the brain is crucial for improving the fundamental understanding of brain function in both health and disease, yet still poses one of the biggest challenges in computational neuroscience. Currently, classical multivariate Granger Causality analyses of directed interactions between single process components in coupled systems are commonly restricted to spatially low- dimensional data, which requires a pre-selection or aggregation of time series as a preprocessing step. In this paper we propose a new fully multivariate Granger Causality approach with embedded dimension reduction that makes it possible to obtain a representation of functional connectivity for spatially high-dimensional data. The resulting functional connectivity networks may consist of several thousand vertices and thus contain more detailed information compared to connectivity networks obtained from approaches based on particular regions of interest. Our large scale Granger Causality approach is applied to synthetic and resting state fMRI data with a focus on how well network community structure, which represents a functional segmentation of the network, is preserved. It is demonstrated that a number of different community detection algorithms, which utilize a variety of algorithmic strategies and exploit topological features differently, reveal meaningful information on the underlying network module structure. PMID:27064897

  17. 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

  18. Functional changes are associated with tracheal structural abnormalities in patients with acromegaly

    PubMed Central

    Camilo, Gustavo Bittencourt; Guimarães, Fernando Silva; Mogami, Roberto; Faria, Alvaro Camilo Dias; Melo, Pedro Lopes

    2016-01-01

    Introduction Although impaired pulmonary function and respiratory sleep disorders are described as responsible for increased mortality in acromegalic patients, little is known about the tracheal abnormalities in this group of patients. Thus, the objectives of this study were to describe the tracheal structural abnormalities and correlate these changes with the respiratory function and clinical data of acromegalic patients. Material and methods This is a cross-sectional study that was carried out at two university hospitals. Twenty acromegalic patients underwent spirometry, forced oscillation technique, and computed tomography (CT) assessments. Dyspnea and daytime sleepiness were assessed using the Modified Medical Research Council (MMRC) scale and the Epworth Sleepiness Scale (ESS), respectively. Forty matched subjects served as controls. Results The acromegalic patients exhibited larger median ratios between forced expiratory flow and forced inspiratory flow at 50% of the forced vital capacity (FEF50%/FIF50%) (2.05 vs. 1.06, p = 0.0001) compared with healthy volunteers. In the CT analysis, acromegalic patients exhibited larger median differences between their cervical and thoracic tracheal diameters (Δ tracheal diameters) (3 vs. 1 mm; p = 0.003). An association was found between FEF50%/FIF50% and the following variables: mean resistance (Rm), cervical tracheal diameter, and Δ tracheal diameters. Rm also exhibited a negative correlation with cervical tracheal diameter. Neither the MMRC scale nor the ESS exhibited any significant correlation with large airway obstruction (LAO) indices or with the measured tracheal diameters. Conclusions Acromegalic patients have tracheal structural abnormalities which are associated with functional indicators of LAO but not with clinical data. PMID:26925121

  19. Intrinsic Functional Connectivity Networks in Healthy Elderly Subjects: A Multiparametric Approach with Structural Connectivity Analysis

    PubMed Central

    Müller, Hans-Peter; Ludolph, Albert C.

    2014-01-01

    Intrinsic functional connectivity magnetic resonance imaging (iFCMRI) provides an encouraging approach for mapping large-scale intrinsic connectivity networks (ICNs) in the “resting” brain. Structural connections as measured by diffusion tensor imaging (DTI) are a major constraint on the identified ICNs. This study aimed at the combined investigation of ten well-defined ICNs in healthy elderly subjects at single subject level as well as at the group level, together with the underlying structural connectivity. IFCMRI and DTI data were acquired in twelve subjects (68 ± 7 years) at a 3T scanner and were studied using the tensor imaging and fiber tracking software package. The seed-based iFCMRI analysis approach was comprehensively performed with DTI analysis, following standardized procedures including an 8-step processing of iFCMRI data. Our findings demonstrated robust ICNs at the single subject level and conclusive brain maps at the group level in the healthy elderly sample, supported by the complementary fiber tractography. The findings demonstrated here provide a methodological framework for future comparisons of pathological (e.g., neurodegenerative) conditions with healthy controls on the basis of multiparametric functional connectivity mapping. PMID:24971361

  20. Deficiency of Cardiolipin Synthase Causes Abnormal Mitochondrial Function and Morphology in Germ Cells of Caenorhabditis elegans*

    PubMed Central

    Sakamoto, Taro; Inoue, Takao; Otomo, Yukae; Yokomori, Nagaharu; Ohno, Motoki; Arai, Hiroyuki; Nakagawa, Yasuhito

    2012-01-01

    Cardiolipin (CL) is a major membrane phospholipid specifically localized in mitochondria. At the cellular level, CL has been shown to have a role in mitochondrial energy production, mitochondrial membrane dynamics, and the triggering of apoptosis. However, the in vivo role of CL in multicellular organisms is largely unknown. In this study, by analyzing deletion mutants of a CL synthase gene (crls-1) in Caenorhabditis elegans, we demonstrated that CL depletion selectively caused abnormal mitochondrial function and morphology in germ cells but not in somatic cell types such as muscle cells. crls-1 mutants reached adulthood but were sterile with reduced germ cell proliferation and impaired oogenesis. In the gonad of crls-1 mutants, mitochondrial membrane potential was significantly decreased, and the structure of the mitochondrial cristae was disrupted. Contrary to the abnormalities in the gonad, somatic tissues in crls-1 mutants appeared normal with respect to cell proliferation, mitochondrial function, and mitochondrial morphology. Increased susceptibility to CL depletion in germ cells was also observed in mutants of phosphatidylglycerophosphate synthase, an enzyme responsible for producing phosphatidylglycerol, a precursor phospholipid of CL. We propose that the contribution of CL to mitochondrial function and morphology is different among the cell types in C. elegans. PMID:22174409

  1. [Interneuronal functional connections in the canine sensomotor cortex].

    PubMed

    Dolbakian, E E; Tarakanova, T A

    1993-01-01

    Multiple unit activity (MUA) of the sensomotor cortex was recorded from chronically implanted semimicroelectrodes in dogs. The spike trains of 6-8 neural units were selected from MUA. The character and temporal parameters of interneuronal functional connections were examined by the method of computerized cross-interval analysis. For this purpose the autocorrelation and cross-interval histograms were constructed. One of the main results was complete absence of symmetrical central peaks (shared input). The functional interrelations of selected neurons were characterized by unilateral and bilateral nonsymmetrical excitatory connections with short (1-10 ms), middle (10-80 ms) and late (80-2000 vs) delays. The peculiarities of these interneuronal connections are discussed. PMID:8485189

  2. Homotopic reciprocal functional connectivity between anterior human insulae.

    PubMed

    Lacuey, Nuria; Zonjy, Bilal; Kahriman, Emine S; Marashly, Ahmad; Miller, Jonathan; Lhatoo, Samden D; Lüders, Hans O

    2016-06-01

    The aim of this study was to investigate functional connectivity between right and left insulae in the human brain. We studied a patient with implanted depth electrodes for epilepsy surgery evaluation with stereotactically placed symmetric depth electrodes in both insulae. Bipolar 1 Hz electrical stimulation of the right and left posterior short gyri in the anterior insula evoked responses in the contralateral insular structures. These responses showed a latency of 8-24 ms. This report demonstrates for the first time bi-directional homotopic and heterotopic functional connectivity between right and left anterior insulae. The short latency of the evoked responses suggests mono- or oligo-synaptic connections, most likely via the corpus callosum. PMID:25993901

  3. Altered regional activity and inter-regional functional connectivity in psychogenic non-epileptic seizures.

    PubMed

    Li, Rong; Li, Yibo; An, Dongmei; Gong, Qiyong; Zhou, Dong; Chen, Huafu

    2015-01-01

    Although various imaging studies have focused on detecting the cerebral function underlying psychogenic non-epileptic seizures (PNES), the nature of PNES remains poorly understood. In this study, we combined the resting state fMRI with fractional amplitude of low-frequency fluctuations (fALFF) and functional connectivity based on the seed voxel linear correlation approach to examine the alterations of regional and inter-regional network cerebral functions in PNES. A total of 20 healthy controls and 18 patients were enrolled. The PNES patients showed significantly increased fALFF mainly in the dorsolateral prefrontal cortex (DLPFC), parietal cortices, and motor areas, as well as decreased fALFF in the triangular inferior frontal gyrus. Thus, our results add to literature suggesting abnormalities of neural synchrony in PNES. Moreover, PNES exhibited widespread inter-regional neural network deficits, including increased (DLPFC, sensorimotor, and limbic system) and decreased (ventrolateral prefrontal cortex) connectivity, indicating that changes in the regional cerebral function are related to remote inter-regional network deficits. Correlation analysis results revealed that the connectivity between supplementary motor area and anterior cingulate cortex correlated with the PNES frequency, further suggesting the skewed integration of synchronous activity could predispose to the occurrence of PNES. Our findings provided novel evidence to investigate the pathophysiological mechanisms of PNES. PMID:26109123

  4. Functional Connectivity Changes in Second Language Vocabulary Learning

    ERIC Educational Resources Information Center

    Saidi, Ladan Ghazi; Perlbarg, Vincent; Marrelec, Guillaume; Pelegrini-Issac, Melani; Benali, Habib; Ansaldo, Ana-Ines

    2013-01-01

    Functional connectivity changes in the language network (Price, 2010), and in a control network involved in second language (L2) processing (Abutalebi & Green, 2007) were examined in a group of Persian (L1) speakers learning French (L2) words. Measures of network integration that characterize the global integrative state of a network (Marrelec,…

  5. Analytical Operations Relate Structural and Functional Connectivity in the Brain.

    PubMed

    Saggio, Maria Luisa; Ritter, Petra; Jirsa, Viktor K

    2016-01-01

    Resting-state large-scale brain models vary in the amount of biological elements they incorporate and in the way they are being tested. One might expect that the more realistic the model is, the closer it should reproduce real functional data. It has been shown, instead, that when linear correlation across long BOLD fMRI time-series is used as a measure for functional connectivity (FC) to compare simulated and real data, a simple model performs just as well, or even better, than more sophisticated ones. The model in question is a simple linear model, which considers the physiological noise that is pervasively present in our brain while it diffuses across the white-matter connections, that is structural connectivity (SC). We deeply investigate this linear model, providing an analytical solution to straightforwardly compute FC from SC without the need of computationally costly simulations of time-series. We provide a few examples how this analytical solution could be used to perform a fast and detailed parameter exploration or to investigate resting-state non-stationarities. Most importantly, by inverting the analytical solution, we propose a method to retrieve information on the anatomical structure directly from functional data. This simple method can be used to complement or guide DTI/DSI and tractography results, especially for a better assessment of inter-hemispheric connections, or to provide an estimate of SC when only functional data are available. PMID:27536987

  6. Analytical Operations Relate Structural and Functional Connectivity in the Brain

    PubMed Central

    Saggio, Maria Luisa; Ritter, Petra; Jirsa, Viktor K.

    2016-01-01

    Resting-state large-scale brain models vary in the amount of biological elements they incorporate and in the way they are being tested. One might expect that the more realistic the model is, the closer it should reproduce real functional data. It has been shown, instead, that when linear correlation across long BOLD fMRI time-series is used as a measure for functional connectivity (FC) to compare simulated and real data, a simple model performs just as well, or even better, than more sophisticated ones. The model in question is a simple linear model, which considers the physiological noise that is pervasively present in our brain while it diffuses across the white-matter connections, that is structural connectivity (SC). We deeply investigate this linear model, providing an analytical solution to straightforwardly compute FC from SC without the need of computationally costly simulations of time-series. We provide a few examples how this analytical solution could be used to perform a fast and detailed parameter exploration or to investigate resting-state non-stationarities. Most importantly, by inverting the analytical solution, we propose a method to retrieve information on the anatomical structure directly from functional data. This simple method can be used to complement or guide DTI/DSI and tractography results, especially for a better assessment of inter-hemispheric connections, or to provide an estimate of SC when only functional data are available. PMID:27536987

  7. Disrupted Resting-State Functional Connectivity in Nonmedicated Bipolar Disorder.

    PubMed

    Wang, Ying; Zhong, Shuming; Jia, Yanbin; Sun, Yao; Wang, Bing; Liu, Tao; Pan, Jiyang; Huang, Li

    2016-08-01

    Purpose To investigate the whole-brain intrinsic functional connectivity patterns of patients with bipolar disorder (BD). Materials and Methods This prospective study was approved by the research ethics committee, and all participants provided informed consent. Thirty-seven patients with nonmedicated BD II depression and 37 healthy control participants underwent resting-state functional magnetic resonance (MR) imaging. Whole-brain connectivity was analyzed by using a graph theory approach: functional connectivity strength (FCS). Clinical state was assessed by using the 24-item Hamilton Depression Rating Scale and the Young Mania Rating Scale. Two-sample t test and nonparametric correlation analysis were used. Results Compared with healthy control participants, patients with BD II showed decreased FCS in the default mode network (ie, the bilateral medial prefrontal cortex, bilateral middle temporal gyrus, left precuneus, and right posterior cingulate cortex), right supramarginal gyrus and angular gyrus, right superior frontal gyrus, and right superior parietal gyrus and increased FCS in the bilateral temporal pole (including the parahippocampal gyrus and amygdale), left anterior cingulate cortex, left superior temporal gyrus, right lingual gyrus, and left anterior lobe of the cerebellum (P < .05; AlphaSim corrected). Conclusion These results suggest that patients with BD have disrupted intrinsic functional connectivity mainly in the default mode network and limbic system, which might be associated with the pathophysiologic structure of BD. (©) RSNA, 2016. PMID:26909649

  8. Structural and functional brain abnormalities place phenocopy frontotemporal dementia (FTD) in the FTD spectrum

    PubMed Central

    Steketee, Rebecca M.E.; Meijboom, Rozanna; Bron, Esther E.; Osse, Robert Jan; de Koning, Inge; Jiskoot, Lize C.; Klein, Stefan; de Jong, Frank Jan; van der Lugt, Aad; van Swieten, John C.; Smits, Marion

    2016-01-01

    Purpose ‘Phenocopy’ frontotemporal dementia (phFTD) patients may clinically mimic the behavioral variant of FTD (bvFTD), but do not show functional decline or abnormalities upon visual inspection of routine neuroimaging. We aimed to identify abnormalities in gray matter (GM) volume and perfusion in phFTD and to assess whether phFTD belongs to the FTD spectrum. We compared phFTD patients with both healthy controls and bvFTD patients. Materials & methods Seven phFTD and 11 bvFTD patients, and 20 age-matched controls underwent structural T1-weighted magnetic resonance imaging (MRI) and 3D pseudo-continuous arterial spin labeling (pCASL) at 3T. Normalized GM (nGM) volumes and perfusion, corrected for partial volume effects, were quantified regionally as well as in the entire supratentorial cortex, and compared between groups taking into account potential confounding effects of gender and scanner. Results PhFTD patients showed cortical atrophy, most prominently in the right temporal lobe. Apart from this regional atrophy, GM volume was generally not different from either controls or from bvFTD. BvFTD however showed extensive frontotemporal atrophy. Perfusion was increased in the left prefrontal cortex compared to bvFTD and to a lesser extent to controls. Conclusion PhFTD and bvFTD show overlapping cortical structural abnormalities indicating a continuum of changes especially in the frontotemporal regions. Together with functional changes suggestive of a compensatory response to incipient pathology in the left prefrontal regions, these findings are the first to support a possible neuropathological etiology of phFTD and suggest that phFTD may be a neurodegenerative disease on the FTD spectrum. PMID:27222795

  9. Functional evaluation of an inherited abnormal fibrinogen: fibrinogen “Baltimore”

    PubMed Central

    Beck, Eugene A.; Shainoff, John R.; Vogel, Alfred; Jackson, Dudley P.

    1971-01-01

    The rate of clotting and the rate of development and degree of turbidity after addition of thrombin to plasma or purified fibrinogen from a patient with fibrinogen Baltimore was delayed when compared with normal, especially in the presence of low concentrations of thrombin. Optimal coagulation and development of translucent, rather than opaque, clots occurred at a lower pH with the abnormal fibrinogen than with normal. Development of turbidity during clotting of the abnormal plasma or fibrinogen was less than normal at each pH tested, but was maximal in both at approximately pH 6.4. The physical quality of clots formed from fibrinogen Baltimore was abnormal, as demonstrated by a decreased amplitude on thromboelastography. The morphologic appearance of fibrin strands formed from fibrinogen Baltimore by thrombin at pH 7.4 was abnormal when examined by phase contrast or electron microscopy, but those formed by thrombin at pH 6.4 or by thrombin and calcium chloride were similar to, though less compact, than normal fibrin. The periodicity of fibrin formed from fibrinogen Baltimore was similar to normal and was 231-233 Å. A study of the release of the fibrinopeptides from the patient's fibrinogen and its chromatographic subfractions verified the existence of both a normally behaving and a defective form of fibrinogen in the patient's plasma. The defective form differed from normal in three functionally different ways: (a) the rate of release of fibrinopeptides A and AP was slower than normal; (b) no visible clot formation accompanied either partial or complete release of the fibrinopeptides from the defective form in 0.3 M NaCl at pH 7.4; and (c) the defective component possessed a high proportion of phosphorylated, relative to nonphosphorylated, fibrinopeptide A, while the coagulable component contained very little of the phosphorylated peptide (AP). The high phosphate content of the defective component did not appear to be the cause of the abnormality, but may be the

  10. Functional Connectivity Hubs and Networks in the Awake Marmoset Brain

    PubMed Central

    Belcher, Annabelle M.; Yen, Cecil Chern-Chyi; Notardonato, Lucia; Ross, Thomas J.; Volkow, Nora D.; Yang, Yihong; Stein, Elliot A.; Silva, Afonso C.; Tomasi, Dardo

    2016-01-01

    In combination with advances in analytical methods, resting-state fMRI is allowing unprecedented access to a better understanding of the network organization of the brain. Increasing evidence suggests that this architecture may incorporate highly functionally connected nodes, or “hubs”, and we have recently proposed local functional connectivity density (lFCD) mapping to identify highly-connected nodes in the human brain. Here, we imaged awake nonhuman primates to test whether, like the human brain, the marmoset brain contains FC hubs. Ten adult common marmosets (Callithrix jacchus) were acclimated to mild, comfortable restraint using individualized helmets. Following restraint training, resting BOLD data were acquired during eight consecutive 10 min scans for each subject. lFCD revealed prominent cortical and subcortical hubs of connectivity across the marmoset brain; specifically, in primary and secondary visual cortices (V1/V2), higher-order visual association areas (A19M/V6[DM]), posterior parietal and posterior cingulate areas (PGM and A23b/A31), thalamus, dorsal and ventral striatal areas (caudate, putamen, lateral septal nucleus, and anterior cingulate cortex (A24a). lFCD hubs were highly connected to widespread areas of the brain, and further revealed significant network-network interactions. These data provide a baseline platform for future investigations in a nonhuman primate model of the brain’s network topology. PMID:26973476

  11. Resting State Functional Connectivity in Patients with Chronic Hallucinations

    PubMed Central

    Sommer, Iris E.; Clos, Mareike; Meijering, Anne Lotte; Diederen, Kelly M. J.; Eickhoff, Simon B.

    2012-01-01

    Auditory verbal hallucinations (AVH) are not only among the most common but also one of the most distressing symptoms of schizophrenia. Despite elaborate research, the underlying brain mechanisms are as yet elusive. Functional MRI studies have associated the experience of AVH with activation of bilateral language-related areas, in particular the right inferior frontal gyrus (rIFG) and the left superior temporal gyrus (lSTG). While these findings helped to understand the neural underpinnings of hearing voices, they provide little information about possible brain mechanisms that predispose a person to experience AVH, i.e. the traits to hallucinate. In this study, we compared resting state connectivity between 49 psychotic patients with chronic AVH and 49 matched controls using the rIFG and the lSTG as seed regions, to identify functional brain systems underlying the predisposition to hallucinate. The right parahippocampal gyrus showed increased connectivity with the rIFG in patients as compared to controls. Reduced connectivity with the rIFG in patients was found for the right dorsolateral prefrontal cortex. Reduced connectivity with the lSTG in patients was identified in the left frontal operculum as well as the parietal opercular area. Connectivity between the lSTG and the left hippocampus was also reduced in patients and showed a negative correlation with the severity of hallucinations. Concluding, we found aberrant connectivity between the seed regions and medial temporal lobe structures which have a prominent role in memory retrieval. Moreover, we found decreased connectivity between language-related areas, indicating aberrant integration in this system potentially including corollary discharge mechanisms. PMID:22970130

  12. Physiologic abnormalities of cardiac function in progressive systemic sclerosis with diffuse scleroderma

    SciTech Connect

    Follansbee, W.P.; Curtiss, E.I.; Medsger, T.A. Jr.; Steen, V.D.; Uretsky, B.F.; Owens, G.R.; Rodnan, G.P.

    1984-01-19

    To investigate cardiopulmonary function in progressive systemic sclerosis with diffuse scleroderma, we studied 26 patients with maximal exercise and redistribution thallium scans, rest and exercise radionuclide ventriculography, pulmonary-function testing, and chest roentgenography. Although only 6 patients had clinical evidence of cardiac involvement, 20 had abnormal thallium scans, including 10 with reversible exercise-induced defects and 18 with fixed defects (8 had both). Seven of the 10 patients who had exercise-induced defects and underwent cardiac catheterization had normal coronary angiograms. Mean resting left ventricular ejection fraction and mean resting right ventricular ejection fraction were lower in patients with post-exercise left ventricular thallium defect scores above the median (59 +/- 13 per cent vs. 69 +/- 6 per cent, and 36 +/- 12 per cent vs. 47 +/- 7 per cent, respectively). The authors conclude that in progressive systemic sclerosis with diffuse scleroderma, abnormalities of myocardial perfusion are common and appear to be due to a disturbance of the myocardial microcirculation. Both right and left ventricular dysfunction appear to be related to this circulatory disturbance, suggesting ischemically mediated injury.

  13. Dynamic connectivity detection: an algorithm for determining functional connectivity change points in fMRI data

    PubMed Central

    Xu, Yuting; Lindquist, Martin A.

    2015-01-01

    Recently there has been an increased interest in using fMRI data to study the dynamic nature of brain connectivity. In this setting, the activity in a set of regions of interest (ROIs) is often modeled using a multivariate Gaussian distribution, with a mean vector and covariance matrix that are allowed to vary as the experiment progresses, representing changing brain states. In this work, we introduce the Dynamic Connectivity Detection (DCD) algorithm, which is a data-driven technique to detect temporal change points in functional connectivity, and estimate a graph between ROIs for data within each segment defined by the change points. DCD builds upon the framework of the recently developed Dynamic Connectivity Regression (DCR) algorithm, which has proven efficient at detecting changes in connectivity for problems consisting of a small to medium (< 50) number of regions, but which runs into computational problems as the number of regions becomes large (>100). The newly proposed DCD method is faster, requires less user input, and is better able to handle high-dimensional data. It overcomes the shortcomings of DCR by adopting a simplified sparse matrix estimation approach and a different hypothesis testing procedure to determine change points. The application of DCD to simulated data, as well as fMRI data, illustrates the efficacy of the proposed method. PMID:26388711

  14. Genes2FANs: connecting genes through functional association networks

    PubMed Central

    2012-01-01

    Background Protein-protein, cell signaling, metabolic, and transcriptional interaction networks are useful for identifying connections between lists of experimentally identified genes/proteins. However, besides physical or co-expression interactions there are many ways in which pairs of genes, or their protein products, can be associated. By systematically incorporating knowledge on shared properties of genes from diverse sources to build functional association networks (FANs), researchers may be able to identify additional functional interactions between groups of genes that are not readily apparent. Results Genes2FANs is a web based tool and a database that utilizes 14 carefully constructed FANs and a large-scale protein-protein interaction (PPI) network to build subnetworks that connect lists of human and mouse genes. The FANs are created from mammalian gene set libraries where mouse genes are converted to their human orthologs. The tool takes as input a list of human or mouse Entrez gene symbols to produce a subnetwork and a ranked list of intermediate genes that are used to connect the query input list. In addition, users can enter any PubMed search term and then the system automatically converts the returned results to gene lists using GeneRIF. This gene list is then used as input to generate a subnetwork from the user’s PubMed query. As a case study, we applied Genes2FANs to connect disease genes from 90 well-studied disorders. We find an inverse correlation between the counts of links connecting disease genes through PPI and links connecting diseases genes through FANs, separating diseases into two categories. Conclusions Genes2FANs is a useful tool for interpreting the relationships between gene/protein lists in the context of their various functions and networks. Combining functional association interactions with physical PPIs can be useful for revealing new biology and help form hypotheses for further experimentation. Our finding that disease genes in

  15. Functional connectivity of the rodent brain using optical imaging

    NASA Astrophysics Data System (ADS)

    Guevara Codina, Edgar

    The aim of this thesis is to apply functional connectivity in a variety of animal models, using several optical imaging modalities. Even at rest, the brain shows high metabolic activity: the correlation in slow spontaneous fluctuations identifies remotely connected areas of the brain; hence the term "functional connectivity". Ongoing changes in spontaneous activity may provide insight into the neural processing that takes most of the brain metabolic activity, and so may provide a vast source of disease related changes. Brain hemodynamics may be modified during disease and affect resting-state activity. The thesis aims to better understand these changes in functional connectivity due to disease, using functional optical imaging. The optical imaging techniques explored in the first two contributions of this thesis are Optical Imaging of Intrinsic Signals and Laser Speckle Contrast Imaging, together they can estimate the metabolic rate of oxygen consumption, that closely parallels neural activity. They both have adequate spatial and temporal resolution and are well adapted to image the convexity of the mouse cortex. In the last article, a depth-sensitive modality called photoacoustic tomography was used in the newborn rat. Optical coherence tomography and laminar optical tomography were also part of the array of imaging techniques developed and applied in other collaborations. The first article of this work shows the changes in functional connectivity in an acute murine model of epileptiform activity. Homologous correlations are both increased and decreased with a small dependence on seizure duration. These changes suggest a potential decoupling between the hemodynamic parameters in resting-state networks, underlining the importance to investigate epileptic networks with several independent hemodynamic measures. The second study examines a novel murine model of arterial stiffness: the unilateral calcification of the right carotid. Seed-based connectivity analysis

  16. Longitudinal Changes in Functional Brain Connectivity Predicts Conversion to Alzheimer's Disease.

    PubMed

    Serra, Laura; Cercignani, Mara; Mastropasqua, Chiara; Torso, Mario; Spanò, Barbara; Makovac, Elena; Viola, Vanda; Giulietti, Giovanni; Marra, Camillo; Caltagirone, Carlo; Bozzali, Marco

    2016-01-01

    This longitudinal study investigates the modifications in structure and function occurring to typical Alzheimer's disease (AD) brains over a 2-year follow-up, from pre-dementia stages of disease, with the aim of identifying biomarkers of prognostic value. Thirty-one patients with amnestic mild cognitive impairment were recruited and followed-up with clinical, neuropsychological, and MRI assessments. Patients were retrospectively classified as AD Converters or Non-Converters, and the data compared between groups. Cross-sectional MRI data at baseline, assessing volume and functional connectivity abnormalities, confirmed previous findings, showing a more severe pattern of regional grey matter atrophy and default-mode network disconnection in Converters than in Non-Converters. Longitudinally, Converters showed more grey matter atrophy in the frontotemporal areas, accompanied by increased connectivity in the precuneus. Discriminant analysis revealed that functional connectivity of the precuneus within the default mode network at baseline is the parameter able to correctly classify patients in Converters and Non-Converters with high sensitivity, specificity, and accuracy. PMID:26890769

  17. Aging Effects on Whole-Brain Functional Connectivity in Adults Free of Cognitive and Psychiatric Disorders.

    PubMed

    Ferreira, Luiz Kobuti; Regina, Ana Carolina Brocanello; Kovacevic, Natasa; Martin, Maria da Graça Morais; Santos, Pedro Paim; Carneiro, Camila de Godoi; Kerr, Daniel Shikanai; Amaro, Edson; McIntosh, Anthony Randal; Busatto, Geraldo F

    2016-09-01

    Aging is associated with decreased resting-state functional connectivity (RSFC) within the default mode network (DMN), but most functional imaging studies have restricted the analysis to specific brain regions or networks, a strategy not appropriate to describe system-wide changes. Moreover, few investigations have employed operational psychiatric interviewing procedures to select participants; this is an important limitation since mental disorders are prevalent and underdiagnosed and can be associated with RSFC abnormalities. In this study, resting-state fMRI was acquired from 59 adults free of cognitive and psychiatric disorders according to standardized criteria and based on extensive neuropsychological and clinical assessments. We tested for associations between age and whole-brain RSFC using Partial Least Squares, a multivariate technique. We found that normal aging is not only characterized by decreased RSFC within the DMN but also by ubiquitous increases in internetwork positive correlations and focal internetwork losses of anticorrelations (involving mainly connections between the DMN and the attentional networks). Our results reinforce the notion that the aging brain undergoes a dedifferentiation processes with loss of functional diversity. These findings advance the characterization of healthy aging effects on RSFC and highlight the importance of adopting a broad, system-wide perspective to analyze brain connectivity. PMID:26315689

  18. Frontotemporal function]al connectivity and executive functions contribute to episodic memory performance.

    PubMed

    Blankenship, Tashauna L; O'Neill, Meagan; Deater-Deckard, Kirby; Diana, Rachel A; Bell, Martha Ann

    2016-09-01

    The contributions of hemispheric-specific electrophysiology (electroencephalogram or EEG) and independent executive functions (inhibitory control, working memory, cognitive flexibility) to episodic memory performance were examined using abstract paintings. Right hemisphere frontotemporal functional connectivity during encoding and retrieval, measured via EEG alpha coherence, statistically predicted performance on recency but not recognition judgments for the abstract paintings. Theta coherence, however, did not predict performance. Likewise, cognitive flexibility statistically predicted performance on recency judgments, but not recognition. These findings suggest that recognition and recency operate via separate electrophysiological and executive mechanisms. PMID:27388478

  19. Functional connectivity correlates of response inhibition impairment in anorexia nervosa.

    PubMed

    Collantoni, Enrico; Michelon, Silvia; Tenconi, Elena; Degortes, Daniela; Titton, Francesca; Manara, Renzo; Clementi, Maurizio; Pinato, Claudia; Forzan, Monica; Cassina, Matteo; Santonastaso, Paolo; Favaro, Angela

    2016-01-30

    Anorexia nervosa (AN) is a disorder characterized by high levels of cognitive control and behavioral perseveration. The present study aims at exploring inhibitory control abilities and their functional connectivity correlates in patients with AN. Inhibitory control - an executive function that allows the realization of adaptive behavior according to environmental contingencies - has been assessed by means of the Stop-Signal paradigm. The study involved 155 patients with lifetime AN and 102 healthy women. A subsample underwent resting-state functional magnetic resonance imaging and was genotyped for COMT and 5-HTTLPR polymorphisms. AN patients showed an impaired response inhibition and a disruption of the functional connectivity of the ventral attention circuit, a neural network implicated in behavioral response when a stimulus occurs unexpected. The 5-HTTLPR genotype appears to significantly interact with the functional connectivity of ventral attention network in explaining task performance in both patients and controls, suggesting a role of the serotoninergic system in mechanisms of response selection. The disruption of the ventral attention network in patients with AN suggests lower efficiency of bottom-up signal filtering, which might be involved in difficulties to adapt behavioral responses to environmental needs. Our findings deserve further research to confirm their scientific and therapeutic implications. PMID:26655584

  20. Functional connectivity and network analysis of midbrain and brainstem nuclei.

    PubMed

    Bär, Karl-Jürgen; de la Cruz, Feliberto; Schumann, Andy; Koehler, Stefanie; Sauer, Heinrich; Critchley, Hugo; Wagner, Gerd

    2016-07-01

    There is limited understanding of how monoamine-producing nuclei within midbrain and brainstem contribute to the formation and functional dynamics of brain networks across the human neocortex. We used resting state fMRI in 154 healthy participants to elucidate patterns of functional connectivity and network organization between cortical/subcortical regions and midbrain/brainstem nuclei. By means of univariate functional connectivity and graph-based analysis, we show that dopaminergic midbrain centers and the serotonergic dorsal raphe nucleus (DRN) are functionally integrated with the default mode network (DMN), whereas the remaining serotonergic raphe nuclei and the noradrenergic locus coeruleus are functionally integrated with the executive-control network (ECN). The majority of midbrain/brainstem nuclei show a high level of connectedness to other network modules classifying these nuclei as "connector" hubs. The additionally applied probabilistic independent component analysis (PICA) broadly corresponded with the results of the GT analysis, describing similar functionally-relevant cortical networks. Since monoaminergic neurotransmission is essential to neocortical function, and represents an important target for pharmacotherapy, our novel findings contribute to a comprehensive understanding of the functional organization of the human brain. PMID:27046112

  1. Decreased functional connectivity density in pain-related brain regions of female migraine patients without aura.

    PubMed

    Gao, Qing; Xu, Fei; Jiang, Cui; Chen, Zhifeng; Chen, Huafu; Liao, Huaqiang; Zhao, Ling

    2016-02-01

    Migraine is one of the most prevalent neurological disorders which is suggested to be associated with dysfunctions of the central nervous system. The purpose of the present study was to detect the altered functional connectivity architecture in the large-scale network of the whole brain in migraine without aura (MWoA). Meanwhile, the brain functional hubs which are targeted by MWoA could be identified. A new voxel-based method named functional connectivity density (FCD) mapping was applied to resting-state functional magnetic resonance imaging data of 55 female MWoA patients and 44 age-matched female healthy controls (HC). Comparing to HC, MWoA patients showed abnormal short-range FCD values in bilateral hippocampus, bilateral insula, right amygdale, right anterior cingulate cortex, bilateral putamen, bilateral caudate nucleus and the prefrontal cortex. The results suggested decreased intraregional connectivity of these pain-related brain regions in female MWoA. In addition, short-range FCD values in left prefrontal cortex, putamen and caudate nucleus were significantly negatively correlated with duration of disease in MWoA group, implying the repeated migraine attacks over time may consistently affect the resting-state functional connectivity architecture of these brain hubs. Our findings revealed the dysfunction of brain hubs in female MWoA, and suggested the left prefrontal cortex, putamen and caudate nucleus served as sensitive neuroimaging markers for reflecting the disease duration of female MWoA. This may provide us new insights into the changes in the organization of the large-scale brain network in MWoA. PMID:26688226

  2. Resting state functional connectivity in early blind humans

    PubMed Central

    Burton, Harold; Snyder, Abraham Z.; Raichle, Marcus E.

    2014-01-01

    Task-based neuroimaging studies in early blind humans (EB) have demonstrated heightened visual cortex responses to non-visual paradigms. Several prior functional connectivity studies in EB have shown altered connections consistent with these task-based results. But these studies generally did not consider behavioral adaptations to lifelong blindness typically observed in EB. Enhanced cognitive abilities shown in EB include greater serial recall and attention to memory. Here, we address the question of the extent to which brain intrinsic activity in EB reflects such adaptations. We performed a resting-state functional magnetic resonance imaging study contrasting 14 EB with 14 age/gender matched normally sighted controls (NS). A principal finding was markedly greater functional connectivity in EB between visual cortex and regions typically associated with memory and cognitive control of attention. In contrast, correlations between visual cortex and non-deprived sensory cortices were significantly lower in EB. Thus, the available data, including that obtained in prior task-based and resting state fMRI studies, as well as the present results, indicate that visual cortex in EB becomes more heavily incorporated into functional systems instantiating episodic recall and attention to non-visual events. Moreover, EB appear to show a reduction in interactions between visual and non-deprived sensory cortices, possibly reflecting suppression of inter-sensory distracting activity. PMID:24778608

  3. Sex differences in intrinsic brain functional connectivity underlying human shyness.

    PubMed

    Yang, Xun; Wang, Siqi; Kendrick, Keith Maurice; Wu, Xi; Yao, Li; Lei, Du; Kuang, Weihong; Bi, Feng; Huang, Xiaoqi; He, Yong; Gong, Qiyong

    2015-12-01

    Shyness is a fundamental trait associated with social-emotional maladaptive behaviors, including many forms of psychopathology. Neuroimaging studies have demonstrated that hyper-responsivity to social and emotional stimuli occurs in the frontal cortex and limbic system in shy individuals, but the relationship between shyness and brain-wide functional connectivity remains incompletely understood. Using resting-state functional magnetic resonance imaging, we addressed this issue by exploring the relationship between regional functional connectivity strength (rFCS) and scores of shyness in a cohort of 61 healthy young adults and controlling for the effects of social and trait anxiety scores. We observed that the rFCS of the insula positively correlated with shyness scores regardless of sex. Furthermore, we found that there were significant sex-by-shyness interactions in the dorsal anterior cingulate cortex and insula (two core nodes of the salience network) as well as the subgenual anterior cingulate cortex: the rFCS values of these regions positively correlated with shyness scores in females but negatively correlated in males. Taken together, we provide evidence for intrinsic functional connectivity differences in individuals with different degrees of shyness and that these differences are sex-dependent. These findings might have important implications on the understanding of biological mechanisms underlying emotional and cognitive processing associated with shyness. PMID:25994971

  4. Resting Functional Connectivity of Language Networks: Characterization and Reproducibility

    PubMed Central

    Tomasi, Dardo; Volkow, Nora D.

    2011-01-01

    The neural basis of language comprehension and production has been associated with superior temporal (Wernicke’s) and inferior frontal (Broca’s) cortical areas respectively. However, recent resting state functional connectivity (RSFC) and lesion studies implicate a more extended network in language processing. Using a large RSFC dataset from 970 healthy subjects and seed regions in Broca’s and Wernicke’s we recapitulate this extended network that includes adjoining prefrontal, temporal and parietal regions but also bilateral caudate and left putamen/globus pallidus and subthalamic nucleus. We also show that the language network has predominance of short-range functional connectivity (except posterior Wernicke’s area that exhibited predominant long-range connectivity), which is consistent with reliance on local processing. Predominantly, the long-range connectivity was left lateralized (except anterior Wernicke’s area that exhibited rightward lateralization). The language network also exhibited anticorrelated activity with auditory (only for Wernickes’s area) and visual cortices that suggests integrated sequential activity with regions involved with listening or reading words. Assessment of the intra subject’s reproducibility of this network and its characterization in individuals with language dysfunction is needed to determine its potential as a biomarker for language disorders. PMID:22212597

  5. EEG functional connectivity, axon delays and white matter disease

    PubMed Central

    Nunez, Paul L.; Srinivasan, Ramesh; Fields, R. Douglas

    2016-01-01

    Objective Both structural and functional brain connectivities are closely linked to white matter disease. We discuss several such links of potential interest to neurologists, neurosurgeons, radiologists, and non-clinical neuroscientists. Methods Treatment of brains as genuine complex systems suggests major emphasis on the multi-scale nature of brain connectivity and dynamic behavior. Cross-scale interactions of local, regional, and global networks are apparently responsible for much of EEG's oscillatory behaviors. Finite axon propagation speed, often assumed to be infinite in local network models, is central to our conceptual framework. Results Myelin controls axon speed, and the synchrony of impulse traffic between distant cortical regions appears to be critical for optimal mental performance and learning. Results Several experiments suggest that axon conduction speed is plastic, thereby altering the regional and global white matter connections that facilitate binding of remote local networks. Conclusions Combined EEG and high resolution EEG can provide distinct multi-scale estimates of functional connectivity in both healthy and diseased brains with measures like frequency and phase spectra, covariance, and coherence. Significance White matter disease may profoundly disrupt normal EEG coherence patterns, but currently these kinds of studies are rare in scientific labs and essentially missing from clinical environments. PMID:24815984

  6. Functional and Structural Abnormalities in Deferoxamine Retinopathy: A Review of the Literature

    PubMed Central

    Di Nicola, Maura; Barteselli, Giulio; Dell'Arti, Laura; Ratiglia, Roberto; Viola, Francesco

    2015-01-01

    Deferoxamine mesylate (DFO) is the most commonly used iron-chelating agent to treat transfusion-related hemosiderosis. Despite the clear advantages for the use of DFO, numerous DFO-related systemic toxicities have been reported in the literature, as well as sight-threatening ocular toxicity involving the retinal pigment epithelium (RPE). The damage to the RPE can lead to visual field defects, color-vision defects, abnormal electrophysiological tests, and permanent visual deterioration. The purpose of this review is to provide an updated summary of the ocular findings, including both functional and structural abnormalities, in DFO-treated patients. In particular, we pay particular attention to analyzing results of multimodal technologies for retinal imaging, which help ophthalmologists in the early diagnosis and correct management of DFO retinopathy. Fundus autofluorescence, for example, is not only useful for screening patients at high-risk of DFO retinopathy, but is also a prerequisite for identify specific high-risk patterns of RPE changes that are relevant for the prognosis of the disease. In addition, optical coherence tomography may have a clinical usefulness in detecting extent and location of different retinal changes in DFO retinopathy. Finally, this review wants to underline the need for universally approved guidelines for screening and followup of this particular disease. PMID:26167477

  7. Abnormal Compartmentalization of Cartilage Matrix Components in Mice Lacking Collagen X: Implications for Function

    PubMed Central

    Kwan, Kin Ming; Pang, Michael K.M.; Zhou, Sheila; Cowan, Soot Keng; Kong, Richard Y.C.; Pfordte, Tim; Olsen, Bjorn R.; Sillence, David O.; Tam, Patrick P.L.; Cheah, Kathryn S.E.

    1997-01-01

    There are conflicting views on whether collagen X is a purely structural molecule, or regulates bone mineralization during endochondral ossification. Mutations in the human collagen α1(X) gene (COL10A1) in Schmid metaphyseal chondrodysplasia (SMCD) suggest a supportive role. But mouse collagen α1(X) gene (Col10a1) null mutants were previously reported to show no obvious phenotypic change. We have generated collagen X deficient mice, which shows that deficiency does have phenotypic consequences which partly resemble SMCD, such as abnormal trabecular bone architecture. In particular, the mutant mice develop coxa vara, a phenotypic change common in human SMCD. Other consequences of the mutation are reduction in thickness of growth plate resting zone and articular cartilage, altered bone content, and atypical distribution of matrix components within growth plate cartilage. We propose that collagen X plays a role in the normal distribution of matrix vesicles and proteoglycans within the growth plate matrix. Collagen X deficiency impacts on the supporting properties of the growth plate and the mineralization process, resulting in abnormal trabecular bone. This hypothesis would accommodate the previously conflicting views of the function of collagen X and of the molecular pathogenesis of SMCD. PMID:9015315

  8. Positron Emission Tomography Reveals Abnormal Topological Organization in Functional Brain Network in Diabetic Patients

    PubMed Central

    Qiu, Xiangzhe; Zhang, Yanjun; Feng, Hongbo; Jiang, Donglang

    2016-01-01

    Recent studies have demonstrated alterations in the topological organization of structural brain networks in diabetes mellitus (DM). However, the DM-related changes in the topological properties in functional brain networks are unexplored so far. We therefore used fluoro-D-glucose positron emission tomography (FDG-PET) data to construct functional brain networks of 73 DM patients and 91 sex- and age-matched normal controls (NCs), followed by a graph theoretical analysis. We found that both DM patients and NCs had a small-world topology in functional brain network. In comparison to the NC group, the DM group was found to have significantly lower small-world index, lower normalized clustering coefficients and higher normalized characteristic path length. Moreover, for diabetic patients, the nodal centrality was significantly reduced in the right rectus, the right cuneus, the left middle occipital gyrus, and the left postcentral gyrus, and it was significantly increased in the orbitofrontal region of the left middle frontal gyrus, the left olfactory region, and the right paracentral lobule. Our results demonstrated that the diabetic brain was associated with disrupted topological organization in the functional PET network, thus providing functional evidence for the abnormalities of brain networks in DM. PMID:27303259

  9. Neurological Gait Abnormalities Moderate the Functional Brain Signature of the Posture First Hypothesis.

    PubMed

    Holtzer, Roee; Verghese, Joe; Allali, Gilles; Izzetoglu, Meltem; Wang, Cuiling; Mahoney, Jeannette R

    2016-03-01

    The posture first hypothesis suggests that under dual-task walking conditions older adults prioritize gait over cognitive task performance. Functional neural confirmation of this hypothesis, however, is lacking. Herein, we determined the functional neural correlates of the posture first hypothesis and hypothesized that the presence of neurological gait abnormalities (NGA) would moderate associations between brain activations, gait and cognitive performance. Using functional near-infrared spectroscopy we assessed changes in oxygenated hemoglobin levels in the pre-frontal cortex (PFC) during normal walk and walk while talk (WWT) conditions in a large cohort of non-demented older adults (n = 236; age = 75.5 ± 6.49 years; female = 51.7 %). NGA were defined as central (due to brain diseases) or peripheral (neuropathic gait) following a standardized neurological examination protocol. Double dissociations between brain activations and behavior emerged as a function of NGA. Higher oxygenation levels during WWT were related to better cognitive performance (estimate = 0.145; p < 0.001) but slower gait velocity (estimate = -6.336, p < 0.05) among normals. In contrast, higher oxygenation levels during WWT among individuals with peripheral NGA were associated with worse cognitive performance (estimate = -0.355; p < 0.001) but faster gait velocity (estimate = 14.855; p < 0.05). Increased activation in the PFC during locomotion may have a compensatory function that is designed to support gait among individuals with peripheral NGA. PMID:26613725

  10. Cognitive, neurophysiological, and functional correlates of proverb interpretation abnormalities in schizophrenia.

    PubMed

    Kiang, Michael; Light, Gregory A; Prugh, Jocelyn; Coulson, Seana; Braff, David L; Kutas, Marta

    2007-07-01

    A hallmark of schizophrenia is impaired proverb interpretation, which could be due to: (1) aberrant activation of disorganized semantic associations, or (2) working memory (WM) deficits. We assessed 18 schizophrenia patients and 18 normal control participants on proverb interpretation, and evaluated these two hypotheses by examining within patients the correlations of proverb interpretation with disorganized symptoms and auditory WM, respectively. Secondarily, we also explored the relationships between proverb interpretation and a spectrum of cognitive functions including auditory sensory-memory encoding (as indexed by the mismatch negativity (MMN) event-related brain potential (ERP)); executive function; and social/occupational function. As expected, schizophrenia patients produced less accurate and less abstract descriptions of proverbs than did controls. These proverb interpretation difficulties in patients were not significantly correlated with disorganization or other symptom factors, but were significantly correlated (p < .05) with WM impairment, as well as with impairments in sensory-memory encoding, executive function, and social/occupational function. These results offer no support for disorganized associations in abnormal proverb interpretation in schizophrenia, but implicate WM deficits, perhaps as a part of a syndrome related to generalized frontal cortical dysfunction. PMID:17521483

  11. Positron Emission Tomography Reveals Abnormal Topological Organization in Functional Brain Network in Diabetic Patients.

    PubMed

    Qiu, Xiangzhe; Zhang, Yanjun; Feng, Hongbo; Jiang, Donglang

    2016-01-01

    Recent studies have demonstrated alterations in the topological organization of structural brain networks in diabetes mellitus (DM). However, the DM-related changes in the topological properties in functional brain networks are unexplored so far. We therefore used fluoro-D-glucose positron emission tomography (FDG-PET) data to construct functional brain networks of 73 DM patients and 91 sex- and age-matched normal controls (NCs), followed by a graph theoretical analysis. We found that both DM patients and NCs had a small-world topology in functional brain network. In comparison to the NC group, the DM group was found to have significantly lower small-world index, lower normalized clustering coefficients and higher normalized characteristic path length. Moreover, for diabetic patients, the nodal centrality was significantly reduced in the right rectus, the right cuneus, the left middle occipital gyrus, and the left postcentral gyrus, and it was significantly increased in the orbitofrontal region of the left middle frontal gyrus, the left olfactory region, and the right paracentral lobule. Our results demonstrated that the diabetic brain was associated with disrupted topological organization in the functional PET network, thus providing functional evidence for the abnormalities of brain networks in DM. PMID:27303259

  12. Abnormal GABAergic function and face processing in schizophrenia: A pharmacologic-fMRI study.

    PubMed

    Tso, Ivy F; Fang, Yu; Phan, K Luan; Welsh, Robert C; Taylor, Stephan F

    2015-10-01

    The involvement of the gamma-aminobutyric acid (GABA) system in schizophrenia is suggested by postmortem studies and the common use of GABA receptor-potentiating agents in treatment. In a recent study, we used a benzodiazepine challenge to demonstrate abnormal GABAergic function during processing of negative visual stimuli in schizophrenia. This study extended this investigation by mapping GABAergic mechanisms associated with face processing and social appraisal in schizophrenia using a benzodiazepine challenge. Fourteen stable, medicated schizophrenia/schizoaffective patients (SZ) and 13 healthy controls (HC) underwent functional MRI using the blood oxygenation level-dependent (BOLD) technique while they performed the Socio-emotional Preference Task (SePT) on emotional face stimuli ("Do you like this face?"). Participants received single-blinded intravenous saline and lorazepam (LRZ) in two separate sessions separated by 1-3weeks. Both SZ and HC recruited medial prefrontal cortex/anterior cingulate during the SePT, relative to gender identification. A significant drug by group interaction was observed in the medial occipital cortex, such that SZ showed increased BOLD signal to LRZ challenge, while HC showed an expected decrease of signal; the interaction did not vary by task. The altered BOLD response to LRZ challenge in SZ was significantly correlated with increased negative affect across multiple measures. The altered response to LRZ challenge suggests that abnormal face processing and negative affect in SZ are associated with altered GABAergic function in the visual cortex, underscoring the role of impaired visual processing in socio-emotional deficits in schizophrenia. PMID:26363970

  13. Connecting Teratogen-Induced Congenital Heart Defects to Neural Crest Cells and Their Effect on Cardiac Function

    PubMed Central

    Karunamuni, Ganga H.; Ma, Pei; Gu, Shi; Rollins, Andrew M.; Jenkins, Michael W.; Watanabe, Michiko

    2014-01-01

    Neural crest cells play many key roles in embryonic development, as demonstrated by the abnormalities that result from their specific absence or dysfunction. Unfortunately, these key cells are particularly sensitive to abnormalities in various intrinsic and extrinsic factors, such as genetic deletions or ethanol-exposure that lead to morbidity and mortality for organisms. This review discusses the role identified for a segment of neural crest is in regulating the morphogenesis of the heart and associated great vessels. The paradox is that their derivatives constitute a small proportion of cells to the cardiovascular system. Findings supporting that these cells impact early cardiac function raises the interesting possibility that they indirectly control cardiovascular development at least partially through regulating function. Making connections between insults to the neural crest, cardiac function, and morphogenesis is more approachable with technological advances. Expanding our understanding of early functional consequences could be useful in improving diagnosis and testing therapies. PMID:25220155

  14. 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

  15. Intrinsic Functional-Connectivity Networks for Diagnosis: Just Beautiful Pictures?

    PubMed Central

    Moeller, James R.

    2011-01-01

    Abstract Resting-state functional connectivity has become a topic of enormous interest in the Neuroscience community in the last decade. Because resting-state data (1) harbor important information that often is diagnostically relevant and (2) are easy to acquire, there has been a rapid increase in the development of a variety of network analytic techniques for diagnostic applications, stimulating methodological research in general. While we are among those who welcome the increased interest in the resting state and multivariate analytic tools, we would like to draw attention to some entrenched practices that undermine the scientific quality of diagnostic functional-connectivity research, but whose correction is relatively easy to accomplish. With the current commentary we also hope to benefit the field at large and contribute to a healthy debate about research goals and best practices. PMID:22433005

  16. Functional Connectivity Measured with Magnetoencephalography Identifies Persons with HIV Disease

    PubMed Central

    Becker, James T.; Bajo, Ricardo; Fabrizio, Melissa; Sudre, Gustavo; Cuesta, Pablo; Aizenstein, Howard J.; Lopez, Oscar L.; Wolk, David; Parkkonen, Lauri; Maestu, Fernando; Bagic, Anto

    2012-01-01

    There is need for a valid and reliable biomarker for HIV Associated Neurocognitive Disorder (HAND). The purpose of the present study was to provide preliminary evidence of the potential utility of neuronal functional connectivity measures obtained using magnetoencephalography (MEG) to identify HIV-associated changes in brain function. Resting state, eyes closed, MEG data from 10 HIV-infected individuals and 8 seronegative controls were analyzed using mutual information (MI) between all pairs of MEG sensors to determine whether there were functional brain networks that distinguished between subject groups based on cognition (global and learning) or on serostatus. Three networks were identified across all subjects, but after permutation testing (at α < .005) only the one related to HIV serostatus was significant. The network included MEG sensors (planar gradiometers) above the right anterior region connecting to sensors above the left posterior region. A mean MI value was calculated across all connections from the anterior to the posterior groupings; that score distinguished between the serostatus groups with only one error (sensitivity = 1.00, specificity = .88 (X2 = 15.4, df = 1, p < .01, Relative Risk = .11). There were no significant associations between the MI value and the neuropsychological Global Impairment rating, substance abuse, mood disorder, age, education, CD4+ cell counts or HIV viral load. We conclude that using a measure of functional connectivity, it may be possible to distinguish between HIV-infected and uninfected individuals, suggesting that MEG may have the potential to serve as a sensitive, non-invasive biomarker for HAND. PMID:22328062

  17. Increased functional connectivity within mesocortical networks in open people.

    PubMed

    Passamonti, L; Terracciano, A; Riccelli, R; Donzuso, G; Cerasa, A; Vaccaro, Mg; Novellino, F; Fera, F; Quattrone, A

    2015-01-01

    Openness is a personality trait reflecting absorption in sensory experience, preference for novelty, and creativity, and is thus considered a driving force of human evolution. At the brain level, a relation between openness and dopaminergic circuits has been proposed, although evidence to support this hypothesis is lacking. Recent behavioral research has also found that people with mania, a psychopathological condition linked to dopaminergic dysfunctions, may display high levels of openness. However, whether openness is related to dopaminergic circuits has not been determined thus far. We addressed this issue via three functional magnetic resonance imaging (fMRI) experiments in n=46 healthy volunteers. In the first experiment participants lied at rest in the scanner while in the other two experiments they performed active tasks that included the presentation of pleasant odors and pictures of food. Individual differences in openness and other personality traits were assessed via the NEO-PI-R questionnaire (NEO-Personality Inventory-Revised), a widely employed measure of the five-factor model personality traits. Correlation between fMRI and personality data was analyzed via state-of-art methods assessing resting-state and task-related functional connectivity within specific brain networks. Openness was positively associated with the functional connectivity between the right substantia nigra/ventral tegmental area, the major source of dopaminergic inputs in the brain, and the ipsilateral dorsolateral prefrontal cortex (DLPFC), a key region in encoding, maintaining, and updating information that is relevant for adaptive behaviors. Of note, the same connectivity pattern was consistently found across all of the three fMRI experiments. Given the critical role of dopaminergic signal in gating information in DLPFC, the increased functional connectivity within mesocortical networks in open people may explain why these individuals display a wide "mental permeability" to

  18. Exploring functional connectivity networks with multichannel brain array coils.

    PubMed

    Anteraper, Sheeba Arnold; Whitfield-Gabrieli, Susan; Keil, Boris; Shannon, Steven; Gabrieli, John D; Triantafyllou, Christina

    2013-01-01

    The use of multichannel array head coils in functional and structural magnetic resonance imaging (MRI) provides increased signal-to-noise ratio (SNR), higher sensitivity, and parallel imaging capabilities. However, their benefits remain to be systematically explored in the context of resting-state functional connectivity MRI (fcMRI). In this study, we compare signal detectability within and between commercially available multichannel brain coils, a 32-Channel (32Ch), and a 12-Channel (12Ch) at 3T, in a high-resolution regime to accurately map resting-state networks. We investigate whether the 32Ch coil can extract and map fcMRI more efficiently and robustly than the 12Ch coil using seed-based and graph-theory-based analyses. Our findings demonstrate that although the 12Ch coil can be used to reveal resting-state connectivity maps, the 32Ch coil provides increased detailed functional connectivity maps (using seed-based analysis) as well as increased global and local efficiency, and cost (using graph-theory-based analysis), in a number of widely reported resting-state networks. The exploration of subcortical networks, which are scarcely reported due to limitations in spatial-resolution and coil sensitivity, also proved beneficial with the 32Ch coil. Further, comparisons regarding the data acquisition time required to successfully map these networks indicated that scan time can be significantly reduced by 50% when a coil with increased number of channels (i.e., 32Ch) is used. Switching to multichannel arrays in resting-state fcMRI could, therefore, provide both detailed functional connectivity maps and acquisition time reductions, which could further benefit imaging special subject populations, such as patients or pediatrics who have less tolerance in lengthy imaging sessions. PMID:23510203

  19. Convergent and Divergent Functional Connectivity Patterns in Schizophrenia and Depression

    PubMed Central

    Zeng, Ling-Li; Ma, Qiongmin; Hu, Dewen

    2013-01-01

    Major depression and schizophrenia are two of the most serious psychiatric disorders and share similar behavioral symptoms. Whether these similar behavioral symptoms underlie any convergent psychiatric pathological mechanisms is not yet clear. To address this issue, this study sought to investigate the whole-brain resting-state functional magnetic resonance imaging (MRI) of major depression and schizophrenia by using multivariate pattern analysis. Thirty-two schizophrenic patients, 19 major depressive disorder patients and 38 healthy controls underwent resting-state functional MRI scanning. A support vector machine in conjunction with intrinsic discriminant analysis was used to solve the multi-classification problem, resulting in a correct classification rate of 80.9% via leave-one-out cross-validation. The depression and schizophrenia groups both showed altered functional connections associated with the medial prefrontal cortex, anterior cingulate cortex, thalamus, hippocampus, and cerebellum. However, the prefrontal cortex, amygdala, and temporal poles were found to be affected differently by major depression and schizophrenia. Our preliminary study suggests that altered connections within or across the default mode network and the cerebellum may account for the common behavioral symptoms between major depression and schizophrenia. In addition, connections associated with the prefrontal cortex and the affective network showed promise as biomarkers for discriminating between the two disorders. PMID:23844175

  20. Predicting individual brain maturity using dynamic functional connectivity

    PubMed Central

    Qin, Jian; Chen, Shan-Guang; Hu, Dewen; Zeng, Ling-Li; Fan, Yi-Ming; Chen, Xiao-Ping; Shen, Hui

    2015-01-01

    Neuroimaging-based functional connectivity (FC) analyses have revealed significant developmental trends in specific intrinsic connectivity networks linked to cognitive and behavioral maturation. However, knowledge of how brain functional maturation is associated with FC dynamics at rest is limited. Here, we examined age-related differences in the temporal variability of FC dynamics with data publicly released by the Nathan Kline Institute (NKI; n = 183, ages 7–30) and showed that dynamic inter-region interactions can be used to accurately predict individual brain maturity across development. Furthermore, we identified a significant age-dependent trend underlying dynamic inter-network FC, including increasing variability of the connections between the visual network, default mode network (DMN) and cerebellum as well as within the cerebellum and DMN and decreasing variability within the cerebellum and between the cerebellum and DMN as well as the cingulo-opercular network. Overall, the results suggested significant developmental changes in dynamic inter-network interaction, which may shed new light on the functional organization of typical developmental brains. PMID:26236224

  1. Network-level reorganisation of functional connectivity following arm amputation

    PubMed Central

    Makin, Tamar R.; Filippini, Nicola; Duff, Eugene P.; Henderson Slater, David; Tracey, Irene; Johansen-Berg, Heidi

    2015-01-01

    One of the most striking demonstrations of plasticity in the adult human brain follows peripheral injury, such as amputation. In the primary sensorimotor cortex, arm amputation results in massive local remapping of the missing hands' cortical territory. However, little is known about the consequences of sensorimotor deprivation on global brain organisation. Here, we used resting-state fMRI to identify large-scale reorganisation beyond the primary sensorimotor cortex in arm amputees, compared with two-handed controls. Specifically, we characterised changes in functional connectivity between the cortical territory of the missing hand in the primary sensorimotor cortex (‘missing hand cortex’) and two networks of interest: the sensorimotor network, which is typically strongly associated with the hand cortex, and the default mode network (DMN), which is normally dissociated from it. Functional connectivity values between the missing hand cortex and the sensorimotor network were reduced in amputees, and connectivity was weaker in individuals amputated for longer periods. Lower levels of functional coupling between the missing hand cortex and the sensorimotor network were also associated with emerged coupling of this cortex with the DMN. Our results demonstrate that plasticity following arm amputation is not restricted to local remapping occurring within the sensorimotor homunculus of the missing hand but rather produces a cascade of cortical reorganisation at a network-level scale. These findings may provide a new framework for understanding how local deprivation following amputation could elicit complex perceptual experiences of phantom sensations, such as phantom pain. PMID:25776216

  2. Convergent and divergent functional connectivity patterns in schizophrenia and depression.

    PubMed

    Yu, Yang; Shen, Hui; Zeng, Ling-Li; Ma, Qiongmin; Hu, Dewen

    2013-01-01

    Major depression and schizophrenia are two of the most serious psychiatric disorders and share similar behavioral symptoms. Whether these similar behavioral symptoms underlie any convergent psychiatric pathological mechanisms is not yet clear. To address this issue, this study sought to investigate the whole-brain resting-state functional magnetic resonance imaging (MRI) of major depression and schizophrenia by using multivariate pattern analysis. Thirty-two schizophrenic patients, 19 major depressive disorder patients and 38 healthy controls underwent resting-state functional MRI scanning. A support vector machine in conjunction with intrinsic discriminant analysis was used to solve the multi-classification problem, resulting in a correct classification rate of 80.9% via leave-one-out cross-validation. The depression and schizophrenia groups both showed altered functional connections associated with the medial prefrontal cortex, anterior cingulate cortex, thalamus, hippocampus, and cerebellum. However, the prefrontal cortex, amygdala, and temporal poles were found to be affected differently by major depression and schizophrenia. Our preliminary study suggests that altered connections within or across the default mode network and the cerebellum may account for the common behavioral symptoms between major depression and schizophrenia. In addition, connections associated with the prefrontal cortex and the affective network showed promise as biomarkers for discriminating between the two disorders. PMID:23844175

  3. Network-level reorganisation of functional connectivity following arm amputation.

    PubMed

    Makin, Tamar R; Filippini, Nicola; Duff, Eugene P; Henderson Slater, David; Tracey, Irene; Johansen-Berg, Heidi

    2015-07-01

    One of the most striking demonstrations of plasticity in the adult human brain follows peripheral injury, such as amputation. In the primary sensorimotor cortex, arm amputation results in massive local remapping of the missing hands' cortical territory. However, little is known about the consequences of sensorimotor deprivation on global brain organisation. Here, we used resting-state fMRI to identify large-scale reorganisation beyond the primary sensorimotor cortex in arm amputees, compared with two-handed controls. Specifically, we characterised changes in functional connectivity between the cortical territory of the missing hand in the primary sensorimotor cortex ('missing hand cortex') and two networks of interest: the sensorimotor network, which is typically strongly associated with the hand cortex, and the default mode network (DMN), which is normally dissociated from it. Functional connectivity values between the missing hand cortex and the sensorimotor network were reduced in amputees, and connectivity was weaker in individuals amputated for longer periods. Lower levels of functional coupling between the missing hand cortex and the sensorimotor network were also associated with emerged coupling of this cortex with the DMN. Our results demonstrate that plasticity following arm amputation is not restricted to local remapping occurring within the sensorimotor homunculus of the missing hand but rather produces a cascade of cortical reorganisation at a network-level scale. These findings may provide a new framework for understanding how local deprivation following amputation could elicit complex perceptual experiences of phantom sensations, such as phantom pain. PMID:25776216

  4. Approaches to local connectivity in autism using resting state functional connectivity MRI.

    PubMed

    Maximo, Jose O; Keown, Christopher L; Nair, Aarti; Müller, Ralph-Axel

    2013-01-01

    While the literature on aberrant long-distance connectivity in autism spectrum disorder (ASD) has grown fast over the past decade, little is known about local connectivity. We used regional homogeneity and local density approaches at different spatial scales to examine local connectivity in 29 children and adolescents with ASD and 29 matched typically developing participants, using resting state functional magnetic resonance imaging data. Across a total of 12 analysis pipelines, the gross pattern of between-group findings was overall stable, with local overconnectivity in the ASD group in occipital and posterior temporal regions and underconnectivity in middle/posterior cingulate, and medial prefrontal regions. This general pattern was confirmed in secondary analyses for low-motion subsamples (n = 20 per group), in which time series segments with >0.25 mm head motion were censored, as well as in an analysis including global signal regression. Local overconnectivity in visual regions appears consistent with preference for local over global visual processing previously reported in ASD, whereas cingulate and medial frontal underconnectivity may relate to aberrant function within the default mode network. PMID:24155702

  5. Impaired functional but preserved structural connectivity in limbic white matter tracts in youth with conduct disorder or oppositional defiant disorder plus psychopathic traits

    PubMed Central

    Finger, Elizabeth Carrie; Marsh, Abigail; Blair, Karina Simone; Majestic, Catherine; Evangelou, Iordanis; Gupta, Karan; Schneider, Marguerite Reid; Sims, Courtney; Pope, Kayla; Fowler, Katherine; Sinclair, Stephen; Tovar-Moll, Fernanda; Pine, Daniel; Blair, Robert James

    2012-01-01

    Youths with conduct disorder or oppositional defiant disorder and psychopathic traits (CD/ODD+PT) are at high risk of adult anti-social behaviour and psychopathy. Neuroimaging studies demonstrate functional abnormalities in orbitofrontal cortex and the amygdala in both youths and adults with psychopathic traits. Diffusion tensor imaging in psychopathic adults demonstrates disrupted structural connectivity between these regions (uncinate fasiculus). The current study examined whether functional neural abnormalities present in youths with CD/ODD+PT are associated with similar white matter abnormalities. Youths with CD/ODD+PT and comparison participants completed 3.0 T diffusion tensor scans and functional MRI scans. Diffusion tensor imaging did not reveal disruption in structural connections within the uncinate fasiculus or other white matter tracts in youths with CD/ODD+PT, despite the demonstration of disrupted amygdala-prefrontal functional connectivity in these youths. These results suggest that disrupted amygdala-frontal white matter connectivity as measured by fractional anisotropy is less sensitive than imaging measurements of functional perturbations in youths with psychopathic traits. If white matter tracts are intact in youths with this disorder, childhood may provide a critical window for intervention and treatment, before significant structural brain abnormalities solidify. PMID:22819939

  6. Cerebral functional connectivity periodically (de)synchronizes with anatomical constraints.

    PubMed

    Liégeois, Raphaël; Ziegler, Erik; Phillips, Christophe; Geurts, Pierre; Gómez, Francisco; Bahri, Mohamed Ali; Yeo, B T Thomas; Soddu, Andrea; Vanhaudenhuyse, Audrey; Laureys, Steven; Sepulchre, Rodolphe

    2016-07-01

    This paper studies the link between resting-state functional connectivity (FC), measured by the correlations of fMRI BOLD time courses, and structural connectivity (SC), estimated through fiber tractography. Instead of a static analysis based on the correlation between SC and FC averaged over the entire fMRI time series, we propose a dynamic analysis, based on the time evolution of the correlation between SC and a suitably windowed FC. Assessing the statistical significance of the time series against random phase permutations, our data show a pronounced peak of significance for time window widths around 20-30 TR (40-60 s). Using the appropriate window width, we show that FC patterns oscillate between phases of high modularity, primarily shaped by anatomy, and phases of low modularity, primarily shaped by inter-network connectivity. Building upon recent results in dynamic FC, this emphasizes the potential role of SC as a transitory architecture between different highly connected resting-state FC patterns. Finally, we show that the regions contributing the most to these whole-brain level fluctuations of FC on the supporting anatomical architecture belong to the default mode and the executive control networks suggesting that they could be capturing consciousness-related processes such as mind wandering. PMID:26197763

  7. [The interneuronal functional connections in the sensorimotor cortex of dogs].

    PubMed

    Dolbakian, E E; Tarakanova, T A; Fadeeva, M A

    1994-01-01

    Multiunit activity of sensorimotor cortex was recorded from chronically implanted semi-microelectrodes in two dogs. Functional interneuronal connections between neuronal spike trains of 6-8 neurons selected from background multiunit activity were studied by the method of cross-correlation analysis. Bin widths 0.5, 1, 2, 3 and further up to 40 ms by step of 1 ms were used. The cross-interval connections were characterized by complete absence of the shared input (central symmetrical peaks) and signs of inhibitory interrelations. The temporal interrelations between selected neurons were characterized by unilateral and bilateral non-symmetrical excitatory connections--ultra-narrow peaks with short (1-10 ms), middle (10-80 ms) and long (80-2000 ms) delays. The existence of such ultra-narrow peaks contradicts "classical" conceptions on the character of cross-interval connections based on model experiments on simple nervous systems. We suppose that special mechanism of synchronization with high temporal accuracy exists in the cortex. PMID:8171888

  8. Cortical brain connectivity evaluated by graph theory in dementia: a correlation study between functional and structural data.

    PubMed

    Vecchio, Fabrizio; Miraglia, Francesca; Curcio, Giuseppe; Altavilla, Riccardo; Scrascia, Federica; Giambattistelli, Federica; Quattrocchi, Carlo Cosimo; Bramanti, Placido; Vernieri, Fabrizio; Rossini, Paolo Maria

    2015-01-01

    A relatively new approach to brain function in neuroscience is the "functional connectivity", namely the synchrony in time of activity in anatomically-distinct but functionally-collaborating brain regions. On the other hand, diffusion tensor imaging (DTI) is a recently developed magnetic resonance imaging (MRI)-based technique with the capability to detect brain structural connection with fractional anisotropy (FA) identification. FA decrease has been observed in the corpus callosum of subjects with Alzheimer's disease (AD) and mild cognitive impairment (MCI, an AD prodromal stage). Corpus callosum splenium DTI abnormalities are thought to be associated with functional disconnections among cortical areas. This study aimed to investigate possible correlations between structural damage, measured by MRI-DTI, and functional abnormalities of brain integration, measured by characteristic path length detected in resting state EEG source activity (40 participants: 9 healthy controls, 10 MCI, 10 mild AD, 11 moderate AD). For each subject, undirected and weighted brain network was built to evaluate graph core measures. eLORETA lagged linear connectivity values were used as weight of the edges of the network. Results showed that callosal FA reduction is associated to a loss of brain interhemispheric functional connectivity characterized by increased delta and decreased alpha path length. These findings suggest that "global" (average network shortest path length representing an index of how efficient is the information transfer between two parts of the network) functional measure can reflect the reduction of fiber connecting the two hemispheres as revealed by DTI analysis and also anticipate in time this structural loss. PMID:25613102

  9. Functional Connectivity of EEG Signals Under Laser Stimulation in Migraine.

    PubMed

    de Tommaso, Marina; Trotta, Gabriele; Vecchio, Eleonora; Ricci, Katia; Van de Steen, Frederik; Montemurno, Anna; Lorenzo, Marta; Marinazzo, Daniele; Bellotti, Roberto; Stramaglia, Sebastiano

    2015-01-01

    In previous studies, migraine patients showed abnormalities in pain-related evoked responses, as reduced habituation to repetitive stimulation. In this study, we aimed to apply a novel analysis of EEG bands synchronization and directed dynamical influences under painful stimuli in migraine patients compared to non-migraine healthy volunteers. Thirty-one migraine without aura outpatients (MIGR) were evaluated and compared to 19 controls (CONT). The right hand was stimulated by means of 30 consecutive CO2 laser stimuli. EEG signal was examined by means of Morlet wavelet, synchronization entropy (SE), and Granger causality (GC), and the statistically validated results were mapped on the corresponding scalp locations. The vertex complex of averaged laser-evoked responses (LEPs) showed reduced habituation compared to CONT. In the prestimulus phase, enhanced SE in the 0, 5-30 Hz range was present in MIGR and CONT between the bilateral temporal-parietal and the frontal regions around the midline. Migraine patients showed an anticipation of EEG changes preceding the painful stimulation compared to CONT. In the poststimulus phase, the same cortical areas were more connected in MIGR vs CONT. In both groups of patients and CONT, the habituation index was negatively correlated with the GC scores. A different pattern of cortical activation after painful stimulation was present in migraine. The increase in cortical connections during repetitive painful stimulation may subtend the phenomenon of LEPs reduced habituation. Brain network analysis may give an aid in understanding subtle changes of pain processing under laser stimuli in migraine patients. PMID:26635589

  10. TE-dependent spatial and spectral specificity of functional connectivity.

    PubMed

    Wu, Changwei W; Gu, Hong; Zou, Qihong; Lu, Hanbing; Stein, Elliot A; Yang, Yihong

    2012-02-15

    Previous studies suggest that spontaneous fluctuations in the resting-state fMRI (RS-fMRI) signal may reflect fluctuations in transverse relaxation time (T(2)(*)) rather than spin density (S(0)). However, such S(0) and T(2)(*) features have not been well characterized. In this study, spatial and spectral characteristics of functional connectivity on sensorimotor, default-mode, dorsal attention, and primary visual systems were examined using a multiple gradient-echo sequence at 3T. In the spatial domain, we found broad, local correlations at short echo times (TE ≤ 14 ms) due to dominant S(0) contribution, whereas long-range connections mediated by T(2)(*) became explicit at TEs longer than 22 ms. In the frequency domain, compared with the flat spectrum of S(0), spectral power of the T(2)(*)-weighted signal elevated significantly with increasing TE, particularly in the frequency ranges of 0.008-0.023 Hz and 0.037-0.043 Hz. Using the S(0) spectrum as a reference, we propose two indices to measure spectral signal change (SSC) and spectral contrast-to-noise ratio (SCNR), respectively, for quantifying the RS-fMRI signal. These indices demonstrated TE dependency of connectivity-related fluctuation strength, resembling functional contrasts in activation-based fMRI. These findings further confirm that large-scale functional circuit connectivity based on BOLD contrast may be constrained within specific frequency ranges in every brain network, and the spectral features of S(0) and T(2)(*) could be valuable for interpreting and quantifying RS-fMRI data. PMID:22119650

  11. Interoceptive awareness changes the posterior insula functional connectivity profile.

    PubMed

    Kuehn, Esther; Mueller, Karsten; Lohmann, Gabriele; Schuetz-Bosbach, Simone

    2016-04-01

    Interoceptive awareness describes the ability to consciously perceive inner bodily signals, such as one's own heartbeat. The right anterior insula is assumed to mediate this ability. The role of the posterior insula, particularly posterior-to-anterior insula signal flows is less clear in this respect. We scanned 27 healthy people with either high or low interoceptive awareness using 3T fMRI, while they either monitored their own heartbeats, or external tones, respectively. We used a combination of network centrality and bivariate connectivity analyses to characterize changes in cortical signal flows between the posterior insula and the anterior insula during interoceptive awareness or exteroceptive awareness, respectively. We show that heartbeat monitoring was accompanied by reduced network centrality of the right posterior insula, and decreased functional connectivity strengths between the right posterior insula and the right mid and anterior insula. In addition, decreased signal flows between the right posterior insula and the bilateral anterior cingulate cortices, and the bilateral orbitofrontal cortices were observed during interoceptive awareness. Functional connectivity changes were only shown by people with high interoceptive awareness, and occurred specifically within the low-frequency range (i.e., <0.1 Hz). Both groups did not differ in their functional connectivity profiles during rest. Our results show for the first time that interoceptive awareness changes intra-insula signal flows in the low-frequency range. We speculate that the selective inhibition of slow signal progression along the posterior-to-anterior insula pathway during interoceptive awareness allows the salient and noiseless detection of one's own heartbeat. PMID:25613901

  12. Synthetic neuronal datasets for benchmarking directed functional connectivity metrics

    PubMed Central

    Andrade, Alexandre

    2015-01-01

    Background. Datasets consisting of synthetic neural data generated with quantifiable and controlled parameters are a valuable asset in the process of testing and validating directed functional connectivity metrics. Considering the recent debate in the neuroimaging community concerning the use of these metrics for fMRI data, synthetic datasets that emulate the BOLD signal dynamics have played a central role by supporting claims that argue in favor or against certain choices. Generative models often used in studies that simulate neuronal activity, with the aim of gaining insight into specific brain regions and functions, have different requirements from the generative models for benchmarking datasets. Even though the latter must be realistic, there is a tradeoff between realism and computational demand that needs to be contemplated and simulations that efficiently mimic the real behavior of single neurons or neuronal populations are preferred, instead of more cumbersome and marginally precise ones. Methods. This work explores how simple generative models are able to produce neuronal datasets, for benchmarking purposes, that reflect the simulated effective connectivity and, how these can be used to obtain synthetic recordings of EEG and fMRI BOLD signals. The generative models covered here are AR processes, neural mass models consisting of linear and nonlinear stochastic differential equations and populations with thousands of spiking units. Forward models for EEG consist in the simple three-shell head model while the fMRI BOLD signal is modeled with the Balloon-Windkessel model or by convolution with a hemodynamic response function. Results. The simulated datasets are tested for causality with the original spectral formulation for Granger causality. Modeled effective connectivity can be detected in the generated data for varying connection strengths and interaction delays. Discussion. All generative models produce synthetic neuronal data with detectable causal

  13. Hippocampal functional connectivity and episodic memory in early childhood.

    PubMed

    Riggins, Tracy; Geng, Fengji; Blankenship, Sarah L; Redcay, Elizabeth

    2016-06-01

    Episodic memory relies on a distributed network of brain regions, with the hippocampus playing a critical and irreplaceable role. Few studies have examined how changes in this network contribute to episodic memory development early in life. The present addressed this gap by examining relations between hippocampal functional connectivity and episodic memory in 4- and 6-year-old children (n=40). Results revealed similar hippocampal functional connectivity between age groups, which included lateral temporal regions, precuneus, and multiple parietal and prefrontal regions, and functional specialization along the longitudinal axis. Despite these similarities, developmental differences were also observed. Specifically, 3 (of 4) regions within the hippocampal memory network were positively associated with episodic memory in 6-year-old children, but negatively associated with episodic memory in 4-year-old children. In contrast, all 3 regions outside the hippocampal memory network were negatively associated with episodic memory in older children, but positively associated with episodic memory in younger children. These interactions are interpreted within an interactive specialization framework and suggest the hippocampus becomes functionally integrated with cortical regions that are part of the hippocampal memory network in adults and functionally segregated from regions unrelated to memory in adults, both of which are associated with age-related improvements in episodic memory ability. PMID:26900967

  14. Resting state functional connectivity in the human spinal cord

    PubMed Central

    Barry, Robert L; Smith, Seth A; Dula, Adrienne N; Gore, John C

    2014-01-01

    Functional magnetic resonance imaging using blood oxygenation level dependent (BOLD) contrast is well established as one of the most powerful methods for mapping human brain function. Numerous studies have measured how low-frequency BOLD signal fluctuations from the brain are correlated between voxels in a resting state, and have exploited these signals to infer functional connectivity within specific neural circuits. However, to date there have been no previous substantiated reports of resting state correlations in the 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. Our results demonstrate that low-frequency BOLD fluctuations are inherent in the spinal cord as well as the brain, and by analogy to cortical circuits, we hypothesize that these correlations may offer insight into the execution and maintenance of sensory and motor functions both locally and within the cerebrum. DOI: http://dx.doi.org/10.7554/eLife.02812.001 PMID:25097248

  15. 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

  16. Abnormal hepatic function and splenomegaly on the newly diagnosed acute leukemia patients.

    PubMed

    Sharma Poudel, B; Karki, L

    2007-01-01

    To evaluate the liver function, splenomegaly and related factors in the newly diagnosed acute leukemia patients. One hundred of fifty eight acute leukemia patients admitted in our hospital from March 2003 to April 2006 were studied. The related factors such as peripheral WBC count, bone marrow blasts, peripheral blasts, sex, age, AML, ALL affecting the liver function and splenomegaly were evaluated. Sixty two (39.24%) patients presented with splenomegaly. Twelve (7.59%) patients presented with hepatomegaly. Serum ALT was elevated in 54 (34.17%) patients. Similarly, serum AST, GGT, ALP, and Direct bilirubin were elevated in 26 (16.45%), 32 (20.25%), 20 (12.65%), and 22 (13.92%) patients, respectively. Low serum albumin was found in 40 (25.31%) patients. PT was prolonged in 62 (39.24%) patients. Statistical study shows that there is a relation between high WBC counts and elevated serum ALT (P<0.05) and high WBC counts and splenomegaly (P<0.05). Acute leukemia patients with leukocytosis are more prone to develop abnormal liver function and splenomegaly. PMID:18340367

  17. White matter microstructure abnormalities and executive function in adolescents with prenatal cocaine exposure

    PubMed Central

    Lebel, Catherine; Warner, Tamara; Colby, John; Soderberg, Lindsay; Roussotte, Florence; Behnke, Marylou; Davis Eyler, Fonda; Sowell, Elizabeth R.

    2013-01-01

    Children with prenatal exposure to cocaine are at higher risk for negative behavioral function and attention difficulties, and have demonstrated brain diffusion abnormalities in frontal white matter regions. However, brain regions beyond frontal and callosal areas have not been investigated using diffusion tensor imaging (DTI). DTI data were collected on 42 youth aged 14–16 years; subjects were divided into three groups based on detailed exposure histories: those with prenatal exposure to cocaine but not alcohol (PCE, n=12), prenatal exposure to cocaine and alcohol (CAE, n=17), and controls (n=13). Tractography was performed and along-tract diffusion parameters were examined for group differences and correlations with executive function measures. In the right arcuate fasciculus and cingulum, the CAE group had higher fractional anisotropy (FA) and/or lower mean diffusivity (MD) than the other two groups. The PCE group demonstrated lower FA in the right arcuate and higher MD in the splenium of the corpus callosum than controls. Diffusion parameters in tracts with group differences correlated with measures of executive function. In conclusion, these diffusion differences in adolescents with prenatal cocaine exposure suggest localized, long-term structural brain alterations that may underlie attention and response inhibition difficulties. PMID:23769420

  18. Impact of language on functional connectivity for audiovisual speech integration.

    PubMed

    Shinozaki, Jun; Hiroe, Nobuo; Sato, Masa-Aki; Nagamine, Takashi; Sekiyama, Kaoru

    2016-01-01

    Visual information about lip and facial movements plays a role in audiovisual (AV) speech perception. Although this has been widely confirmed, previous behavioural studies have shown interlanguage differences, that is, native Japanese speakers do not integrate auditory and visual speech as closely as native English speakers. To elucidate the neural basis of such interlanguage differences, 22 native English speakers and 24 native Japanese speakers were examined in behavioural or functional Magnetic Resonance Imaging (fMRI) experiments while mono-syllabic speech was presented under AV, auditory-only, or visual-only conditions for speech identification. Behavioural results indicated that the English speakers identified visual speech more quickly than the Japanese speakers, and that the temporal facilitation effect of congruent visual speech was significant in the English speakers but not in the Japanese speakers. Using fMRI data, we examined the functional connectivity among brain regions important for auditory-visual interplay. The results indicated that the English speakers had significantly stronger connectivity between the visual motion area MT and the Heschl's gyrus compared with the Japanese speakers, which may subserve lower-level visual influences on speech perception in English speakers in a multisensory environment. These results suggested that linguistic experience strongly affects neural connectivity involved in AV speech integration. PMID:27510407

  19. Impact of language on functional connectivity for audiovisual speech integration

    PubMed Central

    Shinozaki, Jun; Hiroe, Nobuo; Sato, Masa-aki; Nagamine, Takashi; Sekiyama, Kaoru

    2016-01-01

    Visual information about lip and facial movements plays a role in audiovisual (AV) speech perception. Although this has been widely confirmed, previous behavioural studies have shown interlanguage differences, that is, native Japanese speakers do not integrate auditory and visual speech as closely as native English speakers. To elucidate the neural basis of such interlanguage differences, 22 native English speakers and 24 native Japanese speakers were examined in behavioural or functional Magnetic Resonance Imaging (fMRI) experiments while mono-syllabic speech was presented under AV, auditory-only, or visual-only conditions for speech identification. Behavioural results indicated that the English speakers identified visual speech more quickly than the Japanese speakers, and that the temporal facilitation effect of congruent visual speech was significant in the English speakers but not in the Japanese speakers. Using fMRI data, we examined the functional connectivity among brain regions important for auditory-visual interplay. The results indicated that the English speakers had significantly stronger connectivity between the visual motion area MT and the Heschl’s gyrus compared with the Japanese speakers, which may subserve lower-level visual influences on speech perception in English speakers in a multisensory environment. These results suggested that linguistic experience strongly affects neural connectivity involved in AV speech integration. PMID:27510407

  20. Predicting clinical responses in major depression using intrinsic functional connectivity.

    PubMed

    Qin, Jian; Shen, Hui; Zeng, Ling-Li; Jiang, Weixiong; Liu, Li; Hu, Dewen

    2015-08-19

    There has been increasing interest in multivariate pattern analysis (MVPA) as a means of distinguishing psychiatric patients from healthy controls using brain imaging. However, it remains unclear whether MVPA methods can accurately estimate the medication status of psychiatric patients. This study aims to develop an MVPA approach to accurately predict the antidepressant medication status of individuals with major depression on the basis of whole-brain resting-state functional connectivity MRI (rs-fcMRI). We investigated data from rs-fcMRI of 24 medication-naive depressed patients, 16 out of whom subsequently underwent antidepressant treatment and achieved clinical recovery, and 29 demographically similar controls. By training a linear support vector machine classifier and combining it with principal component analysis, the medication-naive patients were identified from the healthy controls with 100% accuracy. In addition, we found reliable correlations between MVPA prediction scores and clinical symptom severity. Moreover, the most discriminative functional connections were located within or across the cerebellum and default mode, affective, and sensorimotor networks, indicating that these networks may play important roles in major depression. Most importantly, only ∼30% of these discriminative connections were normalized in clinically recovered patients after antidepressant treatment. The current study may not only show the feasibility of estimating medication status by MVPA of whole-brain rs-fcMRI data in major depression but also shed new light on the pathological mechanism of this disorder. PMID:26164454

  1. 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. PMID:25533270

  2. Neurobiological Changes of Schizotypy: Evidence From Both Volume-Based Morphometric Analysis and Resting-State Functional Connectivity

    PubMed Central

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

    2015-01-01

    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. PMID:25533270

  3. Cluster pair correlation function of simple fluids: energetic connectivity criteria.

    PubMed

    Pugnaloni, Luis A; Zarragoicoechea, Guillermo J; Vericat, Fernando

    2006-11-21

    We consider the clustering of Lennard-Jones particles by using an energetic connectivity criterion proposed long ago by Hill [J. Chem. Phys. 32, 617 (1955)] for the bond between pairs of particles. The criterion establishes that two particles are bonded (directly connected) if their relative kinetic energy is less than minus their relative potential energy. Thus, in general, it depends on the direction as well as on the magnitude of the velocities and positions of the particles. An integral equation for the pair connectedness function, proposed by two of the authors [Phys. Rev. E 61, R6067 (2000)], is solved for this criterion and the results are compared with those obtained from molecular dynamics simulations and from a connectedness Percus-Yevick-type integral equation for a velocity-averaged version of Hill's energetic criterion. PMID:17129128

  4. Global Functional Connectivity Differences between Sleep-Like States in Urethane Anesthetized Rats Measured by fMRI

    PubMed Central

    Paasonen, Jaakko; Shatillo, Artem; Lipponen, Arto; Salo, Raimo; Aliev, Rubin; Tanila, Heikki; Gröhn, Olli

    2016-01-01

    Sleep is essential for nervous system functioning and sleep disorders are associated with several neurodegenerative diseases. However, the macroscale connectivity changes in brain networking during different sleep states are poorly understood. One of the hindering factors is the difficulty to combine functional connectivity investigation methods with spontaneously sleeping animals, which prevents the use of numerous preclinical animal models. Recent studies, however, have implicated that urethane anesthesia can uniquely induce different sleep-like brain states, resembling rapid eye movement (REM) and non-REM (NREM) sleep, in rodents. Therefore, the aim of this study was to assess changes in global connectivity and topology between sleep-like states in urethane anesthetized rats, using blood oxygenation level dependent (BOLD) functional magnetic resonance imaging. We detected significant changes in corticocortical (increased in NREM-like state) and corticothalamic connectivity (increased in REM-like state). Additionally, in graph analysis the modularity, the measure of functional integration in the brain, was higher in NREM-like state than in REM-like state, indicating a decrease in arousal level, as in normal sleep. The fMRI findings were supported by the supplementary electrophysiological measurements. Taken together, our results show that macroscale functional connectivity changes between sleep states can be detected robustly with resting-state fMRI in urethane anesthetized rats. Our findings pave the way for studies in animal models of neurodegenerative diseases where sleep abnormalities are often one of the first markers for the disorder development. PMID:27168145

  5. [Emotion Disorders and Abnormal Perspiration].

    PubMed

    Umeda, Satoshi

    2016-08-01

    This article reviewed the relationship between emotional disorders and abnormal perspiration. First, I focused on local brain areas related to emotional processing, and summarized the functions of the emotional network involving those local areas. Functional disorders followed by the damage in the amygdala, orbitofrontal cortex, and insular cortex were reviewed, including related abnormal perspiration. I then addressed the mechanisms of how autonomic disorders influence emotional processing. Finally, possible future directions for integrated understanding of the connection between neural activities and bodily reactions were discussed. PMID:27503817

  6. Functional connectivity of negative emotional processing in adolescent depression

    PubMed Central

    Ho, Tiffany C.; Yang, Guang; Wu, Jing; Cassey, Pete; Brown, Scott D.; Hoang, Napoleon; Chan, Melanie; Connolly, Colm G.; Blom, Eva Henje; Duncan, Larissa G.; Chesney, Margaret A.; Paulus, Martin P.; Max, Jeffrey E.; Patel, Ronak; Simmons, Alan N.; Yang, Tony T.

    2013-01-01

    BACKGROUND The subgenual anterior cingulate cortex (sgACC) and its connected circuitry have been heavily implicated in emotional functioning in adolescent-onset major depressive disorder (MDD). While several recent studies have examined sgACC functional connectivity (FC) in depressed youth at rest, no studies to date have investigated sgACC FC in adolescent depression during negative emotional processing. METHODS Nineteen medication-naïve adolescents with MDD and 19 matched healthy controls (HCL) performed an implicit fear facial affect recognition task during functional magnetic resonance imaging (fMRI). We defined seeds in bilateral sgACC and assessed FC using the psychophysiological interaction method. We also applied cognitive behavioral modeling to estimate group differences in perceptual sensitivity in this task. Finally, we correlated connectivity strength with clinical data and perceptual sensitivity. RESULTS Depressed adolescents showed increased sgACC-amygdala FC and decreased sgACC-fusiform gyrus, sgACC-precuneus, sgACC-insula, and sgACC-middle frontal gyrus FC compared to HCL (p<0.05, corrected). Among the MDD, sgACC-precuneus FC negatively correlated with depression severity (p<0.05, corrected). Lastly, MDD adolescents exhibited poorer perceptual sensitivity in the task than HCL, and individual differences in perceptual sensitivity significantly correlated with sgACC FC and depression scores (p<0.05, corrected). LIMITATIONS Subjects were clinically homogenous, possibly limiting generalizability of the findings. CONCLUSIONS Adolescent depression is associated with biased processing of negative stimuli that may be driven by sgACC dysregulation and may possibly lead to an imbalance among intrinsic functional brain networks. This work also establishes the use of combining neuroimaging and cognitive behavioral modeling methods to investigate cognitive and neural differences between psychiatric and healthy populations. PMID:24268546

  7. Functional Connectivity of the Caudal Anterior Cingulate Cortex Is Decreased in Autism

    PubMed Central

    Zhou, Yuanyue; Shi, Lijuan; Cui, Xilong; Wang, Suhong; Luo, Xuerong

    2016-01-01

    The anterior cingulate cortex (ACC) is frequently reported to have functionally distinct sub-regions that play key roles in different intrinsic networks. However, the contribution of the ACC, which is connected to several cortical areas and the limbic system, to autism is not clearly understood, although it may be involved in dysfunctions across several distinct but related functional domains. By comparing resting-state fMRI data from persons with autism and healthy controls, we sought to identify the abnormalities in the functional connectivity (FC) of ACC sub-regions in autism. The analyses found autism-related reductions in FC between the left caudal ACC and the right rolandic operculum, insula, postcentral gyrus, superior temporal gyrus, and the middle temporal gyrus. The FC (z-scores) between the left caudal ACC and the right insula was negatively correlated with the Stereotyped Behaviors and Restricted Interests scores of the autism group. These findings suggest that the caudal ACC is recruited selectively in the pathomechanism of autism. PMID:26985666

  8. Diastolic abnormalities in systemic sclerosis: evidence for associated defective cardiac functional reserve.

    PubMed Central

    Valentini, G; Vitale, D F; Giunta, A; Maione, S; Gerundo, G; Arnese, M; Tirri, E; Pelaggi, N; Giacummo, A; Tirri, G; Condorelli, M

    1996-01-01

    OBJECTIVE: To investigate the pattern of diastolic abnormalities in patients with systemic sclerosis (SSc) and the relationship between impaired ventricular filling and systolic function. METHODS: Twenty four patients with SSc underwent M-mode and two dimensional echocardiography using echo-Doppler and gated blood pool cardiac angiography, both at rest and after exercise. RESULTS: An impaired diastolic relaxation of the left ventricle was detected in 10 of the 24 patients with SSc. Left ventricular ejection fraction at rest in these 10 patients with impaired ventricular filling did not differ from that in the remaining 14 patients, but eight of the 10 failed to increase their ejection fraction during exercise, compared with two of the 14 with normal ventricular filling (p = 0.003). CONCLUSION: Impaired relaxation of the left ventricle is a recently described feature of scleroderma heart disease. Diastolic dysfunction in SSc could depend on myocardial fibrosis or myocardial ischaemia, or both. It was found to be associated with a defective cardiac functional reserve. However, its prognostic significance remains to be clarified. PMID:8774164

  9. Kinesin family 17 (osmotic avoidance abnormal-3) is dispensable for photoreceptor morphology and function.

    PubMed

    Jiang, Li; Tam, Beatrice M; Ying, Guoxing; Wu, Sen; Hauswirth, William W; Frederick, Jeanne M; Moritz, Orson L; Baehr, Wolfgang

    2015-12-01

    In Caenorhabditis elegans, homodimeric [kinesin family (KIF) 17, osmotic avoidance abnormal-3 (OSM-3)] and heterotrimeric (KIF3) kinesin-2 motors are required to establish sensory cilia by intraflagellar transport (IFT) where KIF3 and KIF17 cooperate to build the axoneme core and KIF17 builds the distal segments. However, the function of KIF17 in vertebrates is unresolved. We expressed full-length and motorless KIF17 constructs in mouse rod photoreceptors using adeno-associated virus in Xenopus laevis rod photoreceptors using a transgene and in ciliated IMCD3 cells. We found that tagged KIF17 localized along the rod outer segment axoneme when expressed in mouse and X. laevis photoreceptors, whereas KIF3A was restricted to the proximal axoneme. Motorless KIF3A and KIF17 mutants caused photoreceptor degeneration, likely through dominant negative effects on IFT. KIF17 mutant lacking the motor domain translocated to nuclei after exposure of a C-terminal nuclear localization signal. Germ-line deletion of Kif17 in mouse did not affect photoreceptor function. A rod-specific Kif3/Kif17 double knockout mouse demonstrated that KIF17 and KIF3 do not act synergistically and did not prevent rhodopsin trafficking to rod outer segments. In summary, the nematode model of KIF3/KIF17 cooperation apparently does not apply to mouse photoreceptors in which the photosensory cilium is built exclusively by KIF3. PMID:26229057

  10. Altered resting-state EEG source functional connectivity in schizophrenia: the effect of illness duration

    PubMed Central

    Di Lorenzo, Giorgio; Daverio, Andrea; Ferrentino, Fabiola; Santarnecchi, Emiliano; Ciabattini, Fabio; Monaco, Leonardo; Lisi, Giulia; Barone, Ylenia; Di Lorenzo, Cherubino; Niolu, Cinzia; Seri, Stefano; Siracusano, Alberto

    2015-01-01

    Despite the increasing body of evidence supporting the hypothesis of schizophrenia as a disconnection syndrome, studies of resting-state EEG Source Functional Connectivity (EEG-SFC) in people affected by schizophrenia are sparse. The aim of the present study was to investigate resting-state EEG-SFC in 77 stable, medicated patients with schizophrenia (SCZ) compared to 78 healthy volunteers (HV). In order to study the effect of illness duration, SCZ were divided in those with a short duration of disease (SDD; n = 25) and those with a long duration of disease (LDD; n = 52). Resting-state EEG recordings in eyes closed condition were analyzed and lagged phase synchronization (LPS) indices were calculated for each ROI pair in the source-space EEG data. In delta and theta bands, SCZ had greater EEG-SFC than HV; a higher theta band connectivity in frontal regions was observed in LDD compared with SDD. In the alpha band, SCZ showed lower frontal EEG-SFC compared with HV whereas no differences were found between LDD and SDD. In the beta1 band, SCZ had greater EEG-SFC compared with HVs and in the beta2 band, LDD presented lower frontal and parieto-temporal EEG-SFC compared with HV. In the gamma band, SDD had greater connectivity values compared with LDD and HV. This study suggests that resting state brain network connectivity is abnormally organized in schizophrenia, with different patterns for the different EEG frequency components and that EEG can be a powerful tool to further elucidate the complexity of such disordered connectivity. PMID:25999835

  11. Abnormal functional specialization within medial prefrontal cortex in high-functioning autism: a multi-voxel similarity analysis

    PubMed Central

    Meuwese, Julia D.I.; Towgood, Karren J.; Frith, Christopher D.; Burgess, Paul W.

    2009-01-01

    Multi-voxel pattern analyses have proved successful in ‘decoding’ mental states from fMRI data, but have not been used to examine brain differences associated with atypical populations. We investigated a group of 16 (14 males) high-functioning participants with autism spectrum disorder (ASD) and 16 non-autistic control participants (12 males) performing two tasks (spatial/verbal) previously shown to activate medial rostral prefrontal cortex (mrPFC). Each task manipulated: (i) attention towards perceptual versus self-generated information and (ii) reflection on another person's mental state (‘mentalizing'versus ‘non-mentalizing’) in a 2 × 2 design. Behavioral performance and group-level fMRI results were similar between groups. However, multi-voxel similarity analyses revealed strong differences. In control participants, the spatial distribution of activity generalized significantly between task contexts (spatial/verbal) when examining the same function (attention/mentalizing) but not when comparing different functions. This pattern was disrupted in the ASD group, indicating abnormal functional specialization within mrPFC, and demonstrating the applicability of multi-voxel pattern analysis to investigations of atypical populations. PMID:19174370

  12. Abnormal functional specialization within medial prefrontal cortex in high-functioning autism: a multi-voxel similarity analysis.

    PubMed

    Gilbert, Sam J; Meuwese, Julia D I; Towgood, Karren J; Frith, Christopher D; Burgess, Paul W

    2009-04-01

    Multi-voxel pattern analyses have proved successful in 'decoding' mental states from fMRI data, but have not been used to examine brain differences associated with atypical populations. We investigated a group of 16 (14 males) high-functioning participants with autism spectrum disorder (ASD) and 16 non-autistic control participants (12 males) performing two tasks (spatial/verbal) previously shown to activate medial rostral prefrontal cortex (mrPFC). Each task manipulated: (i) attention towards perceptual versus self-generated information and (ii) reflection on another person's mental state ('mentalizing'versus 'non-mentalizing') in a 2 x 2 design. Behavioral performance and group-level fMRI results were similar between groups. However, multi-voxel similarity analyses revealed strong differences. In control participants, the spatial distribution of activity generalized significantly between task contexts (spatial/verbal) when examining the same function (attention/mentalizing) but not when comparing different functions. This pattern was disrupted in the ASD group, indicating abnormal functional specialization within mrPFC, and demonstrating the applicability of multi-voxel pattern analysis to investigations of atypical populations. PMID:19174370

  13. Characteristics of Brains in Autism Spectrum Disorder: Structure, Function and Connectivity across the Lifespan

    PubMed Central

    Ha, Sungji; Sohn, In-Jung; Kim, Namwook; Sim, Hyeon Jeong

    2015-01-01

    Autism spectrum disorder (ASD) is a highly prevalent neurodevelopmental disorder characterized by impaired social communication and restricted and repetitive behaviors (RRBs). Over the past decade, neuroimaging studies have provided considerable insights underlying neurobiological mechanisms of ASD. In this review, we introduce recent findings from brain imaging studies to characterize the brains of ASD across the human lifespan. Results of structural Magnetic Resonance Imaging (MRI) studies dealing with total brain volume, regional brain structure and cortical area are summarized. Using task-based functional MRI (fMRI), many studies have shown dysfunctional activation in critical areas of social communication and RRBs. We also describe several data to show abnormal connectivity in the ASD brains. Finally, we suggest the possible strategies to study ASD brains in the future. PMID:26713076

  14. Cerebellar Clustering and Functional Connectivity During Pain Processing.

    PubMed

    Diano, M; D'Agata, F; Cauda, F; Costa, T; Geda, E; Sacco, K; Duca, S; Torta, D M; Geminiani, G C

    2016-06-01

    The cerebellum has been traditionally considered a sensory-motor structure, but more recently has been related to other cognitive and affective functions. Previous research and meta-analytic studies suggested that it could be involved in pain processing. Our aim was to distinguish the functional networks subserved by the cerebellum during pain processing. We used functional magnetic resonance imaging (fMRI) on 12 subjects undergoing mechanical pain stimulation and resting state acquisition. For the analysis of data, we used fuzzy c-mean to cluster cerebellar activity of each participant during nociception. The mean time courses of the clusters were used as regressors in a general linear model (GLM) analysis to explore brain functional connectivity (FC) of the cerebellar clusters. We compared our results with the resting state FC of the same cluster and explored with meta-analysis the behavior profile of the FC networks. We identified three significant clusters: cluster V, involving the culmen and quadrangular lobules (vermis IV-V, hemispheres IV-V-VI); cluster VI, involving the posterior quadrangular lobule and superior semilunar lobule (hemisphere VI, crus 1, crus 2), and cluster VII, involving the inferior semilunar lobule (VIIb, crus1, crus 2). Cluster V was more connected during pain with sensory-motor areas, cluster VI with cognitive areas, and cluster VII with emotional areas. Our results indicate that during the application of mechanical punctate stimuli, the cerebellum is not only involved in sensory functions but also with areas typically associated with cognitive and affective functions. Cerebellum seems to be involved in various aspects of nociception, reflecting the multidimensionality of pain perception. PMID:26202672

  15. Altered Default Network Resting State Functional Connectivity in Patients with a First Episode of Psychosis

    PubMed Central

    Alonso-Solís, Anna; Corripio, Iluminada; de Castro-Manglano, Pilar; Duran-Sindreu, Santiago; Garcia-Garcia, Manuel; Proal, Erika; Nuñez-Marín, Fidel; Soutullo, Cesar; Alvarez, Enric; Gómez-Ansón, Beatriz; Kelly, Clare; Castellanos, F. Xavier

    2012-01-01

    Background Default network (DN) abnormalities have been identified in patients with chronic schizophrenia using “resting state” functional magnetic resonance imaging (R-fMRI). Here, we examined the integrity of the DN in patients experiencing their first episode of psychosis (FEP) compared with sex- and age-matched healthy controls. Methods We collected R-fMRI data from 19 FEP patients (mean age 24.9±4.8 yrs, 14 males) and 19 healthy controls (26.1±4.8 yrs, 14 males) at 3 Tesla. Following standard preprocessing, we examined the functional connectivity (FC) of two DN subsystems and the two DN hubs (P<0.0045, corrected). Results Patients with FEP exhibited abnormal FC that appeared largely restricted to the dorsomedial prefrontal cortex (dMPFC) DN subsystem. Relative to controls, FEP patients exhibited weaker positive FC between dMPFC and posterior cingulate cortex (PCC) and precuneus, extending laterally through the parietal lobe to the posterior angular gyrus. Patients with FEP exhibited weaker negative FC between the lateral temporal cortex and the intracalcarine cortex, bilaterally. The PCC and temporo-parietal junction also exhibited weaker negative FC with the right fusiform gyrus extending to the lingual gyrus and lateral occipital cortex, in FEP patients, compared to controls. By contrast, patients with FEP showed stronger negative FC between the temporal pole and medial motor cortex, anterior precuneus and posterior mid-cingulate cortex. Conclusions Abnormalities in the dMPFC DN subsystem in patients with a FEP suggest that FC patterns are altered even in the early stages of psychosis. PMID:22633527

  16. Functional Connectivity during Modulation of Tinnitus with Orofacial Maneuvers

    PubMed Central

    Lee, Megan H.; Solowski, Nancy; Wineland, Andre; Okuyemi, Oluwafunmilola; Nicklaus, Joyce; Kallogjeri, Dorina; Piccirillo, Jay F.; Burton, Harold

    2014-01-01

    Objective To determine changes in cortical neural networks as defined by resting-state functional connectivity magnetic resonance imaging during voluntary modulation of tinnitus with orofacial maneuvers. Study Design Cross-sectional study. Setting Academic medical center. Subjects and Methods Participants were scanned during the maneuver and also at baseline to serve as their own control. The authors chose, a priori, 58 seed regions to evaluate previously described cortical neural networks by computing temporal correlations between all seed region pairs. Seed regions whose correlations significantly differed between rest and maneuver (P < .05, uncorrected) entered into a second-stage analysis of computing the correlation coefficient between the seed region and time courses in each of the remaining brain voxels. A threshold-free cluster enhancement permutation analysis evaluated the distribution of these correlation coefficients after transformation to Fisher z scores and registration to a surface-based reconstruction using Freesurfer. Results The median age for the 16 subjects was 54 years (range, 27–72 years), and all had subjective, unilateral or bilateral, nonpulsatile tinnitus for 6 months or longer. In 9 subjects who could voluntarily increase the loudness of their tinnitus, there were no significant differences in functional connectivity in any cortical networks. A separate analysis evaluated results from 3 patients who decreased the loudness of their tinnitus. Four subjects were excluded because of excessive motion in the scanner. Conclusion The absence of significant differences in functional connectivity due to voluntary orofacial maneuvers that increased tinnitus loudness failed to confirm prior reports of altered cerebral blood flows during somatomotor behaviors. PMID:22675003

  17. Intrinsic functional connectivity of periaqueductal gray subregions in humans.

    PubMed

    Coulombe, Marie-Andree; Erpelding, Nathalie; Kucyi, Aaron; Davis, Karen Deborah

    2016-04-01

    The periaqueductal gray matter (PAG) is a key brain region of the descending pain modulation pathway. It is also involved in cardiovascular functions, anxiety, and fear; however, little is known about PAG subdivisions in humans. The aims of this study were to use resting-state fMRI-based functional connectivity (FC) to parcellate the human PAG and to determine FC of its subregions. To do this, we acquired resting-state fMRI scans from 79 healthy subjects and (1) used a data-driven method to parcellate the PAG, (2) used predefined seeds in PAG subregions to evaluate PAG FC to the whole brain, and (3) examined sex differences in PAG FC. We found that clustering of the left and right PAG yielded similar patterns of caudal, middle, and rostral subdivisions in the coronal plane, and dorsal and ventral subdivisions in the sagittal plane. FC analysis of predefined subregions revealed that the ventolateral(VL)-PAG was supfunctionally connected to brain regions associated with descending pain modulation (anterior cingulate cortex (ACC), upper pons/medulla), whereas the lateral (L) and dorsolateral (DL) subregions were connected with brain regions implicated in executive functions (prefrontal cortex, striatum, hippocampus). We also found sex differences in FC including areas implicated in pain, salience, and analgesia including the ACC and the insula in women, and the MCC, parahippocampal gyrus, and the temporal pole in men. The organization of the human PAG thus provides a framework to understand the circuitry underlying the broad range of responses to pain and its modulation in men and women. Hum Brain Mapp 37:1514-1530, 2016. © 2016 Wiley Periodicals, Inc. PMID:26821847

  18. Enhanced functional connectivity involving the ventromedial hypothalamus following methamphetamine exposure

    PubMed Central

    Zuloaga, Damian G.; Iancu, Ovidiu D.; Weber, Sydney; Etzel, Desiree; Marzulla, Tessa; Stewart, Blair; Allen, Charles N.; Raber, Jacob

    2015-01-01

    Methamphetamine (MA) consumption causes disruption of many biological rhythms including the sleep-wake cycle. This circadian effect is seen shortly following MA exposure and later in life following developmental MA exposure. MA phase shifts, entrains the circadian clock and can also alter the entraining effect of light by currently unknown mechanisms. We analyzed and compared immunoreactivity of the immediate early gene c-Fos, a marker of neuronal activity, to assess neuronal activation 2 h following MA exposure in the light and dark phases. We used network analyses of correlation patterns derived from global brain immunoreactivity patterns of c-Fos, to infer functional connectivity between brain regions. There were five distinct patterns of neuronal activation. In several brain areas, neuronal activation following exposure to MA was stronger in the light than the dark phase, highlighting the importance of considering circadian periods of increased effects of MA in defining experimental conditions and understanding the mechanisms underlying detrimental effects of MA exposure to brain function. Functional connectivity between the ventromedial hypothalamus (VMH) and other brain areas, including the paraventricular nucleus of the hypothalamus and basolateral and medial amygdala, was enhanced following MA exposure, suggesting a role for the VMH in the effects of MA on the brain. PMID:26441501

  19. Prenatal Drug Exposure Affects Neonatal Brain Functional Connectivity

    PubMed Central

    Salzwedel, Andrew P.; Vachet, Clement; Gerig, Guido; Lin, Weili

    2015-01-01

    Prenatal drug exposure, particularly prenatal cocaine exposure (PCE), incurs great public and scientific interest because of its associated neurodevelopmental consequences. However, the neural underpinnings of PCE remain essentially uncharted, and existing studies in school-aged children and adolescents are confounded greatly by postnatal environmental factors. In this study, leveraging a large neonate sample (N = 152) and non-invasive resting-state functional magnetic resonance imaging, we compared human infants with PCE comorbid with other drugs (such as nicotine, alcohol, marijuana, and antidepressant) with infants with similar non-cocaine poly drug exposure and drug-free controls. We aimed to characterize the neural correlates of PCE based on functional connectivity measurements of the amygdala and insula at the earliest stage of development. Our results revealed common drug exposure-related connectivity disruptions within the amygdala–frontal, insula–frontal, and insula–sensorimotor circuits. Moreover, a cocaine-specific effect was detected within a subregion of the amygdala–frontal network. This pathway is thought to play an important role in arousal regulation, which has been shown to be irregular in PCE infants and adolescents. These novel results provide the earliest human-based functional delineations of the neural-developmental consequences of prenatal drug exposure and thus open a new window for the advancement of effective strategies aimed at early risk identification and intervention. PMID:25855194

  20. Prenatal drug exposure affects neonatal brain functional connectivity.

    PubMed

    Salzwedel, Andrew P; Grewen, Karen M; Vachet, Clement; Gerig, Guido; Lin, Weili; Gao, Wei

    2015-04-01

    Prenatal drug exposure, particularly prenatal cocaine exposure (PCE), incurs great public and scientific interest because of its associated neurodevelopmental consequences. However, the neural underpinnings of PCE remain essentially uncharted, and existing studies in school-aged children and adolescents are confounded greatly by postnatal environmental factors. In this study, leveraging a large neonate sample (N = 152) and non-invasive resting-state functional magnetic resonance imaging, we compared human infants with PCE comorbid with other drugs (such as nicotine, alcohol, marijuana, and antidepressant) with infants with similar non-cocaine poly drug exposure and drug-free controls. We aimed to characterize the neural correlates of PCE based on functional connectivity measurements of the amygdala and insula at the earliest stage of development. Our results revealed common drug exposure-related connectivity disruptions within the amygdala-frontal, insula-frontal, and insula-sensorimotor circuits. Moreover, a cocaine-specific effect was detected within a subregion of the amygdala-frontal network. This pathway is thought to play an important role in arousal regulation, which has been shown to be irregular in PCE infants and adolescents. These novel results provide the earliest human-based functional delineations of the neural-developmental consequences of prenatal drug exposure and thus open a new window for the advancement of effective strategies aimed at early risk identification and intervention. PMID:25855194

  1. Functional hierarchy underlies preferential connectivity disturbances in schizophrenia.

    PubMed

    Yang, Genevieve J; Murray, John D; Wang, Xiao-Jing; Glahn, David C; Pearlson, Godfrey D; Repovs, Grega; Krystal, John H; Anticevic, Alan

    2016-01-12

    Schizophrenia may involve an elevated excitation/inhibition (E/I) ratio in cortical microcircuits. It remains unknown how this regulatory disturbance maps onto neuroimaging findings. To address this issue, we implemented E/I perturbations within a neural model of large-scale functional connectivity, which predicted hyperconnectivity following E/I elevation. To test predictions, we examined resting-state functional MRI in 161 schizophrenia patients and 164 healthy subjects. As predicted, patients exhibited elevated functional connectivity that correlated with symptom levels, and was most prominent in association cortices, such as the fronto-parietal control network. This pattern was absent in patients with bipolar disorder (n = 73). To account for the pattern observed in schizophrenia, we integrated neurobiologically plausible, hierarchical differences in association vs. sensory recurrent neuronal dynamics into our model. This in silico architecture revealed preferential vulnerability of association networks to E/I imbalance, which we verified empirically. Reported effects implicate widespread microcircuit E/I imbalance as a parsimonious mechanism for emergent inhomogeneous dysconnectivity in schizophrenia. PMID:26699491

  2. The Selectivity and Functional Connectivity of the Anterior Temporal Lobes

    PubMed Central

    Reddish, Mark; Bellgowan, Patrick S. F.; Martin, Alex

    2010-01-01

    One influential account asserts that the anterior temporal lobe (ATL) is a domain-general hub for semantic memory. Other evidence indicates it is part of a domain-specific social cognition system. Arbitrating these accounts using functional magnetic resonance imaging has previously been difficult because of magnetic susceptibility artifacts in the region. The present study used parameters optimized for imaging the ATL, and had subjects encode facts about unfamiliar people, buildings, and hammers. Using both conjunction and region of interest analyses, person-selective responses were observed in both the left and right ATL. Neither building-selective, hammer-selective nor domain-general responses were observed in the ATLs, although they were observed in other brain regions. These findings were supported by “resting-state” functional connectivity analyses using independent datasets from the same subjects. Person-selective ATL clusters were functionally connected with the brain's wider social cognition network. Rather than serving as a domain-general semantic hub, the ATLs work in unison with the social cognition system to support learning facts about others. PMID:19620621

  3. Disrupted Functional Connectivity for Controlled Visual Processing as a Basis for Impaired Spatial Working Memory in Schizophrenia

    PubMed Central

    Kang, Seung Suk; Sponheim, Scott R.; Chafee, Matthew V.; MacDonald, Angus W.

    2011-01-01

    Although regional brain abnormalities underlying spatial working memory (SWM) deficits in schizophrenia have been identified, little is known about which brain circuits are functionally disrupted in the SWM network in schizophrenia. We investigated SWM-related interregional functional connectivity in schizophrenia using functional magnetic resonance imaging (fMRI) data collected during a memory task that required analysis of spatial information in object structure. Twelve schizophrenia patients and eleven normal control subjects participated. Patients had SWM performance deficits and deficient neural activation in various brain areas, especially in the high SWM load condition. Examination of the covariation of regional brain activations elicited by the SWM task revealed evidence of functional disconnection between prefrontal and posterior visual association areas in schizophrenia. Under low SMW load, we found reduced functional associations between dorsolateral prefrontal cortex (DLPFC) and inferior temporal cortex (ITC) in the right hemisphere in patients. Under high SWM load, we found evidence for further functional disconnection in patients, including additional reduced functional associations between left DLPFC and right visual areas, including the posterior parietal cortex (PPC), fusiform gyrus, and V1, as well as between right inferior frontal cortex and right PPC. Greater prefrontal-posterior cortical functional connectivity was associated with better SWM performance in controls, but not in patients. These results suggest that prefrontal-posterior functional connectivity associated with the maintenance and control of visual information is central to SWM, and that disruption of this functional network underlies SWM deficits in schizophrenia. PMID:21703287

  4. Altered functional connectivity within the central reward network in overweight and obese women

    PubMed Central

    Coveleskie, K; Gupta, A; Kilpatrick, L A; Mayer, E D; Ashe-McNalley, C; Stains, J; Labus, J S; Mayer, E A

    2015-01-01

    Background/Objectives: Neuroimaging studies in obese subjects have identified abnormal activation of key regions of central reward circuits, including the nucleus accumbens (NAcc), in response to food-related stimuli. We aimed to examine whether women with elevated body mass index (BMI) show structural and resting state (RS) functional connectivity alterations within regions of the reward network. Subjects/Methods: Fifty healthy, premenopausal women, 19 overweight and obese (high BMI=26–38 kg m−2) and 31 lean (BMI=19–25 kg m−2) were selected from the University of California Los Angeles' Oppenheimer Center for Neurobiology of Stress database. Structural and RS functional scans were collected. Group differences in grey matter volume (GMV) of the NAcc, oscillation dynamics of intrinsic brain activity and functional connectivity of the NAcc to regions within the reward network were examined. Results: GMV of the left NAcc was significantly greater in the high BMI group than in the lean group (P=0.031). Altered frequency distributions were observed in women with high BMI compared with lean group in the left NAcc (P=0.009) in a medium-frequency (MF) band, and in bilateral anterior cingulate cortex (ACC) (P=0.014, <0.001) and ventro-medial prefrontal cortex (vmPFC) (P=0.034, <0.001) in a high-frequency band. Subjects with high BMI had greater connectivity of the left NAcc with bilateral ACC (P=0.024) and right vmPFC (P=0.032) in a MF band and with the left ACC (P=0.03) in a high frequency band. Conclusions: Overweight and obese women in the absence of food-related stimuli show significant structural and functional alterations within regions of reward-related brain networks, which may have a role in altered ingestive behaviors. PMID:25599560

  5. Functional Connectivity Alterations in Epilepsy from Resting-State Functional MRI

    PubMed Central

    Majeed, Waqas; Rajpoot, Nasir

    2015-01-01

    The study of functional brain connectivity alterations induced by neurological disorders and their analysis from resting state functional Magnetic Resonance Imaging (rfMRI) is generally considered to be a challenging task. The main challenge lies in determining and interpreting the large-scale connectivity of brain regions when studying neurological disorders such as epilepsy. We tackle this challenging task by studying the cortical region connectivity using a novel approach for clustering the rfMRI time series signals and by identifying discriminant functional connections using a novel difference statistic measure. The proposed approach is then used in conjunction with the difference statistic to conduct automatic classification experiments for epileptic and healthy subjects using the rfMRI data. Our results show that the proposed difference statistic measure has the potential to extract promising discriminant neuroimaging markers. The extracted neuroimaging markers yield 93.08% classification accuracy on unseen data as compared to 80.20% accuracy on the same dataset by a recent state-of-the-art algorithm. The results demonstrate that for epilepsy the proposed approach confirms known functional connectivity alterations between cortical regions, reveals some new connectivity alterations, suggests potential neuroimaging markers, and predicts epilepsy with high accuracy from rfMRI scans. PMID:26252668

  6. Intrinsic functional connectivity differentiates minimally conscious from unresponsive patients.

    PubMed

    Demertzi, Athena; Antonopoulos, Georgios; Heine, Lizette; Voss, Henning U; Crone, Julia Sophia; de Los Angeles, Carlo; Bahri, Mohamed Ali; Di Perri, Carol; Vanhaudenhuyse, Audrey; Charland-Verville, Vanessa; Kronbichler, Martin; Trinka, Eugen; Phillips, Christophe; Gomez, Francisco; Tshibanda, Luaba; Soddu, Andrea; Schiff, Nicholas D; Whitfield-Gabrieli, Susan; Laureys, Steven

    2015-09-01

    Despite advances in resting state functional magnetic resonance imaging investigations, clinicians remain with the challenge of how to implement this paradigm on an individualized basis. Here, we assessed the clinical relevance of resting state functional magnetic resonance imaging acquisitions in patients with disorders of consciousness by means of a systems-level approach. Three clinical centres collected data from 73 patients in minimally conscious state, vegetative state/unresponsive wakefulness syndrome and coma. The main analysis was performed on the data set coming from one centre (Liège) including 51 patients (26 minimally conscious state, 19 vegetative state/unresponsive wakefulness syndrome, six coma; 15 females; mean age 49 ± 18 years, range 11-87; 16 traumatic, 32 non-traumatic of which 13 anoxic, three mixed; 35 patients assessed >1 month post-insult) for whom the clinical diagnosis with the Coma Recovery Scale-Revised was congruent with positron emission tomography scanning. Group-level functional connectivity was investigated for the default mode, frontoparietal, salience, auditory, sensorimotor and visual networks using a multiple-seed correlation approach. Between-group inferential statistics and machine learning were used to identify each network's capacity to discriminate between patients in minimally conscious state and vegetative state/unresponsive wakefulness syndrome. Data collected from 22 patients scanned in two other centres (Salzburg: 10 minimally conscious state, five vegetative state/unresponsive wakefulness syndrome; New York: five minimally conscious state, one vegetative state/unresponsive wakefulness syndrome, one emerged from minimally conscious state) were used to validate the classification with the selected features. Coma Recovery Scale-Revised total scores correlated with key regions of each network reflecting their involvement in consciousness-related processes. All networks had a high discriminative capacity (>80%) for

  7. Spontaneous physiological variability modulates dynamic functional connectivity in resting-state functional magnetic resonance imaging.

    PubMed

    Nikolaou, F; Orphanidou, C; Papakyriakou, P; Murphy, K; Wise, R G; Mitsis, G D

    2016-05-13

    It is well known that the blood oxygen level-dependent (BOLD) signal measured by functional magnetic resonance imaging (fMRI) is influenced-in addition to neuronal activity-by fluctuations in physiological signals, including arterial CO2, respiration and heart rate/heart rate variability (HR/HRV). Even spontaneous fluctuations of the aforementioned physiological signals have been shown to influence the BOLD fMRI signal in a regionally specific manner. Related to this, estimates of functional connectivity between different brain regions, performed when the subject is at rest, may be confounded by the effects of physiological signal fluctuations. Moreover, resting functional connectivity has been shown to vary with respect to time (dynamic functional connectivity), with the sources of this variation not fully elucidated. In this context, we examine the relation between dynamic functional connectivity patterns and the time-varying properties of simultaneously recorded physiological signals (end-tidal CO2 and HR/HRV) using resting-state fMRI measurements from 12 healthy subjects. The results reveal a modulatory effect of the aforementioned physiological signals on the dynamic resting functional connectivity patterns for a number of resting-state networks (default mode network, somatosensory, visual). By using discrete wavelet decomposition, we also show that these modulation effects are more pronounced in specific frequency bands. PMID:27044987

  8. Estimating functional connectivity in an electrically coupled interneuron network

    PubMed Central

    Alcami, Pepe; Marty, Alain

    2013-01-01

    Even though it has been known for some time that in many mammalian brain areas interneurons are electrically coupled, a quantitative description of the network electrical connectivity and its impact on cellular passive properties is still lacking. Approaches used so far to solve this problem are limited because they do not readily distinguish junctions among direct neighbors from indirect junctions involving intermediary, multiply connected cells. In the cerebellar cortex, anatomical and functional evidence indicates electrical coupling between molecular layer interneurons (basket and stellate cells). An analysis of the capacitive currents obtained under voltage clamp in molecular layer interneurons of juvenile rats or mice reveals an exponential component with a time constant of ∼20 ms, which represents capacitive loading of neighboring cells through gap junctions. These results, taken together with dual cell recording of electrical synapses, have led us to estimate the number of direct neighbors to be ∼4 for rat basket cells and ∼1 for rat stellate cells. The weighted number of neighbors (number of neighbors, both direct and indirect, weighted with the percentage of voltage deflection at steady state) was 1.69 in basket cells and 0.23 in stellate cells. The last numbers indicate the spread of potential changes in the network and serve to estimate the contribution of gap junctions to cellular input conductance. In conclusion the present work offers effective tools to analyze the connectivity of electrically connected interneuron networks, and it indicates that in juvenile rodents, electrical communication is stronger among basket cells than among stellate cells. PMID:24248377

  9. Graph theoretical analysis of resting magnetoencephalographic functional connectivity networks

    PubMed Central

    Rutter, Lindsay; Nadar, Sreenivasan R.; Holroyd, Tom; Carver, Frederick W.; Apud, Jose; Weinberger, Daniel R.; Coppola, Richard

    2013-01-01

    Complex networks have been observed to comprise small-world properties, believed to represent an optimal organization of local specialization and global integration of information processing at reduced wiring cost. Here, we applied magnitude squared coherence to resting magnetoencephalographic time series in reconstructed source space, acquired from controls and patients with schizophrenia, and generated frequency-dependent adjacency matrices modeling functional connectivity between virtual channels. After configuring undirected binary and weighted graphs, we found that all human networks demonstrated highly localized clustering and short characteristic path lengths. The most conservatively thresholded networks showed efficient wiring, with topographical distance between connected vertices amounting to one-third as observed in surrogate randomized topologies. Nodal degrees of the human networks conformed to a heavy-tailed exponentially truncated power-law, compatible with the existence of hubs, which included theta and alpha bilateral cerebellar tonsil, beta and gamma bilateral posterior cingulate, and bilateral thalamus across all frequencies. We conclude that all networks showed small-worldness, minimal physical connection distance, and skewed degree distributions characteristic of physically-embedded networks, and that these calculations derived from graph theoretical mathematics did not quantifiably distinguish between subject populations, independent of bandwidth. However, post-hoc measurements of edge computations at the scale of the individual vertex revealed trends of reduced gamma connectivity across the posterior medial parietal cortex in patients, an observation consistent with our prior resting activation study that found significant reduction of synthetic aperture magnetometry gamma power across similar regions. The basis of these small differences remains unclear. PMID:23874288

  10. Physiologic assessment before video thoracoscopic resection for lung cancer in patients with abnormal pulmonary function

    PubMed Central

    Benattia, Amira; Debeaumont, David; Guyader, Vincent; Tardif, Catherine; Peillon, Christophe; Cuvelier, Antoine

    2016-01-01

    Background Impaired respiratory function may prevent curative surgery for patients with non-small cell lung cancer (NSCLC). Video-assisted thoracoscopic surgery (VATS) reduces postoperative morbility-mortality and could change preoperative assessment practices and therapeutic decisions. We evaluated the relation between preoperative pulmonary function tests and the occurrence of postoperative complications after VATS pulmonary resection in patients with abnormal pulmonary function. Methods We included 106 consecutive patients with ≤80% predicted value of presurgical expiratory volume in one second (FEV1) and/or diffusing capacity of carbon monoxide (DLCO) and who underwent VATS pulmonary resection for NSCLC from a prospective surgical database. Results Patients (64±9.5 years) had lobectomy (n=91), segmentectomy (n=7), bilobectomy (n=4), or pneumonectomy (n=4). FEV1 and DLCO preoperative averages were 68%±21% and 60%±18%. Operative mortality was 1.89%. Only FEV1 was predictive of postoperative complications [odds ratio (OR), 0.96; 95% confidence interval (CI), 0.926–0.991, P=0.016], but there was no determinable threshold. Twenty-five patients underwent incremental exercise testing. Desaturations during exercise (OR, 0.462; 95% CI, 0.191–0.878, P=0.039) and heart rate (HR) response (OR, 0.953; 95% CI, 0.895–0.993, P=0.05) were associated with postoperative complications. Conclusions FEV1 but not DLCO was a significant predictor of pulmonary complications after VATS pulmonary resection despite a low rate of severe morbidity. Incremental exercise testing seems more discriminating. Further investigation is required in a larger patient population to change current pre-operative threshold in a new era of minimally invasive surgery. PMID:27293834

  11. Adolescent Intermittent Alcohol Exposure: Persistence of Structural and Functional Hippocampal Abnormalities into Adulthood

    PubMed Central

    Risher, Mary-Louise; Fleming, Rebekah L.; Risher, Christopher; Miller, K. M.; Klein, Rebecca C.; Wills, Tiffany; Acheson, Shawn K.; Moore, Scott D.; Wilson, Wilkie A.; Eroglu, Cagla; Swartzwelder, H. S.

    2015-01-01

    Background Human adolescence is a crucial stage of neurological development during which ethanol (EtOH) consumption is often at its highest. Alcohol abuse during adolescence may render individuals at heightened risk for subsequent alcohol abuse disorders, cognitive dysfunction, or other neurological impairments by irreversibly altering long-term brain function. To test this possibility, we modeled adolescent alcohol abuse (i.e., intermittent EtOH exposure during adolescence [AIE]) in rats to determine whether adolescent exposure to alcohol leads to long-term structural and functional changes that are manifested in adult neuronal circuitry. Methods We specifically focused on hippocampal area CA1, a brain region associated with learning and memory. Using electrophysiological, immunohistochemical, and neuroanatomical approaches, we measured post-AIE changes in synaptic plasticity, dendritic spine morphology, and synaptic structure in adulthood. Results We found that AIE-pretreated adult rats manifest robust long-term potentiation, induced at stimulus intensities lower than those required in controls, suggesting a state of enhanced synaptic plasticity. Moreover, AIE resulted in an increased number of dendritic spines with characteristics typical of immaturity. Immunohistochemistry-based analysis of synaptic structures indicated a significant decrease in the number of co-localized pre- and postsynaptic puncta. This decrease is driven by an overall decrease in 2 postsynaptic density proteins, PSD-95 and SAP102. Conclusions Taken together, these findings reveal that repeated alcohol exposure during adolescence results in enduring structural and functional abnormalities in the hippocampus. These synaptic changes in the hippocampal circuits may help to explain learning-related behavioral changes in adult animals preexposed to AIE. PMID:25916839

  12. Characterizing dynamic local functional connectivity in the human brain.

    PubMed

    Deng, Lifu; Sun, Junfeng; Cheng, Lin; Tong, Shanbao

    2016-01-01

    Functional connectivity (FC), obtained from functional magnetic resonance imaging (fMRI), brings insights into the functional organization of the brain. Recently, rich and complex behaviour of brain has been revealed by the dynamic fluctuation of FC, which had previously been regarded as confounding 'noise'. While the dynamics of long-distance, inter-regional FC has been extensively studied, the dynamics of local FC within a few millimetres in space remains largely unexplored. In this study, the local FC was depicted by regional homogeneity (ReHo), and the dynamics of local FC was obtained using sliding windows method. We observed a robust positive correlation between ReHo and its temporal variability, which was shown to be an intrinsic feature of the brain rather than a pure stochastic effect. Furthermore, fluctuation of ReHo was associated with global functional organization: (i) brain regions with higher centrality of inter-regional FC tended to possess higher ReHo variability; (ii) coherence of ReHo fluctuation was higher within brain's functional modules. Finally, we observed alteration of ReHo variability during a motor task compared with resting-state. Our findings associated the temporal fluctuation of ReHo with brain function, opening up the possibility of dynamic local FC study in the future. PMID:27231194

  13. Characterizing dynamic local functional connectivity in the human brain

    PubMed Central

    Deng, Lifu; Sun, Junfeng; Cheng, Lin; Tong, Shanbao

    2016-01-01

    Functional connectivity (FC), obtained from functional magnetic resonance imaging (fMRI), brings insights into the functional organization of the brain. Recently, rich and complex behaviour of brain has been revealed by the dynamic fluctuation of FC, which had previously been regarded as confounding ‘noise’. While the dynamics of long-distance, inter-regional FC has been extensively studied, the dynamics of local FC within a few millimetres in space remains largely unexplored. In this study, the local FC was depicted by regional homogeneity (ReHo), and the dynamics of local FC was obtained using sliding windows method. We observed a robust positive correlation between ReHo and its temporal variability, which was shown to be an intrinsic feature of the brain rather than a pure stochastic effect. Furthermore, fluctuation of ReHo was associated with global functional organization: (i) brain regions with higher centrality of inter-regional FC tended to possess higher ReHo variability; (ii) coherence of ReHo fluctuation was higher within brain’s functional modules. Finally, we observed alteration of ReHo variability during a motor task compared with resting-state. Our findings associated the temporal fluctuation of ReHo with brain function, opening up the possibility of dynamic local FC study in the future. PMID:27231194

  14. Abnormal Functional Activation and Connectivity in the Working Memory Network in Early-Onset Schizophrenia

    ERIC Educational Resources Information Center

    Kyriakopoulos, Marinos; Dima, Danai; Roiser, Jonathan P.; Corrigall, Richard; Barker, Gareth J.; Frangou, Sophia

    2012-01-01

    Objective: Disruption within the working memory (WM) neural network is considered an integral feature of schizophrenia. The WM network, and the dorsolateral prefrontal cortex (DLPFC) in particular, undergo significant remodeling in late adolescence. Potential interactions between developmental changes in the WM network and disease-related…

  15. Preliminary differences in resting state MEG functional connectivity pre- and post-ketamine in major depressive disorder.

    PubMed

    Nugent, Allison C; Robinson, Stephen E; Coppola, Richard; Zarate, Carlos A

    2016-08-30

    Functional neuroimaging techniques including magnetoencephalography (MEG) have demonstrated that the brain is organized into networks displaying correlated activity. Group connectivity differences between healthy controls and participants with major depressive disorder (MDD) can be detected using temporal independent components analysis (ICA) on beta-bandpass filtered Hilbert envelope MEG data. However, the response of these networks to treatment is unknown. Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, exerts rapid antidepressant effects. We obtained MEG recordings before and after open-label infusion of 0.5mg/kg ketamine in MDD subjects (N=13) and examined networks previously shown to differ between healthy individuals and those with MDD. Connectivity between the amygdala and an insulo-temporal component decreased post-ketamine in MDD subjects towards that observed in control subjects at baseline. Decreased baseline connectivity of the subgenual anterior cingulate cortex (sgACC) with a bilateral precentral network had previously been observed in MDD compared to healthy controls, and the change in connectivity post-ketamine was proportional to the change in sgACC glucose metabolism in a subset (N=8) of subjects receiving [11F]FDG-PET imaging. Ketamine appeared to reduce connectivity, regardless of whether connectivity was abnormally high or low compared to controls at baseline. These preliminary findings suggest that sgACC connectivity may be directly related to glutamate levels. PMID:27362845

  16. Decreased interhemispheric functional connectivity in subtypes of Parkinson's disease.

    PubMed

    Hu, Xiaofei; Zhang, Jiuquan; Jiang, Xiaomei; Zhou, Chaoyang; Wei, Luqing; Yin, Xuntao; Wu, Ya; Li, Jing; Zhang, Yanling; Wang, Jian

    2015-03-01

    Parkinson's disease (PD) can be classified into tremor-dominant (TD) subtype and akinetic-rigid (AR) subtype, which exhibit different clinical courses and prognoses. However, the neural mechanisms underlying different subtypes of PD are not well understood. Using voxel-mirrored homotopic connectivity (VMHC), we examined the homotopic resting-state functional connectivity patterns in akinetic-rigid PD (AR-PD) and tremor-dominant PD (TD-PD) to study the neural basis for these disparate manifestations of PD. Twenty-one TD-PD patients, 29 AR-PD patients and 26 normal control subjects participated in this study. Resting-state fMRI data were analyzed using VMHC. Correlations between VMHC values and each clinical characteristic were also calculated. Compared with normal control subjects and subjects with AR-PD, subjects with TD-PD exhibited significantly lower VMHC values in the posterior lobe of the cerebellum. Moreover, tremor scores and VMHC values for the cerebellum were found to be significantly negatively correlated in TD-PD patients. By contrast, subjects with AR-PD exhibited lower VMHC values in the precentral gyrus compared with normal control subjects. These findings suggest that functional coordination between homotopic brain regions is impaired in AR-PD and TD-PD patients. This study provides evidence of both cerebellum-related connectivity deficits in TD-PD. The finding that VMHC values and tremor scores were significantly correlated suggests that VMHC measurements may be of potential clinical relevance in TD-PD. PMID:25577177

  17. Condition-dependent functional connectivity: syntax networks in bilinguals

    PubMed Central

    Dodel, Silke; Golestani, Narly; Pallier, Christophe; ElKouby, Vincent; Le Bihan, Denis; Poline, Jean-Baptiste

    2005-01-01

    This paper introduces a method to study the variation of brain functional connectivity networks with respect to experimental conditions in fMRI data. It is related to the psychophysiological interaction technique introduced by Friston et al. and extends to networks of correlation modulation (CM networks). Extended networks containing several dozens of nodes are determined in which the links correspond to consistent correlation modulation across subjects. In addition, we assess inter-subject variability and determine networks in which the condition-dependent functional interactions can be explained by a subject-dependent variable. We applied the technique to data from a study on syntactical production in bilinguals and analysed functional interactions differentially across tasks (word reading or sentence production) and across languages. We find an extended network of consistent functional interaction modulation across tasks, whereas the network comparing languages shows fewer links. Interestingly, there is evidence for a specific network in which the differences in functional interaction across subjects can be explained by differences in the subjects' syntactical proficiency. Specifically, we find that regions, including ones that have previously been shown to be involved in syntax and in language production, such as the left inferior frontal gyrus, putamen, insula, precentral gyrus, as well as the supplementary motor area, are more functionally linked during sentence production in the second, compared with the first, language in syntactically more proficient bilinguals than in syntactically less proficient ones. Our approach extends conventional activation analyses to the notion of networks, emphasizing functional interactions between regions independently of whether or not they are activated. On the one hand, it gives rise to testable hypotheses and allows an interpretation of the results in terms of the previous literature, and on the other hand, it provides a

  18. Network Analysis of Intrinsic Functional Brain Connectivity in Alzheimer's Disease

    PubMed Central

    Supekar, Kaustubh; Menon, Vinod; Rubin, Daniel; Musen, Mark; Greicius, Michael D.

    2008-01-01

    Functional brain networks detected in task-free (“resting-state”) functional magnetic resonance imaging (fMRI) have a small-world architecture that reflects a robust functional organization of the brain. Here, we examined whether this functional organization is disrupted in Alzheimer's disease (AD). Task-free fMRI data from 21 AD subjects and 18 age-matched controls were obtained. Wavelet analysis was applied to the fMRI data to compute frequency-dependent correlation matrices. Correlation matrices were thresholded to create 90-node undirected-graphs of functional brain networks. Small-world metrics (characteristic path length and clustering coefficient) were computed using graph analytical methods. In the low frequency interval 0.01 to 0.05 Hz, functional brain networks in controls showed small-world organization of brain activity, characterized by a high clustering coefficient and a low characteristic path length. In contrast, functional brain networks in AD showed loss of small-world properties, characterized by a significantly lower clustering coefficient (p<0.01), indicative of disrupted local connectivity. Clustering coefficients for the left and right hippocampus were significantly lower (p<0.01) in the AD group compared to the control group. Furthermore, the clustering coefficient distinguished AD participants from the controls with a sensitivity of 72% and specificity of 78%. Our study provides new evidence that there is disrupted organization of functional brain networks in AD. Small-world metrics can characterize the functional organization of the brain in AD, and our findings further suggest that these network measures may be useful as an imaging-based biomarker to distinguish AD from healthy aging. PMID:18584043

  19. Claudin-16 Deficiency Impairs Tight Junction Function in Ameloblasts, Leading to Abnormal Enamel Formation.

    PubMed

    Bardet, Claire; Courson, Frédéric; Wu, Yong; Khaddam, Mayssam; Salmon, Benjamin; Ribes, Sandy; Thumfart, Julia; Yamaguti, Paulo M; Rochefort, Gael Y; Figueres, Marie-Lucile; Breiderhoff, Tilman; Garcia-Castaño, Alejandro; Vallée, Benoit; Le Denmat, Dominique; Baroukh, Brigitte; Guilbert, Thomas; Schmitt, Alain; Massé, Jean-Marc; Bazin, Dominique; Lorenz, Georg; Morawietz, Maria; Hou, Jianghui; Carvalho-Lobato, Patricia; Manzanares, Maria Cristina; Fricain, Jean-Christophe; Talmud, Deborah; Demontis, Renato; Neves, Francisco; Zenaty, Delphine; Berdal, Ariane; Kiesow, Andreas; Petzold, Matthias; Menashi, Suzanne; Linglart, Agnes; Acevedo, Ana Carolina; Vargas-Poussou, Rosa; Müller, Dominik; Houillier, Pascal; Chaussain, Catherine

    2016-03-01

    Claudin-16 protein (CLDN16) is a component of tight junctions (TJ) with a restrictive distribution so far demonstrated mainly in the kidney. Here, we demonstrate the expression of CLDN16 also in the tooth germ and show that claudin-16 gene (CLDN16) mutations result in amelogenesis imperfecta (AI) in the 5 studied patients with familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC). To investigate the role of CLDN16 in tooth formation, we studied a murine model of FHHNC and showed that CLDN16 deficiency led to altered secretory ameloblast TJ structure, lowering of extracellular pH in the forming enamel matrix, and abnormal enamel matrix protein processing, resulting in an enamel phenotype closely resembling human AI. This study unravels an association of FHHNC owing to CLDN16 mutations with AI, which is directly related to the loss of function of CLDN16 during amelogenesis. Overall, this study indicates for the first time the importance of a TJ protein in tooth formation and underlines the need to establish a specific dental follow-up for these patients. PMID:26426912

  20. Abnormal cleavage of APP impairs its functions in cell adhesion and migration.

    PubMed

    Sheng, Baiyang; Song, Bo; Zheng, Zhenhuan; Zhou, Fangfang; Lu, Guangyuan; Zhao, Nanming; Zhang, Xiufang; Gong, Yandao

    2009-02-01

    Amyloid precursor protein (APP) is expressed ubiquitously but its wrong cleavage only occurs in central nervous system. In this research, overexpression of wild type human APP695 was found to stimulate the adhesion and migration of N2a cells. In the cells co-transfected by familial Alzheimer's disease (FAD)-linked Swedish mutant of APP695 gene plus big up tri, openE9 deleted presenilin1 gene (N2a/Swe. big up tri, open9), however, this stimulating function was impaired compared to that in the cells co-transfected by Swedish mutant of APP695 gene plus dominant negative mutant of presenilin1 D385A gene (N2a/Swe.385). Furthermore, it was also found that the phosphorylation of FAK Tyr-861 and GSK-3beta Ser-9 was reduced in N2a/Swe.Delta9 cells, which can be possibly taken as a reasonable explanation for the underlying mechanism. Our results suggest that impaired cell adhesion and migration induced by abnormal cleavage of APP could contribute to the pathological effects in FAD brain. PMID:19056463

  1. Serotonin transporter variant drives preventable gastrointestinal abnormalities in development and function.

    PubMed

    Margolis, Kara Gross; Li, Zhishan; Stevanovic, Korey; Saurman, Virginia; Israelyan, Narek; Anderson, George M; Snyder, Isaac; Veenstra-VanderWeele, Jeremy; Blakely, Randy D; Gershon, Michael D

    2016-06-01

    Autism spectrum disorder (ASD) is an increasingly common behavioral condition that frequently presents with gastrointestinal (GI) disturbances. It is not clear, however, how gut dysfunction relates to core ASD features. Multiple, rare hyperfunctional coding variants of the serotonin (5-HT) transporter (SERT, encoded by SLC6A4) have been identified in ASD. Expression of the most common SERT variant (Ala56) in mice increases 5-HT clearance and causes ASD-like behaviors. Here, we demonstrated that Ala56-expressing mice display GI defects that resemble those seen in mice lacking neuronal 5-HT. These defects included enteric nervous system hypoplasia, slow GI transit, diminished peristaltic reflex activity, and proliferation of crypt epithelial cells. An opposite phenotype was seen in SERT-deficient mice and in progeny of WT dams given the SERT antagonist fluoxetine. The reciprocal phenotypes that resulted from increased or decreased SERT activity support the idea that 5-HT signaling regulates enteric neuronal development and can, when disturbed, cause long-lasting abnormalities of GI function. Administration of a 5-HT4 agonist to Ala56 mice during development prevented Ala56-associated GI perturbations, suggesting that excessive SERT activity leads to inadequate 5-HT4-mediated neurogenesis. We propose that deficient 5-HT signaling during development may contribute to GI and behavioral features of ASD. The consequences of therapies targeting SERT during pregnancy warrant further evaluation. PMID:27111230

  2. Serotonin transporter variant drives preventable gastrointestinal abnormalities in development and function

    PubMed Central

    Margolis, Kara Gross; Li, Zhishan; Stevanovic, Korey; Saurman, Virginia; Anderson, George M.; Snyder, Isaac; Blakely, Randy D.; Gershon, Michael D.

    2016-01-01

    Autism spectrum disorder (ASD) is an increasingly common behavioral condition that frequently presents with gastrointestinal (GI) disturbances. It is not clear, however, how gut dysfunction relates to core ASD features. Multiple, rare hyperfunctional coding variants of the serotonin (5-HT) transporter (SERT, encoded by SLC6A4) have been identified in ASD. Expression of the most common SERT variant (Ala56) in mice increases 5-HT clearance and causes ASD-like behaviors. Here, we demonstrated that Ala56-expressing mice display GI defects that resemble those seen in mice lacking neuronal 5-HT. These defects included enteric nervous system hypoplasia, slow GI transit, diminished peristaltic reflex activity, and proliferation of crypt epithelial cells. An opposite phenotype was seen in SERT-deficient mice and in progeny of WT dams given the SERT antagonist fluoxetine. The reciprocal phenotypes that resulted from increased or decreased SERT activity support the idea that 5-HT signaling regulates enteric neuronal development and can, when disturbed, cause long-lasting abnormalities of GI function. Administration of a 5-HT4 agonist to Ala56 mice during development prevented Ala56-associated GI perturbations, suggesting that excessive SERT activity leads to inadequate 5-HT4–mediated neurogenesis. We propose that deficient 5-HT signaling during development may contribute to GI and behavioral features of ASD. The consequences of therapies targeting SERT during pregnancy warrant further evaluation. PMID:27111230

  3. Heritability of the network architecture of intrinsic brain functional connectivity.

    PubMed

    Sinclair, Benjamin; Hansell, Narelle K; Blokland, Gabriëlla A M; Martin, Nicholas G; Thompson, Paul M; Breakspear, Michael; de Zubicaray, Greig I; Wright, Margaret J; McMahon, Katie L

    2015-11-01

    The brain's functional network exhibits many features facilitating functional specialization, integration, and robustness to attack. Using graph theory to characterize brain networks, studies demonstrate their small-world, modular, and "rich-club" properties, with deviations reported in many common neuropathological conditions. Here we estimate the heritability of five widely used graph theoretical metrics (mean clustering coefficient (γ), modularity (Q), rich-club coefficient (ϕnorm), global efficiency (λ), small-worldness (σ)) over a range of connection densities (k=5-25%) in a large cohort of twins (N=592, 84 MZ and 89 DZ twin pairs, 246 single twins, age 23 ± 2.5). We also considered the effects of global signal regression (GSR). We found that the graph metrics were moderately influenced by genetic factors h(2) (γ=47-59%, Q=38-59%, ϕnorm=0-29%, λ=52-64%, σ=51-59%) at lower connection densities (≤ 15%), and when global signal regression was implemented, heritability estimates decreased substantially h(2) (γ=0-26%, Q=0-28%, ϕnorm=0%, λ=23-30%, σ=0-27%). Distinct network features were phenotypically correlated (|r|=0.15-0.81), and γ, Q, and λ were found to be influenced by overlapping genetic factors. Our findings suggest that these metrics may be potential endophenotypes for psychiatric disease and suitable for genetic association studies, but that genetic effects must be interpreted with respect to methodological choices. PMID:26226088

  4. Mapping resting-state functional connectivity using perfusion MRI

    PubMed Central

    Chuang, Kai-Hsiang; van Gelderen, Peter; Merkle, Hellmut; Bodurka, Jerzy; Ikonomidou, Vasiliki N.; Koretsky, Alan P.; Duyn, Jeff H.; Talagala, S. Lalith

    2008-01-01

    Resting-state, low frequency (< 0.08 Hz) fluctuations of blood oxygenation level dependent (BOLD) magnetic resonance signal have been shown to exhibit high correlation among functionally connected regions. However, correlations of cerebral blood flow (CBF) fluctuations during the resting state have not been extensively studied. The main challenges of using arterial spin labeling perfusion magnetic resonance imaging to detect CBF fluctuations are low sensitivity, low temporal resolution, and contamination from BOLD. This work demonstrates CBF-based quantitative functional connectivity mapping by combining continuous arterial spin labeling (CASL) with a neck labeling coil and a multi-channel receiver coil to achieve high perfusion sensitivity. In order to reduce BOLD contamination, the CBF signal was extracted from the CASL signal time course by high frequency filtering. This processing strategy is compatible with sinc interpolation for reducing the timing mismatch between control and label images and has the flexibility of choosing an optimal filter cutoff frequency to minimize BOLD fluctuations. Most subjects studied showed high CBF correlation in bilateral sensorimotor areas with good suppression of BOLD contamination. Root-mean-square CBF fluctuation contributing to bilateral correlation was estimated to be 29% ± 19% (N = 13) of the baseline perfusion, while BOLD fluctuation was 0.26% ± 0.14% of the mean intensity (at 3T and 12.5 ms echo time). PMID:18314354

  5. Error-Related Functional Connectivity of the Habenula in Humans

    PubMed Central

    Ide, Jaime S.; Li, Chiang-Shan R.

    2011-01-01

    Error detection is critical to the shaping of goal-oriented behavior. Recent studies in non-human primates delineated a circuit involving the lateral habenula (LH) and ventral tegmental area (VTA) in error detection. Neurons in the LH increased activity, preceding decreased activity in the VTA, to a missing reward, indicating a feedforward signal from the LH to VTA. In the current study we used connectivity analyses to reveal this pathway in humans. In 59 adults performing a stop signal task during functional magnetic resonance imaging, we identified brain regions showing greater psychophysiological interaction with the habenula during stop error as compared to stop success trials. These regions included a cluster in the VTA/substantia nigra (SN), internal segment of globus pallidus, bilateral amygdala, and insula. Furthermore, using Granger causality and mediation analyses, we showed that the habenula Granger caused the VTA/SN, establishing the direction of this interaction, and that the habenula mediated the functional connectivity between the amygdala and VTA/SN during error processing. To our knowledge, these findings are the first to demonstrate a feedforward influence of the habenula on the VTA/SN during error detection in humans. PMID:21441989

  6. Fast construction of voxel-level functional connectivity graphs

    PubMed Central

    2014-01-01

    Background Graph-based analysis of fMRI data has recently emerged as a promising approach to study brain networks. Based on the assessment of synchronous fMRI activity at separate brain sites, functional connectivity graphs are constructed and analyzed using graph-theoretical concepts. Most previous studies investigated region-level graphs, which are computationally inexpensive, but bring along the problem of choosing sensible regions and involve blurring of more detailed information. In contrast, voxel-level graphs provide the finest granularity attainable from the data, enabling analyses at superior spatial resolution. They are, however, associated with considerable computational demands, which can render high-resolution analyses infeasible. In response, many existing studies investigating functional connectivity at the voxel-level reduced the computational burden by sacrificing spatial resolution. Methods Here, a novel, time-efficient method for graph construction is presented that retains the original spatial resolution. Performance gains are instead achieved through data reduction in the temporal domain based on dichotomization of voxel time series combined with tetrachoric correlation estimation and efficient implementation. Results By comparison with graph construction based on Pearson’s r, the technique used by the majority of previous studies, we find that the novel approach produces highly similar results an order of magnitude faster. Conclusions Its demonstrated performance makes the proposed approach a sensible and efficient alternative to customary practice. An open source software package containing the created programs is freely available for download. PMID:24947161

  7. Functional neuroanatomy of bipolar disorder: structure, function, and connectivity in an amygdala–anterior paralimbic neural system

    PubMed Central

    Blond, Benjamin N; Fredericks, Carolyn A; Blumberg, Hilary P

    2013-01-01

    Objectives In past decades, neuroimaging research in bipolar disorder has demonstrated a convergence of findings in an amygdala–anterior paralimbic cortex neural system. This paper reviews behavioral neurology literature that first suggested a central role for this neural system in the disorder and the neuroimaging evidence that supports it. Methods Relevant articles are reviewed to provide an amygdala–anterior paralimbic cortex neural system model of bipolar disorder, including articles from the fields of behavioral neurology and neuroanatomy, and neuroimaging. Results The literature is highly supportive of key roles for the amygdala, anterior paralimbic cortices, and connections among these structures in the emotional dysregulation of bipolar disorder. The functions subserved by their more widely distributed connection sites suggest that broader system dysfunction could account for the range of functions—from neurovegetative to cognitive—disrupted in the disorder. Abnormalities in some components of this neural system are apparent by adolescence, while others, such as those in rostral prefrontal regions, appear to progress over adolescence and young adulthood, suggesting a neurodevelopmental model of the disorder. However, some findings conflict, which may reflect the small sample sizes of some studies, and clinical heterogeneity and methodological differences across studies. Conclusions Consistent with models derived from early behavioral neurology studies, neuroimaging studies support a central role for an amygdala–anterior paralimbic neural system in bipolar disorder, and implicate abnormalities in the development of this system in the disorder. This system will be an important focus of future studies on the developmental pathophysiology, detection, treatment, and prevention of the disorder. PMID:22631619

  8. Brain structures and functional connectivity associated with individual differences in Internet tendency in healthy young adults.

    PubMed

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

    2015-04-01

    Internet addiction (IA) incurs significant social and financial costs in the form of physical side-effects, academic and occupational impairment, and serious relationship problems. The majority of previous studies on Internet addiction disorders (IAD) have focused on structural and functional abnormalities, while few studies have simultaneously investigated the structural and functional brain alterations underlying individual differences in IA tendencies measured by questionnaires in a healthy sample. Here we combined structural (regional gray matter volume, rGMV) and functional (resting-state functional connectivity, rsFC) information to explore the neural mechanisms underlying IAT in a large sample of 260 healthy young adults. The results showed that IAT scores were significantly and positively correlated with rGMV in the right dorsolateral prefrontal cortex (DLPFC, one key node of the cognitive control network, CCN), which might reflect reduced functioning of inhibitory control. More interestingly, decreased anticorrelations between the right DLPFC and the medial prefrontal cortex/rostral anterior cingulate cortex (mPFC/rACC, one key node of the default mode network, DMN) were associated with higher IAT scores, which might be associated with reduced efficiency of the CCN and DMN (e.g., diminished cognitive control and self-monitoring). Furthermore, the Stroop interference effect was positively associated with the volume of the DLPFC and with the IA scores, as well as with the connectivity between DLPFC and mPFC, which further indicated that rGMV variations in the DLPFC and decreased anticonnections between the DLPFC and mPFC may reflect addiction-related reduced inhibitory control and cognitive efficiency. These findings suggest the combination of structural and functional information can provide a valuable basis for further understanding of the mechanisms and pathogenesis of IA. PMID:25698637

  9. Functional connectivity and graph theory in preclinical Alzheimer's disease.

    PubMed

    Brier, Matthew R; Thomas, Jewell B; Fagan, Anne M; Hassenstab, Jason; Holtzman, David M; Benzinger, Tammie L; Morris, John C; Ances, Beau M

    2014-04-01

    Alzheimer's disease (AD) has a long preclinical phase in which amyloid and tau cerebral pathology accumulate without producing cognitive symptoms. Resting state functional connectivity magnetic resonance imaging has demonstrated that brain networks degrade during symptomatic AD. It is unclear to what extent these degradations exist before symptomatic onset. In this study, we investigated graph theory metrics of functional integration (path length), functional segregation (clustering coefficient), and functional distinctness (modularity) as a function of disease severity. Further, we assessed whether these graph metrics were affected in cognitively normal participants with cerebrospinal fluid evidence of preclinical AD. Clustering coefficient and modularity, but not path length, were reduced in AD. Cognitively normal participants who harbored AD biomarker pathology also showed reduced values in these graph measures, demonstrating brain changes similar to, but smaller than, symptomatic AD. Only modularity was significantly affected by age. We also demonstrate that AD has a particular effect on hub-like regions in the brain. We conclude that AD causes large-scale disconnection that is present before onset of symptoms. PMID:24216223

  10. Prefrontal Dopaminergic Receptor Abnormalities and Executive Functions in Parkinson’s Disease

    PubMed Central

    Ko, Ji Hyun; Antonelli, Francesca; Monchi, Oury; Ray, Nicola; Rusjan, Pablo; Houle, Sylvain; Lang, Anthony E.; Christopher, Leigh; Strafella, Antonio P.

    2012-01-01

    The main pattern of cognitive impairments seen in early to moderate stages of Parkinson’s disease (PD) includes deficits of executive functions. These nonmotor complications have a significant impact on the quality of life and day-to-day activities of PD patients and are not effectively managed by current therapies, a problem which is almost certainly due to the fact that the disease extends beyond the nigrostriatal system. To investigate the role of extrastriatal dopamine in executive function in PD, PD patients and a control group were studied with positron-emission-tomography using a high-affinity dopamine D2/D3 receptor tracer, [11C]FLB-457. All participants were scanned twice while performing an executive task and a control task. Patients were off medication for at least 12 h. The imaging analysis revealed that parkinsonian patients had lower [11C]FLB-457 binding than control group independently of task conditions across different brain regions. Cognitive assessment measures were positively correlated with [11C]FLB-457 binding in the bilateral dorsolateral prefrontal cortex and anterior cingulate cortex only in control group, but not in PD patients. Within the control group, during the executive task (as compared to control task), there was evidence of reduced [11C]FLB-457 binding (indicative of increased dopamine release) in the right orbitofrontal cortex. In contrast, PD patients did not show any reduction in binding during the executive task (as compared with control task). These findings suggest that PD patients present significant abnormalities in extrastriatal dopamine associated with executive processing. These observations provide important insights on the pathophysiology of cognitive dysfunction in PD. PMID:22331665

  11. Increased Functional Connectivity Between Subcortical and Cortical Resting-State Networks in Autism Spectrum Disorder

    PubMed Central

    Cerliani, Leonardo; Mennes, Maarten; Thomas, Rajat M.; Di Martino, Adriana; Thioux, Marc; Keysers, Christian

    2016-01-01

    Importance Individuals with autism spectrum disorder (ASD) exhibit severe difficulties in social interaction, motor coordination, behavioral flexibility, and atypical sensory processing, with considerable interindividual variability. This heterogeneous set of symptoms recently led to investigating the presence of abnormalities in the interaction across large-scale brain networks. To date, studies have focused either on constrained sets of brain regions or whole-brain analysis, rather than focusing on the interaction between brain networks. Objectives To compare the intrinsic functional connectivity between brain networks in a large sample of individuals with ASD and typically developing control subjects and to estimate to what extent group differences would predict autistic traits and reflect different developmental trajectories. Design, Setting, and Participants We studied 166 male individuals (mean age, 17.6 years; age range, 7-50 years) diagnosed as having DSM-IV-TR autism or Asperger syndrome and 193 typical developing male individuals (mean age, 16.9 years; age range, 6.5-39.4 years) using resting-state functional magnetic resonance imaging (MRI). Participants were matched for age, IQ, head motion, and eye status (open or closed) in the MRI scanner. We analyzed data from the Autism Brain Imaging Data Exchange (ABIDE), an aggregated MRI data set from 17 centers, made public in August 2012. Main Outcomes and Measures We estimated correlations between time courses of brain networks extracted using a data-driven method (independent component analysis). Subsequently, we associated estimates of interaction strength between networks with age and autistic traits indexed by the Social Responsiveness Scale. Results Relative to typically developing control participants, individuals with ASD showed increased functional connectivity between primary sensory networks and subcortical networks (thalamus and basal ganglia) (all t ≥ 3.13, P < .001 corrected). The strength of

  12. Graves' disease, Celiac disease and liver function abnormalities in a patient--clinical manifestation and diagnostic difficulties.

    PubMed

    Góra-Gębka, Magdalena; Woźniak, Małgorzata; Cielecka-Kuszyk, Joanna; Korpal-Szczyrska, Maria; Sznurkowska, Katarzyna; Zagierski, Maciej; Jankowska, Irena; Plata-Nazar, Katarzyna; Kamińska, Barbara; Liberek, Anna

    2014-01-01

    Autoimmune diseases due to probable common pathogenesis tend to coexist in some patients. Complex clinical presentation with diverse timing of particular symptoms and sophisticated treatment with numerous side effects, may cause diagnostic difficulties, especially in children. The paper presents diagnostic difficulties and pitfalls in a child with Graves' disease, celiac disease and liver function abnormalities. PMID:24904927

  13. Quetiapine modulates functional connectivity in brain aggression networks.

    PubMed

    Klasen, Martin; Zvyagintsev, Mikhail; Schwenzer, Michael; Mathiak, Krystyna A; Sarkheil, Pegah; Weber, René; Mathiak, Klaus

    2013-07-15

    Aggressive behavior is associated with dysfunctions in an affective regulation network encompassing amygdala and prefrontal areas such as orbitofrontal (OFC), anterior cingulate (ACC), and dorsolateral prefrontal cortex (DLPFC). In particular, prefrontal regions have been postulated to control amygdala activity by inhibitory projections, and this process may be disrupted in aggressive individuals. The atypical antipsychotic quetiapine successfully attenuates aggressive behavior in various disorders; the underlying neural processes, however, are unknown. A strengthened functional coupling in the prefrontal-amygdala system may account for these anti-aggressive effects. An inhibition of this network has been reported for virtual aggression in violent video games as well. However, there have been so far no in-vivo observations of pharmacological influences on corticolimbic projections during human aggressive behavior. In a double-blind, placebo-controlled study, quetiapine and placebo were administered for three successive days prior to an fMRI experiment. In this experiment, functional brain connectivity was assessed during virtual aggressive behavior in a violent video game and an aggression-free control task in a non-violent modification. Quetiapine increased the functional connectivity of ACC and DLPFC with the amygdala during virtual aggression, whereas OFC-amygdala coupling was attenuated. These effects were observed neither for placebo nor for the non-violent control. These results demonstrate for the first time a pharmacological modification of aggression-related human brain networks in a naturalistic setting. The violence-specific modulation of prefrontal-amygdala networks appears to control aggressive behavior and provides a neurobiological model for the anti-aggressive effects of quetiapine. PMID:23501053

  14. Dynamic Resting State Functional Connectivity in Awake and Anesthetized Rodents

    PubMed Central

    Liang, Zhifeng; Liu, Xiao; Zhang, Nanyin

    2014-01-01

    Since its introduction, resting-state functional magnetic resonance imaging (rsfMRI) has been a powerful tool for investigating functional neural networks in both normal and pathological conditions. When measuring resting-state functional connectivity (RSFC), most rsfMRI approaches do not consider its temporal variations and thus only provide the averaged RSFC over the scan time. Recently, there has been a surge of interest to investigate the dynamic characteristics of RSFC in humans, and promising results have been yielded. However, our knowledge regarding the dynamic RSFC in animals remains sparse. In the present study we utilized the single-volume coactivation method to systematically study the dynamic properties of RSFC within the networks of infralimbic cortex (IL) and primary somatosensory cortex (S1) in both awake and anesthetized rats. Our data showed that both IL and S1 networks could be decomposed into several spatially reproducible but temporally changing co-activation patterns (CAPs), suggesting that dynamic RSFC was indeed a characteristic feature in rodents. In addition, we demonstrated that anesthesia profoundly impacted the dynamic RSFC of neural circuits subserving cognitive and emotional functions but had less effects on sensorimotor systems. Finally, we examined the temporal characteristics of each CAP, and found that individual CAPs exhibited consistent temporal evolution patterns. Together, these results suggest that dynamic RSFC might be a general phenomenon in vertebrate animals. In addition, this study has paved the way for further understanding the alterations of dynamic RSFC in animal models of brain disorders. PMID:25315787

  15. Intranasal Oxytocin Normalizes Amygdala Functional Connectivity in Posttraumatic Stress Disorder.

    PubMed

    Koch, Saskia B J; van Zuiden, Mirjam; Nawijn, Laura; Frijling, Jessie L; Veltman, Dick J; Olff, Miranda

    2016-07-01

    The neuropeptide oxytocin (OT) has been suggested as a promising pharmacological agent for medication-enhanced psychotherapy in posttraumatic stress disorder (PTSD) because of its anxiolytic and prosocial properties. We therefore investigated the behavioral and neurobiological effects of a single intranasal OT administration (40 IU) in PTSD patients. We conducted a randomized, placebo-controlled, cross-over resting-state fMRI study in male and female police officers with (n=37, 21 males) and without PTSD (n=40, 20 males). We investigated OT administration effects on subjective anxiety and functional connectivity of basolateral (BLA) and centromedial (CeM) amygdala subregions with prefrontal and salience processing areas. In PTSD patients, OT administration resulted in decreased subjective anxiety and nervousness. Under placebo, male PTSD patients showed diminished right CeM to left ventromedial prefrontal cortex (vmPFC) connectivity compared with male trauma-exposed controls, which was reinstated after OT administration. Additionally, female PTSD patients showed enhanced right BLA to bilateral dorsal anterior cingulate cortex (dACC) connectivity compared with female trauma-exposed controls, which was dampened after OT administration. Although caution is warranted, our findings tentatively suggest that OT has the potential to diminish anxiety and fear expression of the amygdala in PTSD, either via increased control of the vmPFC over the CeM (males) or via decreased salience processing of the dACC and BLA (females). Our findings add to accumulating evidence that OT administration could potentially enhance treatment response in PTSD. PMID:26741286

  16. Disrupted Structural and Functional Connectivity in Prefrontal-Hippocampus Circuitry in First-Episode Medication-Naïve Adolescent Depression

    PubMed Central

    Geng, Haiyang; Wu, Feng; Kong, Lingtao; Tang, Yanqing; Zhou, Qian; Chang, Miao; Zhou, Yifang; Jiang, Xiaowei; Li, Songbai; Wang, Fei

    2016-01-01

    Background Evidence implicates abnormalities in prefrontal-hippocampus neural circuitry in major depressive disorder (MDD). This study investigates the potential disruptions in prefrontal-hippocampus structural and functional connectivity, as well as their relationship in first-episode medication-naïve adolescents with MDD in order to investigate the early stage of the illness without confounds of illness course and medication exposure. Methods Diffusion tensor imaging and resting-state functional magnetic resonance imaging (rs-fMRI) data were acquired from 26 first-episode medication-naïve MDD adolescents and 31 healthy controls (HC). Fractional anisotropy (FA) values of the fornix and the prefrontal-hippocampus functional connectivity was compared between MDD and HC groups. The correlation between the FA value of fornix and the strength of the functional connectivity in the prefrontal cortex (PFC) region showing significant differences between the two groups was identified. Results Compared with the HC group, adolescent MDD group had significant lower FA values in the fornix, as well as decreased functional connectivity in four PFC regions. Significant negative correlations were observed between fornix FA values and functional connectivity from hippocampus to PFC within the HC group. There was no significant correlation between the fornix FA and the strength of functional connectivity within the adolescent MDD group. Conclusions First-episode medication-naïve adolescent MDD showed decreased structural and functional connectivity as well as deficits of the association between structural and functional connectivity shown in HC in the PFC-hippocampus neural circuitry. These findings suggest that abnormal PFC-hippocampus neural circuitry may present in the early onset of MDD and play an important role in the neuropathophysiology of MDD. PMID:26863301

  17. 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.

  18. Self-Reported Sleep Correlates with Prefrontal-Amygdala Functional Connectivity and Emotional Functioning

    PubMed Central

    Killgore, William D. S.

    2013-01-01

    Study Objectives: Prior research suggests that sleep deprivation is associated with declines in some aspects of emotional intelligence and increased severity on indices of psychological disturbance. Sleep deprivation is also associated with reduced prefrontal-amygdala functional connectivity, potentially reflecting impaired top-down modulation of emotion. It remains unknown whether this modified connectivity may be observed in relation to more typical levels of sleep curtailment. We examined whether self-reported sleep duration the night before an assessment would be associated with these effects. Design: Participants documented their hours of sleep from the previous night, completed the Bar-On Emotional Quotient Inventory (EQ-i), Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT), and Personality Assessment Inventory (PAI), and underwent resting-state functional magnetic resonance imaging (fMRI). Setting: Outpatient neuroimaging center at a private psychiatric hospital. Participants: Sixty-five healthy adults (33 men, 32 women), ranging in age from 18-45 y. Interventions: N/A. Measurements and Results: Greater self-reported sleep the preceding night was associated with higher scores on all scales of the EQ-i but not the MSCEIT, and with lower symptom severity scores on half of the psychopathology scales of the PAI. Longer sleep was also associated with stronger negative functional connectivity between the right ventromedial prefrontal cortex and amygdala. Moreover, greater negative connectivity between these regions was associated with higher EQ-i and lower symptom severity on the PAI. Conclusions: Self-reported sleep duration from the preceding night was negatively correlated with prefrontal-amygdala connectivity and the severity of subjective psychological distress, while positively correlated with higher perceived emotional intelligence. More sleep was associated with higher emotional and psychological strength. Citation: Killgore WDS. Self

  19. Abnormal barrier function in the pathogenesis of ichthyosis: Therapeutic implications for lipid metabolic disorders☆

    PubMed Central

    Elias, Peter M.; Williams, Mary L.; Feingold, Kenneth R.

    2013-01-01

    Ichthyoses, including inherited disorders of lipid metabolism, display a permeability barrier abnormality in which the severity of the clinical phenotype parallels the prominence of the barrier defect. The pathogenesis of the cutaneous phenotype represents the consequences of the mutation for epidermal function, coupled with a “best attempt” by affected epidermis to generate a competent barrier in a terrestrial environment. A compromised barrier in normal epidermis triggers a vigorous set of metabolic responses that rapidly normalizes function, but ichthyotic epidermis, which is inherently compromised, only partially succeeds in this effort. Unraveling mechanisms that account for barrier dysfunction in the ichthyoses has identified multiple, subcellular, and biochemical processes that contribute to the clinical phenotype. Current treatment of the ichthyoses remains largely symptomatic: directed toward reducing scale or corrective gene therapy. Reducing scale is often minimally effective. Gene therapy is impeded by multiple pitfalls, including difficulties in transcutaneous drug delivery, high costs, and discomfort of injections. We have begun to use information about disease pathogenesis to identify novel, pathogenesis-based therapeutic strategies for the ichthyoses. The clinical phenotype often reflects not only a deficiency of pathway end product due to reduced-function mutations in key synthetic enzymes but often also accumulation of proximal, potentially toxic metabolites. As a result, depending upon the identified pathomechanism(s) for each disorder, the accompanying ichthyosis can be treated by topical provision of pathway product (eg, cholesterol), with or without a proximal enzyme inhibitor (eg, simvastatin), to block metabolite production. Among the disorders of distal cholesterol metabolism, the cutaneous phenotype in Congenital Hemidysplasia with Ichthyosiform Erythroderma and Limb Defects (CHILD syndrome) and X-linked ichthyosis reflect metabolite

  20. Altered functional connectivity of the default mode network in Williams syndrome: a multimodal approach.

    PubMed

    Sampaio, Adriana; Moreira, Pedro Silva; Osório, Ana; Magalhães, Ricardo; Vasconcelos, Cristiana; Férnandez, Montse; Carracedo, Angel; Alegria, Joana; Gonçalves, Óscar F; Soares, José Miguel

    2016-07-01

    Resting state brain networks are implicated in a variety of relevant brain functions. Importantly, abnormal patterns of functional connectivity (FC) have been reported in several neurodevelopmental disorders. In particular, the Default Mode Network (DMN) has been found to be associated with social cognition. We hypothesize that the DMN may be altered in Williams syndrome (WS), a neurodevelopmental genetic disorder characterized by an unique cognitive and behavioral phenotype. In this study, we assessed the architecture of the DMN using fMRI in WS patients and typically developing matched controls (sex and age) in terms of FC and volumetry of the DMN. Moreover, we complemented the analysis with a functional connectome approach. After excluding participants due to movement artifacts (n = 3), seven participants with WS and their respective matched controls were included in the analyses. A decreased FC between the DMN regions was observed in the WS group when compared with the typically developing group. Specifically, we found a decreased FC in a posterior hub of the DMN including the precuneus, calcarine and the posterior cingulate of the left hemisphere. The functional connectome approach showed a focalized and global increased FC connectome in the WS group. The reduced FC of the posterior hub of the DMN in the WS group is consistent with immaturity of the brain FC patterns and may be associated with the singularity of their visual spatial phenotype. PMID:27412230

  1. Abnormal Mitochondrial Function and Impaired Granulosa Cell Differentiation in Androgen Receptor Knockout Mice

    PubMed Central

    Wang, Ruey-Sheng; Chang, Heng-Yu; Kao, Shu-Huei; Kao, Cheng-Heng; Wu, Yi-Chen; Yeh, Shuyuan; Tzeng, Chii-Reuy; Chang, Chawnshang

    2015-01-01

    In the ovary, the paracrine interactions between the oocyte and surrounded granulosa cells are critical for optimal oocyte quality and embryonic development. Mice lacking the androgen receptor (AR−/−) were noted to have reduced fertility with abnormal ovarian function that might involve the promotion of preantral follicle growth and prevention of follicular atresia. However, the detailed mechanism of how AR in granulosa cells exerts its effects on oocyte quality is poorly understood. Comparing in vitro maturation rate of oocytes, we found oocytes collected from AR−/− mice have a significantly poor maturating rate with 60% reached metaphase II and 30% remained in germinal vesicle breakdown stage, whereas 95% of wild-type AR (AR+/+) oocytes had reached metaphase II. Interestingly, we found these AR−/− female mice also had an increased frequency of morphological alterations in the mitochondria of granulosa cells with reduced ATP generation (0.18 ± 0.02 vs. 0.29 ± 0.02 µM/mg protein; p < 0.05) and aberrant mitochondrial biogenesis. Mechanism dissection found loss of AR led to a significant decrease in the expression of peroxisome proliferator-activated receptor γ (PPARγ) co-activator 1-β (PGC1-β) and its sequential downstream genes, nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factor A (TFAM), in controlling mitochondrial biogenesis. These results indicate that AR may contribute to maintain oocyte quality and fertility via controlling the signals of PGC1-β-mediated mitochondrial biogenesis in granulosa cells. PMID:25941928

  2. Abnormalities of motor function, transcription and cerebellar structure in mouse models of THAP1 dystonia.

    PubMed

    Ruiz, Marta; Perez-Garcia, Georgina; Ortiz-Virumbrales, Maitane; Méneret, Aurelie; Morant, Andrika; Kottwitz, Jessica; Fuchs, Tania; Bonet, Justine; Gonzalez-Alegre, Pedro; Hof, Patrick R; Ozelius, Laurie J; Ehrlich, Michelle E

    2015-12-20

    DYT6 dystonia is caused by mutations in THAP1 [Thanatos-associated (THAP) domain-containing apoptosis-associated protein] and is autosomal dominant and partially penetrant. Like other genetic primary dystonias, DYT6 patients have no characteristic neuropathology, and mechanisms by which mutations in THAP1 cause dystonia are unknown. Thap1 is a zinc-finger transcription factor, and most pathogenic THAP1 mutations are missense and are located in the DNA-binding domain. There are also nonsense mutations, which act as the equivalent of a null allele because they result in the generation of small mRNA species that are likely rapidly degraded via nonsense-mediated decay. The function of Thap1 in neurons is unknown, but there is a unique, neuronal 50-kDa Thap1 species, and Thap1 levels are auto-regulated on the mRNA level. Herein, we present the first characterization of two mouse models of DYT6, including a pathogenic knockin mutation, C54Y and a null mutation. Alterations in motor behaviors, transcription and brain structure are demonstrated. The projection neurons of the deep cerebellar nuclei are especially altered. Abnormalities vary according to genotype, sex, age and/or brain region, but importantly, overlap with those of other dystonia mouse models. These data highlight the similarities and differences in age- and cell-specific effects of a Thap1 mutation, indicating that the pathophysiology of THAP1 mutations should be assayed at multiple ages and neuronal types and support the notion of final common pathways in the pathophysiology of dystonia arising from disparate mutations. PMID:26376866

  3. Midcingulate cortex: Structure, connections, homologies, functions and diseases.

    PubMed

    Vogt, Brent A

    2016-07-01

    Midcingulate cortex (MCC) has risen in prominence as human imaging identifies unique structural and functional activity therein and this is the first review of its structure, connections, functions and disease vulnerabilities. The MCC has two divisions (anterior, aMCC and posterior, pMCC) that represent functional units and the cytoarchitecture, connections and neurocytology of each is shown with immunohistochemistry and receptor binding. The MCC is not a division of anterior cingulate cortex (ACC) and the "dorsal ACC" designation is a misnomer as it incorrectly implies that MCC is a division of ACC. Interpretation of findings among species and developing models of human diseases requires detailed comparative studies which is shown here for five species with flat maps and immunohistochemistry (human, monkey, rabbit, rat, mouse). The largest neurons in human cingulate cortex are in layer Vb of area 24 d in pMCC which project to the spinal cord. This area is part of the caudal cingulate premotor area which is involved in multisensory orientation of the head and body in space and neuron responses are tuned for the force and direction of movement. In contrast, the rostral cingulate premotor area in aMCC is involved in action-reinforcement associations and selection based on the amount of reward or aversive properties of a potential movement. The aMCC is activated by nociceptive information from the midline, mediodorsal and intralaminar thalamic nuclei which evoke fear and mediates nocifensive behaviors. This subregion also has high dopaminergic afferents and high dopamine-1 receptor binding and is engaged in reward processes. Opposing pain/avoidance and reward/approach functions are selected by assessment of potential outcomes and error detection according to feedback-mediated, decision making. Parietal afferents differentially terminate in MCC and provide for multisensory control in an eye- and head-centric manner. Finally, MCC vulnerability in human disease confirms

  4. High-resolution network biology: connecting sequence with function

    PubMed Central

    Ryan, Colm J.; Cimermančič, Peter; Szpiech, Zachary A.; Sali, Andrej; Hernandez, Ryan D.; Krogan, Nevan J.

    2014-01-01

    Proteins are not monolithic entities; rather, they can contain multiple domains that mediate distinct interactions, and their functionality can be regulated through post-translational modifications at multiple distinct sites. Traditionally, network biology has ignored such properties of proteins and has instead examined either the physical interactions of whole proteins or the consequences of removing entire genes. In this Review, we discuss experimental and computational methods to increase the resolution of protein– protein, genetic and drug–gene interaction studies to the domain and residue levels. Such work will be crucial for using interaction networks to connect sequence and structural information, and to understand the biological consequences of disease-associated mutations, which will hopefully lead to more effective therapeutic strategies. PMID:24197012

  5. Abnormal functional integration of thalamic low frequency oscillation in the BOLD signal after acute heroin treatment.

    PubMed

    Denier, Niklaus; Schmidt, André; Gerber, Hana; Vogel, Marc; Huber, Christian G; Lang, Undine E; Riecher-Rossler, Anita; Wiesbeck, Gerhard A; Radue, Ernst-Wilhelm; Walter, Marc; Borgwardt, Stefan

    2015-12-01

    Heroin addiction is a severe relapsing brain disorder associated with impaired cognitive control, including deficits in attention allocation. The thalamus has a high density of opiate receptors and is critically involved in orchestrating cortical activity during cognitive control. However, there have been no studies on how acute heroin treatment modulates thalamic activity. In a cross-over, double-blind, vehicle-controlled study, 29 heroin-maintained outpatients were studied after heroin and placebo administration, while 20 healthy controls were included for the placebo condition only. Resting-state functional magnetic resonance imaging was used to analyze functional integration of the thalamus by three different resting state analysis techniques. Thalamocortical functional connectivity (FC) was analyzed by seed-based correlation, while intrinsic thalamic oscillation was assessed by analysis of regional homogeneity (ReHo) and the fractional amplitude of low frequency fluctuations (fALFF). Relative to the placebo treatment and healthy controls, acute heroin administration reduced thalamocortical FC to cortical regions, including the frontal cortex, while the reductions in FC to the mediofrontal cortex, orbitofrontal cortex, and frontal pole were positively correlated with the plasma level of morphine, the main psychoactive metabolite of heroin. Furthermore, heroin treatment was associated with increased thalamic ReHo and fALFF values, whereas fALFF following heroin exposure correlated negatively with scores of attentional control. The heroin-associated increase in fALFF was mainly dominated by slow-4 (0.027-0.073 Hz) oscillations. Our findings show that there are acute effects of heroin within the thalamocortical system and may shed new light on the role of the thalamus in cognitive control in heroin addiction. Future research is needed to determine the underlying physiological mechanisms and their role in heroin addiction. PMID:26441146

  6. The Influence of Head Motion on Intrinsic Functional Connectivity MRI

    PubMed Central

    Van Dijk, Koene R.A.; Sabuncu, Mert R.; Buckner, Randy L.

    2011-01-01

    Functional connectivity MRI (fcMRI) has been widely applied to explore group and individual differences. A confounding factor is head motion. Children move more than adults, older adults more than younger adults, and patients more than controls. Head motion varies considerably among individuals within the same population. Here we explored the influence of head motion on fcMRI estimates. Mean head displacement, maximum head displacement, the number of micro movements (> 0.1 mm), and head rotation were estimated in 1000 healthy, young adult subjects each scanned for two resting-state runs on matched 3T scanners. The majority of fcMRI variation across subjects was not linked to estimated head motion. However, head motion had significant, systematic effects on fcMRI network measures. Head motion was associated with decreased functional coupling in the default and frontoparietal control networks – two networks characterized by coupling among distributed regions of association cortex. Other network measures increased with motion including estimates of local functional coupling and coupling between left and right motor regions – a region pair sometimes used as a control in studies to establish specificity. Comparisons between groups of individuals with subtly different levels of head motion yielded difference maps that could be mistaken for neuronal effects in other contexts. These effects are important to consider when interpreting variation between groups and across individuals. PMID:21810475

  7. Functional connectivity of the striatum in experts of stenography

    PubMed Central

    Ito, Takehito; Matsuda, Tetsuya; Shimojo, Shinsuke

    2015-01-01

    Introduction Stenography, or shorthand, is a unique set of skills that involves intensive training which is nearly life-long and orchestrating various brain functional modules, including auditory, linguistic, cognitive, mnemonic, and motor. Stenography provides cognitive neuroscientists with a unique opportunity to investigate the neural mechanisms underlying the neural plasticity that enables such a high degree of expertise. However, shorthand is quickly being replaced with voice recognition technology. We took this nearly final opportunity to scan the brains of the last alive shorthand experts of the Japanese language. Methods Thirteen right-handed stenographers and fourteen right-handed controls participated in the functional magnetic resonance imaging (fMRI) study. Results The fMRI data revealed plastic reorganization of the neural circuits around the putamen. The acquisition of expert skills was accompanied by structural and functional changes in the area. The posterior putamen is known as the execution center of acquired sensorimotor skills. Compared to nonexperts, the posterior putamen in stenographers had high covariation with the cerebellum and midbrain.The stenographers' brain developed different neural circuits from those of the nonexpert brain. Conclusions The current data illustrate the vigorous plasticity in the putamen and in its connectivity to other relevant areas in the expert brain. This is a case of vigorous neural plastic reorganization in response to massive overtraining, which is rare especially considering that it occurred in adulthood. PMID:25874166

  8. Neurolinguistics: Structure, Function, and Connectivity in the Bilingual Brain.

    PubMed

    Wong, Becky; Yin, Bin; O'Brien, Beth

    2016-01-01

    Advances in neuroimaging techniques and analytic methods have led to a proliferation of studies investigating the impact of bilingualism on the cognitive and brain systems in humans. Lately, these findings have attracted much interest and debate in the field, leading to a number of recent commentaries and reviews. Here, we contribute to the ongoing discussion by compiling and interpreting the plethora of findings that relate to the structural, functional, and connective changes in the brain that ensue from bilingualism. In doing so, we integrate theoretical models and empirical findings from linguistics, cognitive/developmental psychology, and neuroscience to examine the following issues: (1) whether the language neural network is different for first (dominant) versus second (nondominant) language processing; (2) the effects of bilinguals' executive functioning on the structure and function of the "universal" language neural network; (3) the differential effects of bilingualism on phonological, lexical-semantic, and syntactic aspects of language processing on the brain; and (4) the effects of age of acquisition and proficiency of the user's second language in the bilingual brain, and how these have implications for future research in neurolinguistics. PMID:26881224

  9. Neurolinguistics: Structure, Function, and Connectivity in the Bilingual Brain

    PubMed Central

    Wong, Becky; Yin, Bin; O'Brien, Beth

    2016-01-01

    Advances in neuroimaging techniques and analytic methods have led to a proliferation of studies investigating the impact of bilingualism on the cognitive and brain systems in humans. Lately, these findings have attracted much interest and debate in the field, leading to a number of recent commentaries and reviews. Here, we contribute to the ongoing discussion by compiling and interpreting the plethora of findings that relate to the structural, functional, and connective changes in the brain that ensue from bilingualism. In doing so, we integrate theoretical models and empirical findings from linguistics, cognitive/developmental psychology, and neuroscience to examine the following issues: (1) whether the language neural network is different for first (dominant) versus second (nondominant) language processing; (2) the effects of bilinguals' executive functioning on the structure and function of the “universal” language neural network; (3) the differential effects of bilingualism on phonological, lexical-semantic, and syntactic aspects of language processing on the brain; and (4) the effects of age of acquisition and proficiency of the user's second language in the bilingual brain, and how these have implications for future research in neurolinguistics. PMID:26881224

  10. Topographical functional connectivity patterns exist in the congenitally, prelingually deaf.

    PubMed

    Striem-Amit, Ella; Almeida, Jorge; Belledonne, Mario; Chen, Quanjing; Fang, Yuxing; Han, Zaizhu; Caramazza, Alfonso; Bi, Yanchao

    2016-01-01

    Congenital deafness causes large changes in the auditory cortex structure and function, such that without early childhood cochlear-implant, profoundly deaf children do not develop intact, high-level, auditory functions. But how is auditory cortex organization affected by congenital, prelingual, and long standing deafness? Does the large-scale topographical organization of the auditory cortex develop in people deaf from birth? And is it retained despite cross-modal plasticity? We identified, using fMRI, topographic tonotopy-based functional connectivity (FC) structure in humans in the core auditory cortex, its extending tonotopic gradients in the belt and even beyond that. These regions show similar FC structure in the congenitally deaf throughout the auditory cortex, including in the language areas. The topographic FC pattern can be identified reliably in the vast majority of the deaf, at the single subject level, despite the absence of hearing-aid use and poor oral language skills. These findings suggest that large-scale tonotopic-based FC does not require sensory experience to develop, and is retained despite life-long auditory deprivation and cross-modal plasticity. Furthermore, as the topographic FC is retained to varying degrees among the deaf subjects, it may serve to predict the potential for auditory rehabilitation using cochlear implants in individual subjects. PMID:27427158

  11. Topographical functional connectivity patterns exist in the congenitally, prelingually deaf

    PubMed Central

    Striem-Amit, Ella; Almeida, Jorge; Belledonne, Mario; Chen, Quanjing; Fang, Yuxing; Han, Zaizhu; Caramazza, Alfonso; Bi, Yanchao

    2016-01-01

    Congenital deafness causes large changes in the auditory cortex structure and function, such that without early childhood cochlear-implant, profoundly deaf children do not develop intact, high-level, auditory functions. But how is auditory cortex organization affected by congenital, prelingual, and long standing deafness? Does the large-scale topographical organization of the auditory cortex develop in people deaf from birth? And is it retained despite cross-modal plasticity? We identified, using fMRI, topographic tonotopy-based functional connectivity (FC) structure in humans in the core auditory cortex, its extending tonotopic gradients in the belt and even beyond that. These regions show similar FC structure in the congenitally deaf throughout the auditory cortex, including in the language areas. The topographic FC pattern can be identified reliably in the vast majority of the deaf, at the single subject level, despite the absence of hearing-aid use and poor oral language skills. These findings suggest that large-scale tonotopic-based FC does not require sensory experience to develop, and is retained despite life-long auditory deprivation and cross-modal plasticity. Furthermore, as the topographic FC is retained to varying degrees among the deaf subjects, it may serve to predict the potential for auditory rehabilitation using cochlear implants in individual subjects. PMID:27427158

  12. Disruption of Ah Receptor Signaling during Mouse Development Leads to Abnormal Cardiac Structure and Function in the Adult.

    PubMed

    Carreira, Vinicius S; Fan, Yunxia; Kurita, Hisaka; Wang, Qin; Ko, Chia-I; Naticchioni, Mindi; Jiang, Min; Koch, Sheryl; Zhang, Xiang; Biesiada, Jacek; Medvedovic, Mario; Xia, Ying; Rubinstein, Jack; Puga, Alvaro

    2015-01-01

    The Developmental Origins of Health and Disease (DOHaD) Theory proposes that the environment encountered during fetal life and infancy permanently shapes tissue physiology and homeostasis such that damage resulting from maternal stress, poor nutrition or exposure to environmental agents may be at the heart of adult onset disease. Interference with endogenous developmental functions of the aryl hydrocarbon receptor (AHR), either by gene ablation or by exposure in utero to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a potent AHR ligand, causes structural, molecular and functional cardiac abnormalities and altered heart physiology in mouse embryos. To test if embryonic effects progress into an adult phenotype, we investigated whether Ahr ablation or TCDD exposure in utero resulted in cardiac abnormalities in adult mice long after removal of the agent. Ten-months old adult Ahr-/- and in utero TCDD-exposed Ahr+/+ mice showed sexually dimorphic abnormal cardiovascular phenotypes characterized by echocardiographic findings of hypertrophy, ventricular dilation and increased heart weight, resting heart rate and systolic and mean blood pressure, and decreased exercise tolerance. Underlying these effects, genes in signaling networks related to cardiac hypertrophy and mitochondrial function were differentially expressed. Cardiac dysfunction in mouse embryos resulting from AHR signaling disruption seems to progress into abnormal cardiac structure and function that predispose adults to cardiac disease, but while embryonic dysfunction is equally robust in males and females, the adult abnormalities are more prevalent in females, with the highest severity in Ahr-/- females. The findings reported here underscore the conclusion that AHR signaling in the developing heart is one potential target of environmental factors associated with cardiovascular disease. PMID:26555816

  13. Disruption of Ah Receptor Signaling during Mouse Development Leads to Abnormal Cardiac Structure and Function in the Adult

    PubMed Central

    Carreira, Vinicius S.; Fan, Yunxia; Kurita, Hisaka; Wang, Qin; Ko, Chia-I; Naticchioni, Mindi; Jiang, Min; Koch, Sheryl; Zhang, Xiang; Biesiada, Jacek; Medvedovic, Mario; Xia, Ying; Rubinstein, Jack; Puga, Alvaro

    2015-01-01

    The Developmental Origins of Health and Disease (DOHaD) Theory proposes that the environment encountered during fetal life and infancy permanently shapes tissue physiology and homeostasis such that damage resulting from maternal stress, poor nutrition or exposure to environmental agents may be at the heart of adult onset disease. Interference with endogenous developmental functions of the aryl hydrocarbon receptor (AHR), either by gene ablation or by exposure in utero to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a potent AHR ligand, causes structural, molecular and functional cardiac abnormalities and altered heart physiology in mouse embryos. To test if embryonic effects progress into an adult phenotype, we investigated whether Ahr ablation or TCDD exposure in utero resulted in cardiac abnormalities in adult mice long after removal of the agent. Ten-months old adult Ahr-/- and in utero TCDD-exposed Ahr+/+ mice showed sexually dimorphic abnormal cardiovascular phenotypes characterized by echocardiographic findings of hypertrophy, ventricular dilation and increased heart weight, resting heart rate and systolic and mean blood pressure, and decreased exercise tolerance. Underlying these effects, genes in signaling networks related to cardiac hypertrophy and mitochondrial function were differentially expressed. Cardiac dysfunction in mouse embryos resulting from AHR signaling disruption seems to progress into abnormal cardiac structure and function that predispose adults to cardiac disease, but while embryonic dysfunction is equally robust in males and females, the adult abnormalities are more prevalent in females, with the highest severity in Ahr-/- females. The findings reported here underscore the conclusion that AHR signaling in the developing heart is one potential target of environmental factors associated with cardiovascular disease. PMID:26555816

  14. Morphologic and Functional Connectivity Alterations of Corticostriatal and Default Mode Network in Treatment-Naïve Patients with Obsessive-Compulsive Disorder

    PubMed Central

    Hou, Jingming; Song, Lingheng; Zhang, Wei; Wu, Wenjing; Wang, Jian; Zhou, Daiquan; Qu, Wei; Guo, Junwei; Gu, Shanshan; He, Mei; Xie, Bing; Li, Haitao

    2013-01-01

    Background Previous studies have demonstrated that structural deficits and functional connectivity imbalances might underlie the pathophysiology of obsessive-compulsive disorder (OCD). The purpose of the present study was to investigate gray matter deficits and abnormal resting-state networks in patients with OCD and further investigate the association between the anatomic and functional alterations and clinical symptoms. Methods Participants were 33 treatment-naïve OCD patients and 33 matched healthy controls. Voxel-based morphometry was used to investigate the regions with gray matter abnormalities and resting-state functional connectivity analysis was further conducted between each gray matter abnormal region and the remaining voxels in the brain. Results Compared with healthy controls, patients with OCD showed significantly increased gray matter volume in the left caudate, left thalamus, and posterior cingulate cortex, as well as decreased gray matter volume in the bilateral medial orbitofrontal cortex, left anterior cingulate cortex, and left inferior frontal gyrus. By using the above morphologic deficits areas as seed regions, functional connectivity analysis found abnormal functional integration in the cortical-striatum-thalamic-cortical (CSTC) circuits and default mode network. Subsequent correlation analyses revealed that morphologic deficits in the left thalamus and increased functional connectivity within the CSTC circuits positively correlated with the total Y-BOCS score. Conclusion This study provides evidence that morphologic and functional alterations are seen in CSTC circuits and default mode network in treatment-naïve OCD patients. The association between symptom severity and the CSTC circuits suggests that anatomic and functional alterations in CSTC circuits are especially important in the pathophysiology of OCD. PMID:24358320

  15. Pulmonary function abnormalities in adult patients with acute exacerbation of bronchiectasis: A retrospective risk factor analysis.

    PubMed

    Ma, Yanliang; Niu, Yuqian; Tian, Guizhen; Wei, Jingan; Gao, Zhancheng

    2015-08-01

    Lung function impairments, especially airflow obstruction, are important features during acute exacerbation in patients with bronchiectasis. Recognition of the risk factors associated with airflow obstruction is important in the management of these exacerbations. The medical records of adult patients admitted to the Peking University People's Hospital, Beijing, China, from 2004 to 2011 with a diagnosis of bronchiectasis were reviewed retrospectively. Univariate and multivariate analyses were used to evaluate the risk factors associated with airflow obstruction. Airflow obstruction was found in 55.6% of 156 patients hospitalized with acute exacerbation of bronchiectasis, and the risk factors associated with airflow obstruction included young age (≤14 years old) at diagnosis (odds ratio (OR) = 3.454, 95% confidence interval (CI) 1.709-6.982, p = 0.001) as well as the presence of chronic obstructive pulmonary disease (COPD; OR = 14.677, 95% CI 5.696-37.819, p = 0.001), asthma (OR = 3.063, 95% CI 1.403-6.690, p = 0.005), and wheezing on auscultation (OR = 3.279, 95% CI 1.495-7.194, p = 0.003). The C-reactive protein (13.9 mg/dl vs. 6.89 mg/dl, p = 0.005), partial pressure of arterial oxygen (66.7 ± 8.57 mmHg vs. 89.56 ± 12.80 mmHg, p < 0.001), and partial pressure of arterial carbon dioxide (40.52 ± 2.77 mmHg vs. 42.87 ± 5.39 mmHg, p = 0.02) profiles were different between patients with or without airflow obstruction. In addition, patients colonized with potential pathogenic microorganisms had a decreased diffusing capacity (56.0% vs. 64.7%, p = 0.04). Abnormal pulmonary function was common in hospitalized patients with bronchiectasis exacerbations. Airflow obstruction was correlated with the patient's age at diagnosis, as well as the presence of combined COPD and asthma, and wheezing on auscultation, which also resulted in more severe systemic inflammation and hypoxemia. PMID:25882894

  16. Brain functional connectivity and the pathophysiology of schizophrenia.

    PubMed

    Angelopoulos, E

    2014-01-01

    In the last decade there is extensive evidence to suggest that cognitive functions depending on coordination of distributed neuronal responses are associated with synchronized oscillatory activity in various frequency ranges suggesting a functional mechanism of neural oscillations in cortical networks. In addition to their role in normal brain functioning, there is increasing evidence that altered oscillatory activity may be associated with certain neuropsychiatric disorders, such as schizophrenia. Consequently, disturbances in neural synchronization may represent the functional relationship of disordered connectivity of cortical networks underlying the characteristic fragmentation of mind and behavior in schizophrenia. In recent studies the synchronization of oscillatory activity in the experience of characteristic symptoms such as auditory verbal hallucinations and thought blocks have been studied in patients with schizophrenia. Studies involving analysis of EEG activity obtained from individuals in resting state (in cage Faraday, isolated from external influences and with eyes closed). In patients with schizophrenia and persistent auditory verbal hallucinations (AVHs) observed a temporary increase in the synchronization phase of α and high θ oscillations of the electroencephalogram (EEG) compared with those of healthy controls and patients without AVHs . This functional hyper-connection manifested in time windows corresponding to experience AVHs, as noted by the patients during the recording of EEG and observed in speech related cortical areas. In another study an interaction of theta and gamma oscillations engages in the production and experience of AVHs. The results showed increased phase coupling between theta and gamma EEG rhythms in the left temporal cortex during AVHs experiences. A more recent study, approaches the thought blocking experience in terms of functional brain connectivity. Thought blocks (TBs) are characterized by regular interruptions of

  17. Characterization of neuromuscular synapse function abnormalities in multiple Duchenne muscular dystrophy mouse models.

    PubMed

    van der Pijl, Elizabeth M; van Putten, Maaike; Niks, Erik H; Verschuuren, Jan J G M; Aartsma-Rus, Annemieke; Plomp, Jaap J

    2016-06-01

    Duchenne muscular dystrophy (DMD) is an X-linked myopathy caused by dystrophin deficiency. Dystrophin is present intracellularly at the sarcolemma, connecting actin to the dystrophin-associated glycoprotein complex. Interestingly, it is enriched postsynaptically at the neuromuscular junction (NMJ), but its synaptic function is largely unknown. Utrophin, a dystrophin homologue, is also concentrated at the NMJ, and upregulated in DMD. It is possible that the absence of dystrophin at NMJs in DMD causes neuromuscular transmission defects that aggravate muscle weakness. We studied NMJ function in mdx mice (lacking dystrophin) and wild type mice. In addition, mdx/utrn(+/-) and mdx/utrn(-/-) mice (lacking utrophin) were used to investigate influences of utrophin levels. The three Duchenne mouse models showed muscle weakness when comparatively tested in vivo, with mdx/utrn(-/-) mice being weakest. Ex vivo muscle contraction and electrophysiological studies showed a reduced safety factor of neuromuscular transmission in all models. NMJs had ~ 40% smaller miniature endplate potential amplitudes compared with wild type, indicating postsynaptic sensitivity loss for the neurotransmitter acetylcholine. However, nerve stimulation-evoked endplate potential amplitudes were unchanged. Consequently, quantal content (i.e. the number of acetylcholine quanta released per nerve impulse) was considerably increased. Such a homeostatic compensatory increase in neurotransmitter release is also found at NMJs in myasthenia gravis, where autoantibodies reduce acetylcholine receptors. However, high-rate nerve stimulation induced exaggerated endplate potential rundown. Study of NMJ morphology showed that fragmentation of acetylcholine receptor clusters occurred in all models, being most severe in mdx/utrn(-/-) mice. Overall, we showed mild 'myasthenia-like' neuromuscular synaptic dysfunction in several Duchenne mouse models, which possibly affects muscle weakness and degeneration. PMID:27037492

  18. The Association between Resting Functional Connectivity and Visual Creativity

    PubMed Central

    Li, Wenfu; Yang, Junyi; Zhang, Qinglin; Li, Gongying; Qiu, Jiang

    2016-01-01

    Resting-state functional connectivity (RSFC), the temporal correlation of intrinsic activation between different brain regions, has become one of the most fascinating field in the functional imaging studies. To better understand the association between RSFC and individual creativity, we used RSFC and the figure Torrance Tests of Creative Thinking (TTCT-F) to investigate the relationship between creativity measured by TTCT and RSFC within two different brain networks, default mode network and the cognitive control network, in a large healthy sample (304). We took the medial prefrontal cortex (MPFC) and the bilateral dorsolateral prefrontal cortices (DLPFC) to be the seed regions and investigated the association across subjects between the score of TTCT-F and the strength of RSFC between these seed regions and other voxels in the whole brain. Results revealed that the strength of RSFC with the MPFC was significantly and negatively correlated with the score of TTCT-F in the precuneus. Meanwhile, we also found that the strength of RSFC with the left DLPFC was significantly and positively correlated with the score of TTCT-F in the right DLPFC. It suggests that the decreased RSFC within DMN and the increased RSFC within CCN presents a potential interaction mechanism between different region for higher creativity. PMID:27138732

  19. The Association between Resting Functional Connectivity and Visual Creativity.

    PubMed

    Li, Wenfu; Yang, Junyi; Zhang, Qinglin; Li, Gongying; Qiu, Jiang

    2016-01-01

    Resting-state functional connectivity (RSFC), the temporal correlation of intrinsic activation between different brain regions, has become one of the most fascinating field in the functional imaging studies. To better understand the association between RSFC and individual creativity, we used RSFC and the figure Torrance Tests of Creative Thinking (TTCT-F) to investigate the relationship between creativity measured by TTCT and RSFC within two different brain networks, default mode network and the cognitive control network, in a large healthy sample (304). We took the medial prefrontal cortex (MPFC) and the bilateral dorsolateral prefrontal cortices (DLPFC) to be the seed regions and investigated the association across subjects between the score of TTCT-F and the strength of RSFC between these seed regions and other voxels in the whole brain. Results revealed that the strength of RSFC with the MPFC was significantly and negatively correlated with the score of TTCT-F in the precuneus. Meanwhile, we also found that the strength of RSFC with the left DLPFC was significantly and positively correlated with the score of TTCT-F in the right DLPFC. It suggests that the decreased RSFC within DMN and the increased RSFC within CCN presents a potential interaction mechanism between different region for higher creativity. PMID:27138732

  20. Network analysis of functional brain connectivity in borderline personality disorder using resting-state fMRI.

    PubMed

    Xu, Tingting; Cullen, Kathryn R; Mueller, Bryon; Schreiner, Mindy W; Lim, Kelvin O; Schulz, S Charles; Parhi, Keshab K

    2016-01-01

    Borderline personality disorder (BPD) is associated with symptoms such as affect dysregulation, impaired sense of self, and self-harm behaviors. Neuroimaging research on BPD has revealed structural and functional abnormalities in specific brain regions and connections. However, little is known about the topological organizations of brain networks in BPD. We collected resting-state functional magnetic resonance imaging (fMRI) data from 20 patients with BPD and 10 healthy controls, and constructed frequency-specific functional brain networks by correlating wavelet-filtered fMRI signals from 82 cortical and subcortical regions. We employed graph-theory based complex network analysis to investigate the topological properties of the brain networks, and employed network-based statistic to identify functional dysconnections in patients. In the 0.03-0.06 Hz frequency band, compared to controls, patients with BPD showed significantly larger measures of global network topology, including the size of largest connected graph component, clustering coefficient, small-worldness, and local efficiency, indicating increased local cliquishness of the functional brain network. Compared to controls, patients showed lower nodal centrality at several hub nodes but greater centrality at several non-hub nodes in the network. Furthermore, an interconnected subnetwork in 0.03-0.06 Hz frequency band was identified that showed significantly lower connectivity in patients. The links in the subnetwork were mainly long-distance connections between regions located at different lobes; and the mean connectivity of this subnetwork was negatively correlated with the increased global topology measures. Lastly, the key network measures showed high correlations with several clinical symptom scores, and classified BPD patients against healthy controls with high accuracy based on linear discriminant analysis. The abnormal topological properties and connectivity found in this study may add new knowledge

  1. Network analysis of functional brain connectivity in borderline personality disorder using resting-state fMRI

    PubMed Central

    Xu, Tingting; Cullen, Kathryn R.; Mueller, Bryon; Schreiner, Mindy W.; Lim, Kelvin O.; Schulz, S. Charles; Parhi, Keshab K.

    2016-01-01

    Borderline personality disorder (BPD) is associated with symptoms such as affect dysregulation, impaired sense of self, and self-harm behaviors. Neuroimaging research on BPD has revealed structural and functional abnormalities in specific brain regions and connections. However, little is known about the topological organizations of brain networks in BPD. We collected resting-state functional magnetic resonance imaging (fMRI) data from 20 patients with BPD and 10 healthy controls, and constructed frequency-specific functional brain networks by correlating wavelet-filtered fMRI signals from 82 cortical and subcortical regions. We employed graph-theory based complex network analysis to investigate the topological properties of the brain networks, and employed network-based statistic to identify functional dysconnections in patients. In the 0.03–0.06 Hz frequency band, compared to controls, patients with BPD showed significantly larger measures of global network topology, including the size of largest connected graph component, clustering coefficient, small-worldness, and local efficiency, indicating increased local cliquishness of the functional brain network. Compared to controls, patients showed lower nodal centrality at several hub nodes but greater centrality at several non-hub nodes in the network. Furthermore, an interconnected subnetwork in 0.03–0.06 Hz frequency band was identified that showed significantly lower connectivity in patients. The links in the subnetwork were mainly long-distance connections between regions located at different lobes; and the mean connectivity of this subnetwork was negatively correlated with the increased global topology measures. Lastly, the key network measures showed high correlations with several clinical symptom scores, and classified BPD patients against healthy controls with high accuracy based on linear discriminant analysis. The abnormal topological properties and connectivity found in this study may add new

  2. Altered functional connectivity of the cingulate subregions in schizophrenia.

    PubMed

    Wang, D; Zhou, Y; Zhuo, C; Qin, W; Zhu, J; Liu, H; Xu, L; Yu, C

    2015-01-01

    Schizophrenia patients have shown altered resting-state functional connectivity (rsFC) of the cingulate cortex; however, it is unknown whether rsFCs of the cingulate subregions are differentially affected in this disorder. We aimed to clarify the issue by comparing rsFCs of each cingulate subregion between healthy controls and schizophrenia patients. A total of 102 healthy controls and 94 schizophrenia patients underwent resting-state functional magnetic resonance imaging with a sensitivity-encoded spiral-in imaging sequence to reduce susceptibility-induced signal loss and distortion. The cingulate cortex was divided into nine subregions, including the subgenual anterior cingulate cortex (ACC), areas 24 and 32 of the pregenual ACC, areas 24 and 32 of the anterior mid-cingulate cortex (aMCC), posterior MCC (pMCC), dorsal (dPCC) and ventral (vPCC) posterior cingulate cortex (PCC) and retrosplenial cortex (RSC). The rsFCs of each cingulate subregion were compared between the two groups and the atrophy effect was considered. Results with and without global signal regression were reported. Most cingulate subregions exhibited decreased rsFCs in schizophrenia after global signal regression (GSR). Without GSR, only increased rsFC was found in schizophrenia, which primarily restricted to the aMCC, PCC and RSC. Some of these increased rsFCs were also significant after GSR. These findings suggest that GSR can greatly affect between-group differences in rsFCs and the consistently increased rsFCs may challenge the functional disconnection hypothesis of schizophrenia. PMID:26035059

  3. Differential Patterns of Abnormal Activity and Connectivity in the Amygdala-Prefrontal Circuitry in Bipolar-I and Bipolar-NOS Youth

    ERIC Educational Resources Information Center

    Ladouceur, Cecile D.; Farchione, Tiffany; Diwadkar, Vaibhav; Pruitt, Patrick; Radwan, Jacqueline; Axelson, David A.; Birmaher, Boris; Phillips, Mary L.

    2011-01-01

    Objective: The functioning of neural systems supporting emotion processing and regulation in youth with bipolar disorder not otherwise specified (BP-NOS) remains poorly understood. We sought to examine patterns of activity and connectivity in youth with BP-NOS relative to youth with bipolar disorder type I (BP-I) and healthy controls (HC). Method:…

  4. Highly adaptive tests for group differences in brain functional connectivity.

    PubMed

    Kim, Junghi; Pan, Wei

    2015-01-01

    Resting-state functional magnetic resonance imaging (rs-fMRI) and other technologies have been offering evidence and insights showing that altered brain functional networks are associated with neurological illnesses such as Alzheimer's disease. Exploring brain networks of clinical populations compared to those of controls would be a key inquiry to reveal underlying neurological processes related to such illnesses. For such a purpose, group-level inference is a necessary first step in order to establish whether there are any genuinely disrupted brain subnetworks. Such an analysis is also challenging due to the high dimensionality of the parameters in a network model and high noise levels in neuroimaging data. We are still in the early stage of method development as highlighted by Varoquaux and Craddock (2013) that "there is currently no unique solution, but a spectrum of related methods and analytical strategies" to learn and compare brain connectivity. In practice the important issue of how to choose several critical parameters in estimating a network, such as what association measure to use and what is the sparsity of the estimated network, has not been carefully addressed, largely because the answers are unknown yet. For example, even though the choice of tuning parameters in model estimation has been extensively discussed in the literature, as to be shown here, an optimal choice of a parameter for network estimation may not be optimal in the current context of hypothesis testing. Arbitrarily choosing or mis-specifying such parameters may lead to extremely low-powered tests. Here we develop highly adaptive tests to detect group differences in brain connectivity while accounting for unknown optimal choices of some tuning parameters. The proposed tests combine statistical evidence against a null hypothesis from multiple sources across a range of plausible tuning parameter values reflecting uncertainty with the unknown truth. These highly adaptive tests are not only

  5. Highly adaptive tests for group differences in brain functional connectivity

    PubMed Central

    Kim, Junghi; Pan, Wei

    2015-01-01

    Resting-state functional magnetic resonance imaging (rs-fMRI) and other technologies have been offering evidence and insights showing that altered brain functional networks are associated with neurological illnesses such as Alzheimer's disease. Exploring brain networks of clinical populations compared to those of controls would be a key inquiry to reveal underlying neurological processes related to such illnesses. For such a purpose, group-level inference is a necessary first step in order to establish whether there are any genuinely disrupted brain subnetworks. Such an analysis is also challenging due to the high dimensionality of the parameters in a network model and high noise levels in neuroimaging data. We are still in the early stage of method development as highlighted by Varoquaux and Craddock (2013) that “there is currently no unique solution, but a spectrum of related methods and analytical strategies” to learn and compare brain connectivity. In practice the important issue of how to choose several critical parameters in estimating a network, such as what association measure to use and what is the sparsity of the estimated network, has not been carefully addressed, largely because the answers are unknown yet. For example, even though the choice of tuning parameters in model estimation has been extensively discussed in the literature, as to be shown here, an optimal choice of a parameter for network estimation may not be optimal in the current context of hypothesis testing. Arbitrarily choosing or mis-specifying such parameters may lead to extremely low-powered tests. Here we develop highly adaptive tests to detect group differences in brain connectivity while accounting for unknown optimal choices of some tuning parameters. The proposed tests combine statistical evidence against a null hypothesis from multiple sources across a range of plausible tuning parameter values reflecting uncertainty with the unknown truth. These highly adaptive tests are not

  6. Mice That Lack Thrombospondin 2 Display Connective Tissue Abnormalities That Are Associated with Disordered Collagen Fibrillogenesis, an Increased Vascular Density, and a Bleeding Diathesis

    PubMed Central

    Kyriakides, Themis R.; Zhu, Yu-Hong; Smith, Lynne T.; Bain, Steven D.; Yang, Zhantao; Lin, Ming T.; Danielson, Keith G.; Iozzo, Renato V.; LaMarca, Mary; McKinney, Cindy E.; Ginns, Edward I.; Bornstein, Paul

    1998-01-01

    Thrombospondin (TSP) 2, and its close relative TSP1, are extracellular proteins whose functions are complex, poorly understood, and controversial. In an attempt to determine the function of TSP2, we disrupted the Thbs2 gene by homologous recombination in embryonic stem cells, and generated TSP2-null mice by blastocyst injection and appropriate breeding of mutant animals. Thbs2−/− mice were produced with the expected Mendelian frequency, appeared overtly normal, and were fertile. However, on closer examination, these mice displayed a wide variety of abnormalities. Collagen fiber patterns in skin were disordered, and abnormally large fibrils with irregular contours were observed by electron microscopy in both skin and tendon. As a functional correlate of these findings, the skin was fragile and had reduced tensile strength, and the tail was unusually flexible. Mutant skin fibroblasts were defective in attachment to a substratum. An increase in total density and in cortical thickness of long bones was documented by histology and quantitative computer tomography. Mutant mice also manifested an abnormal bleeding time, and histologic surveys of mouse tissues, stained with an antibody to von Willebrand factor, showed a significant increase in blood vessels. The basis for the unusual phenotype of the TSP2-null mouse could derive from the structural role that TSP2 might play in collagen fibrillogenesis in skin and tendon. However, it seems likely that some of the diverse manifestations of this genetic disorder result from the ability of TSP2 to modulate the cell surface properties of mesenchymal cells, and thus, to affect cell functions such as adhesion and migration. PMID:9442117

  7. The Effects of Long Duration Bed Rest on Brain Functional Connectivity and Sensorimotor Functioning

    NASA Technical Reports Server (NTRS)

    Cassady, K.; Koppelmans, V.; De Dios, Y.; Stepanyan, V.; Szecsy, D.; Gadd, N.; Wood, S.; Reuter-Lorenz, P.; Castenada, R. Riascos; Kofman, I.; Bloomberg, J.; Mulavara, A; Seidler, R.

    2016-01-01

    Long duration spaceflight has been associated with detrimental alterations in human sensorimotor functioning. Prolonged exposure to a head-down tilt (HDT) position during long duration bed rest can resemble several effects of the microgravity environment such as reduced sensory inputs, body unloading and increased cephalic fluid distribution. The question of whether microgravity affects other central nervous system functions such as brain functional connectivity and its relationship with behavior is largely unknown, but of importance to the health and performance of astronauts both during and post-flight. In the present study, we investigate the effects of prolonged exposure to HDT bed rest on resting state brain functional connectivity and its association with behavioral changes in 17 male participants. To validate that our findings were not due to confounding factors such as time or task practice, we also acquired resting state functional magnetic resonance imaging (rs-fMRI) and behavioral measurements from 14 normative control participants at four time points. Bed rest participants remained in bed with their heads tilted down six degrees below their feet for 70 consecutive days. Rs-fMRI and behavioral data were obtained at seven time points averaging around: 12 and 8 days prior to bed rest; 7, 50, and 70 days during bed rest; and 8 and 12 days after bed rest. 70 days of HDT bed rest resulted in significant increases in functional connectivity during bed rest followed by a reversal of changes in the post bed rest recovery period between motor cortical and somatosensory areas of the brain. In contrast, decreases in connectivity were observed between temporoparietal regions. Furthermore, post-hoc correlation analyses revealed a significant relationship between motor-somatosensory network connectivity and standing balance performance changes; participants that exhibited the greatest increases in connectivity strength showed the least deterioration in postural

  8. Functional magnetic resonance imaging in disorders of consciousness: preliminary results of an innovative analysis of brain connectivity

    PubMed Central

    de Pasquale, Francesco; Caravasso, Chiara Falletta; Péran, Patrice; Catani, Sheila; Tuovinen, Noora; Sabatini, Umberto; Formisano, Rita

    2015-01-01

    Summary The aim of this preliminary study was to present a new approach for connectivity analysis in patients with severe acquired brain injury (ABI) that overcomes some of the difficulties created by anatomical abnormalities due to the brain injury. Using a data-driven approach, resting-state structural MRI (sMRI) and functional MRI (fMRI) data from three severe ABI patients – two with disorders of consciousness (DOC) and one who had recovered consciousness (non-DOC) – were integrated and analyzed. Parameters extracted from the distribution of the connectivity values, such as mean, standard deviation and skeweness, were considered. The distribution parameters estimated seem to provide an accurate multivariate classification of the considered cases that can be summarized as follows: connectivity in the severe ABI patients with DOC was on average lower than in the severe ABI non-DOC patient and healthy subjects. The dispersion of connectivity values of the severe ABI patients, non-DOC and DOC, was comparable, however the shape of the distribution was different in the non-DOC patient. Eventually, seed-based connectivity maps of the default mode network show a pattern of increasing disruption of this network from the healthy subjects to non-DOC and DOC patients. Consistent results are obtained using an ICA-based approach. PMID:26910178

  9. Alterations in Amygdala Functional Connectivity Reflect Early Temperament

    PubMed Central

    Roy, Amy Krain; Benson, Brenda E.; Degnan, Kathryn A.; Perez-Edgar, Koraly; Pine, Daniel S.; Fox, Nathan A.; Ernst, Monique

    2014-01-01

    Behavioral inhibition (BI) is a temperament identified early in life that is associated with increased risk for anxiety disorders. Amygdala hyperresponsivity, found both in behaviorally inhibited and anxious individuals, suggests that amygdala dysfunction may represent a marker of anxiety risk. However, broader amygdala networks have not been examined in individuals with a history of childhood BI. This study uses resting state fMRI to assess amygdala intrinsic functional connectivity (iFC) in 38 healthy young adults (19 with a history of BI, 19 with no history of BI) selected from a longitudinal study. Centromedial, basolateral, and superficial amygdala iFCs were compared between groups and examined in relation to self-report measures of anxiety. Group differences were observed in amygdala iFC with prefrontal cortex, striatum, anterior insula, and cerebellum. Adults characterized with BI in childhood endorsed greater state anxiety prior to entering the scanner, which was associated with several of the group differences. Findings support enduring effects of BI on amygdala circuitry, even in the absence of current psychopathology. PMID:25261727

  10. Functional abnormalities in the cortical processing of sound complexity and musical consonance in schizophrenia: evidence from an evoked potential study

    PubMed Central

    2013-01-01

    Background Previous studies have demonstrated functional and structural temporal lobe abnormalities located close to the auditory cortical regions in schizophrenia. The goal of this study was to determine whether functional abnormalities exist in the cortical processing of musical sound in schizophrenia. Methods Twelve schizophrenic patients and twelve age- and sex-matched healthy controls were recruited, and participants listened to a random sequence of two kinds of sonic entities, intervals (tritones and perfect fifths) and chords (atonal chords, diminished chords, and major triads), of varying degrees of complexity and consonance. The perception of musical sound was investigated by the auditory evoked potentials technique. Results Our results showed that schizophrenic patients exhibited significant reductions in the amplitudes of the N1 and P2 components elicited by musical stimuli, to which consonant sounds contributed more significantly than dissonant sounds. Schizophrenic patients could not perceive the dissimilarity between interval and chord stimuli based on the evoked potentials responses as compared with the healthy controls. Conclusion This study provided electrophysiological evidence of functional abnormalities in the cortical processing of sound complexity and music consonance in schizophrenia. The preliminary findings warrant further investigations for the underlying mechanisms. PMID:23721126

  11. Role of local and distant functional connectivity density in the development of minimal hepatic encephalopathy

    PubMed Central

    Qi, Rongfeng; Zhang, Long Jiang; Chen, Hui Juan; Zhong, Jianhui; Luo, Song; Ke, Jun; Xu, Qiang; Kong, Xiang; Liu, Chang; Lu, Guang Ming

    2015-01-01

    The progression of functional connectivity (FC) patterns from non-hepatic encephalopathy (non-HE) to minimal HE (MHE) is not well known. This resting-state functional magnetic resonance imaging (rs-fMRI) study investigated the evolution of intrinsic FC patterns from non-HE to MHE. A total of 103 cirrhotic patients (MHE, n = 34 and non-HE, n = 69) and 103 healthy controls underwent rs-fMRI scanning. Maps of distant and local FC density (dFCD and lFCD, respectively) were compared among MHE, non-HE, and healthy control groups. Decreased lFCD in anterior cingulate cortex, pre- and postcentral gyri, cuneus, lingual gyrus, and putamen was observed in both MHE and non-HE patients relative to controls. There was no difference in lFCD between MHE and non-HE groups. The latter showed decreased dFCD in inferior parietal lobule, cuneus, and medial frontal cortex relative to controls; however, MHE patients showed decreased dFCD in frontal and parietal cortices as well as increased dFCD in thalamus and caudate head relative to control and non-HE groups. Abnormal FCD values in some regions correlated with MHE patients’ neuropsychological performance. In conclusion, lFCD and dFCD were perturbed in MHE. Impaired dFCD in regions within the cortico-striato-thalamic circuit may be more closely associated with the development of MHE. PMID:26329994

  12. Dynamic functional connectivity of the default mode network tracks daydreaming.

    PubMed

    Kucyi, Aaron; Davis, Karen D

    2014-10-15

    Humans spend much of their time engaged in stimulus-independent thoughts, colloquially known as "daydreaming" or "mind-wandering." A fundamental question concerns how awake, spontaneous brain activity represents the ongoing cognition of daydreaming versus unconscious processes characterized as "intrinsic." Since daydreaming involves brief cognitive events that spontaneously fluctuate, we tested the hypothesis that the dynamics of brain network functional connectivity (FC) are linked with daydreaming. We determined the general tendency to daydream in healthy adults based on a daydreaming frequency scale (DDF). Subjects then underwent both resting state functional magnetic resonance imaging (rs-fMRI) and fMRI during sensory stimulation with intermittent thought probes to determine the occurrences of mind-wandering events. Brain regions within the default mode network (DMN), purported to be involved in daydreaming, were assessed for 1) static FC across the entire fMRI scans, and 2) dynamic FC based on FC variability (FCV) across 30s progressively sliding windows of 2s increments within each scan. We found that during both resting and sensory stimulation states, individual differences in DDF were negatively correlated with static FC between the posterior cingulate cortex and a ventral DMN subsystem involved in future-oriented thought. Dynamic FC analysis revealed that DDF was positively correlated with FCV within the same DMN subsystem in the resting state but not during stimulation. However, dynamic but not static FC, in this subsystem, was positively correlated with an individual's degree of self-reported mind-wandering during sensory stimulation. These findings identify temporal aspects of spontaneous DMN activity that reflect conscious and unconscious processes. PMID:24973603

  13. Connectivity

    ERIC Educational Resources Information Center

    Grush, Mary, Ed.

    2006-01-01

    Connectivity has dramatically changed the landscape of higher education IT. From "on-demand" services for net-gen students and advanced eLearning systems for faculty, to high-performance computing grid resources for researchers, IT now provides more networked services than ever to connect campus constituents to each other and to the world.…

  14. In search of neural mechanisms of mirror neuron dysfunction in schizophrenia: resting state functional connectivity approach.

    PubMed

    Zaytseva, Yuliya; Bendova, Marie; Garakh, Zhanna; Tintera, Jaroslav; Rydlo, Jan; Spaniel, Filip; Horacek, Jiri

    2015-09-01

    It has been repeatedly shown that schizophrenia patients have immense alterations in goal-directed behaviour, social cognition, and social interactions, cognitive abilities that are presumably driven by the mirror neurons system (MNS). However, the neural bases of these deficits still remain unclear. Along with the task-related fMRI and EEG research tapping into the mirror neuron system, the characteristics of the resting state activity in the particular areas that encompass mirror neurons might be of interest as they obviously determine the baseline of the neuronal activity. Using resting state fMRI, we investigated resting state functional connectivity (FC) in four predefined brain structures, ROIs (inferior frontal gyrus, superior parietal lobule, premotor cortex and superior temporal gyrus), known for their mirror neurons activity, in 12 patients with first psychotic episode and 12 matched healthy individuals. As a specific hypothesis, based on the knowledge of the anatomical inputs of thalamus to all preselected ROIs, we have investigated the FC between thalamus and the ROIs. Of all ROIs included, seed-to-voxel connectivity analysis revealed significantly decreased FC only in left posterior superior temporal gyrus (STG) and the areas in visual cortex and cerebellum in patients as compared to controls. Using ROI-to-ROI analysis (thalamus and selected ROIs), we have found an increased FC of STG and bilateral thalamus whereas the FC of these areas was decreased in controls. Our results suggest that: (1) schizophrenia patients exhibit FC of STG which corresponds to the previously reported changes of superior temporal gyrus in schizophrenia and might contribute to the disturbances of specific functions, such as emotional processing or spatial awareness; (2) as the thalamus plays a pivotal role in the sensory gating, providing the filtering of the redundant stimulation, the observed hyperconnectivity between the thalami and the STGs in patients with schizophrenia

  15. Comparative connective tissue structure-function relationships in biologic pumps.

    PubMed

    Factor, S M; Robinson, T F

    1988-02-01

    A complex connective tissue framework exists in mammalian hearts that surrounds and interconnects individual myocytes and fascicles of cells. Recent evidence suggests that this connective tissue plays a role in maintaining shape, modulating contractile forces, and mediating elastic recoil during cavity filling and contraction. In order to analyze the involvement of connective tissue in pump contraction and recoil, we examined silver impregnated connective tissue in rat hearts which spontaneously jet through fluid ex vivo by contracting their cavities forcefully and then sucking fluid for the next cycle, and compared them to frog hearts which beat actively under the same conditions, but do not demonstrate jet propulsion. A further analysis was carried out in unrelated but analogous models: the squid and octopus. The former jets rapidly through the ocean, while the latter moves sinuously along the seabed. We observed highly interconnected myocytes in the rat heart, whereas frog myocytes are individually wrapped by connective tissue but are not interconnected. The squid mantle muscle is surrounded by a complex connective tissue grid that is tethered to each muscle cell, whereas the octopus mantle muscle cells are surrounded by connective tissue but are not tethered. These observations suggest that myocyte connective tissue tethering may be necessary for muscle cavities to generate forceful and coordinated contractions sufficient for rapid ejection and suction of fluid. PMID:2448546

  16. Identification of Sparse Neural Functional Connectivity using Penalized Likelihood Estimation and Basis Functions

    PubMed Central

    Song, Dong; Wang, Haonan; Tu, Catherine Y.; Marmarelis, Vasilis Z.; Hampson, Robert E.; Deadwyler, Sam A.; Berger, Theodore W.

    2013-01-01

    One key problem in computational neuroscience and neural engineering is the identification and modeling of functional connectivity in the brain using spike train data. To reduce model complexity, alleviate overfitting, and thus facilitate model interpretation, sparse representation and estimation of functional connectivity is needed. Sparsities include global sparsity, which captures the sparse connectivities between neurons, and local sparsity, which reflects the active temporal ranges of the input-output dynamical interactions. In this paper, we formulate a generalized functional additive model (GFAM) and develop the associated penalized likelihood estimation methods for such a modeling problem. A GFAM consists of a set of basis functions convolving the input signals, and a link function generating the firing probability of the output neuron from the summation of the convolutions weighted by the sought model coefficients. Model sparsities are achieved by using various penalized likelihood estimations and basis functions. Specifically, we introduce two variations of the GFAM using a global basis (e.g., Laguerre basis) and group LASSO estimation, and a local basis (e.g., B-spline basis) and group bridge estimation, respectively. We further develop an optimization method based on quadratic approximation of the likelihood function for the estimation of these models. Simulation and experimental results show that both group-LASSO-Laguerre and group-bridge-B-spline can capture faithfully the global sparsities, while the latter can replicate accurately and simultaneously both global and local sparsities. The sparse models outperform the full models estimated with the standard maximum likelihood method in out-of-sample predictions. PMID:23674048

  17. Functional total anomalous pulmonary venous connection via levoatriocardinal vein.

    PubMed

    Hayashi, Taiyu; Ozawa, Katsusuke; Sugibayashi, Rika; Wada, Seiji; Ono, Hiroshi

    2016-07-01

    We report a fetal case of double outlet right ventricle, mitral atresia, and intact atrial septum. Although the pulmonary veins were connected to the left atrium, pulmonary venous blood drained into the right superior vena cava via the stenotic levoatriocardinal vein (LACV), which resulted in a circulation resembling total anomalous pulmonary venous connection (TAPVC) with pulmonary venous obstruction. Since the pulmonary veins were connected to both the stenotic LACV and the "dead-end" left atrium, the pulmonary venous flow had a to-and-fro pattern along with atrial relaxation and contraction. Postnatal echocardiography and computed tomography confirmed the diagnosis of normally connected but anomalously draining pulmonary veins via the LACV. Surgical creation of an atrial septal defect on the day of birth successfully relieved pulmonary venous obstruction. Normally connected but anomalously draining pulmonary veins via the LACV should be considered for TAPVC differential diagnosis in fetuses with a left-side heart obstruction. PMID:27460400

  18. Transport on Riemannian manifold for functional connectivity-based classification.

    PubMed

    Ng, Bernard; Dressler, Martin; Varoquaux, Gaël; Poline, Jean Baptiste; Greicius, Michael; Thirion, Bertrand

    2014-01-01

    We present a Riemannian approach for classifying fMRI connectivity patterns before and after intervention in longitudinal studies. A fundamental difficulty with using connectivity as features is that covariance matrices live on the positive semi-definite cone, which renders their elements inter-related. The implicit independent feature assumption in most classifier learning algorithms is thus violated. In this paper, we propose a matrix whitening transport for projecting the covariance estimates onto a common tangent space to reduce the statistical dependencies between their elements. We show on real data that our approach provides significantly higher classification accuracy than directly using Pearson's correlation. We further propose a non-parametric scheme for identifying significantly discriminative connections from classifier weights. Using this scheme, a number of neuroanatomically meaningful connections are found, whereas no significant connections are detected with pure permutation testing. PMID:25485405

  19. Reduced Integration and Differentiation of the Imitation Network in Autism: A Combined Functional Connectivity Magnetic Resonance Imaging and Diffusion-Weighted Imaging Study

    PubMed Central

    Fishman, Inna; Datko, Michael; Cabrera, Yuliana; Carper, Ruth A.; Müller, Ralph-Axel

    2016-01-01

    Objective Converging evidence indicates that brain abnormalities in autism spectrum disorder (ASD) involve atypical network connectivity, but few studies have integrated functional with structural connectivity measures. This multimodal investigation examined functional and structural connectivity of the imitation network in children and adolescents with ASD, and its links with clinical symptoms. Methods Resting state functional magnetic resonance imaging and diffusion-weighted imaging were performed in 35 participants with ASD and 35 typically developing controls, aged 8 to 17 years, matched for age, gender, intelligence quotient, and head motion. Results Within-network analyses revealed overall reduced functional connectivity (FC) between distributed imitation regions in the ASD group. Whole brain analyses showed that underconnectivity in ASD occurred exclusively in regions belonging to the imitation network, whereas overconnectivity was observed between imitation nodes and extraneous regions. Structurally, reduced fractional anisotropy and increased mean diffusivity were found in white matter tracts directly connecting key imitation regions with atypical FC in ASD. These differences in microstructural organization of white matter correlated with weaker FC and greater ASD symptomatology. Interpretation Findings demonstrate atypical connectivity of the brain network supporting imitation in ASD, characterized by a highly specific pattern. This pattern of underconnectivity within, but overconnectivity outside the functional network is in contrast with typical development and suggests reduced network integration and differentiation in ASD. Our findings also indicate that atypical connectivity of the imitation network may contribute to ASD clinical symptoms, highlighting the role of this fundamental social cognition ability in the pathophysiology of ASD. PMID:26418284

  20. Alterations in Functional Connectivity for Language in Prematurely Born Adolescents

    ERIC Educational Resources Information Center

    Schafer, Robin J.; Lacadie, Cheryl; Vohr, Betty; Kesler, Shelli R.; Katz, Karol H.; Schneider, Karen C.; Pugh, Kenneth R.; Makuch, Robert W.; Reiss, Allan L.; Constable, R. Todd; Ment, Laura R.

    2009-01-01

    Recent data suggest recovery of language systems but persistent structural abnormalities in the prematurely born. We tested the hypothesis that subjects who were born prematurely develop alternative networks for processing language. Subjects who were born prematurely (n = 22; 600-1250 g birth weight), without neonatal brain injury on neonatal…