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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. Abnormal thalamocortical structural and functional connectivity in juvenile myoclonic epilepsy

    PubMed Central

    O’Muircheartaigh, Jonathan; Vollmar, Christian; Barker, Gareth J.; Kumari, Veena; Symms, Mark R.; Thompson, Pam; Duncan, John S.; Koepp, Matthias J.

    2012-01-01

    Juvenile myoclonic epilepsy is the most common idiopathic generalized epilepsy, characterized by frequent myoclonic jerks, generalized tonic-clonic seizures and, less commonly, absences. Neuropsychological and, less consistently, anatomical studies have indicated frontal lobe dysfunction in the disease. Given its presumed thalamo–cortical basis, we investigated thalamo–cortical structural connectivity, as measured by diffusion tensor imaging, in a cohort of 28 participants with juvenile myoclonic epilepsy and detected changes in an anterior thalamo–cortical bundle compared with healthy control subjects. We then investigated task-modulated functional connectivity from the anterior thalamic region identified using functional magnetic resonance imaging in a task consistently shown to be impaired in this group, phonemic verbal fluency. We demonstrate an alteration in task-modulated connectivity in a region of frontal cortex directly connected to the thalamus via the same anatomical bundle, and overlapping with the supplementary motor area. Further, we show that the degree of abnormal connectivity is related to disease severity in those with active seizures. By integrating methods examining structural and effective interregional connectivity, these results provide convincing evidence for abnormalities in a specific thalamo–cortical circuit, with reduced structural and task-induced functional connectivity, which may underlie the functional abnormalities in this idiopathic epilepsy. PMID:23250883

  3. 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

  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 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

  6. 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

  7. 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

  8. Selective functional connectivity abnormality of the transition zone of the inferior parietal lobule in schizophrenia.

    PubMed

    Liu, Xingyun; Zhuo, Chuanjun; Qin, Wen; Zhu, Jiajia; Xu, Lixue; Xu, Yongjie; Yu, Chunshui

    2016-01-01

    Structural and functional alterations in the inferior parietal lobule (IPL) in schizophrenia have been frequently reported; however, the IPL connectivity changes in schizophrenia remain largely unknown. Based on heterogeneity of the IPL in structure, connection and function, we hypothesize that the resting-state functional connectivities (rsFCs) of the IPL subregions are differentially affected in schizophrenia. This study included 95 schizophrenia patients and 104 healthy controls. The IPL subregions were defined according to a previous in vivo connection-based parcellation study. We calculated the rsFC of each IPL subregion and compared them between the two groups while controlling for the effects of age, gender, and grey matter volume. Among the six subregions of the left IPL and the five subregions of the right IPL, only the bilateral PFm (a transition zone of the IPL) subregions exhibited abnormal rsFC in schizophrenia. Specifically, the left PFm showed increased rsFC with the bilateral lingual gyri in schizophrenia patients than in healthy controls. The right PFm exhibited increased rsFC with the right lingual gyrus and inferior occipital gyrus, and bilateral mid-cingulate and sensorimotor cortices in schizophrenia patients. These findings suggest a selective rsFC abnormality in the IPL subregions in schizophrenia, characterized by the increased rsFC between the PFm subregion of the IPL and the visual and sensorimotor areas. PMID:27354957

  9. Abnormal functional connectivity in focal hand dystonia: Mutual information analysis in EEG

    PubMed Central

    Jin, Seung-Hyun; Lin, Peter; Auh, Sungyoung; Hallett, Mark

    2011-01-01

    The aim of the present study was to investigate functional connectivity (FC) in focal hand dystonia (FHD) patients to understand the pathophysiology underlying their abnormality in movement. We recorded EEG from 58 electrodes in 15 FHD patients and 15 healthy volunteers during rest and a simple finger-tapping task that did not induce any dystonic symptoms. We investigated the mutual information (MI), which provides a quantitative measure of linear and nonlinear coupling, in the alpha, beta and gamma bands. Mean MI of all 58 channels and mean of the channels of interest (COIs) representative of regional FC over sensorimotor areas (C3, CP3, C4, CP4, FCz and Cz) were evaluated. For both groups, we found enhanced MI during the task compared to the rest condition specifically in the beta and gamma bands for mean MI of all channels, and in all bands for mean MI of COIs. Comparing the FHD patients to the healthy volunteers, for both rest and task, there was reduced MI in the beta band for both mean MI of all channels and mean MI of COIs. Regarding the properties of the connectivity in the beta band, we found that the majority of the MI differences were from linear connectivity. The abnormal beta band FC in FHD patients suggests deficient brain connectivity. PMID:21506166

  10. Abnormal functional connectivity of the medial cortex in euthymic bipolar II disorder.

    PubMed

    Marchand, William R; Lee, James N; Johnson, Susanna; Gale, Phillip; Thatcher, John

    2014-06-01

    This project utilized functional MRI (fMRI) and a motor activation paradigm to investigate neural circuitry in euthymic bipolar II disorder. We hypothesized that circuitry involving the cortical midline structures (CMS) would demonstrate abnormal functional connectivity. Nineteen subjects with recurrent bipolar disorder and 18 controls were studied using fMRI and a motor activation paradigm. We used functional connectivity analyses to identify circuits with aberrant connectivity. We found increased functional connectivity among bipolar subjects compared to healthy controls in two CMS circuits. One circuit included the medial aspect of the left superior frontal gyrus and the dorsolateral region of the left superior frontal gyrus. The other included the medial aspect of the right superior frontal gyrus, the dorsolateral region of the left superior frontal gyrus and the right medial frontal gyrus and surrounding region. Our results indicate that CMS circuit dysfunction persists in the euthymic state and thus may represent trait pathology. Future studies should address whether these circuits contribute to relapse of illness. Our results also suggest the possibility that aberrations of superior frontal circuitry may impact default mode network and cognitive processes.

  11. 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

  12. Functional Connectivity Abnormalities of Brain Regions with Structural Deficits in Young Adult Male Smokers

    PubMed Central

    Bu, Limei; Yu, Dahua; Su, Shaoping; Ma, Yao; von Deneen, Karen M.; Luo, Lin; Zhai, Jinquan; Liu, Bo; Cheng, Jiadong; Guan, Yanyan; Li, Yangding; Bi, Yanzhi; Xue, Ting; Lu, Xiaoqi; Yuan, Kai

    2016-01-01

    Smoking is one of the most prevalent dependence disorders. Previous studies have detected structural and functional deficits in smokers. However, few studies focused on the changes of resting state functional connectivity (RSFC) of the brain regions with structural deficits in young adult smokers. Twenty-six young adult smokers and 26 well-matched healthy non-smokers participated in our study. Voxel-based morphometry (VBM) and RSFC were employed to investigate the structural and functional changes in young adult smokers. Compared with healthy non-smokers, young smokers showed increased gray matter (GM) volume in the left putamen and decreased GM volume in the left anterior cingulate cortex (ACC). Moreover, GM volume in the left ACC has a negative correlation trend with pack-years and GM volume in the left putamen was positively correlated with pack-years. The left ACC and putamen with abnormal volumes were chosen as the regions of interest (ROIs) for the RSFC analysis. We found that smokers showed increased RSFC between the left ACC and right amygdala and between the left putamen and right anterior insula. We revealed structural and functional deficits within the frontostriatal circuits in young smokers, which may shed new insights into the neural mechanisms of smoking. PMID:27757078

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

    2016-02-16

    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.

  18. 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

  19. 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

  20. Abnormal functional connectivity density in patients with ischemic white matter lesions

    PubMed Central

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

    2016-01-01

    Abstract 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

  1. 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

  2. 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

  3. 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

  4. 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.

  5. Abnormal Asymmetry of Brain Connectivity in Schizophrenia

    PubMed Central

    Ribolsi, Michele; Daskalakis, Zafiris J.; Siracusano, Alberto; Koch, Giacomo

    2014-01-01

    Recently, a growing body of data has revealed that beyond a dysfunction of connectivity among different brain areas in schizophrenia patients (SCZ), there is also an abnormal asymmetry of functional connectivity compared with healthy subjects. The loss of the cerebral torque and the abnormalities of gyrification, with an increased or more complex cortical folding in the right hemisphere may provide an anatomical basis for such aberrant connectivity in SCZ. Furthermore, diffusion tensor imaging studies have shown a significant reduction of leftward asymmetry in some key white-matter tracts in SCZ. In this paper, we review the studies that investigated both structural brain asymmetry and asymmetry of functional connectivity in healthy subjects and SCZ. From an analysis of the existing literature on this topic, we can hypothesize an overall generally attenuated asymmetry of functional connectivity in SCZ compared to healthy controls. Such attenuated asymmetry increases with the duration of the disease and correlates with psychotic symptoms. Finally, we hypothesize that structural deficits across the corpus callosum may contribute to the abnormal asymmetry of intra-hemispheric connectivity in schizophrenia. PMID:25566030

  6. Schizophrenia, abnormal connection, and brain evolution.

    PubMed

    Randall, P L

    1983-03-01

    Abnormalities of functional connection between specialized areas in the human brain may underlie the symptoms which constitute the schizophrenia syndrome. Callosal and intrahemispheric fibres may be equally involved. The clinical emergence of symptoms in the later stages of brain maturation may be dependent on myelination of these fibre groups, both of which have extended myelination cycles. Ontogenetically earlier variants of the same mechanism could theoretically result in dyslexia and the syndromes of Kanner and Gilles de la Tourette. As new and unique extensions of specialized function emerge within the evolving brain, biological trial and error of connection both within and between them may produce individuals possessing phylogenetically advanced abilities, or equally, others possessing a wide range of abnormalities including those which comprise the schizophrenia syndrome. A dormant phenotypic potential for schizophrenia may exist in individuals who never develop symptoms during the course of a lifetime though some of these may become clinically apparent under the influence of various precipitating factors. It is concluded that abnormal functional connection and its normal and "supernormal" counterparts may be natural, essential, and inevitable consequences of brain evolution, and that this may have been so throughout the history of vertebrate brain evolution.

  7. Functional magnetic resonance imaging reveals abnormal brain connectivity in EGR3 gene transfected rat model of schizophrenia.

    PubMed

    Song, Tianbin; Nie, Binbin; Ma, Ensen; Che, Jing; Sun, Shilong; Wang, Yuli; Shan, Baoci; Liu, Yawu; Luo, Senlin; Ma, Guolin; Li, Kefeng

    2015-05-01

    Schizophrenia is characterized by the disorder of "social brain". However, the alternation of connectivity density in brain areas of schizophrenia patients remains largely unknown. In this study, we successfully created a rat model of schizophrenia by the transfection of EGR3 gene into rat brain. We then investigated the connectivity density of schizophrenia susceptible regions in rat brain using functional magnetic resonance imaging (fMRI) in combination with multivariate Granger causality (GC) model. We found that the average signal strength in prefrontal lobe and hippocampus of schizophrenia model group was significantly higher than the control group. Bidirectional Granger causality connection was observed between hippocampus and thalamic in schizophrenia model group. Both connectivity density and Granger causality connection were changed in prefrontal lobe, hippocampus and thalamus after risperidone treatment. Our results indicated that fMRI in combination with GC connection analysis may be used as an important method in diagnosis of schizophrenia and evaluation the effect of antipsychotic treatment. These findings support the connectivity disorder hypothesis of schizophrenia and increase our understanding of the neural mechanisms of schizophrenia.

  8. 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

  9. 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

  10. Whole-brain functional connectivity during emotional word classification in medication-free Major Depressive Disorder: Abnormal salience circuitry and relations to positive emotionality☆

    PubMed Central

    van Tol, Marie-José; Veer, Ilya M.; van der Wee, Nic J.A.; Aleman, André; van Buchem, Mark A.; Rombouts, Serge A.R.B.; Zitman, Frans G.; Veltman, Dick J.; Johnstone, Tom

    2013-01-01

    Major Depressive Disorder (MDD) has been associated with biased processing and abnormal regulation of negative and positive information, which may result from compromised coordinated activity of prefrontal and subcortical brain regions involved in evaluating emotional information. We tested whether patients with MDD show distributed changes in functional connectivity with a set of independently derived brain networks that have shown high correspondence with different task demands, including stimulus salience and emotional processing. We further explored if connectivity during emotional word processing related to the tendency to engage in positive or negative emotional states. In this study, 25 medication-free MDD patients without current or past comorbidity and matched controls (n = 25) performed an emotional word-evaluation task during functional MRI. Using a dual regression approach, individual spatial connectivity maps representing each subject's connectivity with each standard network were used to evaluate between-group differences and effects of positive and negative emotionality (extraversion and neuroticism, respectively, as measured with the NEO-FFI). Results showed decreased functional connectivity of the medial prefrontal cortex, ventrolateral prefrontal cortex, and ventral striatum with the fronto-opercular salience network in MDD patients compared to controls. In patients, abnormal connectivity was related to extraversion, but not neuroticism. These results confirm the hypothesis of a relative (para)limbic–cortical decoupling that may explain dysregulated affect in MDD. As connectivity of these regions with the salience network was related to extraversion, but not to general depression severity or negative emotionality, dysfunction of this network may be responsible for the failure to sustain engagement in rewarding behavior. PMID:24179829

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

    PubMed

    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

  12. 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

  13. Liver abnormalities in connective tissue diseases.

    PubMed

    De Santis, Maria; Crotti, Chiara; Selmi, Carlo

    2013-08-01

    The liver is a lymphoid organ involved in the immune response and in the maintenance of tolerance to self molecules, but it is also a target of autoimmune reactions, as observed in primary liver autoimmune diseases (AILD) such as autoimmune hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis. Further, the liver is frequently involved in connective tissue diseases (CTD), most commonly in the form of liver function test biochemical changes with predominant cholestatic or hepatocellular patterns. CTD commonly affecting the liver include systemic lupus erythematosus, antiphospholypid syndrome, primary Sjögren's syndrome, systemic sclerosis, dermatomyositis, polimyositis, and anti-synthetase syndrome, while overlap syndromes between AILD and CTD may also be diagnosed. Although liver cirrhosis and failure are extremely rare in patients with CTD, unusual liver conditions such as nodular regenerative hyperplasia or Budd-Chiari syndrome have been reported with increasing frequency in patients with CTD. Acute or progressing liver involvement is generally related to viral hepatitis reactivation or to a concomitant AILD, so it appears to be fundamental to screen patients for HBV and HCV infection, in order to provide the ideal therapeutic regimen and avoid life-threatening reactivations. Finally, it is important to remember that the main cause of biochemical liver abnormalities in patients with CTD is a drug-induced alteration or coexisting viral hepatitis. The present article will provide a general overview of the liver involvement in CTD to allow rheumatologists to discriminate the most common clinical scenarios.

  14. 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

  15. Reconciling abnormalities of brain network structure and function in schizophrenia.

    PubMed

    Fornito, Alex; Bullmore, Edward T

    2015-02-01

    Schizophrenia is widely regarded as a disorder of abnormal brain connectivity. Magnetic resonance imaging (MRI) suggests that patients show robust reductions of structural connectivity. However, corresponding changes in functional connectivity do not always follow, with increased functional connectivity being reported in many cases. Here, we consider different methodological and mechanistic accounts that might reconcile these apparently contradictory findings and argue that increased functional connectivity in schizophrenia likely represents a pathophysiological dysregulation of brain activity arising from abnormal neurodevelopmental wiring of structural connections linking putative hub regions of association cortex to other brain areas. Elucidating the pathophysiological significance of connectivity abnormalities in schizophrenia will be contingent on better understanding how network structure shapes and constrains function.

  16. 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

  17. Connective tissue abnormalities in MRL/1 mice.

    PubMed Central

    Edwards, J C; Cooke, A; Moore, A R; Collins, C; Hay, F; Willoughby, D A

    1986-01-01

    Pathological changes in the connective tissue of the limbs of MRL/1 mice are described. Focal infiltrates of polymorphs or large mononuclear cells, or both, were seen both in synovial lining and subcutaneous tissue. Infiltrates were associated with vasculitis in some cases. Deposits of amorphous material were seen in and around joints and in foot pads. The material was more particulate and refractile than typical 'fibrinoid' and showed a positive Feulgen reaction. It was not surrounded by palisading cells and when seen in synovial tissue was not usually associated with changes in synovial lining cells. No obvious difference was seen between intra-articular and extra-articular lesions. Lesions in subcutaneous tissue occurred exclusively in the foot pads. Lymphocyte infiltration was not prominent at any site and no follicle formation was seen. Of two colonies studied, only one showed a significant increase in lining cell numbers in synovial tissue. Exercised animals had a similar distribution and severity of disease to those of matched controls. All lesions described were distinguishable from non-specific inflammatory lesions in normal control mice and MRL/++ mice on assessment of unmarked sections. The relation between these connective tissue lesions and the changes found in human chronic synovitis is discussed. Images PMID:3729576

  18. 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.

  19. 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

  20. Abnormal Brain Connectivity Patterns in Adults with ADHD: A Coherence Study

    PubMed Central

    Sato, João Ricardo; Hoexter, Marcelo Queiroz; Castellanos, Xavier Francisco; Rohde, Luis A.

    2012-01-01

    Studies based on functional magnetic resonance imaging (fMRI) during the resting state have shown decreased functional connectivity between the dorsal anterior cingulate cortex (dACC) and regions of the Default Mode Network (DMN) in adult patients with Attention-Deficit/Hyperactivity Disorder (ADHD) relative to subjects with typical development (TD). Most studies used Pearson correlation coefficients among the BOLD signals from different brain regions to quantify functional connectivity. Since the Pearson correlation analysis only provides a limited description of functional connectivity, we investigated functional connectivity between the dACC and the posterior cingulate cortex (PCC) in three groups (adult patients with ADHD, n = 21; TD age-matched subjects, n = 21; young TD subjects, n = 21) using a more comprehensive analytical approach – unsupervised machine learning using a one-class support vector machine (OC-SVM) that quantifies an abnormality index for each individual. The median abnormality index for patients with ADHD was greater than for TD age-matched subjects (p = 0.014); the ADHD and young TD indices did not differ significantly (p = 0.480); the median abnormality index of young TD was greater than that of TD age-matched subjects (p = 0.016). Low frequencies below 0.05 Hz and around 0.20 Hz were the most relevant for discriminating between ADHD patients and TD age-matched controls and between the older and younger TD subjects. In addition, we validated our approach using the fMRI data of children publicly released by the ADHD-200 Competition, obtaining similar results. Our findings suggest that the abnormal coherence patterns observed in patients with ADHD in this study resemble the patterns observed in young typically developing subjects, which reinforces the hypothesis that ADHD is associated with brain maturation deficits. PMID:23049834

  1. 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

  2. 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

  3. Abnormal causal connectivity by structural deficits in first-episode, drug-naive schizophrenia at rest.

    PubMed

    Guo, Wenbin; Liu, Feng; Liu, Jianrong; Yu, Liuyu; Zhang, Jian; Zhang, Zhikun; Xiao, Changqing; Zhai, Jinguo; Zhao, Jingping

    2015-01-01

    Anatomical deficits and resting-state functional connectivity (FC) alterations in prefrontal-thalamic-cerebellar circuit have been implicated in the neurobiology of schizophrenia. However, the effect of structural deficits in schizophrenia on causal connectivity of this circuit remains unclear. This study was conducted to examine the causal connectivity biased by structural deficits in first-episode, drug-naive schizophrenia patients. Structural and resting-state functional magnetic resonance imaging (fMRI) data were obtained from 49 first-episode, drug-naive schizophrenia patients and 50 healthy controls. Data were analyzed by voxel-based morphometry and Granger causality analysis. The causal connectivity of the integrated prefrontal-thalamic (limbic)-cerebellar (sensorimotor) circuit was partly affected by structural deficits in first-episode, drug-naive schizophrenia as follows: (1) unilateral prefrontal-sensorimotor connectivity abnormalities (increased driving effect from the left medial prefrontal cortex [MPFC] to the sensorimotor regions); (2) bilateral limbic-sensorimotor connectivity abnormalities (increased driving effect from the right anterior cingulate cortex [ACC] to the sensorimotor regions and decreased feedback from the sensorimotor regions to the right ACC); and (3) bilateral increased and decreased causal connectivities among the sensorimotor regions. Some correlations between the gray matter volume of the seeds, along with their causal effects and clinical variables (duration of untreated psychosis and symptom severity), were also observed in the patients. The findings indicated the partial effects of structural deficits in first-episode, drug-naive schizophrenia on the prefrontal-thalamic (limbic)-cerebellar (sensorimotor) circuit. Schizophrenia may reinforce the driving connectivities from the left MPFC or right ACC to the sensorimotor regions and may disrupt bilateral causal connectivities among the sensorimotor regions.

  4. 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

  5. Thalamic shape and connectivity abnormalities in children with attention-deficit/hyperactivity disorder.

    PubMed

    Xia, Shugao; Li, Xiaobo; Kimball, Ariane E; Kelly, Mary S; Lesser, Iris; Branch, Craig

    2012-11-30

    Attention-deficit/hyperactivity disorder (ADHD) is characterized by widespread structural and functional abnormalities in the cortico-striato-thalmo-cortical (CSTC) loops that subserve attention and executive functions. In this study, we analyzed thalamic shape and its white matter connections using structural magnetic resonance imaging and diffusion (DTI) data acquired from children with ADHD (n=19) and controls (n=19). Shape morphology of the thalamus was assessed using shape-based analysis, while connectivity between the thalamus and other brain regions was determined using probabilistic diffusion tractography. Shape-based analysis indicated significant regional atrophy in the left thalamus in children with ADHD compared to controls. Group analyses of white matter connectivity measures showed significantly decreased mean fractional anisotropy (FA) and volume of the tracts between thalamus and striatum, hippocampus, and prefrontal lobe in children with ADHD compared to controls. The structural abnormalities within the thalamus and the reduced integrity of the white matter tracks between the thalamus and other brain regions, as shown from the results of this study, may be the anatomical bases of the impaired cognitive performances in the attention and executive function domains in ADHD.

  6. Strengthening connections: functional connectivity and brain plasticity.

    PubMed

    Kelly, Clare; Castellanos, F Xavier

    2014-03-01

    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 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 hypotheses 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.

  7. 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

  8. Grid Connected Functionality

    DOE Data Explorer

    Baker, Kyri; Jin, Xin; Vaidynathan, Deepthi; Jones, Wesley; Christensen, Dane; Sparn, Bethany; Woods, Jason; Sorensen, Harry; Lunacek, Monte

    2016-08-04

    Dataset demonstrating the potential benefits that residential buildings can provide for frequency regulation services in the electric power grid. In a hardware-in-the-loop (HIL) implementation, simulated homes along with a physical laboratory home are coordinated via a grid aggregator, and it is shown that their aggregate response has the potential to follow the regulation signal on a timescale of seconds. Connected (communication-enabled), devices in the National Renewable Energy Laboratory's (NREL's) Energy Systems Integration Facility (ESIF) received demand response (DR) requests from a grid aggregator, and the devices responded accordingly to meet the signal while satisfying user comfort bounds and physical hardware limitations.

  9. Altered Functional Connectivity in Essential Tremor

    PubMed Central

    Benito-León, Julián; Louis, Elan D.; Romero, Juan Pablo; Hernández-Tamames, Juan Antonio; Manzanedo, Eva; Álvarez-Linera, Juan; Bermejo-Pareja, Félix; Posada, Ignacio; Rocon, Eduardo

    2015-01-01

    Abstract Essential tremor (ET) has been associated with a spectrum of clinical features, with both motor and nonmotor elements, including cognitive deficits. We employed resting-state functional magnetic resonance imaging (fMRI) to assess whether brain networks that might be involved in the pathogenesis of nonmotor manifestations associated with ET are altered, and the relationship between abnormal connectivity and ET severity and neuropsychological function. Resting-state fMRI data in 23 ET patients (12 women and 11 men) and 22 healthy controls (HC) (12 women and 10 men) were analyzed using independent component analysis, in combination with a “dual-regression” technique, to identify the group differences of resting-state networks (RSNs) (default mode network [DMN] and executive, frontoparietal, sensorimotor, cerebellar, auditory/language, and visual networks). All participants underwent a neuropsychological and neuroimaging session, where resting-state data were collected. Relative to HC, ET patients showed increased connectivity in RSNs involved in cognitive processes (DMN and frontoparietal networks) and decreased connectivity in the cerebellum and visual networks. Changes in network integrity were associated not only with ET severity (DMN) and ET duration (DMN and left frontoparietal network), but also with cognitive ability. Moreover, in at least 3 networks (DMN and frontoparietal networks), increased connectivity was associated with worse performance on different cognitive domains (attention, executive function, visuospatial ability, verbal memory, visual memory, and language) and depressive symptoms. Further, in the visual network, decreased connectivity was associated with worse performance on visuospatial ability. ET was associated with abnormal brain connectivity in major RSNs that might be involved in both motor and nonmotor symptoms. Our findings underscore the importance of examining RSNs in this population as a biomarker of disease. PMID:26656325

  10. 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…

  11. 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

  12. 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

  13. Aortic tear and dissection related to connective tissues abnormalities resembling Marfan syndrome in a Great Dane.

    PubMed

    Lenz, Jennifer A; Bach, Jonathan F; Bell, Cynthia M; Stepien, Rebecca L

    2015-06-01

    Aortic tears and acute aortic dissection are rarely reported in dogs. This report describes a case of aortic dissection and probable sinus of Valsalva rupture in a young Great Dane with associated histopathologic findings suggestive of a connective tissue abnormality.

  14. Abnormal Neural Connectivity in Schizophrenia and fMRI-Brain-Computer Interface as a Potential Therapeutic Approach

    PubMed Central

    Ruiz, Sergio; Birbaumer, Niels; Sitaram, Ranganatha

    2012-01-01

    Considering that single locations of structural and functional abnormalities are insufficient to explain the diverse psychopathology of schizophrenia, new models have postulated that the impairments associated with the disease arise from a failure to integrate the activity of local and distributed neural circuits: the “abnormal neural connectivity hypothesis.” In the last years, new evidence coming from neuroimaging have supported and expanded this theory. However, despite the increasing evidence that schizophrenia is a disorder of neural connectivity, so far there are no treatments that have shown to produce a significant change in brain connectivity, or that have been specifically designed to alleviate this problem. Brain-Computer Interfaces based on real-time functional Magnetic Resonance Imaging (fMRI-BCI) are novel techniques that have allowed subjects to achieve self-regulation of circumscribed brain regions. In recent studies, experiments with this technology have resulted in new findings suggesting that this methodology could be used to train subjects to enhance brain connectivity, and therefore could potentially be used as a therapeutic tool in mental disorders including schizophrenia. The present article summarizes the findings coming from hemodynamics-based neuroimaging that support the abnormal connectivity hypothesis in schizophrenia, and discusses a new approach that could address this problem. PMID:23525496

  15. 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

  16. 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

  17. 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.

  18. 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

  19. 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.

  20. Connective tissue spectrum abnormalities associated with spontaneous cerebrospinal fluid leaks: a prospective study.

    PubMed

    Reinstein, Eyal; Pariani, Mitchel; Bannykh, Serguei; Rimoin, David L; Schievink, Wouter I

    2013-04-01

    We aimed to assess the frequency of connective tissue abnormalities among patients with cerebrospinal fluid (CSF) leaks in a prospective study using a large cohort of patients. We enrolled a consecutive group of 50 patients, referred for consultation because of CSF leak. All patients have been carefully examined for the presence of connective tissue abnormalities, and based on findings, patients underwent genetic testing. Ancillary diagnostic studies included echocardiography, eye exam, and histopathological examinations of skin and dura biopsies in selected patients. We identified nine patients with heritable connective tissue disorders, including Marfan syndrome, Ehlers-Danlos syndrome and other unclassified forms. In seven patients, spontaneous CSF leak was the first noted manifestation of the genetic disorder. We conclude that spontaneous CSF leaks are associated with a spectrum of connective tissue abnormalities and may be the first noted clinical presentation of the genetic disorder. We propose that there is a clinical basis for considering spontaneous CSF leak as a clinical manifestation of heritable connective tissue disorders, and we suggest that patients with CSF leaks should be screened for connective tissue and vascular abnormalities.

  1. 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.

  2. 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

  3. 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

  4. 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

  5. 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…

  6. Resting state magnetoencephalography functional connectivity in traumatic brain injury

    PubMed Central

    Tarapore, Phiroz E.; Findlay, Anne M.; LaHue, Sara C.; Lee, Hana; Honma, Susanne M.; Mizuiri, Danielle; Luks, Tracy L.; Manley, Geoffrey T.; Nagarajan, Srikantan S.; Mukherjee, Pratik

    2014-01-01

    Object Traumatic brain injury (TBI) is one of the leading causes of morbidity worldwide. One mechanism by which blunt head trauma may disrupt normal cognition and behavior is through alteration of functional connectivity between brain regions. In this pilot study, the authors applied a rapid automated resting state magnetoencephalography (MEG) imaging technique suitable for routine clinical use to test the hypothesis that there is decreased functional connectivity in patients with TBI compared with matched controls, even in cases of mild TBI. Furthermore, they posit that these abnormal reductions in MEG functional connectivity can be detected even in TBI patients without specific evidence of traumatic lesions on 3-T MR images. Finally, they hypothesize that the reductions of functional connectivity can improve over time across serial MEG scans during recovery from TBI. Methods Magnetoencephalography maps of functional connectivity in the alpha (8- to 12-Hz) band from 21 patients who sustained a TBI were compared with those from 18 age- and sex-matched controls. Regions of altered functional connectivity in each patient were detected in automated fashion through atlas-based registration to the control database. The extent of reduced functional connectivity in the patient group was tested for correlations with clinical characteristics of the injury as well as with findings on 3-T MRI. Finally, the authors compared initial connectivity maps with 2-year follow-up functional connectivity in a subgroup of 5 patients with TBI. Results Fourteen male and 7 female patients (17–53 years old, median 29 years) were enrolled. By Glasgow Coma Scale (GCS) criteria, 11 patients had mild, 1 had moderate, and 3 had severe TBI, and 6 had no GCS score recorded. On 3-T MRI, 16 patients had abnormal findings attributable to the trauma and 5 had findings in the normal range. As a group, the patients with TBI had significantly lower functional connectivity than controls (p < 0.01). Three

  7. Altered default mode network functional connectivity in schizotypal personality disorder.

    PubMed

    Zhang, Qing; Shen, Jing; Wu, Jianlin; Yu, Xiao; Lou, Wutao; Fan, Hongyu; Shi, Lin; Wang, Defeng

    2014-12-01

    The default mode network (DMN) has been identified to play a critical role in many mental disorders, but such abnormalities have not yet been determined in patients with schizotypal personality disorder (SPD). The purpose of this study was to analyze the alteration of the DMN functional connectivity in subjects with (SPD) and compared it to healthy control subjects. Eighteen DSM-IV diagnosed SPD subjects (all male, average age: 19.7±0.9) from a pool of 3000 first year college students, and eighteen age and gender matched healthy control subjects were recruited (all male, average age: 20.3±0.9). Independent component analysis (ICA) was used to analyze the DMN functional connectivity alteration. Compared to the healthy control group, SPD subjects had significantly decreased functional connectivity in the frontal areas, including the superior and medial frontal gyrus, and greater functional connectivity in the bilateral superior temporal gyrus and sub-lobar regions, including the bilateral putamen and caudate. Compared to subjects with SPD, the healthy control group showed decreased functional connectivity in the bilateral posterior cingulate gyrus, but showed greater functional connectivity in the right transverse temporal gyrus and left middle temporal gyrus. The healthy control group also showed greater activation in the cerebellum compared to the SPD group. These findings suggest that DMN functional connectivity, particularly that involving cognitive or emotional regulation, is altered in SPD subjects, and thus may be helpful in studying schizophrenia.

  8. Abnormal Left-Sided Orbitomedial Prefrontal Cortical–Amygdala Connectivity during Happy and Fear Face Processing: A Potential Neural Mechanism of Female MDD

    PubMed Central

    de Almeida, Jorge Renner Cardoso; Kronhaus, Dina Michaela; Sibille, Etienne L.; Langenecker, Scott A.; Versace, Amelia; LaBarbara, Edmund James; Phillips, Mary Louise

    2011-01-01

    Background: Pathophysiologic processes supporting abnormal emotion regulation in major depressive disorder (MDD) are poorly understood. We previously found abnormal inverse left-sided ventromedial prefrontal cortical–amygdala effective connectivity to happy faces in females with MDD. We aimed to replicate and expand this previous finding in an independent participant sample, using a more inclusive neural model, and a novel emotion processing paradigm. Methods: Nineteen individuals with MDD in depressed episode (12 females), and 19 healthy individuals, age, and gender matched, performed an implicit emotion processing and automatic attentional control paradigm to examine abnormalities in prefrontal cortical–amygdala neural circuitry during happy, angry, fearful, and sad face processing measured with functional magnetic resonance imaging in a 3-T scanner. Effective connectivity was estimated with dynamic causal modeling in a trinodal neural model including two anatomically defined prefrontal cortical regions, ventromedial prefrontal cortex, and subgenual cingulate cortex (sgACC), and the amygdala. Results: We replicated our previous finding of abnormal inverse left-sided top-down ventromedial prefrontal cortical–amygdala connectivity to happy faces in females with MDD (p = 0.04), and also showed a similar pattern of abnormal inverse left-sided sgACC–amygdala connectivity to these stimuli (p = 0.03). These findings were paralleled by abnormally reduced positive left-sided ventromedial prefrontal cortical–sgACC connectivity to happy faces in females with MDD (p = 0.008), and abnormally increased positive left-sided sgACC–amygdala connectivity to fearful faces in females, and all individuals, with MDD (p = 0.008; p = 0.003). Conclusion: Different patterns of abnormal prefrontal cortical–amygdala connectivity to happy and fearful stimuli might represent neural mechanisms for the excessive self-reproach and comorbid anxiety that

  9. [The general practitioner and abnormal liver function tests].

    PubMed

    Hallez, R

    1997-09-01

    In case of abnormal liver function tests, it's necessary to distinguish different situations, starting from this first data. We will successively consider: the high and moderate acute increases of aminotransferase, the chronic increases of aminotransferase, the isolated cholestase picture and the isolated increases of gamma GT or of bilirubine. We will finish with a partial survey about drug-induced liver diseases.

  10. Association of cervical artery dissection with connective tissue abnormalities in skin and arteries.

    PubMed

    Brandt, T; Morcher, M; Hausser, I

    2005-01-01

    Spontaneous cervical artery dissections (sCAD) often occur in otherwise healthy individuals without known risk factors for stroke and frequently develop spontaneously without relevant trauma. An underlying arteriopathy leading to a so-called 'weakness of the vessel wall' and predisposing certain individuals to dissection has often been postulated. Therefore, the morphology of connective tissue, a main component of vessel wall and environment, was investigated in carotids and skin. While the overall morphology of dermal connective tissue is normal, about half of patients with sCAD show mild ultrastructural connective tissue alterations. These ultrastructural morphological aberrations can be designated either as 'Ehlers-Danlos syndrome (EDS) III-like', resembling mild findings in patients with the hypermobility type of EDS (EDS III); or coined 'EDS IV-like' with collagen fibers containing fibrils with highly variable diameters resembling mild findings in vascular EDS; or the abnormalities are restricted to the elastic fibers (with fragmentation and minicalcifications) without significant alterations in the morphology of the collagen fibrils. These findings had some similarity with the morphology found in heterozygous carriers of pseudoxanthoma elasticum. A grading scale according to the severity of the findings has been introduced. Similar connective tissue abnormalities were detected in some first-degree relatives of patients with sCAD showing hereditary at least in a subgroup. They can serve as a phenotypic marker for further genetic studies in patients with sCAD and large families to possibly identify the underlying basic molecular defect(s). Very few of patients (<5%) with sCAD and connective tissue abnormalities have clinical manifestations of skin, joint, or skeletal abnormalities of a defined heritable connective tissue disorder. In specimens of arterial walls of carotid, aortic, and renal arteries of patients with sCAD, pronounced systemic, histopathological

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

    PubMed

    Yao, Ye; Palaniyappan, Lena; Liddle, Peter; Zhang, Jie; Francis, Susan; Feng, Jianfeng

    2015-11-01

    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 (structurally unconstrained) to more direct

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

    PubMed

    Yao, Ye; Palaniyappan, Lena; Liddle, Peter; Zhang, Jie; Francis, Susan; Feng, Jianfeng

    2015-11-01

    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 (structurally unconstrained) to more direct

  13. Abnormalities in fronto-striatal connectivity within language networks relate to differences in grey-matter heterogeneity in Asperger syndrome.

    PubMed

    Radulescu, Eugenia; Minati, Ludovico; Ganeshan, Balaji; Harrison, Neil A; Gray, Marcus A; Beacher, Felix D C C; Chatwin, Chris; Young, Rupert C D; Critchley, Hugo D

    2013-01-01

    Asperger syndrome (AS) is an Autism Spectrum Disorder (ASD) characterised by qualitative impairment in the development of emotional and social skills with relative preservation of general intellectual abilities, including verbal language. People with AS may nevertheless show atypical language, including rate and frequency of speech production. We previously observed that abnormalities in grey matter homogeneity (measured with texture analysis of structural MR images) in AS individuals when compared with controls are also correlated with the volume of caudate nucleus. Here, we tested a prediction that these distributed abnormalities in grey matter compromise the functional integrity of brain networks supporting verbal communication skills. We therefore measured the functional connectivity between caudate nucleus and cortex during a functional neuroimaging study of language generation (verbal fluency), applying psycho-physiological interaction (PPI) methods to test specifically for differences attributable to grey matter heterogeneity in AS participants. Furthermore, we used dynamic causal modelling (DCM) to characterise the causal directionality of these differences in interregional connectivity during word production. Our results revealed a diagnosis-dependent influence of grey matter heterogeneity on the functional connectivity of the caudate nuclei with right insula/inferior frontal gyrus and anterior cingulate, respectively with the left superior frontal gyrus and right precuneus. Moreover, causal modelling of interactions between inferior frontal gyri, caudate and precuneus, revealed a reliance on bottom-up (stimulus-driven) connections in AS participants that contrasted with a dominance of top-down (cognitive control) connections from prefrontal cortex observed in control participants. These results provide detailed support for previously hypothesised central disconnectivity in ASD and specify discrete brain network targets for diagnosis and therapy in ASD.

  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

    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

  16. 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

  17. Cardiorespiratory responses to exercise after anatomic repair of atrioventricular discordance with abnormal ventriculoarterial connection.

    PubMed

    Yasuda, Kenji; Ohuchi, Hideo; Ono, Yasuo; Yagihara, Toshikatsu; Echigo, Shigeyuki

    2007-01-01

    We evaluated exercise tolerance and cardiorespiratory responses to exercise in patients with atrioventricular discordance (AVD) and abnormal ventriculoarterial connection after anatomic repair. Cardiopulmonary treadmill exercise testing with gas measurement was done 62 times in 19 patients with AVD who had undergone anatomic repair at the National Cardiovascular Center. Exercise duration, oxygen uptake (V(O2)) and heart rate at anaerobic threshold and peak, and oxygen pulse during exercise were significantly lower in patients with AVD after anatomic repair than in controls. Carbon dioxide ventilatory equivalent during exercise was worse in patients with AVD after anatomic repair than in controls. Percentage peak V(O2) significantly correlated positively with percentage peak oxygen pulse and tended to correlate positively with the heart rate increments. Patients with AVD after anatomic repair exhibit impaired responses of heart rate and oxygen pulse with lower exercise capacity. Careful attention should be paid to patients with AVD after anatomic repair in terms of their functional capacity as well as other postoperative complications.

  18. 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

  19. Random geometric graphs with general connection functions.

    PubMed

    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. PMID:27078372

  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. Effect of ramipril therapy on abnormal left atrial appendage function.

    PubMed

    Asker, M; Timucin, O B; Asker, S; Karadag, M F

    2011-01-01

    This study investigated whether ramipril treatment has a beneficial effect on left atrial appendage (LAA) function in patients with systemic hypertension in sinus rhythm. Patients with untreated systemic hypertension and normal left ventricular systolic function in sinus rhythm (n = 20; six males/14 females; age 35 - 69 years, mean ± SD 52.8 ± 8.9 years) were evaluated using transthoracic and transoesophageal echocardiography at baseline and after 6 months of treatment with 5 mg/day ramipril. Mean systolic and diastolic blood pressures decreased significantly after ramipril therapy. Baseline LAA emptying velocity was below the age-related reference value for this parameter, indicating abnormal LAA function. There were significant increases in the LAA filling and emptying velocities after ramipril treatment. It is concluded that the decrease in blood pressure and haemodynamic improvements brought about by ramipril therapy resulted in improved LAA function in hypertensive patients with normal left ventricular systolic function in sinus rhythm.

  3. Situs inversus and ciliary abnormalities: 20 years later, what is the connection?

    PubMed

    Pennekamp, Petra; Menchen, Tabea; Dworniczak, Bernd; Hamada, Hiroshi

    2015-01-01

    Heterotaxy (also known as situs ambiguous) and situs inversus totalis describe disorders of laterality in which internal organs do not display their typical pattern of asymmetry. First described around 1600 by Girolamo Fabrizio, numerous case reports about laterality disorders in humans were published without any idea about the underlying cause. Then, in 1976, immotile cilia were described as the cause of a human syndrome that was previously clinically described, both in 1904 by AK Siewert and in 1933 by Manes Kartagener, as an association of situs inversus with chronic sinusitis and bronchiectasis, now commonly known as Kartagener's syndrome. Despite intense research, the underlying defect of laterality disorders remained unclear. Nearly 20 years later in 1995, Björn Afzelius discussed five hypotheses to explain the connection between ciliary defects and loss of laterality control in a paper published in the International Journal of Developmental Biology asking: 'Situs inversus and ciliary abnormalities: What is the connection?'. Here, nearly 20 research years later, we revisit some of the key findings that led to the current knowledge about the connection between situs inversus and ciliary abnormalities. PMID:25589952

  4. 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…

  5. 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.

  6. 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.

  7. 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

  8. 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

  9. 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.

  10. 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

  11. 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

  12. 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

  13. Abnormal Pulmonary Function in Adults with Sickle Cell Anemia

    PubMed Central

    Klings, Elizabeth S.; Wyszynski, Diego F.; Nolan, Vikki G.; Steinberg, Martin H.

    2006-01-01

    Rationale: Pulmonary complications of sickle cell anemia (Hb-SS) commonly cause morbidity, yet few large studies of pulmonary function tests (PFTs) in this population have been reported. Objectives: PFTs (spirometry, lung volumes, and diffusion capacity for carbon monoxide [DLCO]) from 310 adults with Hb-SS were analyzed to determine the pattern of pulmonary dysfunction and their association with other systemic complications of sickle cell disease. Methods: Raw PFT data were compared with predicted values. Each subject was subclassified into one of five groups: obstructive physiology, restrictive physiology, mixed obstructive/restrictive physiology, isolated low DLCO, or normal. The association between laboratory data of patients with decreased DLCO or restrictive physiology and those of normal subjects was assessed by multivariate linear regression. Measurements and Main Results: Normal PFTs were present in only 31 of 310 (10%) patients. Overall, adults with Hb-SS were characterized by decreased total lung capacities (70.2 ± 14.7% predicted) and DlCO (64.5 ± 19.9%). The most common PFT patterns were restrictive physiology (74%) and isolated low DlCO (13%). Decreased DLCO was associated with thrombocytosis (p = 0.05), with hepatic dysfunction (elevated alanine aminotransferase; p = 0.07), and a trend toward renal dysfunction (elevated blood urea nitrogen and creatinine; p = 0.05 and 0.07, respectively). Conclusions: Pulmonary function is abnormal in 90% of adult patients with Hb-SS. Common abnormalities include restrictive physiology and decreased DLCO. Decreased DLCO may indicate more severe sickle vasculopathy characterized by impaired hepatic and renal function. PMID:16556694

  14. Functional connectivity density alterations in schizophrenia

    PubMed Central

    Zhuo, Chuanjun; Zhu, Jiajia; Qin, Wen; Qu, Hongru; Ma, Xiaolei; Tian, Hongjun; Xu, Qingying; Yu, Chunshui

    2014-01-01

    Background: Schizophrenia is characterized by altered resting-state functional connectivity. Most previous studies have focused on changes in connectivity strengths; however, the alterations in connectivity density in schizophrenia remain largely unknown. Here, we aimed to investigate changes in resting-state functional connectivity density (rsFCD) in schizophrenia. Methods: A total of 95 schizophrenia patients and 93 sex- and age-matched healthy controls (HCs) underwent resting-state functional MRI examinations. The rsFCD, which reflects the total number of functional connections between a given brain voxel and all other voxels in the entire brain, was calculated for each voxel of each subject. Voxel-based comparisons were performed to identify brain regions with significant rsFCD differences between patients and controls (P < 0.05, corrected). Results: Compared with HCs, patients with schizophrenia showed significantly increased rsFCD in the bilateral striatum and hippocampus and significantly decreased rsFCD in the bilateral sensorimotor cortices and right occipital cortex. However, the rsFCD values of these brain regions were not correlated with antipsychotic dosage, illness duration, or clinical symptom severity. Conclusions: The striatal and hippocampal regions and parietal-occipital regions exhibited completely different changes in rsFCD in schizophrenia, which roughly correspond to dopamine activity in these regions in schizophrenia. These findings support the connectivity disorder hypothesis of schizophrenia and increase our understanding of the neural mechanisms of schizophrenia. PMID:25477799

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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.

  20. Altered functional connectivity among default, attention, and control networks in idiopathic generalized epilepsy.

    PubMed

    Wei, H L; An, J; Zeng, L L; Shen, H; Qiu, S J; Hu, D W

    2015-05-01

    Numerous resting-state fMRI studies have demonstrated altered functional connectivity within canonical intrinsic connectivity networks (ICNs) in patients with idiopathic generalized epilepsy (IGE). It is possible that the widespread ICN abnormalities on electroencephalography in IGE derive from abnormal functional interactions between ICNs. To test this possibility, we explored the functional connectivity between the subnetworks of the default mode network (DMN), attention network (ATN), and frontoparietal control network (FPN) using independent component analysis of resting-state fMRI data collected from 27 patients with IGE characterized by generalized tonic-clonic seizures (GTCS) and 29 matched healthy controls. It was observed that the left FPN exhibited increased connectivity with the anterior DMN and ventral ATN, while the right FPN exhibited increased connectivity with the anterior and posterior DMNs in the patients with IGE-GTCS. Furthermore, the functional connectivity between the anterior DMN and ventral ATN was negative in healthy controls but positive in the patients with IGE-GTCS. In addition, the anterior DMN exhibited increased intranetwork functional connectivity in the right frontal pole in IGE-GTCS. These findings suggest that IGE-GTCS is likely associated with a disrupted brain organization probably derived from abnormal functional interactions among ICNs. Furthermore, the alterations in the functional architecture of the ICNs may be related to deficits in mentation and attention in IGE-GTCS, providing informative evidence for the understanding of the pathophysiology of IGE-GTCS.

  1. 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.

  2. Functional interactions as a survival strategy against abnormal aggregation

    PubMed Central

    Laura, Masino; Giuseppe, Nicastro; Lesley, Calder; Michele, Vendruscolo; Annalisa, Pastore

    2011-01-01

    Protein aggregation is under intense scrutiny because of its role in human disease. Although increasing evidence indicates that protein native states are highly protected against aggregation, the specific protection mechanisms are poorly understood. Insight into such mechanisms can be gained through study of the relatively few proteins that aggregate under native conditions. Ataxin-3, the protein responsible for Spinocerebellar ataxia type 3, a polyglutamine expansion disease, represents one of such examples. Polyglutamine expansion is central for determining solubility and aggregation rates of ataxin-3, but these properties are profoundly modulated by its N-terminal Josephin domain. This work aims at identifying the regions that promote Josephin fibrillogenesis and rationalizing the mechanisms that protect Josephin and nonexpanded ataxin-3 from aberrant aggregation. Using different biophysical techniques, aggregation propensity predictions and rational design of amino acid substitutions, we show that Josephin has an intrinsic tendency to fibrillize under native conditions and that fibrillization is promoted by two solvent-exposed patches, which are also involved in recognition of natural substrates, such as ubiquitin. Indeed, designed mutations at these patches or substrate binding significantly reduce Josephin aggregation kinetics. Our results provide evidence that protein nonpathologic function can play an active role in preventing aberrant fibrillization and suggest the molecular mechanism whereby this occurs in ataxin-3.—Masino, L., Nicastro, G., Calder, L., Vendruscolo, M., Pastore, A. Functional interactions as a survival strategy against abnormal aggregation. PMID:20810784

  3. 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

  4. Abnormal climbing fibre-Purkinje cell synaptic connections in the essential tremor cerebellum

    PubMed Central

    Lin, Chi-Ying; Louis, Elan D.; Faust, Phyllis L.; Koeppen, Arnulf H.; Vonsattel, Jean-Paul G.

    2014-01-01

    Structural changes in Purkinje cells have been identified in the essential tremor cerebellum, although the mechanisms that underlie these changes remain poorly understood. Climbing fibres provide one of the major excitatory inputs to Purkinje cells, and climbing fibre-Purkinje cell connections are essential for normal cerebellar-mediated motor control. The distribution of climbing fibre-Purkinje cell synapses on Purkinje cell dendrites is dynamically regulated and may be altered in disease states. The aim of the present study was to examine the density and distribution of climbing fibre-Purkinje cell synapses using post-mortem cerebellar tissue of essential tremor cases and controls. Using vesicular glutamate transporter type 2 immunohistochemistry, we labelled climbing fibre-Purkinje cell synapses of 12 essential tremor cases and 13 age-matched controls from the New York Brain Bank. Normally, climbing fibres form synapses mainly on the thick, proximal Purkinje cell dendrites in the inner portion of the molecular layer, whereas parallel fibres form synapses on the thin, distal Purkinje cell spiny branchlets. We observed that, compared with controls, essential tremor cases had decreased climbing fibre-Purkinje cell synaptic density, more climbing fibres extending to the outer portion of the molecular layer, and more climbing fibre-Purkinje cell synapses on the thin Purkinje cell spiny branchlets. Interestingly, in essential tremor, the increased distribution of climbing fibre-Purkinje cell synapses on the thin Purkinje cell branchlets was inversely associated with clinical tremor severity, indicating a close relationship between the altered distribution of climbing fibre-Purkinje cell connections and tremor. These findings suggest that abnormal climbing fibre-Purkinje cell connections could be of importance in the pathogenesis of essential tremor. PMID:25273997

  5. 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…

  6. 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.

  7. Impact of autocorrelation on functional connectivity.

    PubMed

    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

    2014-11-15

    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.

  8. Pattern Genes Suggest Functional Connectivity of Organs.

    PubMed

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

    2016-05-26

    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.

  9. 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.

  10. 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

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

    PubMed

    Bian, Yunpeng; He, Xiaoxuan; Hu, Sheng; Li, Chuanfu; Xu, Chunsheng; Kan, Hongxing; Xue, Qiuju; Yang, Jun; 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

  12. 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

  13. 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)

  14. 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.

  15. Multiscale fingerprinting of neuronal functional connectivity

    PubMed Central

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

    2014-01-01

    SUMMARY 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

  16. Filaggrin genotype in ichthyosis vulgaris predicts abnormalities in epidermal structure and function.

    PubMed

    Gruber, Robert; Elias, Peter M; Crumrine, Debra; Lin, Tzu-Kai; Brandner, Johanna M; Hachem, Jean-Pierre; Presland, Richard B; Fleckman, Philip; Janecke, Andreas R; Sandilands, Aileen; McLean, W H Irwin; Fritsch, Peter O; Mildner, Michael; Tschachler, Erwin; Schmuth, Matthias

    2011-05-01

    Although it is widely accepted that filaggrin (FLG) deficiency contributes to an abnormal barrier function in ichthyosis vulgaris and atopic dermatitis, the pathomechanism of how FLG deficiency provokes a barrier abnormality in humans is unknown. We report here that the presence of FLG mutations in Caucasians predicts dose-dependent alterations in epidermal permeability barrier function. Although FLG is an intracellular protein, the barrier abnormality occurred solely via a paracellular route in affected stratum corneum. Abnormal barrier function correlated with alterations in keratin filament organization (perinuclear retraction), impaired loading of lamellar body contents, followed by nonuniform extracellular distribution of secreted organelle contents, and abnormalities in lamellar bilayer architecture. In addition, we observed reductions in corneodesmosome density and tight junction protein expression. Thus, FLG deficiency provokes alterations in keratinocyte architecture that influence epidermal functions localizing to the extracellular matrix. These results clarify how FLG mutations impair epidermal permeability barrier function.

  17. 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

  18. 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.

  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 Time-Varying Analysis Reveals Aberrant Variations of Functional Connectivity in Autism

    PubMed Central

    Yao, Zhijun; Hu, Bin; Xie, Yuanwei; Zheng, Fang; Liu, Guangyao; Chen, Xuejiao; Zheng, Weihao

    2016-01-01

    Recently, studies based on time-varying functional connectivity have unveiled brain states diversity in some neuropsychiatric disorders, such as schizophrenia and major depressive disorder. However, time-varying functional connectivity analysis of resting-state functional Magnetic Resonance Imaging (fMRI) have been rarely performed on the Autism Spectrum Disorder (ASD). Hence, we performed time-varying connectivity analysis on resting-state fMRI data to investigate brain states mutation in ASD children. ASD showed an imbalance of connectivity state and aberrant ratio of connectivity with different strengths in the whole brain network, and decreased connectivity associated precuneus/posterior cingulate gyrus with medial prefrontal gyrus in default mode network. As compared to typical development children, weak relevance condition (the strength of a large number of connectivities in the state was less than means minus standard deviation of all connection strength) was maintained for a longer time between brain areas of ASD children, and ratios of weak connectivity in brain states varied dramatically in the ASD. In the ASD, the abnormal brain state might be related to repetitive behaviors and stereotypical interests, and macroscopically reflect disruption of gamma-aminobutyric acid at the cellular level. The detection of brain states based on time-varying functional connectivity analysis of resting-state fMRI might be conducive for diagnosis and early intervention of ASD before obvious clinical symptoms.

  1. Resting-State Time-Varying Analysis Reveals Aberrant Variations of Functional Connectivity in Autism

    PubMed Central

    Yao, Zhijun; Hu, Bin; Xie, Yuanwei; Zheng, Fang; Liu, Guangyao; Chen, Xuejiao; Zheng, Weihao

    2016-01-01

    Recently, studies based on time-varying functional connectivity have unveiled brain states diversity in some neuropsychiatric disorders, such as schizophrenia and major depressive disorder. However, time-varying functional connectivity analysis of resting-state functional Magnetic Resonance Imaging (fMRI) have been rarely performed on the Autism Spectrum Disorder (ASD). Hence, we performed time-varying connectivity analysis on resting-state fMRI data to investigate brain states mutation in ASD children. ASD showed an imbalance of connectivity state and aberrant ratio of connectivity with different strengths in the whole brain network, and decreased connectivity associated precuneus/posterior cingulate gyrus with medial prefrontal gyrus in default mode network. As compared to typical development children, weak relevance condition (the strength of a large number of connectivities in the state was less than means minus standard deviation of all connection strength) was maintained for a longer time between brain areas of ASD children, and ratios of weak connectivity in brain states varied dramatically in the ASD. In the ASD, the abnormal brain state might be related to repetitive behaviors and stereotypical interests, and macroscopically reflect disruption of gamma-aminobutyric acid at the cellular level. The detection of brain states based on time-varying functional connectivity analysis of resting-state fMRI might be conducive for diagnosis and early intervention of ASD before obvious clinical symptoms. PMID:27695408

  2. 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

  3. Altered Functional Connectivity Patterns of the Insular Subregions in Psychogenic Nonepileptic Seizures.

    PubMed

    Li, Rong; Liu, Kai; Ma, Xujing; Li, Zhiqiang; Duan, Xujun; An, Dongmei; Gong, Qiyong; Zhou, Dong; Chen, Huafu

    2015-07-01

    Neuroimaging studies have demonstrated that psychogenic nonepileptic seizures (PNES) are characterized by unstable cognitive-emotional and motor system, which is engaged in hyperactivity of limbic regions and sensorimotor area. The insula, which is a part of the limbic system, includes various subregions with some distinct connectivity patterns separately. However, whether these insular subregions show different connectivity patterns respectively in PNES remains largely unknown. We aimed to investigate the functional connectivity (FC) of insular subregions in PNES and extend the understanding of the complex pathophysiological mechanisms of this disease. A resting-state FC based on the insular subregions were conducted in 18 patients and 20 healthy controls. We examined the differences in FC values between PNES patients and controls using two sample t test. Our results showed patients had significantly stronger FC between insular subregions and sensorimotor network, lingual gyrus, superior parietal gyrus and putamen, which suggested a hyperlink pattern of insular subregions involved in abnormal emotion regulation, cognitive processes and motor function in PNES. Pearson correlation analysis between the mean FC values within abnormal regions and the frequency of PNES further indicated PNES exhibited abnormal functional organization whose stressful emotion of patients have great direct influence on their motor functions. The differentially impaired functional connectivity patterns of insular subregions might provide new insights into the complex neurological mechanism of PNES.

  4. Functional connectivity of primary motor cortex is dependent on genetic burden in prodromal Huntington disease.

    PubMed

    Koenig, Katherine A; Lowe, Mark J; Harrington, Deborah L; Lin, Jian; Durgerian, Sally; Mourany, Lyla; Paulsen, Jane S; Rao, Stephen M

    2014-09-01

    Subtle changes in motor function have been observed in individuals with prodromal Huntington disease (prHD), but the underlying neural mechanisms are not well understood nor is the cumulative effect of the disease (disease burden) on functional connectivity. The present study examined the resting-state functional magnetic resonance imaging (rs-fMRI) connectivity of the primary motor cortex (M1) in 16 gene-negative (NEG) controls and 48 gene-positive prHD participants with various levels of disease burden. The results showed that the strength of the left M1 connectivity with the ipsilateral M1 and somatosensory areas decreased as disease burden increased and correlated with motor symptoms. Weakened M1 connectivity within the motor areas was also associated with abnormalities in long-range connections that evolved with disease burden. In this study, M1 connectivity was decreased with visual centers (bilateral cuneus), but increased with a hub of the default mode network (DMN; posterior cingulate cortex). Changes in connectivity measures were associated with worse performance on measures of cognitive-motor functioning. Short- and long-range functional connectivity disturbances were also associated with volume loss in the basal ganglia, suggesting that weakened M1 connectivity is partly a manifestation of striatal atrophy. Altogether, the results indicate that the prodromal phase of HD is associated with abnormal interhemispheric interactions among motor areas and disturbances in the connectivity of M1 with visual centers and the DMN. These changes may, respectively, contribute to increased motor symptoms, visuomotor integration problems, and deficits in the executive control of movement as individuals approach a manifest diagnosis.

  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.

  6. Catchment Classification: Connecting Climate, Structure and Function

    NASA Astrophysics Data System (ADS)

    Sawicz, K. A.; Wagener, T.; Sivapalan, M.; Troch, P. A.; Carrillo, G. A.

    2010-12-01

    Hydrology does not yet possess a generally accepted catchment classification framework. Such a classification framework needs to: [1] give names to things, i.e. the main classification step, [2] permit transfer of information, i.e. regionalization of information, [3] permit development of generalizations, i.e. to develop new theory, and [4] provide a first order environmental change impact assessment, i.e., the hydrologic implications of climate, land use and land cover change. One strategy is to create a catchment classification framework based on the notion of catchment functions (partitioning, storage, and release). Results of an empirical study presented here connects climate and structure to catchment function (in the form of select hydrologic signatures), based on analyzing over 300 US catchments. Initial results indicate a wide assortment of signature relationships with properties of climate, geology, and vegetation. The uncertainty in the different regionalized signatures varies widely, and therefore there is variability in the robustness of classifying ungauged basins. This research provides insight into the controls of hydrologic behavior of a catchment, and enables a classification framework applicable to gauged and ungauged across the study domain. This study sheds light on what we can expect to achieve in mapping climate, structure and function in a top-down manner. Results of this study complement work done using a bottom-up physically-based modeling framework to generalize this approach (Carrillo et al., this session).

  7. Alterations in functional connectivity for language in prematurely born adolescents.

    PubMed

    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

    2009-03-01

    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 cranial ultrasound, and 26 term control subjects were examined with a functional magnetic resonance imaging (fMRI) semantic association task, the Wechsler Intelligence Scale for Children-III (WISC-III) and the Clinical Evaluation of Language Fundamentals (CELF). In-magnet task accuracy and response times were calculated, and fMRI data were evaluated for the effect of group on blood oxygen level dependent (BOLD) activation, the correlation between task accuracy and activation and the functional connectivity between regions activating to task. Although there were differences in verbal IQ and CELF scores between the preterm (PT) and term control groups, there were no significant differences for either accuracy or response time for the in-magnet task. Both groups activated classic semantic processing areas including the left superior and middle temporal gyri and inferior frontal gyrus, and there was no significant difference in activation patterns between groups. Clear differences between the groups were observed in the correlation between task accuracy and activation to task at P < 0.01, corrected for multiple comparisons. Left inferior frontal gyrus correlated with accuracy only for term controls and left sensory motor areas correlated with accuracy only for PT subjects. Left middle temporal gyri correlated with task accuracy for both groups. Connectivity analyses at P < 0.001 revealed the importance of a circuit between left middle temporal gyri and inferior frontal gyrus for both groups. In addition, the PT subjects evidenced greater connectivity between traditional language areas and sensory motor areas but significantly

  8. 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

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

    PubMed

    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.

  10. Cytoarchitectural and Functional Abnormalities of the Inferior Colliculus in Sudden Unexplained Perinatal Death

    PubMed Central

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

    2015-01-01

    Abstract 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

  11. Implicit function theorem as a realization of the Lagrange principle. Abnormal points

    SciTech Connect

    Arutyunov, A V

    2000-02-28

    A smooth non-linear map is studied in a neighbourhood of an abnormal (degenerate) point. Inverse function and implicit function theorems are proved. The proof is based on the examination of a family of constrained extremal problems; second-order necessary conditions, which make sense also in the abnormal case, are used in the process. If the point under consideration is normal, then these conditions turn into the classical ones.

  12. Default mode network functional and structural connectivity after traumatic brain injury.

    PubMed

    Sharp, David J; Beckmann, Christian F; Greenwood, Richard; Kinnunen, Kirsi M; Bonnelle, Valerie; De Boissezon, Xavier; Powell, Jane H; Counsell, Serena J; Patel, Maneesh C; Leech, Robert

    2011-08-01

    Traumatic brain injury often results in cognitive impairments that limit recovery. The underlying pathophysiology of these impairments is uncertain, which restricts clinical assessment and management. Here, we use magnetic resonance imaging to test the hypotheses that: (i) traumatic brain injury results in abnormalities of functional connectivity within key cognitive networks; (ii) these changes are correlated with cognitive performance; and (iii) functional connectivity within these networks is influenced by underlying changes in structural connectivity produced by diffuse axonal injury. We studied 20 patients in the chronic phase after traumatic brain injury compared with age-matched controls. Network function was investigated in detail using functional magnetic resonance imaging to analyse both regional brain activation, and the interaction of brain regions within a network (functional connectivity). We studied patients during performance of a simple choice-reaction task and at 'rest'. Since functional connectivity reflects underlying structural connectivity, diffusion tensor imaging was used to quantify axonal injury, and test whether structural damage correlated with functional change. The patient group showed typical impairments in information processing and attention, when compared with age-matched controls. Patients were able to perform the task accurately, but showed slow and variable responses. Brain regions activated by the task were similar between the groups, but patients showed greater deactivation within the default mode network, in keeping with an increased cognitive load. A multivariate analysis of 'resting' state functional magnetic resonance imaging was then used to investigate whether changes in network function were present in the absence of explicit task performance. Overall, default mode network functional connectivity was increased in the patient group. Patients with the highest functional connectivity had the least cognitive impairment. In

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

    PubMed

    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

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

    PubMed

    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

  16. 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

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

    PubMed

    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

  18. 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

  19. 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

  20. Altered functional connectivity of the language network in ASD: role of classical language areas and cerebellum.

    PubMed

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

    2014-01-01

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

  1. 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…

  2. Abnormal Red Cell Structure and Function in Neuroacanthocytosis

    PubMed Central

    Cluitmans, Judith C. A.; Tomelleri, Carlo; Yapici, Zuhal; Dinkla, Sip; Bovee-Geurts, Petra; Chokkalingam, Venkatachalam; De Franceschi, Lucia; Brock, Roland; Bosman, Giel J. G. C. M.

    2015-01-01

    Background Panthothenate kinase-associated neurodegeneration (PKAN) belongs to a group of hereditary neurodegenerative disorders known as neuroacanthocytosis (NA). This genetically heterogeneous group of diseases is characterized by degeneration of neurons in the basal ganglia and by the presence of deformed red blood cells with thorny protrusions, acanthocytes, in the circulation. Objective The goal of our study is to elucidate the molecular mechanisms underlying this aberrant red cell morphology and the corresponding functional consequences. This could shed light on the etiology of the neurodegeneration. Methods We performed a qualitative and semi-quantitative morphological, immunofluorescent, biochemical and functional analysis of the red cells of several patients with PKAN and, for the first time, of the red cells of their family members. Results We show that the blood of patients with PKAN contains not only variable numbers of acanthocytes, but also a wide range of other misshapen red cells. Immunofluorescent and immunoblot analyses suggest an altered membrane organization, rather than quantitative changes in protein expression. Strikingly, these changes are not limited to the red blood cells of PKAN patients, but are also present in the red cells of heterozygous carriers without neurological problems. Furthermore, changes are not only present in acanthocytes, but also in other red cells, including discocytes. The patients’ cells, however, are more fragile, as observed in a spleen-mimicking device. Conclusion These morphological, molecular and functional characteristics of red cells in patients with PKAN and their family members offer new tools for diagnosis and present a window into the pathophysiology of neuroacanthocytosis. PMID:25933379

  3. Reduced functional connectivity within and between 'social' resting state networks in autism spectrum conditions.

    PubMed

    von dem Hagen, Elisabeth A H; Stoyanova, Raliza S; Baron-Cohen, Simon; Calder, Andrew J

    2013-08-01

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

  4. Functional abnormalities of experimental autogenous vein graft neoendothelium.

    PubMed Central

    Cross, K S; el-Sanadiki, M N; Murray, J J; Mikat, E M; McCann, R L; Hagen, P O

    1988-01-01

    When a vein is grafted into the arterial circulation, the endothelium of the graft is damaged. Regeneration of an intact neoendothelium occurs, but the functional properties of this surface have not been clarified. In this study, the functional integrity of the neoendothelium of veins grafted into the carotid artery of the rabbit was assessed through the use of acetylcholine and histamine to stimulate the production of the important endothelium-derived relaxing factor (EDRF). Control veins, precontracted with norepinephrine [10(-5) M], relaxed after exposure to acetylcholine [( 10(-7) M], 42.4% +/- 6.4%, p = 0.008) and histamine [( 10(-6) M], 30.6% +/- 4.3%, p = 0.03). This relaxation response was abolished after mechanical removal of the endothelium. By contrast, neither acetylcholine nor histamine caused an endothelium-dependent relaxation in the vein grafts, even though scanning electron microscopy demonstrated the presence of a morphologically intact endothelium. However, addition of stabilized EDRF purified from cultured endothelial cells induced relaxation of the vein grafts (35.8% +/- 3.6%, p = 0.002). These data indicate that vein graft endothelium is unable to produce EDRF in response to exposure to acetylcholine or histamine. The inability to produce this potent smooth muscle cell relaxing factor and anti-aggregatory substance may be a predisposition to vein graft failure. Images Figs. 4A-C. Fig. 4. (Continued) Fig. 4. (Continued) Figs. 5A-C. Fig. 5. (Continued) Fig. 5. (Continued) Fig. 6. PMID:3263843

  5. 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.

  6. 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.

  7. 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

  8. 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

  9. 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

  10. Injury alters intrinsic functional connectivity within the primate spinal cord.

    PubMed

    Chen, Li Min; Mishra, Arabinda; Yang, Pai-Feng; Wang, Feng; Gore, John C

    2015-05-12

    Recent demonstrations of correlated low-frequency MRI signal variations between subregions of the spinal cord at rest in humans, similar to those found in the brain, suggest that such resting-state functional connectivity constitutes a common feature of the intrinsic organization of the entire central nervous system. We report our detection of functional connectivity within the spinal cords of anesthetized squirrel monkeys at rest and show that the strength of connectivity within these networks is altered by the effects of injuries. By quantifying the low-frequency MRI signal correlations between different horns within spinal cord gray matter, we found distinct functional connectivity relationships between the different sensory and motor horns, a pattern that was similar to activation patterns evoked by nociceptive heat or tactile stimulation of digits. All horns within a single spinal segment were functionally connected, with the strongest connectivity occurring between ipsilateral dorsal and ventral horns. Each horn was strongly connected to the same horn on neighboring segments, but this connectivity reduced drastically along the spinal cord. Unilateral injury to the spinal cord significantly weakened the strength of the intrasegment horn-to-horn connectivity only on the injury side and in slices below the lesion. These findings suggest resting-state functional connectivity may be a useful biomarker of functional integrity in injured and recovering spinal cords. PMID:25902510

  11. Changes in brain functional network connectivity after stroke.

    PubMed

    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

  12. Early-stage visual processing abnormalities in high-functioning autism spectrum disorder (ASD).

    PubMed

    Baruth, Joshua M; Casanova, Manuel F; Sears, Lonnie; Sokhadze, Estate

    2010-06-01

    It has been reported that individuals with autism spectrum disorder (ASD) have abnormal responses to the sensory environment. For these individuals sensory overload can impair functioning, raise physiological stress, and adversely affect social interaction. Early-stage (i.e. within 200ms of stimulus onset) auditory processing abnormalities have been widely examined in ASD using event-related potentials (ERP), while ERP studies investigating early-stage visual processing in ASD are less frequent. We wanted to test the hypothesis of early-stage visual processing abnormalities in ASD by investigating ERPs elicited in a visual oddball task using illusory figures. Our results indicate that individuals with ASD have abnormally large cortical responses to task irrelevant stimuli over both parieto-occipital and frontal regions-of-interest (ROI) during early stages of visual processing compared to the control group. Furthermore, ASD patients showed signs of an overall disruption in stimulus discrimination, and had a significantly higher rate of motor response errors.

  13. 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

  14. 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.

  15. Dynamic BOLD functional connectivity in humans and its electrophysiological correlates.

    PubMed

    Tagliazucchi, Enzo; von Wegner, Frederic; Morzelewski, Astrid; Brodbeck, Verena; Laufs, Helmut

    2012-01-01

    Neural oscillations subserve many human perceptual and cognitive operations. Accordingly, brain functional connectivity is not static in time, but fluctuates dynamically following the synchronization and desynchronization of neural populations. This dynamic functional connectivity has recently been demonstrated in spontaneous fluctuations of the Blood Oxygen Level-Dependent (BOLD) signal, measured with functional Magnetic Resonance Imaging (fMRI). We analyzed temporal fluctuations in BOLD connectivity and their electrophysiological correlates, by means of long (≈50 min) joint electroencephalographic (EEG) and fMRI recordings obtained from two populations: 15 awake subjects and 13 subjects undergoing vigilance transitions. We identified positive and negative correlations between EEG spectral power (extracted from electrodes covering different scalp regions) and fMRI BOLD connectivity in a network of 90 cortical and subcortical regions (with millimeter spatial resolution). In particular, increased alpha (8-12 Hz) and beta (15-30 Hz) power were related to decreased functional connectivity, whereas gamma (30-60 Hz) power correlated positively with BOLD connectivity between specific brain regions. These patterns were altered for subjects undergoing vigilance changes, with slower oscillations being correlated with functional connectivity increases. Dynamic BOLD functional connectivity was reflected in the fluctuations of graph theoretical indices of network structure, with changes in frontal and central alpha power correlating with average path length. Our results strongly suggest that fluctuations of BOLD functional connectivity have a neurophysiological origin. Positive correlations with gamma can be interpreted as facilitating increased BOLD connectivity needed to integrate brain regions for cognitive performance. Negative correlations with alpha suggest a temporary functional weakening of local and long-range connectivity, associated with an idling state. PMID

  16. 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

  17. Altered functional connectivity in default mode network in absence epilepsy: a resting-state fMRI study.

    PubMed

    Luo, Cheng; Li, Qifu; Lai, Yongxiu; Xia, Yang; Qin, Yun; Liao, Wei; Li, Shasha; Zhou, Dong; Yao, Dezhong; Gong, Qiyong

    2011-03-01

    Dysfunctional default mode network (DMN) has been observed in various mental disorders, including epilepsy (see review Broyd et al. [2009]: Neurosci Biobehav Rev 33:279–296). Because interictal epileptic discharges may affect DMN, resting-state fMRI was used in this study to determine DMN functional connectivity in 14 healthy controls and 12 absence epilepsy patients. To avoid interictal epileptic discharge effects, testing was performed within interictal durations when there were no interictal epileptic discharges. Cross-correlation functional connectivity analysis with seed at posterior cingulate cortex, as well as region-wise calculation in DMN, revealed decreased integration within DMN in the absence epilepsy patients. Region-wise functional connectivity among the frontal, parietal, and temporal lobe was significantly decreased in the patient group. Moreover, functional connectivity between the frontal and parietal lobe revealed a significant negative correlation with epilepsy duration. These findings indicated DMN abnormalities in patients with absence epilepsy, even during resting interictal durations without interictal epileptic discharges. Abnormal functional connectivity in absence epilepsy may reflect abnormal anatomo-functional architectural integration in DMN, as a result of cognitive mental impairment and unconsciousness during absence seizure. PMID:21319269

  18. Fostering Connections between Classes of Polynomial Functions.

    ERIC Educational Resources Information Center

    Buck, Judy Curran

    The typical path of instruction in high school algebra courses for the study of polynomial functions has been from linear functions, to quadratic functions, to polynomial functions of degree greater than two. This paper reports results of clinical interviews with an Algebra II student. The interviews were used to probe into the student's…

  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. 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.

  1. 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.

  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. 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

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

    PubMed

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

    2015-07-01

    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

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

    PubMed

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

    2015-07-01

    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.

  6. 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…

  7. Low yield of unselected testing in patients with acutely abnormal liver function tests

    PubMed Central

    Chadwick, Andrew

    2015-01-01

    Objectives To audit the diagnostic yield and cost implications of the use of a ‘liver screen’ for inpatients with abnormal liver function tests. Design We performed a retrospective audit of inpatients with abnormal liver function tests. We analysed all investigations ordered including biochemistry, immunology, virology and radiology. The final diagnosis was ascertained in each case, and the diagnostic yield and cost per positive diagnosis for each investigation were calculated. Setting St Thomas’ NHS Trust. Participants All inpatients investigated for abnormal liver function tests over a 12-month period. Main outcome measures We calculated the percentage of courses due to each diagnosis, the yield of each investigation and the cost per positive diagnosis for each investigation. Results A total of 308 patients were included, and a final diagnosis was made in 224 patients (73%) on the basis of both clinical data and investigations. There was considerable heterogeneity in the tests included in an acute liver screen. History and ultrasound yielded the most diagnoses (40% and 30%, respectively). The yield of autoimmune and metabolic screens was minimal. Conclusions Our results demonstrate the low yield of unselected testing in patients with abnormal liver function tests. A thorough history, ultrasound and testing for blood-borne viruses are the cornerstones of diagnosis. Specialist input should be sought before further testing. Prospective studies to evaluate the yield and cost-effectiveness of different testing strategies are needed. PMID:26770816

  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. Synchrony, connectivity, and functional similarity in auditory midbrain local circuits.

    PubMed

    Atencio, Craig A; Shen, Victor; Schreiner, Christoph E

    2016-10-29

    The central nucleus of the inferior colliculus (ICC) contains a laminar structure that functions as an organizing substrate of ascending inputs and local processing. While topographic distributions of ICC response parameters within and across laminae have been reported, the functional micro-organization of the ICC is less well understood. For pairs of neighboring ICC neurons, we examined the nature of functional connectivity and receptive field preferences to gain a better understanding of the structure and function of local circuits. By recording from pairs of adjacent neurons and presenting pure-tone and dynamic broad-band stimulation, we estimated functional connectivity and local differences in frequency response areas (FRAs), spectrotemporal receptive fields (STRFs), nonlinear input/output functions, and single-spike information. From the cross-covariance functions we identified putative unidirectional as well as bidirectional excitatory/inhibitory interactions. STRFs of neighboring neurons strongly conserve best frequency, and moderately agree in STRF similarity, bandwidth, temporal response type, best modulation frequency, nonlinearity structure, and degree of information processing. Excitatory connectivity was stronger and temporally more precise than for inhibitory connections. Neither connection strength nor degree of synchrony correlated with receptive field parameters. The functional similarity of local pairs of ICC neurons was substantially less than for local pairs in the granular layers of primary auditory cortex (AI). These results imply that while the ICC is an obligatory nexus of ascending information, local neurons are comparatively weakly connected and exhibit considerable receptive field variability, potentially reflecting the heterogeneity of converging inputs to ICC functional zones.

  12. 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

  13. Multivariate classification of social anxiety disorder using whole brain functional connectivity.

    PubMed

    Liu, Feng; Guo, Wenbin; Fouche, Jean-Paul; Wang, Yifeng; Wang, Wenqin; Ding, Jurong; Zeng, Ling; Qiu, Changjian; Gong, Qiyong; Zhang, Wei; Chen, Huafu

    2015-01-01

    Recent research has shown that social anxiety disorder (SAD) is accompanied by abnormalities in brain functional connections. However, these findings are based on group comparisons, and, therefore, little is known about whether functional connections could be used in the diagnosis of an individual patient with SAD. Here, we explored the potential of the functional connectivity to be used for SAD diagnosis. Twenty patients with SAD and 20 healthy controls were scanned using resting-state functional magnetic resonance imaging. The whole brain was divided into 116 regions based on automated anatomical labeling atlas. The functional connectivity between each pair of regions was computed using Pearson's correlation coefficient and used as classification feature. Multivariate pattern analysis was then used to classify patients from healthy controls. The pattern classifier was designed using linear support vector machine. Experimental results showed a correct classification rate of 82.5 % (p < 0.001) with sensitivity of 85.0 % and specificity of 80.0 %, using a leave-one-out cross-validation method. It was found that the consensus connections used to distinguish SAD were largely located within or across the default mode network, visual network, sensory-motor network, affective network, and cerebellar regions. Specifically, the right orbitofrontal region exhibited the highest weight in classification. The current study demonstrated that functional connectivity had good diagnostic potential for SAD, thus providing evidence for the possible use of whole brain functional connectivity as a complementary tool in clinical diagnosis. In addition, this study confirmed previous work and described novel pathophysiological mechanisms of SAD.

  14. 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.

  15. 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…

  16. 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

  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.

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

    PubMed Central

    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

  19. 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

  20. 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.

  1. Resting-State Functional Connectivity in Late-Life Depression: Higher Global Connectivity and More Long Distance Connections

    PubMed Central

    Bohr, Iwo Jerzy; Kenny, Eva; Blamire, Andrew; O’Brien, John T.; Thomas, Alan J.; Richardson, Jonathan; Kaiser, Marcus

    2013-01-01

    Functional magnetic resonance imaging recordings in the resting-state (RS) from the human brain are characterized by spontaneous low-frequency fluctuations in the blood oxygenation level dependent signal that reveal functional connectivity (FC) via their spatial synchronicity. This RS study applied network analysis to compare FC between late-life depression (LLD) patients and control subjects. Raw cross-correlation matrices (CM) for LLD were characterized by higher FC. We analyzed the small-world (SW) and modular organization of these networks consisting of 110 nodes each as well as the connectivity patterns of individual nodes of the basal ganglia. Topological network measures showed no significant differences between groups. The composition of top hubs was similar between LLD and control subjects, however in the LLD group posterior medial-parietal regions were more highly connected compared to controls. In LLD, a number of brain regions showed connections with more distant neighbors leading to an increase of the average Euclidean distance between connected regions compared to controls. In addition, right caudate nucleus connectivity was more diffuse in LLD. In summary, LLD was associated with overall increased FC strength and changes in the average distance between connected nodes, but did not lead to global changes in SW or modular organization. PMID:23316175

  2. Bayesian Estimation of Conditional Independence Graphs Improves Functional Connectivity Estimates

    PubMed Central

    Hinne, Max; Janssen, Ronald J.; Heskes, Tom; van Gerven, Marcel A.J.

    2015-01-01

    Functional connectivity concerns the correlated activity between neuronal populations in spatially segregated regions of the brain, which may be studied using functional magnetic resonance imaging (fMRI). This coupled activity is conveniently expressed using covariance, but this measure fails to distinguish between direct and indirect effects. A popular alternative that addresses this issue is partial correlation, which regresses out the signal of potentially confounding variables, resulting in a measure that reveals only direct connections. Importantly, provided the data are normally distributed, if two variables are conditionally independent given all other variables, their respective partial correlation is zero. In this paper, we propose a probabilistic generative model that allows us to estimate functional connectivity in terms of both partial correlations and a graph representing conditional independencies. Simulation results show that this methodology is able to outperform the graphical LASSO, which is the de facto standard for estimating partial correlations. Furthermore, we apply the model to estimate functional connectivity for twenty subjects using resting-state fMRI data. Results show that our model provides a richer representation of functional connectivity as compared to considering partial correlations alone. Finally, we demonstrate how our approach can be extended in several ways, for instance to achieve data fusion by informing the conditional independence graph with data from probabilistic tractography. As our Bayesian formulation of functional connectivity provides access to the posterior distribution instead of only to point estimates, we are able to quantify the uncertainty associated with our results. This reveals that while we are able to infer a clear backbone of connectivity in our empirical results, the data are not accurately described by simply looking at the mode of the distribution over connectivity. The implication of this is that

  3. 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

  4. 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…

  5. 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

  6. Assessing thalamocortical functional connectivity with Granger causality.

    PubMed

    Chen, Cheng; Maybhate, Anil; Israel, David; Thakor, Nitish V; Jia, Xiaofeng

    2013-09-01

    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 ( , 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.

  7. Resting-state fMRI functional connectivity: a new perspective to evaluate pain modulation in migraine?

    PubMed

    Colombo, Bruno; Rocca, Maria Assunta; Messina, Roberta; Guerrieri, Simone; Filippi, Massimo

    2015-05-01

    Resting-state (RS) functional magnetic resonance imaging (fMRI) is a relatively novel tool which explores connectivity between functionally linked, but anatomically separated, brain regions. The use of this technique has allowed the identification, at rest, of the main brain functional networks without requiring subjects to perform specific active tasks. Methodologically, several approaches can be applied for the analysis of RS fMRI, including seed-based, independent component analysis-based and/or cluster-based methods. The most consistently described RS network is the so-called "default mode network". Using RS fMRI, several studies have identified functional connectivity abnormalities in migraine patients, mainly located at the level of the pain-processing network. RS functional connectivity is generally increased in pain-processing network, whereas is decreased in pain modulatory circuits. Significant abnormalities of RS functional connectivity occur also in affective networks, the default mode network and the executive control network. These results provide a strong characterization of migraine as a brain dysfunction affecting intrinsic connectivity of brain networks, possibly reflecting the impact of long lasting pain on brain function. PMID:26017510

  8. 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

  9. 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

  10. 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

  11. Functional Connectivity Density and Balance in Young Patients with Traumatic Axonal Injury

    PubMed Central

    Siugzdaite, Roma; Drijkoningen, David; Marinazzo, Daniele; Swinnen, Stephan P.

    2015-01-01

    Abstract Our previous study provided some evidence for the relationship between abnormal structural connectivity and poor balance performance in young traumatic axonal injury (TAI) patients. An enhanced understanding of the functional connectivity following TAI may allow targeted treatments geared toward improving brain function and postural control. Twelve patients with TAI and 28 normally developing children (aged 9–19 years) performed the sensory organization test (SOT) protocol of the EquiTest (Neurocom). All participants were scanned using resting-state functional magnetic resonance imaging series along with anatomical scans. We applied “functional connectivity density mapping” (FCDM), a voxel-wise data-driven method that calculates individual functional connectivity maps to obtain both short-range and long-range FCD. Findings revealed that the TAI group scored generally lower than the control group on the SOT, especially when proprioceptive feedback was compromised. Between-group maps noted significantly decreased long-range FCD in the TAI group in frontal and subcortical regions and significantly increased short-range FCD in frontal regions, left inferior parietal, and cerebellar lobules. Moreover, lower balance levels in TAI patients were associated with a lower long-range FCD in left putamen and cerebellar vermis. These findings suggest that long-range connections may be more vulnerable to TAI than short-range connections. Moreover, higher values of short-range FCD may suggest adaptive mechanisms in the TAI group. Finally, this study supports the view that FCDM is a valuable tool for selectively predicting functional motor deficits in TAI patients. PMID:25327385

  12. Functional Connectivity Density and Balance in Young Patients with Traumatic Axonal Injury.

    PubMed

    Caeyenberghs, Karen; Siugzdaite, Roma; Drijkoningen, David; Marinazzo, Daniele; Swinnen, Stephan P

    2015-09-01

    Our previous study provided some evidence for the relationship between abnormal structural connectivity and poor balance performance in young traumatic axonal injury (TAI) patients. An enhanced understanding of the functional connectivity following TAI may allow targeted treatments geared toward improving brain function and postural control. Twelve patients with TAI and 28 normally developing children (aged 9-19 years) performed the sensory organization test (SOT) protocol of the EquiTest (Neurocom). All participants were scanned using resting-state functional magnetic resonance imaging series along with anatomical scans. We applied "functional connectivity density mapping" (FCDM), a voxel-wise data-driven method that calculates individual functional connectivity maps to obtain both short-range and long-range FCD. Findings revealed that the TAI group scored generally lower than the control group on the SOT, especially when proprioceptive feedback was compromised. Between-group maps noted significantly decreased long-range FCD in the TAI group in frontal and subcortical regions and significantly increased short-range FCD in frontal regions, left inferior parietal, and cerebellar lobules. Moreover, lower balance levels in TAI patients were associated with a lower long-range FCD in left putamen and cerebellar vermis. These findings suggest that long-range connections may be more vulnerable to TAI than short-range connections. Moreover, higher values of short-range FCD may suggest adaptive mechanisms in the TAI group. Finally, this study supports the view that FCDM is a valuable tool for selectively predicting functional motor deficits in TAI patients. PMID:25327385

  13. 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

  14. 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

  15. Early-stage visual processing abnormalities in high-functioning autism spectrum disorder (ASD)

    PubMed Central

    Baruth, Joshua M.; Casanova, Manuel F.; Sears, Lonnie; Sokhadze, Estate

    2012-01-01

    It has been reported that individuals with autism spectrum disorder (ASD) have abnormal responses to the sensory environment. For these individuals sensory overload can impair functioning, raise physiological stress, and adversely affect social interaction. Early-stage (i.e. within 200ms of stimulus onset) auditory processing abnormalities have been widely examined in ASD using event-related potentials (ERP), while ERP studies investigating early-stage visual processing in ASD are less frequent. We wanted to test the hypothesis of early-stage visual processing abnormalities in ASD by investigating ERPs elicited in a visual oddball task using illusory figures. Our results indicate that individuals with ASD have abnormally large cortical responses to task irrelevant stimuli over both parieto-occipital and frontal regions-of-interest (ROI) during early stages of visual processing compared to the control group. Furthermore, ASD patients showed signs of an overall disruption in stimulus discrimination, and had a significantly higher rate of motor response errors. PMID:22563527

  16. Abnormal functional brain asymmetry in depression: evidence of biologic commonality between major depression and dysthymia.

    PubMed

    Bruder, Gerard E; Stewart, Jonathan W; Hellerstein, David; Alvarenga, Jorge E; Alschuler, Daniel; McGrath, Patrick J

    2012-04-30

    Prior studies have found abnormalities of functional brain asymmetry in patients having a major depressive disorder (MDD). This study aimed to replicate findings of reduced right hemisphere advantage for perceiving dichotic complex tones in depressed patients, and to determine whether patients having "pure" dysthymia show the same abnormality of perceptual asymmetry as MDD. It also examined gender differences in lateralization, and the extent to which abnormalities of perceptual asymmetry in depressed patients are dependent on gender. Unmedicated patients having either a MDD (n=96) or "pure" dysthymic disorder (n=42) and healthy controls (n=114) were tested on dichotic fused-words and complex-tone tests. Patient and control groups differed in right hemisphere advantage for complex tones, but not left hemisphere advantage for words. Reduced right hemisphere advantage for tones was equally present in MDD and dysthymia, but was more evident among depressed men than depressed women. Also, healthy men had greater hemispheric asymmetry than healthy women for both words and tones, whereas this gender difference was not seen for depressed patients. Dysthymia and MDD share a common abnormality of hemispheric asymmetry for dichotic listening.

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

    PubMed

    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).

  18. Default Mode Network Functional Connectivity: A Promising Biomarker for Diagnosing Minimal Hepatic Encephalopathy

    PubMed Central

    Qi, Rongfeng; Zhang, Long Jiang; Luo, Song; Ke, Jun; Kong, Xiang; Xu, Qiang; Liu, Chang; Lu, Heng; Lu, Guang Ming

    2014-01-01

    Abstract To investigate the contribution of brain default mode network (DMN) in the early diagnosis of the minimal hepatic encephalopathy (MHE), the mildest form of HE from cirrhotic patients by using resting-state functional magnetic resonance imaging (rs-fMRI). This study was approved by the local ethical committee, and a written informed consent was obtained from each participant. A total of 103 cirrhotic patients (34 MHE, 69 non-HE) and 103 matched healthy controls underwent rs-fMRI scanning. The DMN correlation map was acquired by using unbiased seed-based functional connectivity analysis and compared among MHE patients, non-HE patients, and healthy controls with analysis of variance tests. Pearson correlation analysis was performed between the abnormal DMN connectivity and neuropsychological performances. Receiver operator characteristic (ROC) analysis was used to evaluate the contribution of DMN connectivity strength in the differential diagnosis between MHE and non-HE. Compared with the healthy controls, MHE and non-HE patients showed decreased DMN connectivity in medial prefrontal cortex (MPFC), left superior frontal gyrus (SFG), left temporal lobe, and bilateral middle temporal gyri (MTG). The MHE patients showed even more decreased connectivity in MPFC, left SFG, and right MTG when compared with non-HE patients. Pearson correlation analyses revealed that the decreased connectivity strength of some DMN regions correlated with patients’ neuropsychological tests scores. Connectivity strength of the MPFC, right MTG, and left SFG could differentiate MHE from non-HE, of which the MPFC had the highest effectiveness (sensitivity = 81.5%, specificity = 70.4%). Cirrhotic patients had gradually reduced DMN functional connectivty from non-HE patients to MHE patients. DMN function, especially the MPFC, might be a useful imaging marker for differentiating MHE from cirrhotic patients. PMID:25501083

  19. Globus Pallidus Interna in Tourette Syndrome: Decreased Local Activity and Disrupted Functional Connectivity

    PubMed Central

    Ji, Gong-Jun; Liao, Wei; Yu, Yang; Miao, Huan-Huan; Feng, Yi-Xuan; Wang, Kai; Feng, Jian-Hua; Zang, Yu-Feng

    2016-01-01

    Globus pallidus interna (GPi) is an effective deep brain stimulation site for the treatment of Tourette syndrome (TS), and plays a crucial role in the pathophysiology of TS. To investigate the functional network feature of GPi in TS patients, we retrospectively studied 24 boys with ‘pure’ TS and 32 age-/education-matched healthy boys by resting state functional magnetic resonance images. Amplitude of low-frequency fluctuation (ALFF) and functional connectivity were used to estimate the local activity in GPi and its functional coordinate with the whole brain regions, respectively. We found decreased ALFF in patients’ bilateral GPi, which was also negatively correlated with clinical symptoms. Functional connectivity analysis indicated abnormal regions within motor and motor-control networks in patients (inferior part of sensorimotor area, cerebellum, prefrontal cortex, cingulate gyrus, caudate nucleus, and brain stem). Transcranial magnetic stimulation sites defined by previous studies (“hand knob” area, premotor area, and supplementary motor area) did not show significantly different functional connectivity with GPi between groups. In summary, this study characterized the disrupted functional network of GPi and provided potential regions-of-interest for further basic and clinical studies on TS. PMID:27799898

  20. 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

  1. 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

  2. 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.

  3. 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

  4. 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

  5. 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

  6. Synchrony, connectivity, and functional similarity in auditory midbrain local circuits.

    PubMed

    Atencio, Craig A; Shen, Victor; Schreiner, Christoph E

    2016-10-29

    The central nucleus of the inferior colliculus (ICC) contains a laminar structure that functions as an organizing substrate of ascending inputs and local processing. While topographic distributions of ICC response parameters within and across laminae have been reported, the functional micro-organization of the ICC is less well understood. For pairs of neighboring ICC neurons, we examined the nature of functional connectivity and receptive field preferences to gain a better understanding of the structure and function of local circuits. By recording from pairs of adjacent neurons and presenting pure-tone and dynamic broad-band stimulation, we estimated functional connectivity and local differences in frequency response areas (FRAs), spectrotemporal receptive fields (STRFs), nonlinear input/output functions, and single-spike information. From the cross-covariance functions we identified putative unidirectional as well as bidirectional excitatory/inhibitory interactions. STRFs of neighboring neurons strongly conserve best frequency, and moderately agree in STRF similarity, bandwidth, temporal response type, best modulation frequency, nonlinearity structure, and degree of information processing. Excitatory connectivity was stronger and temporally more precise than for inhibitory connections. Neither connection strength nor degree of synchrony correlated with receptive field parameters. The functional similarity of local pairs of ICC neurons was substantially less than for local pairs in the granular layers of primary auditory cortex (AI). These results imply that while the ICC is an obligatory nexus of ascending information, local neurons are comparatively weakly connected and exhibit considerable receptive field variability, potentially reflecting the heterogeneity of converging inputs to ICC functional zones. PMID:27544405

  7. 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

  8. 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

  9. Helping Students-Connect Functions and Their Representations

    ERIC Educational Resources Information Center

    Moore-Russo, Deborah; Golzy, John B.

    2005-01-01

    The description about the changed instruction to encourage student exploration of the graphical and then the algebraic representations of functions is presented, which enables the students to understand how the graph, equation, and table of a function are related. The activity addresses both the Learning Principle and the Connection standard and…

  10. 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

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

    PubMed Central

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

    2014-01-01

    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

  12. 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.

  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. 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

  15. Resting-state functional connectivity of the human hypothalamus.

    PubMed

    Kullmann, Stephanie; Heni, Martin; Linder, Katarzyna; Zipfel, Stephan; Häring, Hans-Ulrich; Veit, Ralf; Fritsche, Andreas; Preissl, Hubert

    2014-12-01

    The hypothalamus is of enormous importance for multiple bodily functions such as energy homeostasis. Especially, rodent studies have greatly contributed to our understanding how specific hypothalamic subregions integrate peripheral and central signals into the brain to control food intake. In humans, however, the neural circuitry of the hypothalamus, with its different subregions, has not been delineated. Hence, the aim of this study was to map the hypothalamus network using resting-state functional connectivity (FC) analyses from the medial hypothalamus (MH) and lateral hypothalamus (LH) in healthy normal-weight adults (n = 49). Furthermore, in a separate sample, we examined differences within the LH and MH networks between healthy normal-weight (n = 25) versus overweight/obese adults (n = 23). FC patterns from the LH and MH revealed significant connections to the striatum, thalamus, brainstem, orbitofrontal cortex, middle and posterior cingulum and temporal brain regions. However, our analysis revealed subtler distinctions within hypothalamic subregions. The LH was functionally stronger connected to the dorsal striatum, anterior cingulum, and frontal operculum, while the MH showed stronger functional connections to the nucleus accumbens and medial orbitofrontal cortex. Furthermore, overweight/obese participants revealed heightened FC in the orbitofrontal cortex and nucleus accumbens within the MH network. Our results indicate that the MH and LH network are tapped into different parts of the dopaminergic circuitry of the brain, potentially modulating food reward based on the functional connections to the ventral and dorsal striatum, respectively. In obese adults, FC changes were observed in the MH network.

  16. 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

  17. Habenula functional resting-state connectivity in pediatric CRPS.

    PubMed

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

    2014-01-01

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

  18. 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

  19. 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

  20. 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.

  1. 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

  2. Functional connectivity between the amygdala and prefrontal cortex in medication-naive individuals with major depressive disorder

    PubMed Central

    Kong, Lingtao; Chen, Kaiyuan; Tang, Yanqing; Wu, Feng; Driesen, Naomi; Womer, Fay; Fan, Guoguang; Ren, Ling; Jiang, Wenyan; Cao, Yang; Blumberg, Hilary P.; Xu, Ke; Wang, Fei

    2013-01-01

    Background Convergent evidence suggests dysfunction within the prefrontal cortex (PFC) and amygdala, important components of a neural system that subserves emotional processing, in individuals with major depressive disorder (MDD). Abnormalities in this system in the left hemisphere and during processing of negative emotional stimuli are especially implicated. In this study, we used functional magnetic resonance imaging (fMRI) to investigate amygdala–PFC functional connectivity during emotional face processing in medication-naive individuals with MDD. Methods Individuals with MDD and healthy controls underwent fMRI scanning while processing 3 types of emotional face stimuli. We compared the strength of functional connectivity from the amygdala between the MDD and control groups. Results Our study included 28 individuals with MDD and 30 controls. Decreased amygdala–left rostral PFC (rPFC) functional connectivity was observed in the MDD group compared with controls for the fear condition (p < 0.05, corrected). No significant differences were found in amygdala connectivity to any cerebral regions between the MDD and control groups for the happy or neutral conditions. Limitations All participants with MDD were experiencing acute episodes, therefore the findings could not be generalized to the entire MDD population. Conclusion Medication-naive individuals with MDD showed decreased amygdala–left rPFC functional connectivity in response to negative emotional stimuli, suggesting that abnormalities in amygdala–left rPFC neural circuitry responses to negative emotional stimuli might play an important role in the pathophysiology of MDD. PMID:24148846

  3. 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

  4. Impaired cortico-striatal functional connectivity in prodromal Huntington's Disease.

    PubMed

    Unschuld, Paul G; Joel, Suresh E; Liu, Xinyang; Shanahan, Megan; Margolis, Russell L; Biglan, Kevin M; Bassett, Susan S; Schretlen, David J; Redgrave, Graham W; van Zijl, Peter C M; Pekar, James J; Ross, Christopher A

    2012-04-18

    Huntington's Disease (HD) is a neurodegenerative disease caused by a CAG triplet-repeat expansion-mutation in the Huntingtin gene. Subjects at risk for HD can be identified by genetic testing in the prodromal phase. Structural changes of basal-ganglia nuclei such as the caudate nucleus are well-replicated findings observable early in prodromal-HD subjects and may be preceded by distinct functional alterations of cortico-striatal circuits. This study aims to assess functional integrity of the motor system as a cortico-striatal circuit with particular clinical relevance in HD. Ten subjects in the prodromal phase of HD and ten matched controls were administered blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) at rest (3T). Functional connectivity was measured as synchrony of BOLD activity between the caudate nucleus and thirteen cortical brain regions (seeds). Basal-ganglia volumes were assessed as established markers of disease progression in prodromal-HD. Linear regression analysis was performed to test for a relationship between structural changes and group differences in functional connectivity. Prodromal-HD subjects showed reduced BOLD synchrony between two seeds in the premotor cortex (BA6) and the caudate nucleus. While similar effect sizes could be observed for reduced basal-ganglia volumes and differences in functional connectivity, coefficients of determination indicate a moderate relationship between functional connectivity and striatal atrophy. Our data show reduced cortico-striatal functional connectivity at rest in prodromal-HD and suggest a relation to early structural brain changes. Additional longitudinal studies are necessary to elucidate the temporal relationship between functional alterations and earliest structural brain changes in prodromal-HD.

  5. Functional connectivity changes in second language vocabulary learning.

    PubMed

    Ghazi Saidi, Ladan; Perlbarg, Vincent; Marrelec, Guillaume; Pélégrini-Issac, Mélani; Benali, Habib; Ansaldo, Ana-Inés

    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, Bellec et al., 2008) were gathered, in the shallow and consolidation phases of L2 vocabulary learning. Functional connectivity remained unchanged across learning phases for L1, whereas total, between- and within-network integration levels decreased as proficiency for L2 increased. The results of this study provide the first functional connectivity evidence regarding the dynamic role of the language processing and cognitive control networks in L2 learning (Abutalebi, Cappa, & Perani, 2005; Altarriba & Heredia, 2008; Leonard et al., 2011; Parker-Jones et al., 2011). Thus, increased proficiency results in a higher degree of automaticity and lower cognitive effort (Segalowitz & Hulstijn, 2005).

  6. 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

  7. 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

  8. 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

  9. 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.

  10. Frequency-specific alterations in functional connectivity in treatment-resistant and -sensitive major depressive disorder.

    PubMed

    He, Zongling; Cui, Qian; Zheng, Junjie; Duan, Xujun; Pang, Yajing; Gao, Qing; Han, Shaoqiang; Long, Zhiliang; Wang, Yifeng; Li, Jiao; Wang, Xiao; Zhao, Jingping; Chen, Huafu

    2016-11-01

    Major depressive disorder (MDD) may involve alterations in brain functional connectivity in multiple neural circuits and present large-scale network dysfunction. Patients with treatment-resistant depression (TRD) and treatment-sensitive depression (TSD) show different responses to antidepressants and aberrant brain functions. This study aims to investigate functional connectivity patterns of TRD and TSD at the whole brain resting state. Seventeen patients with TRD, 17 patients with TSD, and 17 healthy controls matched with age, gender, and years of education were recruited in this study. The brain was divided using an automated anatomical labeling atlas into 90 regions of interest, which were used to construct the entire brain functional networks. An analysis method called network-based statistic was used to explore the dysconnected subnetworks of TRD and TSD at different frequency bands. At resting state, TSD and TRD present characteristic patterns of network dysfunction at special frequency bands. The dysconnected subnetwork of TSD mainly lies in the fronto-parietal top-down control network. Moreover, the abnormal neural circuits of TRD are extensive and complex. These circuits not only depend on the abnormal affective network but also involve other networks, including salience network, auditory network, visual network, and language processing cortex. Our findings reflect that the pathological mechanism of TSD may refer to impairment in cognitive control, whereas TRD mainly triggers the dysfunction of emotion processing and affective cognition. This study reveals that differences in brain functional connectivity at resting state reflect distinct pathophysiological mechanisms in TSD and TRD. These findings may be helpful in differentiating two types of MDD and predicting treatment responses. PMID:27459030

  11. Frequency-specific alterations in functional connectivity in treatment-resistant and -sensitive major depressive disorder.

    PubMed

    He, Zongling; Cui, Qian; Zheng, Junjie; Duan, Xujun; Pang, Yajing; Gao, Qing; Han, Shaoqiang; Long, Zhiliang; Wang, Yifeng; Li, Jiao; Wang, Xiao; Zhao, Jingping; Chen, Huafu

    2016-11-01

    Major depressive disorder (MDD) may involve alterations in brain functional connectivity in multiple neural circuits and present large-scale network dysfunction. Patients with treatment-resistant depression (TRD) and treatment-sensitive depression (TSD) show different responses to antidepressants and aberrant brain functions. This study aims to investigate functional connectivity patterns of TRD and TSD at the whole brain resting state. Seventeen patients with TRD, 17 patients with TSD, and 17 healthy controls matched with age, gender, and years of education were recruited in this study. The brain was divided using an automated anatomical labeling atlas into 90 regions of interest, which were used to construct the entire brain functional networks. An analysis method called network-based statistic was used to explore the dysconnected subnetworks of TRD and TSD at different frequency bands. At resting state, TSD and TRD present characteristic patterns of network dysfunction at special frequency bands. The dysconnected subnetwork of TSD mainly lies in the fronto-parietal top-down control network. Moreover, the abnormal neural circuits of TRD are extensive and complex. These circuits not only depend on the abnormal affective network but also involve other networks, including salience network, auditory network, visual network, and language processing cortex. Our findings reflect that the pathological mechanism of TSD may refer to impairment in cognitive control, whereas TRD mainly triggers the dysfunction of emotion processing and affective cognition. This study reveals that differences in brain functional connectivity at resting state reflect distinct pathophysiological mechanisms in TSD and TRD. These findings may be helpful in differentiating two types of MDD and predicting treatment responses.

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

    PubMed

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

    2016-06-01

    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

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

    PubMed

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

    2016-06-01

    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.

  15. The functional logic of cortico-pulvinar connections.

    PubMed Central

    Shipp, S

    2003-01-01

    The pulvinar is an 'associative' thalamic nucleus, meaning that most of its input and output relationships are formed with the cerebral cortex. The function of this circuitry is little understood and its anatomy, though much investigated, is notably recondite. This is because pulvinar connection patterns disrespect the architectural subunits (anterior, medial, lateral and inferior pulvinar nuclei) that have been the traditional reference system. This article presents a simplified, global model of the organization of cortico-pulvinar connections so as to pursue their structure-function relationships. Connections between the cortex and pulvinar are topographically organized, and as a result the pulvinar contains a 'map' of the cortical sheet. However, the topography is very blurred. Hence the pulvinar connection zones of nearby cortical areas overlap, allowing indirect transcortical communication via the pulvinar. A general observation is that indirect cortico-pulvino-cortical circuits tend to mimic direct cortico-cortical pathways: this is termed 'the replication principle'. It is equally apt for certain pairs (or groups) of nearby cortical areas that happen not to connect with each other. The 'replication' of this non-connection is achieved by discontinuities and dislocations of the cortical topography within the pulvinar, such that the associated pair of connection zones do not overlap. Certain of these deformations can be used to divide the global cortical topography into specific sub-domains, which form the natural units of a connectional subdivision of the pulvinar. A substantial part of the pulvinar also expresses visual topography, reflecting visual maps in occipital cortex. There are just two well-ordered visual maps in the pulvinar, that both receive projections from area V1, and several other occipital areas; the resulting duplication of cortical topography means that each visual map also acts as a separate connection domain. In summary, the model

  16. 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.

  17. 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

  18. The relationship between childhood aerobic fitness and brain functional connectivity.

    PubMed

    Kamijo, Keita; Takeda, Yuji; Takai, Yohei; Haramura, Miki

    2016-10-01

    Several studies have indicated that higher levels of childhood aerobic fitness is associated with superior cognitive function, and this association is disproportionately observed in tasks requiring greater top-down control. We designed the current study to clarify the relationship between childhood fitness and top-down control in terms of functional connectivity among brain regions, by evaluating phase-locking values (PLVs), which is a measure of frequency-specific phase synchrony between electroencephalographic signals during a visual search task. Lower-fit and higher-fit children performed a visual search task that included feature search and conjunction search conditions. The conjunction search condition required greater top-down control to reduce interference from task-irrelevant distractors that shared a basic feature with the target. Results indicated that higher-fit children exhibited higher response accuracy relative to lower-fit children across search conditions. The results of PLVs showed that higher-fit children had greater functional connectivity for the conjunction relative to the feature search condition, whereas lower-fit children showed no difference in functional connectivity between search conditions. Furthermore, PLVs showed different time courses between groups; that is, higher-fit children sustained upregulation of top-down control throughout the task period, whereas lower-fit children transiently upregulated top-down control after stimulus onset and could not sustain the upregulation. These findings suggest that higher levels of childhood aerobic fitness is related to brain functional connectivity involved in the sustained upregulation of top-down control.

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

    PubMed

    Schmidt, Christoph; Pester, Britta; 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.

  20. 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

  1. 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

  2. Phenotypic variability in resting-state functional connectivity: current status.

    PubMed

    Vaidya, Chandan J; Gordon, Evan M

    2013-01-01

    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

  3. Structural, Metabolic, and Functional Brain Abnormalities as a Result of Prenatal Exposure to Drugs of Abuse: Evidence from Neuroimaging

    PubMed Central

    Roussotte, Florence; Soderberg, Lindsay

    2010-01-01

    Prenatal exposure to alcohol and stimulants negatively affects the developing trajectory of the central nervous system in many ways. Recent advances in neuroimaging methods have allowed researchers to study the structural, metabolic, and functional abnormalities resulting from prenatal exposure to drugs of abuse in living human subjects. Here we review the neuroimaging literature of prenatal exposure to alcohol, cocaine, and methamphetamine. Neuroimaging studies of prenatal alcohol exposure have reported differences in the structure and metabolism of many brain systems, including in frontal, parietal, and temporal regions, in the cerebellum and basal ganglia, as well as in the white matter tracts that connect these brain regions. Functional imaging studies have identified significant differences in brain activation related to various cognitive domains as a result of prenatal alcohol exposure. The published literature of prenatal exposure to cocaine and methamphetamine is much smaller, but evidence is beginning to emerge suggesting that exposure to stimulant drugs in utero may be particularly toxic to dopamine-rich basal ganglia regions. Although the interpretation of such findings is somewhat limited by the problem of polysubstance abuse and by the difficulty of obtaining precise exposure histories in retrospective studies, such investigations provide important insights into the effects of drugs of abuse on the structure, function, and metabolism of the developing human brain. These insights may ultimately help clinicians develop better diagnostic tools and devise appropriate therapeutic interventions to improve the condition of children with prenatal exposure to drugs of abuse. PMID:20978945

  4. The relationship between white matter abnormalities and cognitive functions in new-onset juvenile myoclonic epilepsy.

    PubMed

    Ekmekci, Burcu; Bulut, Hacı Taner; Gümüştaş, Funda; Yıldırım, Adem; Kuştepe, Ali

    2016-09-01

    Diffusion tensor imaging (DTI) has revealed evidence of subcortical white matter abnormalities in the frontal area in juvenile myoclonic epilepsy (JME). Decreased fractional anisotropy (FA) and increased mean diffusivity (MD) in the corticothalamic pathway have been detected in adult patients with JME. It has been demonstrated that, in adult patients with JME, frontal dysfunction is related to subcortical white matter damage and decreased volume in frontal cortical gray matter and the thalamus. Many studies have focused on adult patients. Twenty-four patients and 28 controls were evaluated. The group with JME had significantly worse results for the word fluency, trail-B, and Stroop tests that assessed executive functions. A significant decrease in FA values in the dorsolateral prefrontal cortex (DLPFC), the supplementary motor area (SMA), the right thalamus, the posterior cingulate, the corpus callosum anterior, the corona radiata, and the middle frontal white matter (MFWM) and an increase in ADC values in patients with JME were detected. The correlation between FA values in DLPFC and the letter fluency test results was positive, and the correlation with the Stroop and trail-B test results was negative. We found a negative correlation between SMA, anterior thalamus, and MFWM FA values and the trail-B test results and a positive correlation between the SMA, anterior thalamus, and MFWM FA values and the letter fluency test results. We detected white matter and gray matter abnormalities in patients with new-onset JME using DTI. In addition, we determined the relationship between cognitive deficit and microstructural abnormalities by evaluating the correlation between the neuropsychological test battery results and DTI parameters. We evaluated newly diagnosed patients with JME in our study. That leads us to believe that microstructural abnormalities exist from the very beginning of the disease and that they result from the genetic basis of the disease.

  5. 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

  6. 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

  7. Default mode, executive function, and language functional connectivity networks are compromised in mild Alzheimer's disease.

    PubMed

    Weiler, Marina; Fukuda, Aya; Massabki, Lilian H P; Lopes, Tatila M; Franco, Alexandre R; Damasceno, Benito P; Cendes, Fernando; Balthazar, Marcio L F

    2014-03-01

    Alzheimer's disease (AD) is characterized by mental and cognitive problems, particularly with memory, language, visuospatial skills (VS), and executive functions (EF). Advances in the neuroimaging of AD have highlighted dysfunctions in functional connectivity networks (FCNs), especially in the memory related default mode network (DMN). However, little is known about the integrity and clinical significance of FNCs that process other cognitive functions than memory. We evaluated 22 patients with mild AD and 26 healthy controls through a resting state functional MRI scan. We aimed to identify different FCNs: the DMN, language, EF, and VS. Seed-based functional connectivity was calculated by placing a seed in the DMN (posterior cingulate cortex), language (Broca's and Wernicke's areas), EF (right and left dorsolateral prefrontal cortex), and VS networks (right and left associative visual cortex). We also performed regression analyses between individual connectivity maps for the different FCNs and the scores on cognitive tests. We found areas with significant decreases in functional connectivity in patients with mild AD in the DMN and Wernicke's area compared with controls. Increased connectivity in patients was observed in the EF network. Regarding multiple linear regression analyses, a significant correlation was only observed between the connectivity of the DMN and episodic memory (delayed recall) scores. In conclusion, functional connectivity alterations in mild AD are not restricted to the DMN. Other FCNs related to language and EF may be altered. However, we only found significant correlations between cognition and functional connectivity in the DMN and episodic memory performance.

  8. Functional connectivity based parcellation of the human medial temporal lobe.

    PubMed

    Wang, Shao-Fang; Ritchey, Maureen; Libby, Laura A; Ranganath, Charan

    2016-10-01

    Regional differences in large-scale connectivity have been proposed to underlie functional specialization along the anterior-posterior axis of the medial temporal lobe (MTL), including the hippocampus (HC) and the parahippocampal gyrus (PHG). However, it is unknown whether functional connectivity (FC) can be used reliably to parcellate the human MTL. The current study aimed to differentiate subregions of the HC and the PHG based on patterns of whole-brain intrinsic FC. FC maps were calculated for each slice along the longitudinal axis of the PHG and the HC. A hierarchical clustering algorithm was then applied to these data in order to group slices according to the similarity of their connectivity patterns. Surprisingly, three discrete clusters were identified in the PHG. Two clusters corresponded to the parahippocampal cortex (PHC) and the perirhinal cortex (PRC), and these regions showed preferential connectivity with previously described posterior-medial and anterior-temporal networks, respectively. The third cluster corresponded to an anterior PRC region previously described as area 36d, and this region exhibited preferential connectivity with auditory cortical areas and with a network involved in visceral processing. The three PHG clusters showed different profiles of activation during a memory-encoding task, demonstrating that the FC-based parcellation identified functionally dissociable sub-regions of the PHG. In the hippocampus, no sub-regions were identified via the parcellation procedure. These results indicate that connectivity-based methods can be used to parcellate functional regions within the MTL, and they suggest that studies of memory and high-level cognition need to differentiate between PHC, posterior PRC, and anterior PRC.

  9. 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,…

  10. 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

  11. 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

  12. Functional connectivity during rested wakefulness predicts vulnerability to sleep deprivation.

    PubMed

    Yeo, B T Thomas; Tandi, Jesisca; Chee, Michael W L

    2015-05-01

    Significant inter-individual differences in vigilance decline following sleep deprivation exist. We characterized functional connectivity in 68 healthy young adult participants in rested wakefulness and following a night of total sleep deprivation. After whole brain signal regression, functionally connected cortical networks during the well-rested state exhibited reduced correlation following sleep deprivation, suggesting that highly integrated brain regions become less integrated during sleep deprivation. In contrast, anti-correlations in the well-rested state became less so following sleep deprivation, suggesting that highly segregated networks become less segregated during sleep deprivation. Subjects more resilient to vigilance decline following sleep deprivation showed stronger anti-correlations among several networks. The weaker anti-correlations overlapped with connectivity alterations following sleep deprivation. Resilient individuals thus evidence clearer separation of highly segregated cortical networks in the well-rested state. In contrast to corticocortical connectivity, subcortical-cortical connectivity was comparable across resilient and vulnerable groups despite prominent state-related changes in both groups. Because sleep deprivation results in a significant elevation of whole brain signal amplitude, the aforesaid signal changes and group contrasts may be masked in analyses omitting their regression, suggesting possible value in regressing whole brain signal in certain experimental contexts.

  13. 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

  14. 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

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

    PubMed

    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.

  16. Enhanced amygdala-cortical functional connectivity in meditators.

    PubMed

    Leung, Mei-Kei; Chan, Chetwyn C H; Yin, Jing; Lee, Chack-Fan; So, Kwok-Fai; Lee, Tatia M C

    2015-03-17

    Previous studies have demonstrated that meditation is associated with neuroplastic changes in the brain regions including amygdala, anterior cingulate cortex (ACC), and temporal-parietal junction. Extended from these previous works, this study examined the functional connectivity of the amygdala in meditation experts during affective processing and observed that these experts had significantly stronger left amygdala (LA) connectivity with the dorsal ACC (dACC), premotor, and primary somatosensory cortices (PSC) while viewing affectively positive stimuli when compared to the novices. The current findings have implications for further understanding of affective neuroplastic changes associated with meditation in the amygdala. PMID:25623035

  17. 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

  18. Abnormal pulmonary function and associated risk factors in children and adolescents with sickle cell anemia.

    PubMed

    Arteta, Manuel; Campbell, Andrew; Nouraie, Mehdi; Rana, Sohail; Onyekwere, Onyinye C; Ensing, Gregory; Sable, Craig; Dham, Niti; Darbari, Deepika; Luchtman-Jones, Lori; Kato, Gregory J; Gladwin, Mark T; Castro, Oswaldo L; Minniti, Caterina P; Gordeuk, Victor R

    2014-04-01

    Obstructive and restrictive pulmonary changes develop in children with sickle cell disease, but reports conflict as to the type of change that predominates. We prospectively performed spirometry, plethysmography, and lung diffusing capacity in 146 children aged 7 to 20 years with hemoglobin SS or Sβ(0)-thalassemia. Nineteen percent of the patients had obstructive physiology as defined according to guidelines of the American Thoracic Society. In addition, 9% had restrictive physiology and 11% had abnormal but not categorized physiology. Increasing age, patient-reported or family-reported history of asthma or wheezing, and higher lactate dehydrogenase concentration were independent predictors of obstruction as reflected in lower forced expiratory volume in the first second/forced vital capacity. In conclusion, abnormal pulmonary function, most often obstructive, is common in children with hemoglobin SS and Sβ(0)-thalassemia. Full pulmonary function testing should be performed in children with hemoglobin SS or Sβ(0)-thalassemia, especially with history of asthma or wheezing and accentuated elevations in hemolytic markers.

  19. Abnormalities of brain function during a nonverbal theory of mind task in schizophrenia.

    PubMed

    Brunet, Eric; Sarfati, Yves; Hardy-Baylé, Marie-Christine; Decety, Jean

    2003-01-01

    Theory of mind (ToM), the specific ability to attribute thoughts and feelings to oneself and others is generally impaired in schizophrenia. Previous studies demonstrated a deficit of the attribution of intentions to others among patients having formal thought disorder. During nonverbal tasks, such a function requires both the visual perception of human figures and the understanding of their intentions. These processes are considered to involve the superior temporal sulcus and the medial prefrontal cortex, respectively. Are the functional patterns of activation associated with those processes abnormal in schizophrenia? Seven schizophrenic patients on medication performed a nonverbal attribution of intentions task as well as two matched physical logic tasks, with and without human figures, while H2O15 PET-scanning was performed. Data from the patients were compared to those of eight healthy controls matched for verbal IQ and sex. The experimental design allowed dissociating the effect of the perception of human figures from that of the attribution of intentions. During attribution of intentions, significant activations in the right prefrontal cortex were detected in the control subjects. Those activations were not found in the schizophrenic group. However, in both groups, the perception of human figure elicited bilateral activation of the occipitotemporal regions and of the posterior part of the superior temporal sulcus. Schizophrenic patients performing a nonverbal attribution of intentions task have an abnormal cerebral activity. PMID:12887982

  20. Partially restored resting-state functional connectivity in women recovered from anorexia nervosa

    PubMed Central

    Boehm, Ilka; Geisler, Daniel; Tam, Friederike; King, Joseph A.; Ritschel, Franziska; Seidel, Maria; Bernardoni, Fabio; Murr, Julia; Goschke, Thomas; Calhoun, Vince D.; Roessner, Veit; Ehrlich, Stefan

    2016-01-01

    Background We have previously shown increased resting-state functional connectivity (rsFC) in the frontoparietal network (FPN) and the default mode network (DMN) in patients with acute anorexia nervosa. Based on these findings we investigated within-network rsFC in patients recovered from anorexia nervosa to examine whether these abnormalities are a state or trait marker of the disease. To extend the understanding of functional connectivity in patients with anorexia nervosa, we also estimated rsFC between large-scale networks. Methods Girls and women recovered from anorexia nervosa and pair-wise, age- and sex-matched healthy controls underwent a resting-state fMRI scan. Using independent component analyses (ICA), we isolated the FPN, DMN and salience network. We used standard comparisons as well as a hypothesis-based approach to test the findings of our previous rsFC study in this recovered cohort. Temporal correlations between network time-course pairs were computed to investigate functional network connectivity (FNC). Results Thirty-one patients recovered from anorexia nervosa and 31 controls participated in our study. Standard group comparisons revealed reduced rsFC between the dorsolateral prefrontal cortex (dlPFC) and the FPN in the recovered group. Using a hypothesis-based approach we extended the previous finding of increased rsFC between the angular gyrus and the FPN in patients recovered from anorexia nervosa. No group differences in FNC were revealed. Limitations The study design did not allow us to conclude that the difference found in rsFC constitutes a scar effect of the disease. Conclusion This study suggests that some abnormal rsFC patterns found in patients recovered from anorexia nervosa normalize after long-term weight restoration, while distorted rsFC in the FPN, a network that has been associated with cognitive control, may constitute a trait marker of the disorder. PMID:27045551

  1. 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

  2. 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.

  3. 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.

  4. Disrupted functional connectivity of the periaqueductal gray in chronic low back pain

    PubMed Central

    Yu, Rongjun; Gollub, Randy L.; Spaeth, Rosa; Napadow, Vitaly; Wasan, Ajay; Kong, Jian

    2014-01-01

    Chronic low back pain is a common neurological disorder. The periaqueductal gray (PAG) plays a key role in the descending modulation of pain. In this study, we investigated brain resting state PAG functional connectivity (FC) differences between patients with chronic low back pain (cLBP) in low pain or high pain condition and matched healthy controls (HCs). PAG seed based functional connectivity (FC) analysis of the functional MR imaging data was performed to investigate the difference among the connectivity maps in the cLBP in the low or high pain condition and HC groups as well as within the cLBP at differing endogenous back pain intensities. Results showed that FC between the PAG and the ventral medial prefrontal cortex (vmPFC)/rostral anterior cingulate cortex (rACC) increased in cLBP patients compared to matched controls. In addition, we also found significant negative correlations between pain ratings and PAG–vmPFC/rACC FC in cLBP patients after pain-inducing maneuver. The duration of cLBP was negatively correlated with PAG–insula and PAG–amygdala FC before pain-inducing maneuver in the patient group. These findings are in line with the impairments of the descending pain modulation reported in patients with cLBP. Our results provide evidence showing that cLBP patients have abnormal FC in PAG centered pain modulation network during rest. PMID:25379421

  5. 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

  6. 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.

  7. Altered Functional Connectivity in Patients with Subcortical Vascular Cognitive Impairment—A Resting-State Functional Magnetic Resonance Imaging Study

    PubMed Central

    Wang, Yao; Sun, Yawen; Chen, Xue; Xu, Jianrong

    2015-01-01

    Recent neuroimaging studies have shown that people with subcortical vascular cognitive impairment (sVCI) have structural and functional abnormalities in the frontal lobe and subcortical brain sites. In this study, we used seed-based resting-state functional connectivity (rsFC) analysis and voxel-mirrored homotopic connectivity (VMHC) techniques to investigate the alteration of rsFC in patients with sVCI. rsFC and structural magnetic resonance images were acquired for 51 patients with subcortical cerebrovascular disease. All patients were subdivided based on cognitive status into 29 with sVCI and 22 controls; patient characteristics were matched. rsFC of the posterior cingulate cortex (PCC) and VMHC were calculated separately, and rsFC of the PCC and VMHC between the two groups were compared. The regions showing abnormal rsFC of the PCC or VMHC in sVCI patients were adopted as regions of interest for correlation analyses. Our results are as follows: The patients with sVCI exhibited increases in rsFC in the left middle temporal lobe, right inferior temporal lobe and left superior frontal gyrus, and significant decreases in rsFC of the left thalamus with the PCC. sVCI patients showed a significant deficit in VMHC between the bilateral lingual gyrus, putamen, and precentral gyrus. Additionally, the z-memory score was significantly positively associated with connectivity between the left thalamus and the PCC (r = 0.41, p = 0.03, uncorrected) in the sVCI group. Our findings suggest that the frontal lobe and subcortical brain sites play an important role in the pathogenesis of sVCI. Furthermore, rsFC between the left thalamus and the PCC might indicate the severity of sVCI. PMID:26376180

  8. 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

  9. 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

  10. 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

  11. Functional Connectivity in MRI Is Driven by Spontaneous BOLD Events

    PubMed Central

    Allan, Thomas W.; Francis, Susan T.; Caballero-Gaudes, Cesar; Morris, Peter G.; Liddle, Elizabeth B.; Liddle, Peter F.; Brookes, Matthew J.; Gowland, Penny A.

    2015-01-01

    Functional brain signals are frequently decomposed into a relatively small set of large scale, distributed cortical networks that are associated with different cognitive functions. It is generally assumed that the connectivity of these networks is static in time and constant over the whole network, although there is increasing evidence that this view is too simplistic. This work proposes novel techniques to investigate the contribution of spontaneous BOLD events to the temporal dynamics of functional connectivity as assessed by ultra-high field functional magnetic resonance imaging (fMRI). The results show that: 1) spontaneous events in recognised brain networks contribute significantly to network connectivity estimates; 2) these spontaneous events do not necessarily involve whole networks or nodes, but clusters of voxels which act in concert, forming transiently synchronising sub-networks and 3) a task can significantly alter the number of localised spontaneous events that are detected within a single network. These findings support the notion that spontaneous events are the main driver of the large scale networks that are commonly detected by seed-based correlation and ICA. Furthermore, we found that large scale networks are manifestations of smaller, transiently synchronising sub-networks acting dynamically in concert, corresponding to spontaneous events, and which do not necessarily involve all voxels within the network nodes oscillating in unison. PMID:25922945

  12. Developmental topographical disorientation and decreased hippocampal functional connectivity.

    PubMed

    Iaria, Giuseppe; Arnold, Aiden E G F; Burles, Ford; Liu, Irene; Slone, Edward; Barclay, Sarah; Bech-Hansen, Torben N; Levy, Richard M

    2014-11-01

    Developmental topographical disorientation (DTD) is a newly discovered cognitive disorder in which individuals experience a lifelong history of getting lost in both novel and familiar surroundings. Recent studies have shown that such a selective orientation defect relies primarily on the inability of the individuals to form cognitive maps, i.e., mental representations of the surrounding that allow individuals to get anywhere from any location in the environment, although other orientation skills are additionally affected. To date, the neural correlates of this developmental condition are unknown. Here, we tested the hypothesis that DTD may be related to ineffective functional connectivity between the hippocampus (HC; known to be critical for cognitive maps) and other brain regions critical for spatial orientation. A group of individuals with DTD and a group of control subjects underwent a resting-state functional magnetic resonance imaging (rsfMRI) scan. In addition, we performed voxel-based morphometry to investigate potential structural differences between individuals with DTD and controls. The results of the rsfMRI study revealed a decreased functional connectivity between the right HC and the prefrontal cortex (PFC) in individuals with DTD. No structural differences were detected between groups. These findings provide evidence that ineffective functional connectivity between HC and PFC may affect the monitoring and processing of spatial information while moving within an environment, resulting in the lifelong selective inability of individuals with DTD to form cognitive maps that are critical for orienting in both familiar and unfamiliar surroundings. PMID:24976168

  13. Evidence for intact local connectivity but disrupted regional function in the occipital lobe in children and adolescents with schizophrenia.

    PubMed

    White, Tonya; Moeller, Steen; Schmidt, Marcus; Pardo, Jose V; Olman, Cheryl

    2012-08-01

    It has long been known that specific visual frequencies result in greater blood flow to the striate cortex. These peaks are thought to reflect synchrony of local neuronal firing that is reflective of local cortical networks. Since disrupted neural connectivity is a possible etiology for schizophrenia, our goal was to investigate whether localized connectivity, as measured by aberrant synchrony, is abnormal in children and adolescents with schizophrenia. Subjects included 25 children and adolescents with schizophrenia and 39 controls matched for age and gender. Subjects were scanned on a Siemens 3 Tesla Trio scanner while observing flashing checkerboard presented at either 1, 4, 8, or 12 Hz. Image processing included both a standard GLM model and a Fourier transform analysis. Patients had significantly smaller volume of activation in the occipital lobe compared to controls. There were no differences in the integral or percent signal change of the hemodynamic response function for each of the four frequencies. Occipital activation was stable during development between childhood and late adolescence. Finally, both patients and controls demonstrated an increased response between 4 and 8 Hz consistent with synchrony or entrainment in the neuronal response. Children and adolescents with schizophrenia had a significantly lower volume of activation in the occipital lobe in response to the flashing checkerboard task. However, features of intact local connectivity in patients, such as the hemodynamic response function and maximal response at 8 Hz, were normal. These results are consistent with abnormalities in regional connectivity with preserved local connectivity in early-onset schizophrenia.

  14. 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

  15. Connecting teratogen-induced congenital heart defects to neural crest cells and their effect on cardiac function.

    PubMed

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

    2014-09-01

    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 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.

  16. 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

  17. Calorie Restriction Prevents Metabolic Aging Caused by Abnormal SIRT1 Function in Adipose Tissues.

    PubMed

    Xu, Cheng; Cai, Yu; Fan, Pengcheng; Bai, Bo; Chen, Jie; Deng, Han-Bing; Che, Chi-Ming; Xu, Aimin; Vanhoutte, Paul M; Wang, Yu

    2015-05-01

    Adipose tissue is a pivotal organ determining longevity, due largely to its role in maintaining whole-body energy homeostasis and insulin sensitivity. SIRT1 is a NAD-dependent protein deacetylase possessing antiaging activities in a wide range of organisms. The current study demonstrates that mice with adipose tissue-selective overexpression of hSIRT1(H363Y), a dominant-negative mutant that disrupts endogenous SIRT1 activity, show accelerated development of metabolic aging. These mice, referred to as Adipo-H363Y, exhibit hyperglycemia, dyslipidemia, ectopic lipid deposition, insulin resistance, and glucose intolerance at a much younger age than their wild-type littermates. The metabolic defects of Adipo-H363Y are associated with abnormal epigenetic modifications and chromatin remodeling in their adipose tissues, as a result of excess accumulation of biotin, which inhibits endogenous SIRT1 activity, leading to increased inflammation, cellularity, and collagen deposition. The enzyme acetyl-CoA carboxylase 2 plays an important role in biotin accumulation within adipose tissues of Adipo-H363Y. Calorie restriction prevents biotin accumulation, abolishes abnormal histone biotinylation, and completely restores the metabolic and adipose functions of Adipo-H363Y. The effects are mimicked by short-term restriction of biotin intake, an approach potentially translatable to humans for maintaining the epigenetic and chromatin remodeling capacity of adipose tissues and preventing aging-associated metabolic disorders.

  18. 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

  19. 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

  20. 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

  1. 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

  2. Abnormal GABAergic Function and Face Processing in Schizophrenia: A Pharmacologic-fMRI Study

    PubMed Central

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

    2015-01-01

    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 1-3 weeks. 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

  3. 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

  4. 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

  5. Functional brain connectivity phenotypes for schizophrenia drug discovery.

    PubMed

    Dawson, Neil; Morris, Brian J; Pratt, Judith A

    2015-02-01

    While our knowledge of the pathophysiology of schizophrenia has increased dramatically, this has not translated into the development of new and improved drugs to treat this disorder. Human brain imaging and electrophysiological studies have provided dramatic new insight into the mechanisms of brain dysfunction in the disease, with a swathe of recent studies highlighting the differences in functional brain network and neural system connectivity present in the disorder. Only recently has the value of applying these approaches in preclinical rodent models relevant to the disorder started to be recognised. Here we highlight recent findings of altered functional brain connectivity in preclinical rodent models and consider their relevance to those alterations seen in the brains of schizophrenia patients. Furthermore, we highlight the potential translational value of using the paradigm of functional brain connectivity phenotypes in the context of preclinical schizophrenia drug discovery, as a means both to understand the mechanisms of brain dysfunction in the disorder and to reduce the current high attrition rate in schizophrenia drug discovery.

  6. 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

  7. 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

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

    PubMed

    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

    2012-06-30

    Youths with conduct disorder or oppositional defiant disorder and psychopathic traits (CD/ODD+PT) are at high risk of adult antisocial behavior 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 magnetic resonance imaging 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.

  9. Abnormalities of Reproductive Function in Male Obesity Before and After Bariatric Surgery-A Comprehensive Review.

    PubMed

    Rosenblatt, Alberto; Faintuch, Joel; Cecconello, Ivan

    2015-07-01

    Young males represent one of the populations with the steepest increases in the incidence of obesity. They are also prone to significant derangements in sexual health and fertility. Despite a growing number of reports about female reproductive health, in the setting of bariatric surgery, males have received much less attention. In the current review of reproductive abnormalities in severe obese males before and after bariatric surgery, erectile function, hypothalamic-pituitary-gonadal axis status, sex hormones, semen quality, fertility and assisted reproductive techniques, along with analysis of adipokines, gut hormones, and environmental factors are addressed. Available evidence about weight loss benefits, both medical and surgical, are highlighted, along with perspectives for future investigations, which may be relevant for the patient, for the couple, and for the community alike.

  10. Structural and Functional Coronary Artery Abnormalities in Patients With Vasospastic Angina Pectoris.

    PubMed

    Ong, Peter; Aziz, Ahmed; Hansen, Henrik Steen; Prescott, Eva; Athanasiadis, Anastasios; Sechtem, Udo

    2015-01-01

    Coronary spasm is involved in many clinical scenarios, such as stable angina, acute coronary syndrome, sudden cardiac death, non-ischemic cardiomyopathy, arrhythmia and syncope. In recent years, imaging tools such as computerized tomographic angiography, intravascular ultrasound or optical coherence tomography have been applied to study the coronary pathology in patients with vasospastic angina. Patients with vasospastic angina represent a heterogeneous cohort of patients with regard to the extent of concomitant coronary atherosclerosis. They share the common pathophysiological phenomenon of vascular smooth muscle hyperreactivity leading to spasm caused by various factors that may also overlap. Focal coronary spasm is related to epicardial atherosclerosis and in the presence of obstructive coronary artery disease it may be useful to treat the lesion to prevent further spasm. The aim of this article is to review structural and functional coronary artery abnormalities in patients with vasospastic angina.

  11. Abnormalities in Parentally Rated Executive Function in Methamphetamine/Polysubstance Exposed Children

    PubMed Central

    Piper, Brian J.; Acevedo, Summer F.; Kolchugina, Galena K.; Butler, Robert W.; Corbett, Selena M.; Honeycutt, Elizabeth B.; Craytor, Michael J.; Raber, Jacob

    2011-01-01

    Methamphetamine/polysubstance abuse in women of childbearing age is a major concern because of the potential long-term detrimental effects on the brain function of the fetus following in utero exposure. A battery of established tests, including the Wechsler Abbreviated Scale of Intelligence, Conners’ Continuous Performance Test II, Behavioral Rating Inventory of Executive Function, the CMS Family Pictures and Dot Location tests, the Spatial Span test from the WISC-IV-Integrated, and a recently developed spatial learning and memory measure (Memory Island), was used to assess the effects of prenatal drug exposure on neurobehavioral performance. Participants were 7 to 9 year old children from similar socioeconomic backgrounds who either had (N = 31) or had not (N = 35) been exposed to methamphetamine/polysubstance during pregnancy. Compared to unexposed children, exposed children showed pronounced elevations (i.e. more problems) in parental ratings of executive function, including behavioral regulation and metacognition. Exposed children also exhibited subtle reductions in spatial performance in the Memory Island test. In contrast, IQ, Spatial Span, Family Pictures, Dot Location, and vigilance performance was unaffected by prenatal drug exposure history. Thus, children of women who reported using methamphetamine and other recreational drugs during pregnancy showed a selective profile of abnormalities in parentally rated executive function. PMID:21334365

  12. Abnormalities in parentally rated executive function in methamphetamine/polysubstance exposed children.

    PubMed

    Piper, Brian J; Acevedo, Summer F; Kolchugina, Galena K; Butler, Robert W; Corbett, Selena M; Honeycutt, Elizabeth B; Craytor, Michael J; Raber, Jacob

    2011-05-01

    Methamphetamine/polysubstance abuse in women of childbearing age is a major concern because of the potential long-term detrimental effects on the brain function of the fetus following in utero exposure. A battery of established tests, including the Wechsler Abbreviated Scale of Intelligence, Conners' Continuous Performance Test II, Behavioral Rating Inventory of Executive Function, the CMS Family Pictures and Dot Location tests, the Spatial Span test from the WISC-IV-Integrated, and a recently developed spatial learning and memory measure (Memory Island), was used to assess the effects of prenatal drug exposure on neurobehavioral performance. Participants were 7 to 9 year old children from similar socioeconomic backgrounds who either had (N=31) or had not (N=35) been exposed to methamphetamine/polysubstance during pregnancy. Compared to unexposed children, exposed children showed pronounced elevations (i.e. more problems) in parental ratings of executive function, including behavioral regulation and metacognition. Exposed children also exhibited subtle reductions in spatial performance in the Memory Island test. In contrast, IQ, Spatial Span, Family Pictures, Dot Location, and vigilance performance were unaffected by prenatal drug exposure history. Thus, children of women who reported using methamphetamine and other recreational drugs during pregnancy showed a selective profile of abnormalities in parentally rated executive function.

  13. Functional brain abnormalities in psychiatric disorders: neural mechanisms to detect and resolve cognitive conflict and interference.

    PubMed

    Melcher, Tobias; Falkai, Peter; Gruber, Oliver

    2008-11-01

    In the present article, we review functional neuroimaging studies on interference processing and performance monitoring in three groups of psychiatric disorders, (1) mood disorders, (2) schizophrenia, and (3) obsessive-compulsive disorder (OCD). Ad (1) Behavioral performance measures suggest an impaired interference resolution capability in symptomatic bipolar disorder patients. A series of neuroimaging analyses found alterations in the ACC-DLPFC system in mood disorder (unipolar depressed and bipolar) patients, putatively reflective of an abnormal interplay of monitoring and executive neurocognitive functions. Other studies of euthymic bipolar patients showed relatively decreased interference-related activation in rostroventral PFC which conceivably underlies defective inhibitory control. Ad (2) Behavioral Stroop studies revealed a specific performance pattern of schizophrenia patients (normal RT interference but increased error interference and RT facilitation) suggestive of a deficit in ignoring irrelevant (word) information. Moreover, reduced/absent behavioral post-error and post-conflict adaptation effects suggest alterations in performance monitoring and/or adjustment capability in these patients. Neuroimaging findings converge to suggest a disorder-related abnormal neurophysiology in ACC which consistently showed conflict- and error-related hypoactivation that, however, appeared to be modulated by different factors. Moreover, studies suggest a specific deficit in context processing in schizophrenia, evidently related to activation reduction in DLPFC. Ad (3) Behavioral findings provide evidence for impaired interference resolution in OCD. Neuroimaging results consistently showed conflict- and error-related ACC hyperactivation which--conforming OCD pathogenesis models--can be conclusively interpreted as reflecting overactive performance monitoring. Taken together, interference resolution and performance monitoring appeared to be fruitful concepts in the

  14. Abnormal activation of the motor cortical network in idiopathic scoliosis demonstrated by functional MRI.

    PubMed

    Domenech, Julio; García-Martí, G; Martí-Bonmatí, L; Barrios, C; Tormos, J M; Pascual-Leone, A

    2011-07-01

    The aetiology of idiopathic scoliosis (IS) remains unknown, but there is growing support for the possibility of an underlying neurological disorder. Functional magnetic resonance imaging (fMRI) can characterize the abnormal activation of the sensorimotor brain network in movement disorders and could provide further insights into the neuropathogenesis of IS. Twenty subjects were included in the study; 10 adolescents with IS (mean age of 15.2, 8 girls and 2 boys) and 10 age-matched healthy controls. The average Cobb angle of the primary curve in the IS patients was 35° (range 27°-55°). All participants underwent a block-design fMRI experiment in a 1.5-Tesla MRI scanner to explore cortical activation following a simple motor task. Rest periods alternated with activation periods during which participants were required to open and close their hand at an internally paced rate of approximately 1 Hz. Data were analyzed with Statistical Parametric Mapping (SPM5) including age, sex and laterality as nuisance variables to minimise the presence of bias in the results. Compared to controls, IS patients showed significant increases in blood oxygenation level dependent (BOLD) activity in contralateral supplementary motor area when performing the motor task with either hand. No significant differences were observed when testing between groups in the functional activation in the primary motor cortex, premotor cortex and somatosensory cortex. Additionally, the IS group showed a greater interhemispheric asymmetry index than the control group (0.30 vs. 0.13, p < 0.001). This study demonstrates an abnormal pattern of brain activation in secondary motor areas during movement execution in patients with IS. These findings support the hypothesis that a sensorimotor integration disorder underlies the pathogenesis of IS.

  15. 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

  16. Acupuncture modulates resting state hippocampal functional connectivity in Alzheimer disease.

    PubMed

    Wang, Zhiqun; Liang, Peipeng; Zhao, Zhilian; Han, Ying; Song, Haiqing; Xu, Jianyang; Lu, Jie; Li, Kuncheng

    2014-01-01

    Our objective is to clarify the effects of acupuncture on hippocampal connectivity in patients with Alzheimer disease (AD) using functional magnetic resonance imaging (fMRI). Twenty-eight right-handed subjects (14 AD patients and 14 healthy elders) participated in this study. Clinical and neuropsychological examinations were performed on all subjects. MRI was performed using a SIEMENS verio 3-Tesla scanner. The fMRI study used a single block experimental design. We first acquired baseline resting state data during the initial 3 minutes and then performed acupuncture stimulation on the Tai chong and He gu acupoints for 3 minutes. Last, we acquired fMRI data for another 10 minutes after the needle was withdrawn. The preprocessing and data analysis were performed using statistical parametric mapping (SPM5) software. Two-sample t-tests were performed using data from the two groups in different states. We found that during the resting state, several frontal and temporal regions showed decreased hippocampal connectivity in AD patients relative to control subjects. During the resting state following acupuncture, AD patients showed increased connectivity in most of these hippocampus related regions compared to the first resting state. In conclusion, we investigated the effect of acupuncture on AD patients by combing fMRI and traditional acupuncture. Our fMRI study confirmed that acupuncture at Tai chong and He gu can enhance the hippocampal connectivity in AD patients.

  17. 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

  18. TE-Dependent Spatial and Spectral Specificity of Functional Connectivity

    PubMed Central

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

    2012-01-01

    Previous studies suggest that spontaneous fluctuations in the resting-state fMRI (RS-fMRI) signal may reflect fluctuations in transverse relaxation time (T2*) rather than spin density (S0). However, such S0 and T2* 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 S0 contribution, whereas long-range connections mediated by T2* became explicit at TEs longer than 22 ms. In the frequency domain, compared with the flat spectrum of S0, spectral power of the T2*-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 S0 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 S0 and T2* could be valuable for interpreting and quantifying RS-fMRI data. PMID:22119650

  19. Functional connectivity of parietal cortex during temporal selective attention.

    PubMed

    Tyler, Sarah C; Dasgupta, Samhita; Agosta, Sara; Battelli, Lorella; Grossman, Emily D

    2015-04-01

    Perception of natural experiences requires allocation of attention towards features, objects, and events that are moving and changing over time. This allocation of attention is controlled by large-scale brain networks that, when damaged, cause widespread cognitive deficits. In particular, damage to ventral parietal cortex (right lateralized TPJ, STS, supramarginal and angular gyri) is associated with failures to selectively attend to and isolate features embedded within rapidly changing visual sequences (Battelli, Pascual-Leone, & Cavanagh, 2007; Husain, Shapiro, Martin, & Kennard, 1997). In this study, we used fMRI to investigate the neural activity and functional connectivity of intact parietal cortex while typical subjects judged the relative onsets and offsets of rapidly flickering tokens (a phase discrimination task in which right parietal patients are impaired). We found two regions in parietal cortex correlated with task performance: a bilateral posterior TPJ (pTPJ) and an anterior right-lateralized TPJ (R aTPJ). Both regions were deactivated when subjects engaged in the task but showed different patterns of functional connectivity. The bilateral pTPJ was strongly connected to nodes within the default mode network (DMN) and the R aTPJ was connected to the attention network. Accurate phase discriminations were associated with increased functional correlations between sensory cortex (hMT+) and the bilateral pTPJ, whereas accuracy on a control task was associated with yoked activity in the hMT+ and the R aTPJ. We conclude that temporal selective attention is particularly sensitive for revealing information pathways between sensory and core cognitive control networks that, when damaged, can lead to nonspatial attention impairments in right parietal stroke patients. PMID:25747530

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

    PubMed Central

    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

  1. Resting state functional connectivity in the human spinal cord.

    PubMed

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

    2014-08-05

    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.

  2. 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

  3. 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

  4. Neurological abnormalities and neurocognitive functions in healthy elder people: A structural equation modeling analysis

    PubMed Central

    2011-01-01

    Background/Aims Neurological abnormalities have been reported in normal aging population. However, most of them were limited to extrapyramidal signs and soft signs such as motor coordination and sensory integration have received much less attention. Very little is known about the relationship between neurological soft signs and neurocognitive function in healthy elder people. The current study aimed to examine the underlying relationships between neurological soft signs and neurocognition in a group of healthy elderly. Methods One hundred and eighty healthy elderly participated in the current study. Neurological soft signs were evaluated with the subscales of Cambridge Neurological Inventory. A set of neurocognitive tests was also administered to all the participants. Structural equation modeling was adopted to examine the underlying relationship between neurological soft signs and neurocognition. Results No significant differences were found between the male and female elder people in neurocognitive function performances and neurological soft signs. The model fitted well in the elderly and indicated the moderate associations between neurological soft signs and neurocognition, specifically verbal memory, visual memory and working memory. Conclusions The neurological soft signs are more or less statistically equivalent to capture the similar information done by conventional neurocognitive function tests in the elderly. The implication of these findings may serve as a potential neurological marker for the early detection of pathological aging diseases or related mental status such as mild cognitive impairment and Alzheimer's disease. PMID:21827719

  5. 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

  6. 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.

  7. Functional connectivity between right and left mesial temporal structures.

    PubMed

    Lacuey, Nuria; Zonjy, Bilal; Kahriman, Emine S; Kaffashi, Farhad; Miller, Jonathan; Lüders, Hans O

    2015-09-01

    The aim of this study is to investigate functional connectivity between right and left mesial temporal structures using cerebrocerebral evoked potentials. We studied seven patients with drug-resistant focal epilepsy who were explored with stereotactically implanted depth electrodes in bilateral hippocampi. In all patients cerebrocerebral evoked potentials evoked by stimulation of the fornix were evaluated as part of a research project assessing fornix stimulation for control of hippocampal seizures. Stimulation of the fornix elicited responses in the ipsilateral hippocampus in all patients with a mean latency of 4.6 ms (range 2-7 ms). Two patients (29 %) also had contralateral hippocampus responses with a mean latency of 7.5 ms (range 5-12 ms) and without involvement of the contralateral temporal neocortex or amygdala. This study confirms the existence of connections between bilateral mesial temporal structures in some patients and explains seizure discharge spreading between homotopic mesial temporal structures without neocortical involvement. PMID:24908158

  8. [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

  9. [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.

  10. Functional Connectivity of the Caudal Anterior Cingulate Cortex Is Decreased in Autism.

    PubMed

    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.

  11. 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

  12. [Functional cerebral activity in a state of rest: connectivity networks].

    PubMed

    Proal, Erika; Alvarez-Segura, Mar; de la Iglesia-Vayá, María; Martí-Bonmatí, Luis; Castellanos, F Xavier

    2011-03-01

    Functional connectivity can be measured during task-based functional magnetic resonance imaging (fMRI), or in the absence of specific stimuli or tasks. In either case, the study of low frequency fluctuations in the BOLD signal reveals patterns of synchronization which delineate the intrinsic functional architecture of the brain. The scientific community now has available shared resources to accelerate the exploitation of resting state fMRI with the objectives of improving diagnostic methods and leading to better treatments grounded in neuroscience. Fomenting a collaborative scientific culture will accelerate our understanding of the underlying phenonmemna. Recently, the Spanish Resting State Network (SRSN) has joined this collaborative effort by creating a setting to facilitate collaboration among the various neuroscience research groups working in Spanish (http://www.nitrc.org/projects/srsn). PMID:21365601

  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. 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

  15. Reward Abnormalities Among Women with Full and Subthreshold Bulimia Nervosa: A Functional Magnetic Resonance Imaging Study

    PubMed Central

    Bohon, Cara; Stice, Eric

    2010-01-01

    Objective To test the hypothesis that women with full and subthreshold bulimia nervosa show abnormal neural activation in response to food intake and anticipated food intake relative to healthy control women. Method Females with and without full/subthreshold bulimia nervosa recruited from the community (N = 26) underwent functional magnetic resonance imaging (fMRI) during receipt and anticipated receipt of chocolate milkshake and a tasteless control solution. Results Women with bulimia nervosa showed trends for less activation than healthy controls in the right anterior insula in response to anticipated receipt of chocolate milkshake (versus tasteless solution) and in the left middle frontal gyrus, right posterior insula, right precentral gyrus, and right mid dorsal insula in response to consumptions of milkshake (versus tasteless solution). Discussion Bulimia nervosa may be related to potential hypo-functioning of the brain reward system, which may lead these individuals to binge eat to compensate for this reward deficit, though the hypo-responsivity might be a result of a history of binge eating highly palatable foods. PMID:21997421

  16. 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

  17. 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

  18. 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

  19. Plasticity of functional connectivity in the adult spinal cord

    PubMed Central

    Cai, L.L; Courtine, G; Fong, A.J; Burdick, J.W; Roy, R.R; Edgerton, V.R

    2006-01-01

    This paper emphasizes several characteristics of the neural control of locomotion that provide opportunities for developing strategies to maximize the recovery of postural and locomotor functions after a spinal cord injury (SCI). The major points of this paper are: (i) the circuitry that controls standing and stepping is extremely malleable and reflects a continuously varying combination of neurons that are activated when executing stereotypical movements; (ii) the connectivity between neurons is more accurately perceived as a functional rather than as an anatomical phenomenon; (iii) the functional connectivity that controls standing and stepping reflects the physiological state of a given assembly of synapses, where the probability of these synaptic events is not deterministic; (iv) rather, this probability can be modulated by other factors such as pharmacological agents, epidural stimulation and/or motor training; (v) the variability observed in the kinematics of consecutive steps reflects a fundamental feature of the neural control system and (vi) machine-learning theories elucidate the need to accommodate variability in developing strategies designed to enhance motor performance by motor training using robotic devices after an SCI. PMID:16939979

  20. 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

  1. 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.

  2. 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

  3. Functional hierarchy underlies preferential connectivity disturbances in schizophrenia

    PubMed Central

    Yang, Genevieve J.; Murray, John D.; Wang, Xiao-Jing; Glahn, David C.; Pearlson, Godfrey D.; Repovs, Grega; Krystal, John H.; Anticevic, Alan

    2016-01-01

    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

  4. The selectivity and functional connectivity of the anterior temporal lobes.

    PubMed

    Simmons, W Kyle; Reddish, Mark; Bellgowan, Patrick S F; Martin, Alex

    2010-04-01

    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

  5. Enhanced functional connectivity involving the ventromedial hypothalamus following methamphetamine exposure.

    PubMed

    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.

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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.

  12. 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…

  13. 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

  14. Condition-dependent functional connectivity: syntax networks in bilinguals.

    PubMed

    Dodel, Silke; Golestani, Narly; Pallier, Christophe; Elkouby, Vincent; Le Bihan, Denis; Poline, Jean-Baptiste

    2005-05-29

    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

  15. 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

  16. 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

  17. 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

  18. Aging and response conflict solution: Behavioural and functional connectivity changes

    PubMed Central

    Cieslik, Edna C.; Behrwind, Simone D.; Roski, Christian; Caspers, Svenja; Amunts, Katrin; Eickhoff, Simon B.

    2014-01-01

    Healthy aging has been found associated with less efficient response conflict solution, but the cognitive and neural mechanisms remain elusive. In a two-experiment study, we first examined the behavioural consequences of this putative age-related decline for conflicts induced by spatial stimulus–response incompatibility. We then used resting-state functional magnetic resonance imaging data from a large, independent sample of adults (n = 399; 18–85 years) to investigate age differences in functional connectivity between the nodes of a network previously found associated with incompatibility-induced response conflicts in the very same paradigm. As expected, overcoming interference from conflicting response tendencies took longer in older adults, even after accounting for potential mediator variables (general response speed and accuracy, motor speed, visuomotor coordination ability, and cognitive flexibility). Experiment 2 revealed selective age-related decreases in functional connectivity between bilateral anterior insula, pre-supplementary motor area, and right dorsolateral prefrontal cortex. Importantly, these age effects persisted after controlling for regional gray-matter atrophy assessed by voxel-based morphometry. Meta-analytic functional profiling using the BrainMap database showed these age-sensitive nodes to be more strongly linked to highly abstract cognition, as compared with the remaining network nodes, which in turn were more strongly linked to action-related processing. These findings indicate changes in interregional coupling with age among task-relevant network nodes that are not specifically associated with conflict resolution per se. Rather, our behavioural and neural data jointly suggest that healthy aging is associated with difficulties in properly activating non-dominant but relevant task schemata necessary to exert efficient cognitive control over action. PMID:24718622

  19. Relationship of abnormal Tamm-Horsfall glycoprotein localization to renal morphology and function.

    PubMed

    Chambers, R; Groufsky, A; Hunt, J S; Lynn, K L; McGiven, A R

    1986-07-01

    Tamm-Horsfall glycoprotein (TH) distribution was studied using a biotin-avidin immunoperoxidase technique in renal biopsies from 166 consecutive patients and 8 normal kidneys. Tubulointerstitial damage was independently assessed and graded. In 109 patients TH antibodies were measured by ELISA and in 30 of these urinary TH and beta 2-microglobulin excretions were measured by radioimmunoassay. In 124 biopsies only distal tubular epithelium and casts were stained. Glomerular space (8) or interstitial (34) deposits were seen in 42 biopsies; 16/68 with glomerulonephritis, 4/14 with systemic vasculitis, 12/33 with chronic interstitial nephritis, 1/8 with acute interstitial nephritis, 9/43 with other nephropathies. There was no correlation between TH distribution and the degree of tubulointerstitial damage (p greater than 0.5), urinary TH excretion (p greater than 0.05), urinary beta 2-microglobulin excretion (p greater than 0.05), glomerular filtration rate, urinary concentrating ability, or the incidence of pyuria. TH antibodies did not correlate with TH distribution (p greater than 0.5) or the degree of tubulointerstitial damage. Abnormal TH distribution showed no statistical relationship to the degree of tubulointerstitial damage, changes in renal function or levels of TH antibodies.

  20. 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.

  1. Neonatal lupus manifests as isolated neutropenia and mildly abnormal liver functions.

    PubMed

    Kanagasegar, Sivalingam; Cimaz, Rolando; Kurien, Biji T; Brucato, Antonio; Scofield, R Hal

    2002-01-01

    Neonatal lupus is characterized by typical clinical features and the presence of maternal autoantibodies. Mothers can have systemic lupus erythematosus (SLE) or Sjögren's syndrome, but are commonly not affected with any clinical disease. The major clinical manifestations in the infants are cardiac, dermatological and hepatic with rare instances of hemolytic anemia, thrombocytopenia or neutropenia. We describe an infant born to a mother with anti-Ro and anti-La, who had neutropenia and mildly abnormal liver functions without other major clinical features of neonatal lupus such as cardiac or dermatological manifestations. Neutropenia improved as maternal antibody was metabolized. Antibodies from both the infant and mother bound intact neutrophils, and this binding was inhibited by 60 kDa Ro. These data imply neutropenia may be an isolated manifestation of neonatal lupus. We studied the anti-Ro antibodies of 2 other mothers who gave birth to infants with complete congenital heart block and neutropenia. Their sera also bound neutrophils. Because healthy infants do not commonly undergo complete blood counts, the incidence of neutropenia among infants of anti-Ro-positive mothers may be much higher than previously recognized. Furthermore, although other factors may contribute, these data suggest that anti-60 kDa Ro is directly involved in the pathogenesis of neutropenia.

  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. 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

  4. Analysis of functional abnormalities uncovered during preoperative evaluation of donor candidates for living-related liver transplantation.

    PubMed

    Morimoto, T; Awane, M; Tanaka, A; Ikai, I; Nakamura, Y; Yamamoto, Y; Takada, Y; Honda, K; Inamoto, T; Uemoto, S

    1995-02-01

    Functional abnormalities of the liver uncovered during preoperative routine evaluation were analyzed in 109 donor candidates for 100 cases of living-related liver transplantation (LRLT) performed during the period from June, 1990 to May, 1994 at the Second Department of Surgery, Kyoto University Hospital. High serum transaminase (GOT, GPT) levels were noted in 10 (9.2%) cases among 109 candidates, high alkaline phosphatase in 4 (3.7%), hyperbilirubinemia in 3 (2.8%), anemia in 3 and high choline esterase in 3 cases. Positive hepatitis C antibody (HCV) was also noted in 1 case. Fatty liver was detected in 10 (9.2%) cases, cholecystitis in 2 cases, 1 case each of cyst and calcification in the liver by diagnostic imaging (ultra sonograph and/or computed tomography). These abnormalities of the liver necessitated replacing the initial candidate with the other parent in 9 cases, including 1 case without any functional abnormality whose graft liver was too large to fit the recipient abdominal cavity. There were 14 cases of ABO blood type incompatible combination. Switching the initial candidate due to these abnormalities mentioned above resulted in incompatible combinations in 4 of these 14 cases. Although the advantages of the LRLT are the superior viability of the donor graft and the genetic histocompatibility between recipient and donor, to optimize the advantage of LRLT, all donor candidates should be strongly advised to make every effort preoperatively to improve their physical condition in preparation for the LRLT protocol, since many of these abnormalities are typically reversible.

  5. 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

  6. 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

  7. 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.

  8. 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

  9. 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.

  10. A weighted small world network measure for assessing functional connectivity.

    PubMed

    Bolaños, Marcos; Bernat, Edward M; He, Bin; Aviyente, Selin

    2013-01-15

    There is a growing need to develop measures that can characterize complex patterns of functional connectivity among brain regions. Graph theoretic measures have emerged as an important way to characterize the multivariate connectivity between nodes in a network, which have been successfully applied to neurophysiologic activity. In this paper, we propose a new small-world measure based on advances in both the bivariate measures underlying the graph theoretic approach, as well as in the definition of the measure for weighted graphs. Specifically, we recently proposed a new bivariate time-frequency phase-synchrony (TFPS) measure, which quantifies the dynamic nature of the interactions between neuronal oscillations with a higher time-frequency resolution than previous approaches and is better at isolating relevant activity. The proposed graph theoretic measures, weighted clustering coefficient and path length, represent a new approach to the calculation of weighted graph measures based on this improved bivariate TFPS measure. The new graph theoretic measures are applied to two datasets. The first is a well-known social network, Zachary's Karate Club. The second application contains event-related potential (ERP) indexing the well-known error-related negativity (ERN) component related to cognitive control. Results indicate that the new measures outperform the previously published weighted graph measures, and produces expectable results for both applications.

  11. Brain Oscillations and Functional Connectivity during Overt Language Production.

    PubMed

    Ewald, Arne; Aristei, Sabrina; Nolte, Guido; Abdel Rahman, Rasha

    2012-01-01

    In the present study we investigate the communication of different large scale brain sites during an overt language production task with state of the art methods for the estimation of EEG functional connectivity. Participants performed a semantic blocking task in which objects were named in semantically homogeneous blocks of trials consisting of members of a semantic category (e.g., all objects are tools) or in heterogeneous blocks, consisting of unrelated objects. The classic pattern of slower naming times in the homogeneous relative to heterogeneous blocks is assumed to reflect the duration of lexical selection. For the collected data in the homogeneous and heterogeneous conditions the imaginary part of coherency (ImC) was evaluated at different frequencies. The ImC is a measure for detecting the coupling of different brain sites acting on sensor level. Most importantly, the ImC is robust to the artifact of volume conduction. We analyzed the ImC at all pairs of 56 EEG channels across all frequencies. Contrasting the two experimental conditions we found pronounced differences in the theta band at 7 Hz and estimated the most dominant underlying brain sources via a minimum norm inverse solution based on the ImC. As a result of the source localization, we observed connectivity between occipito-temporal and frontal areas, which are well-known to play a major role in lexical-semantic language processes. Our findings demonstrate the feasibility of investigating interactive brain activity during overt language production.

  12. 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

  13. 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

  14. 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

  15. 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.

  16. 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

  17. 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

  18. 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

  19. 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.

  20. 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

  1. Graph theoretical analysis of EEG functional connectivity during music perception.

    PubMed

    Wu, Junjie; Zhang, Junsong; Liu, Chu; Liu, Dongwei; Ding, Xiaojun; Zhou, Changle

    2012-11-01

    The present study evaluated the effect of music on large-scale structure of functional brain networks using graph theoretical concepts. While most studies on music perception used Western music as an acoustic stimulus, Guqin music, representative of Eastern music, was selected for this experiment to increase our knowledge of music perception. Electroencephalography (EEG) was recorded from non-musician volunteers in three conditions: Guqin music, noise and silence backgrounds. Phase coherence was calculated in the alpha band and between all pairs of EEG channels to construct correlation matrices. Each resulting matrix was converted into a weighted graph using a threshold, and two network measures: the clustering coefficient and characteristic path length were calculated. Music perception was found to display a higher level mean phase coherence. Over the whole range of thresholds, the clustering coefficient was larger while listening to music, whereas the path length was smaller. Networks in music background still had a shorter characteristic path length even after the correction for differences in mean synchronization level among background conditions. This topological change indicated a more optimal structure under music perception. Thus, prominent small-world properties are confirmed in functional brain networks. Furthermore, music perception shows an increase of functional connectivity and an enhancement of small-world network organizations.

  2. 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

  3. 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.

  4. 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

  5. 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

  6. The spatial and temporal components of functional connectivity in fragmented landscapes.

    PubMed

    Auffret, Alistair G; Plue, Jan; Cousins, Sara A O

    2015-01-01

    Connectivity is key for understanding how ecological systems respond to the challenges of land-use change and habitat fragmentation. Structural and functional connectivity are both established concepts in ecology, but the temporal component of connectivity deserves more attention. Whereas functional connectivity is often associated with spatial patterns (spatial functional connectivity), temporal functional connectivity relates to the persistence of organisms in time, in the same place. Both temporal and spatial processes determine biodiversity responses to changes in landscape structure, and it is therefore necessary that all aspects of connectivity are considered together. In this perspective, we use a case study to outline why we believe that both the spatial and temporal components of functional connectivity are important for understanding biodiversity patterns in the present-day landscape, and how they can also help us to make better-informed decisions about conserving and restoring landscapes and improving resilience to future change.

  7. Increased functional connectivity common to symptomatic amyotrophic lateral sclerosis and those at genetic risk

    PubMed Central

    Menke, Ricarda A L; Proudfoot, Malcolm; Wuu, Joanne; Andersen, Peter M; Talbot, Kevin; Benatar, Michael; Turner, Martin R

    2016-01-01

    Objective To discern presymptomatic changes in brain structure or function using advanced MRI in carriers of mutations predisposing to amyotrophic lateral sclerosis (ALS). Methods T1-weighted, diffusion weighted and resting state functional MRI data were acquired at 3 T for 12 asymptomatic mutation carriers (psALS), 12 age-matched controls and affected patients with ALS. Cortical thickness analysis, voxel-based morphometry, volumetric and shape analyses of subcortical structures, tract-based spatial statistics of metrics derived from the diffusion tensor, and resting state functional connectivity (FC) analyses were performed. Results Grey matter cortical thickness and shape analysis revealed significant atrophy in patients with ALS (but not psALS) compared with controls in the right primary motor cortex and right caudate. Comparison of diffusion tensor metrics showed widespread fractional anisotropy and radial diffusivity differences in patients with ALS compared to controls and the psALS group, encompassing parts of the corpus callosum, corticospinal tracts and superior longitudinal fasciculus. While FC in the resting-state sensorimotor network was similar in psALS and controls, FC between the cerebellum and a network comprising the precuneus, cingulate & middle frontal lobe was significantly higher in psALS and affected ALS compared to controls. Conclusions Rather than structural brain changes, increased FC may be among the earliest detectable brain abnormalities in asymptomatic carriers of ALS-causing gene mutations. With replication and significant refinement, this technique has potential in the future assessment of neuroprotective strategies. PMID:26733601

  8. The Vitamin D Connection to Pediatric Infections and Immune Function

    PubMed Central

    Walker, Valencia P; Modlin, Robert L.

    2009-01-01

    Over the past twenty years, a resurgence in vitamin D deficiency and nutritional rickets has been reported throughout the world, including the United States. Inadequate serum vitamin D concentrations have also been associated with complications from other health problems, including tuberculosis, cancer (prostate, breast and colon), multiple sclerosis and diabetes. These findings support the concept of vitamin D possessing important pleiotropic actions outside of calcium homeostasis and bone metabolism. In children, an association between nutritional rickets with respiratory compromise has long been recognized. Recent epidemiological studies clearly demonstrate the link between vitamin D deficiency and the increased incidence of respiratory infections. Further research has also elucidated the contribution of vitamin D in the host defense response to infection. However, the mechanism(s) by which vitamin D levels contribute to pediatric infections and immune function has yet to be determined. This knowledge is particularly relevant and timely, because infants and children appear more susceptible to viral rather than bacterial infections in the face of vitamin D deficiency. The connection between vitamin D, infections and immune function in the pediatric population indicates a possible role for vitamin D supplementation in potential interventions and adjuvant therapies. PMID:19190532

  9. The association between resting functional connectivity and creativity.

    PubMed

    Takeuchi, Hikaru; Taki, Yasuyuki; Hashizume, Hiroshi; Sassa, Yuko; Nagase, Tomomi; Nouchi, Rui; Kawashima, Ryuta

    2012-12-01

    The analysis of functional connectivity at rest (rFC) enables us to know how brain regions within and between networks interact. In this study, we used resting-state functional magnetic resonance imaging and a creativity test of divergent thinking (DT) to investigate the relationship between creativity measured by DT and rFC. We took the medial prefrontal cortex (mPFC) to be the seed region and investigated correlations across subjects between the score of the DT test and the strength of rFC between the mPFC and other brain regions. Our results showed that the strength of rFC with the mPFC significantly and positively correlated with creativity as measured by the DT test in the posterior cingulate cortex (PCC). These results showed that higher creativity measured by DT is associated with rFC between the mPFC and the PCC, the key nodes of the default mode network (DMN). Increased rFC between these regions is completely opposite from that is generally expected from the association between higher creativity and reduced deactivation in DMN during an externally directed attention-demanding task shown in our previous study but is similar to the pattern seen in relatives of schizophrenia. These findings are comparable to the previously reported psychological associations between schizotypy and creativity.

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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:…

  15. 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

  16. 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

  17. Disparate connectivity for structural and functional networks is revealed when physical location of the connected nodes is considered.

    PubMed

    Pineda-Pardo, José Ángel; Martínez, Kenia; Solana, Ana Beatriz; Hernández-Tamames, Juan Antonio; Colom, Roberto; del Pozo, Francisco

    2015-03-01

    Macroscopic brain networks have been widely described with the manifold of metrics available using graph theory. However, most analyses do not incorporate information about the physical position of network nodes. Here, we provide a multimodal macroscopic network characterization while considering the physical positions of nodes. To do so, we examined anatomical and functional macroscopic brain networks in a sample of twenty healthy subjects. Anatomical networks are obtained with a graph based tractography algorithm from diffusion-weighted magnetic resonance images (DW-MRI). Anatomical connections identified via DW-MRI provided probabilistic constraints for determining the connectedness of 90 different brain areas. Functional networks are derived from temporal linear correlations between blood-oxygenation level-dependent signals derived from the same brain areas. Rentian Scaling analysis, a technique adapted from very-large-scale integration circuits analyses, shows that functional networks are more random and less optimized than the anatomical networks. We also provide a new metric that allows quantifying the global connectivity arrangements for both structural and functional networks. While the functional networks show a higher contribution of inter-hemispheric connections, the anatomical networks highest connections are identified in a dorsal-ventral arrangement. These results indicate that anatomical and functional networks present different connectivity organizations that can only be identified when the physical locations of the nodes are included in the analysis.

  18. 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

  19. The GST T1 and CYP2E1 genotypes are possible factors causing vinyl chloride induced abnormal liver function.

    PubMed

    Huang, C Y; Huang, K L; Cheng, T J; Wang, J D; Hsieh, L L

    1997-01-01

    Vinyl chloride monomer (VCM) is hepatotoxic as well as carcinogenic in humans. There are reports that exposure to VCM seems to induce abnormal liver function, liver fibrosis, cirrhosis, portal hypertension, and angiosarcoma of the liver. In vivo, VCM is metabolized by cytochrome P450 2E1 (CYP2E1) to form the electrophilic metabolites, chloroethylene oxide (CEO) and chloroacetaldehyde (CAA), which may either cause cell damage or be further metabolized and detoxified by glutathione S-transferases (GSTs). This study investigated whether or not the genotypes CYP2E1, glutathione S-transferase theta (GST T1) and mu (GST M1) correlated with abnormal liver function found in vinyl chloride exposed workers. For this study, 251 workers from five polyvinyl chloride plants were enrolled. The workers were classified into two exposure groups (high and low) and the degree of exposure was determined based on their job titles and airborne VCM concentration. The activity of serum alanine aminotransferase (ALT) was used as the parameter of liver function. The genotypes CYP2E1, GST T1 and GST M1 were determined by polymerase chain reaction and restriction fragment length polymorphism on peripheral white blood cell DNA. Other potential risk factors were also ascertained and the confounding effect was adjusted accordingly. Stratified analyses were used to explore the correlation between the alteration of liver function and the genotypes CYP2E1, GST T1 and GST M1 among the workers exposed to different levels of VCM. The following results were obtained (1) at low VCM exposure, the odds ratio (OR) of positive GST T1 on abnormal ALT was 3.8 (95% CI 1.2-14.5) but the CYP2E1 genotype was not associated with abnormal ALT. (2) At high VCM exposure, a c2c2 CYP2E1 genotype was associated with increased OR on abnormal ALT (OR 5.4, 95% CI 0.7-35.1) and positive GST T1 was significantly associated with decreased OR on abnormal ALT (OR 0.3, 95% CI 0.1-0.9). (3) Multiple linear and logistic regression

  20. Resting state functional connectivity and treatment response in late-life depression

    PubMed Central

    Andreescu, Carmen; Tudorascu, Dana L.; Butters, Meryl A.; Tamburo, Erica; Patel, Meenal; Price, Julie; Karp, Jordan F.; Reynolds, Charles F.; Aizenstein, Howard

    2013-01-01

    Indices of functional connectivity in the default mode network (DMN) are promising neural markers of treatment response in late-life depression. We examined the differences in DMN functional connectivity between treatment-responsive and treatment-resistant depressed older adults. Forty-seven depressed older adults underwent MRI scanning pre- and post- pharmacotherapy. Forty-six never depressed older adults underwent MR scanning as comparison subjects. Treatment response was defined as achieving a Hamilton Depression Rating Scale of 10 or less post-treatment. We analyzed resting state functional connectivity using the posterior cingulate cortex as the seed region-of-interest. The resulting correlation maps were employed to investigate between-group differences. Additionally we examined the association between white matter hyperintensity burden and functional connectivity results. Comparison of pre- and post-treatment scans of depressed participants revealed greater post-treatment functional connectivity in the frontal precentral gyrus. Relative to treatment-responsive participants, treatment-resistant participants had increased functional connectivity in the left striatum. When adjusting for white matter hyperintensity burden, the observed differences lost significance for the PCC-prefrontal functional connectivity, but not for the PCC-striatum functional connectivity. The post-treatment “frontalization” of the DMN connectivity suggests a normalizing effect of antidepressant treatment. Moreover, our study confirms the central role of white matter lesions in disrupting brain functional connectivity. PMID:24144505

  1. Resting state functional connectivity and treatment response in late-life depression.

    PubMed

    Andreescu, Carmen; Tudorascu, Dana L; Butters, Meryl A; Tamburo, Erica; Patel, Meenal; Price, Julie; Karp, Jordan F; Reynolds, Charles F; Aizenstein, Howard

    2013-12-30

    Indices of functional connectivity in the default mode network (DMN) are promising neural markers of treatment response in late-life depression. We examined the differences in DMN functional connectivity between treatment-responsive and treatment-resistant depressed older adults. Forty-seven depressed older adults underwent MRI scanning pre- and post-pharmacotherapy. Forty-six never depressed older adults underwent MR scanning as comparison subjects. Treatment response was defined as achieving a Hamilton Depression Rating Scale of 10 or less post-treatment. We analyzed resting state functional connectivity using the posterior cingulate cortex as the seed region-of-interest. The resulting correlation maps were employed to investigate between-group differences. Additionally we examined the association between white matter hyperintensity burden and functional connectivity results. Comparison of pre- and post-treatment scans of depressed participants revealed greater post-treatment functional connectivity in the frontal precentral gyrus. Relative to treatment-responsive participants, treatment-resistant participants had increased functional connectivity in the left striatum. When adjusting for white matter hyperintensity burden, the observed differences lost significance for the PCC-prefrontal functional connectivity, but not for the PCC-striatum functional connectivity. The post-treatment "frontalization" of the DMN connectivity suggests a normalizing effect of antidepressant treatment. Moreover, our study confirms the central role of white matter lesions in disrupting brain functional connectivity. PMID:24144505

  2. Alterations in amygdala functional connectivity reflect early temperament.

    PubMed

    Roy, Amy Krain; Benson, Brenda E; Degnan, Kathryn A; Perez-Edgar, Koraly; Pine, Daniel S; Fox, Nathan A; Ernst, Monique

    2014-12-01

    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

  3. 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.…

  4. 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

  5. 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

  6. Abnormal liver function in workers exposed to low levels of ethylene dichloride and vinyl chloride monomer.

    PubMed

    Cheng, T J; Huang, M L; You, N C; Du, C L; Chau, T T

    1999-12-01

    We investigated whether exposure to ethylene dichloride (EDC) and vinyl chloride monomer (VCM) resulted in increased risk of liver damage. Epidemiological information, including occupational, medical, smoking, and drinking history, was obtained by interview from 251 male workers. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyltransferase (GGT) were used as indicators of liver damage. Exposure to moderate or low levels of ECD and VCM resulted in a higher risk of developing abnormal ALT levels than did exposure to lower levels of the chemicals. Results were similar for AST. GGT was not associated with EDC or VCM exposure. Combined exposure to EDC and VCM showed a dose-response relationship in association with abnormal ALT levels. We concluded that relatively low concentrations of VCM and EDC cause liver damage.

  7. Abnormal NF-kappa B function characterizes human type 1 diabetes dendritic cells and monocytes.

    PubMed

    Mollah, Zia U A; Pai, Saparna; Moore, Craig; O'Sullivan, Brendan J; Harrison, Matthew J; Peng, Judy; Phillips, Karen; Prins, Johannes B; Cardinal, John; Thomas, Ranjeny

    2008-03-01

    Dendritic cell (DC) differentiation is abnormal in type 1 diabetes mellitus (T1DM). However, the nature of the relationship between this abnormality and disease pathogenesis is unknown. We studied the LPS response in monocytes and monocyte-derived DCs isolated from T1DM patients and from non-T1DM controls. In T1DM patients, late LPS-mediated nuclear DNA binding by RelA, p50, c-Rel, and RelB was impaired as compared with type 2 DM, rheumatoid arthritis, and healthy subjects, associated with impaired DC CD40 and MHC class I induction but normal cytokine production. In TIDM monocytes, RelA and RelB were constitutively activated, and the src homology 2 domain-containing protein tyrosine phosphatase (SHP-1), a negative regulator of NF-kappaB, was overexpressed. Addition of sodium stibogluconate, a SHP-1 inhibitor, to DCs differentiating from monocyte precursors restored their capacity to respond to LPS in approximately 60% of patients. The monocyte and DC NF-kappaB response to LPS is thus a novel phenotypic and likely pathogenetic marker for human T1DM. SHP-1 is at least one NF-kappaB regulatory mechanism which might be induced as a result of abnormal inflammatory signaling responses in T1DM monocytes. PMID:18292540

  8. Resting-state functional connectivity predicts longitudinal change in autistic traits and adaptive functioning in autism.

    PubMed

    Plitt, Mark; Barnes, Kelly Anne; Wallace, Gregory L; Kenworthy, Lauren; Martin, Alex

    2015-12-01

    Although typically identified in early childhood, the social communication symptoms and adaptive behavior deficits that are characteristic of autism spectrum disorder (ASD) persist throughout the lifespan. Despite this persistence, even individuals without cooccurring intellectual disability show substantial heterogeneity in outcomes. Previous studies have found various behavioral assessments [such as intelligence quotient (IQ), early language ability, and baseline autistic traits and adaptive behavior scores] to be predictive of outcome, but most of the variance in functioning remains unexplained by such factors. In this study, we investigated to what extent functional brain connectivity measures obtained from resting-state functional connectivity MRI (rs-fcMRI) could predict the variance left unexplained by age and behavior (follow-up latency and baseline autistic traits and adaptive behavior scores) in two measures of outcome--adaptive behaviors and autistic traits at least 1 y postscan (mean follow-up latency = 2 y, 10 mo). We found that connectivity involving the so-called salience network (SN), default-mode network (DMN), and frontoparietal task control network (FPTCN) was highly predictive of future autistic traits and the change in autistic traits and adaptive behavior over the same time period. Furthermore, functional connectivity involving the SN, which is predominantly composed of the anterior insula and the dorsal anterior cingulate, predicted reliable improvement in adaptive behaviors with 100% sensitivity and 70.59% precision. From rs-fcMRI data, our study successfully predicted heterogeneity in outcomes for individuals with ASD that was unaccounted for by simple behavioral metrics and provides unique evidence for networks underlying long-term symptom abatement.

  9. [Evaluation of systemic involving of the connective tissue in children with different localisation of isolated abnormal chords of the left ventricle (ACLV)].

    PubMed

    Kondrashova, V H; Sheĭko, L P; Kondrashova, N S

    2014-01-01

    Evaluation of the systemic involving of the connective tissue (SICT) under the new Ghent nosology (2010) showed that in children with isolated ACLV born to parents exposed to the Chernobyl disaster, its expression is associated with their location and quantity. The degree of systemic involvement of connective tissue is confirmed by the results of the analysis of features echostructure of isolated ACLV (the presence of thickening and calcification), echomorphometry, assessment of systolic (hypokinetic organization of the central hemodynamics), and the relaxation functions of the heart (initiation of diastolic dysfunction). High level of SICT (score greater than 5) indicates systemic damage to the body and particularly the heart, which requires dynamic monitoring and preventive measures. Found that the diagnostic and monitoring of children with isolated ACLV may be based on registration of systemic involvement of connective tissue with the calculation of points under the new Ghent nosology of 2010.

  10. Guiding functional connectivity estimation by structural connectivity in MEG: an application to discrimination of conditions of mild cognitive impairment.

    PubMed

    Pineda-Pardo, José Angel; Bruña, Ricardo; Woolrich, Mark; Marcos, Alberto; Nobre, Anna C; Maestú, Fernando; Vidaurre, Diego

    2014-11-01

    Whole brain resting state connectivity is a promising biomarker that might help to obtain an early diagnosis in many neurological diseases, such as dementia. Inferring resting-state connectivity is often based on correlations, which are sensitive to indirect connections, leading to an inaccurate representation of the real backbone of the network. The precision matrix is a better representation for whole brain connectivity, as it considers only direct connections. The network structure can be estimated using the graphical lasso (GL), which achieves sparsity through l1-regularization on the precision matrix. In this paper, we propose a structural connectivity adaptive version of the GL, where weaker anatomical connections are represented as stronger penalties on the corresponding functional connections. We applied beamformer source reconstruction to the resting state MEG recordings of 81 subjects, where 29 were healthy controls, 22 were single-domain amnestic Mild Cognitive Impaired (MCI), and 30 were multiple-domain amnestic MCI. An atlas-based anatomical parcellation of 66 regions was obtained for each subject, and time series were assigned to each of the regions. The fiber densities between the regions, obtained with deterministic tractography from diffusion-weighted MRI, were used to define the anatomical connectivity. Precision matrices were obtained with the region specific time series in five different frequency bands. We compared our method with the traditional GL and a functional adaptive version of the GL, in terms of log-likelihood and classification accuracies between the three groups. We conclude that introducing an anatomical prior improves the expressivity of the model and, in most cases, leads to a better classification between groups. PMID:25111472

  11. Guiding functional connectivity estimation by structural connectivity in MEG: an application to discrimination of conditions of mild cognitive impairment

    PubMed Central

    Pineda-Pardo, José Angel; Bruña, Ricardo; Woolrich, Mark; Marcos, Alberto; Nobre, Anna C.; Maestú, Fernando; Vidaurre, Diego

    2014-01-01

    Whole brain resting state connectivity is a promising biomarker that might help to obtain an early diagnosis in many neurological diseases, such as dementia. Inferring resting-state connectivity is often based on correlations, which are sensitive to indirect connections, leading to an inaccurate representation of the real backbone of the network. The precision matrix is a better representation for whole brain connectivity, as it considers only direct connections. The network structure can be estimated using the graphical lasso (GL), which achieves sparsity through l1-regularization on the precision matrix. In this paper, we propose a structural connectivity adaptive version of the GL, where weaker anatomical connections are represented as stronger penalties on the corresponding functional connections. We applied beamformer source reconstruction to the resting state MEG recordings of 81 subjects, where 29 were healthy controls, 22 were single-domain amnestic Mild Cognitive Impaired (MCI), and 30 were multiple-domain amnestic MCI. An atlas-based anatomical parcellation of 66 regions was obtained for each subject, and time series were assigned to each of the regions. The fiber densities between the regions, obtained with deterministic tractography from diffusion-weighted MRI, were used to define the anatomical connectivity. Precision matrices were obtained with the region specific time series in five different frequency bands. We compared our method with the traditional GL and a functional adaptive version of the GL, in terms of log-likelihood and classification accuracies between the three groups. We conclude that introducing an anatomical prior improves the expressivity of the model and, in most cases, leads to a better classification between groups. PMID:25111472

  12. 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…

  13. Estimation of Directed Effective Connectivity from fMRI Functional Connectivity Hints at Asymmetries of Cortical Connectome

    PubMed Central

    Gilson, Matthieu; Moreno-Bote, Ruben; Ponce-Alvarez, Adrián; Ritter, Petra; Deco, Gustavo

    2016-01-01

    The brain exhibits complex spatio-temporal patterns of activity. This phenomenon is governed by an interplay between the internal neural dynamics of cortical areas and their connectivity. Uncovering this complex relationship has raised much interest, both for theory and the interpretation of experimental data (e.g., fMRI recordings) using dynamical models. Here we focus on the so-called inverse problem: the inference of network parameters in a cortical model to reproduce empirically observed activity. Although it has received a lot of interest, recovering directed connectivity for large networks has been rather unsuccessful so far. The present study specifically addresses this point for a noise-diffusion network model. We develop a Lyapunov optimization that iteratively tunes the network connectivity in order to reproduce second-order moments of the node activity, or functional connectivity. We show theoretically and numerically that the use of covariances with both zero and non-zero time shifts is the key to infer directed connectivity. The first main theoretical finding is that an accurate estimation of the underlying network connectivity requires that the time shift for covariances is matched with the time constant of the dynamical system. In addition to the network connectivity, we also adjust the intrinsic noise received by each network node. The framework is applied to experimental fMRI data recorded for subjects at rest. Diffusion-weighted MRI data provide an estimate of anatomical connections, which is incorporated to constrain the cortical model. The empirical covariance structure is reproduced faithfully, especially its temporal component (i.e., time-shifted covariances) in addition to the spatial component that is usually the focus of studies. We find that the cortical interactions, referred to as effective connectivity, in the tuned model are not reciprocal. In particular, hubs are either receptors or feeders: they do not exhibit both strong incoming

  14. Associations Between Abnormal Rod-Mediated Dark Adaptation and Health and Functioning in Older Adults With Normal Macular Health

    PubMed Central

    Owsley, Cynthia; Huisingh, Carrie; Jackson, Gregory R.; Curcio, Christine A.; Szalai, Alexander J.; Dashti, Nassrin; Clark, Mark; Rookard, Kia; McCrory, Mark A.; Wright, Tyler T.; Callahan, Michael A.; Kline, Lanning B.; Witherspoon, C. Douglas; McGwin, Gerald

    2014-01-01

    Purpose. Delayed rod-mediated dark adaptation (DA) is characteristic of early age-related macular degeneration (AMD) and also can be observed in some older adults in normal macular health. We examine cross-sectional associations between rod-mediated DA and risk factors for AMD in older adults in normal macular health. Methods. The sample consisted of adults aged ≥60 years old in normal macular health per grading of fundus photos using an established disease classification system. Rod-mediated DA was measured psychophysically following a photobleach using a computer-automated dark adaptometer with targets centered at 5° on the inferior vertical meridian. The speed of DA was characterized by the rod-intercept value, with abnormal DA defined as rod-intercept ≥ 12.3 minutes. We assessed several health and functional characteristics that the literature has suggested increase AMD risk (e.g., smoking, alcohol use, inflammatory markers, apolipoproteins, low luminance visual acuity, chronic medical conditions, body mass, family history). Results. Among 381 participants (mean age, 68.5 years; SD, 5.5), 78% had normal and 22% had abnormal DA, with the prevalence of abnormal DA increasing with age. After age-adjustment, abnormal DA was associated with increased odds of elevated C-reactive protein (CRP), heavy use of or abstention from alcohol, high blood pressure, and drop in visual acuity under mesopic conditions. Conclusions. Despite having normal macular health according to accepted definitions of AMD presence, approximately one-quarter of older adults recruited from primary eye care clinics had abnormal DA, which was associated with known risk factors for AMD, including elevated CRP. PMID:24854857

  15. Analyzing the resting state functional connectivity in the human language system using near infrared spectroscopy

    PubMed Central

    Molavi, Behnam; May, Lillian; Gervain, Judit; Carreiras, Manuel; Werker, Janet F.; Dumont, Guy A.

    2014-01-01

    We have evaluated the use of phase synchronization to identify resting state functional connectivity (RSFC) in the language system in infants using functional near infrared spectroscopy (fNIRS). We used joint probability distribution of phase between fNIRS channels with a seed channel in the language area to estimate phase relations and to identify the language system network. Our results indicate the feasibility of this method in identifying the language system. The connectivity maps are consistent with anatomical cortical connections and are also comparable to those obtained from functional magnetic resonance imaging (fMRI) functional connectivity studies. The results also indicate left hemisphere lateralization of the language network. PMID:24523685

  16. A Brain-Wide Study of Age-Related Changes in Functional Connectivity.

    PubMed

    Geerligs, Linda; Renken, Remco J; Saliasi, Emi; Maurits, Natasha M; Lorist, Monicque M

    2015-07-01

    Aging affects functional connectivity between brain areas, however, a complete picture of how aging affects integration of information within and between functional networks is missing. We used complex network measures, derived from a brain-wide graph, to provide a comprehensive overview of age-related changes in functional connectivity. Functional connectivity in young and older participants was assessed during resting-state fMRI. The results show that aging has a large impact, not only on connectivity within functional networks but also on connectivity between the different functional networks in the brain. Brain networks in the elderly showed decreased modularity (less distinct functional networks) and decreased local efficiency. Connectivity decreased with age within networks supporting higher level cognitive functions, that is, within the default mode, cingulo-opercular and fronto-parietal control networks. Conversely, no changes in connectivity within the somatomotor and visual networks, networks implicated in primary information processing, were observed. Connectivity between these networks even increased with age. A brain-wide analysis approach of functional connectivity in the aging brain thus seems fundamental in understanding how age affects integration of information.

  17. Abnormal aortic fatty acid composition and small artery function in offspring of rats fed a high fat diet in pregnancy

    PubMed Central

    Ghosh, P; Bitsanis, D; Ghebremeskel, K; Crawford, M A; Poston, L

    2001-01-01

    Disturbances of the in utero environment are associated with an increased risk of cardiovascular disease in adulthood. In this study we have determined whether abnormal vascular function in the adult offspring of rats fed a high saturated fat diet in pregnancy is associated with altered plasma lipids or vascular fatty acid content. Female Sprague-Dawley rats were fed a breeding diet (4 % fat) or a diet high in saturated fat (20 % fat) for 10 days prior to and throughout pregnancy, and during weaning. Female offspring were then fed a maintenance diet (3 % fat) until 160 days of age. Endothelium-dependent relaxation induced by acetylcholine was blunted in isolated branches of the femoral artery from 160-day-old female offspring of dams fed the saturated fat diet when compared with female offspring of dams fed the breeding diet. These offspring exhibited elevated plasma triglyceride and reduced plasma high density lipoprotein cholesterol concentrations. The fatty acid composition of the aortas was abnormal, with a marked reduction in the content of arachidonic and docosahexaenoic acids. This study demonstrates that a high fat diet in pregnant rats produces abnormal vascular function, plasma lipid disturbances and altered vascular fatty acid content in their female offspring during adulthood. PMID:11410637

  18. Detecting resting-state functional connectivity in the language system using functional near-infrared spectroscopy

    NASA Astrophysics Data System (ADS)

    Zhang, Yu-Jin; Lu, Chun-Ming; Biswal, Bharat B.; Zang, Yu-Feng; Peng, Dan-Lin; Zhu, Chao-Zhe

    2010-07-01

    Functional connectivity has become one of the important approaches to understanding the functional organization of the human brain. Recently, functional near-infrared spectroscopy (fNIRS) was demonstrated as a feasible method to study resting-state functional connectivity (RSFC) in the sensory and motor systems. However, whether such fNIRS-based RSFC can be revealed in high-level and complex functional systems remains unknown. In the present study, the feasibility of such an approach is tested on the language system, of which the neural substrates have been well documented in the literature. After determination of a seed channel by a language localizer task, the correlation strength between the low frequency fluctuations of the fNIRS signal at the seed channel and those at all other channels is used to evaluate the language system RSFC. Our results show a significant RSFC between the left inferior frontal cortex and superior temporal cortex, components both associated with dominant language regions. Moreover, the RSFC map demonstrates left lateralization of the language system. In conclusion, the present study successfully utilized fNIRS-based RSFC to study a complex and high-level neural system, and provides further evidence for the validity of the fNIRS-based RSFC approach.

  19. Functional connectivity during language processing in acute cocaine withdrawal-a pilot study

    PubMed Central

    Narayanan, Ananth; White, Catherine A.; Saklayen, Sanjida S.; Abduljalil, Amir; Schmalbrock, Petra; Pepper, Tom H.; Lander, Brad N.; Beversdorf, David Q.

    2011-01-01

    Recent research revealed decreased access to semantic and associative networks in acute cocaine withdrawal. In autism, such behavioral outcomes are associated with decreased functional connectivity using functional magnetic resonance imaging. Therefore, we wished to determine whether connectivity is also decreased in acute cocaine withdrawal. Eight subjects in acute cocaine withdrawal were compared to controls for connectivity in language areas while performing a task involving categorization of words according to semantic and phonological relatedness. Acute withdrawal subjects had significantly less overall connectivity during semantic relatedness, and a trend towards less connectivity during phonological relatedness. Of potential future interest is whether this might serve as an imaging marker for treatment in patients. PMID:22082460

  20. Abnormal Degree Centrality of Bilateral Putamen and Left Superior Frontal Gyrus in Schizophrenia with Auditory Hallucinations: A Resting-state Functional Magnetic Resonance Imaging Study

    PubMed Central

    Chen, Cheng; Wang, Hui-Ling; Wu, Shi-Hao; Huang, Huan; Zou, Ji-Lin; Chen, Jun; Jiang, Tian-Zi; Zhou, Yuan; Wang, Gao-Hua

    2015-01-01

    Background: Dysconnectivity hypothesis of schizophrenia has been increasingly emphasized. Recent researches showed that this dysconnectivity might be related to occurrence of auditory hallucination (AH). However, there is still no consistent conclusion. This study aimed to explore intrinsic dysconnectivity pattern of whole-brain functional networks at voxel level in schizophrenic with AH. Methods: Auditory hallucinated patients group (n = 42 APG), no hallucinated patients group (n = 42 NPG) and normal controls (n = 84 NCs) were analyzed by resting-state functional magnetic resonance imaging. The functional connectivity metrics index (degree centrality [DC]) across the entire brain networks was calculated and evaluated among three groups. Results: DC decreased in the bilateral putamen and increased in the left superior frontal gyrus in all the patients. However, in APG, the changes of DC were more obvious compared with NPG. Symptomology scores were negatively correlated with the DC of bilateral putamen in all patients. AH score of APG positively correlated with the DC in left superior frontal gyrus but negatively correlated with the DC in bilateral putamen. Conclusion: Our findings corroborated that schizophrenia was characterized by functional dysconnectivity, and the abnormal DC in bilateral putamen and left superior frontal gyrus might be crucial in the occurrence of AH. PMID:26612293

  1. A functional Magnetic Resonance Imaging study of neurohemodynamic abnormalities during emotion processing in subjects at high risk for schizophrenia

    PubMed Central

    Venkatasubramanian, Ganesan; Puthumana, Dawn Thomas K.; Jayakumar, Peruvumba N.; Gangadhar, B. N.

    2010-01-01

    Background: Emotion processing abnormalities are considered among the core deficits in schizophrenia. Subjects at high risk (HR) for schizophrenia also show these deficits. Structural neuroimaging studies examining unaffected relatives at high risk for schizophrenia have demonstrated neuroanatomical abnormalities involving neo-cortical and sub-cortical brain regions related to emotion processing. The brain functional correlates of emotion processing in these HR subjects in the context of ecologically valid, real-life dynamic images using functional Magnetic Resonance Imaging (fMRI) has not been examined previously. Aim: To examine the neurohemodynamic abnormalities during emotion processing in unaffected subjects at high risk for schizophrenia in comparison with age-, sex-, handedness- and education-matched healthy controls, using fMRI. Materials and Methods: HR subjects for schizophrenia (n=17) and matched healthy controls (n=16) were examined. The emotion processing of fearful facial expression was examined using a culturally appropriate and valid tool for Indian subjects. The fMRI was performed in a 1.5-T scanner during an implicit emotion processing paradigm. The fMRI analyses were performed using the Statistical Parametric Mapping 2 (SPM2) software. Results: HR subjects had significantly reduced brain activations in left insula, left medial frontal gyrus, left inferior frontal gyrus, right cingulate gyrus, right precentral gyrus and right inferior parietal lobule. Hypothesis-driven region-of-interest analysis revealed hypoactivation of right amygdala in HR subjects. Conclusions: Study findings suggest that neurohemodynamic abnormalities involving limbic and frontal cortices could be potential indicators for increased vulnerability toward schizophrenia. The clinical utility of these novel findings in predicting the development of psychosis needs to be evaluated. PMID:21267363

  2. Functional connectivity patterns reflect individual differences in conflict adaptation.

    PubMed

    Wang, Xiangpeng; Wang, Ting; Chen, Zhencai; Hitchman, Glenn; Liu, Yijun; Chen, Antao

    2015-04-01

    Individuals differ in the ability to utilize previous conflict information to optimize current conflict resolution, which is termed the conflict adaptation effect. Previous studies have linked individual differences in conflict adaptation to distinct brain regions. However, the network-based neural mechanisms subserving the individual differences of the conflict adaptation effect have not been studied. The present study employed a psychophysiological interaction (PPI) analysis with a color-naming Stroop task to examine this issue. The main results were as follows: (1) the anterior cingulate cortex (ACC)-seeded PPI revealed the involvement of the salience network (SN) in conflict adaptation, while the posterior parietal cortex (PPC)-seeded PPI revealed the engagement of the central executive network (CEN). (2) Participants with high conflict adaptation effect showed higher intra-CEN connectivity and lower intra-SN connectivity; while those with low conflict adaptation effect showed higher intra-SN connectivity and lower intra-CEN connectivity. (3) The PPC-centered intra-CEN connectivity positively predicted the conflict adaptation effect; while the ACC-centered intra-SN connectivity had a negative correlation with this effect. In conclusion, our data demonstrated that conflict adaptation is likely supported by the CEN and the SN, providing a new perspective on studying individual differences in conflict adaptation on the basis of large-scale networks. PMID:25721566

  3. Thyroid Function Status and Echocardiographic Abnormalities in Patients with Beta Thalassemia Major in Bahrain

    PubMed Central

    Garadah, Taysir S.; Mahdi, Najat A.; Jaradat, Ahmed M.; Hasan, Zuheir A.; Nagalla, Das S.

    2013-01-01

    Background: Thyroid gland dysfunction and echocardiographic cardiac abnormalities are well-documented in patients with transfusion dependent beta-thalassemia major (β-TM). Aim: This cross-sectional analytic study was conducted to investigate left ventricle (LV) diastolic and systolic function using pulsed Doppler (PD) and tissue Doppler (TD) echocardiography and correlate that with serum level thyroid stimulating hormone in patients with β-TM. Methods: The study was conducted on patients with β-TM (n = 110, age 15.9 ± 8.9 years) and compared with a control group (n = 109, age 15.8 ± 8.9 years). In all participants, echocardiographic indices of PD and TD were performed and blood samples were withdrawn for measuring the serum level of TSH, free T4, and ferritin. A linear regression analysis was performed on TSH level as the dependent variable and serum ferritin as independent. Stepwise multiple regression analysis was used to determine the odds ratio of different biochemical and echo variables on the risk of developing hypothyroidism. Results: Patients with β-TM compared with controls had thicker LV septal wall index (0.65 ± 0.26 vs. 0.44 ± 0.21 cm/M2, P < 0.001), posterior wall index (0.65 ± 0.23 vs. 0.43 ± 0.21 cm/m2, P < 0.01) and larger LVEDD index (4.35 ± 0.69 vs.3.88 ± 0.153 mm/m2, P < 0.001). In addition, β-TM patients had higher transmitral E wave velocity (E) (70.81 ± 10.13 vs. 57.53 ± 10.13 cm/s, P = 0.02) and E/A ratio (1.54 ± 0.18 vs. 1.23 ± 0.17, P < 0.01) and shorter deceleration time (DT) (170.53 ± 13.3 vs. 210.50 ± 19.20 m sec, P < 0.01). Furthermore, the ratio of transmitral E wave velocity to the tissue Doppler E wave at the basal septal mitral annulus (E/Em) was significantly higher in the β-TM group (19.68 ± 2.81 vs. 13.86 ± 1.41, P < 0.05). The tissue Doppler systolic wave (Sm) velocity and the early diastolic wave (Em) were significantly lower in the β-TM group compared with controls with Sm, 4.82 ± 1.2 vs. 6.22 ± 2.1 mm

  4. Large-Scale Brain Networks of the Human Left Temporal Pole: A Functional Connectivity MRI Study

    PubMed Central

    Pascual, Belen; Masdeu, Joseph C.; Hollenbeck, Mark; Makris, Nikos; Insausti, Ricardo; Ding, Song-Lin; Dickerson, Bradford C.

    2015-01-01

    The most rostral portion of the human temporal cortex, the temporal pole (TP), has been described as “enigmatic” because its functional neuroanatomy remains unclear. Comparative anatomy studies are only partially helpful, because the human TP is larger and cytoarchitectonically more complex than in nonhuman primates. Considered by Brodmann as a single area (BA 38), the human TP has been recently parceled into an array of cytoarchitectonic subfields. In order to clarify the functional connectivity of subregions of the TP, we undertook a study of 172 healthy adults using resting-state functional connectivity MRI. Remarkably, a hierarchical cluster analysis performed to group the seeds into distinct subsystems according to their large-scale functional connectivity grouped 87.5% of the seeds according to the recently described cytoarchitectonic subregions of the TP. Based on large-scale functional connectivity, there appear to be 4 major subregions of the TP: 1) dorsal, with predominant connectivity to auditory/somatosensory and language networks; 2) ventromedial, predominantly connected to visual networks; 3) medial, connected to paralimbic structures; and 4) anterolateral, connected to the default-semantic network. The functional connectivity of the human TP, far more complex than its known anatomic connectivity in monkey, is concordant with its hypothesized role as a cortical convergence zone. PMID:24068551

  5. Chemotherapy Altered Brain Functional Connectivity in Women with Breast Cancer: A Pilot Study

    PubMed Central

    Dumas, Julie A.; Makarewicz, Jenna; Schaubhut, Geoffrey J.; Devins, Robert; Albert, Kimberly; Dittus, Kim; Newhouse, Paul A.

    2013-01-01

    Adjuvant chemotherapy is associated with improvements in long-term cancer survival. However, reports of cognitive impairment following treatment emphasize the importance of understanding the long-term effects of chemotherapy on brain functioning. Cognitive deficits found in chemotherapy patients suggest a change in brain functioning that affects specific cognitive domains such as attentional processing and executive functioning. This study examined the processes potentially underlying these changes in cognition by examining brain functional connectivity pre- and post-chemotherapy in women with breast cancer. Functional connectivity examines the temporal correlation between spatially remote brain regions in an effort to understand how brain networks support specific cognitive functions. Nine women diagnosed with breast cancer completed a functional magnetic resonance imaging (fMRI) session before chemotherapy, one month after, and one year after the completion of chemotherapy. Seed-based functional connectivity analyses were completed using seeds in the intraparietal sulcus (IPS) to examine connectivity in the dorsal anterior attention network and in the posterior cingulate cortex (PCC) to examine connectivity in the default mode network. Results showed decreased functional connectivity one month after chemotherapy that partially returned to baseline at one year in the dorsal attention network. Decreased connectivity was seen in the default mode network at one month and one year following chemotherapy. In addition, increased subjective memory complaints were noted at one month and one year post-chemotherapy. These findings suggest a detrimental effect of chemotherapy on brain functional connectivity that is potentially related to subjective cognitive assessment. PMID:23852814

  6. Similarity analysis of functional connectivity with functional near-infrared spectroscopy.

    PubMed

    Dalmis, Mehmet Ufuk; Akin, Ata

    2015-08-01

    One of the remaining challenges in functional connectivity (FC) studies is investigation of the temporal variability of FC networks. Recent studies focusing on the dynamic FC mostly use functional magnetic resonance imaging as an imaging tool to investigate the temporal variability of FC. We attempted to quantify this variability via analyzing the functional near-infrared spectroscopy (fNIRS) signals, which were recorded from the prefrontal cortex (PFC) of 12 healthy subjects during a Stroop test. Mutual information was used as a metric to determine functional connectivity between PFC regions. Two-dimensional correlation based similarity measure was used as a method to analyze within-subject and intersubject consistency of FC maps and how they change in time. We found that within-subject consistency (0.61±0.09 ) is higher than intersubject consistency (0.28±0.13 ). Within-subject consistency was not found to be task-specific. Results also revealed that there is a gradual change in FC patterns during a Stroop session for congruent and neutral conditions, where there is no such trend in the presence of an interference effect. In conclusion, we have demonstrated the between-subject, within-subject, and temporal variability of FC and the feasibility of using fNIRS for studying dynamic FC. PMID:26296233

  7. Abnormal Intrinsic Functional Hubs in Severe Male Obstructive Sleep Apnea: Evidence from a Voxel-Wise Degree Centrality Analysis

    PubMed Central

    Shao, Yi; Gong, Honghan; Zhang, Wei; Zeng, Xianjun; Ye, Chenglong; Nie, Si; Chen, Liting; Peng, Dechang

    2016-01-01

    Purpose Obstructive sleep apnea (OSA) has been associated with changes in brain structure and regional function in certain brain areas. However, the functional features of network organization in the whole brain remain largely uncertain. The purpose of this study was to identify the OSA-related spatial centrality distribution of the whole brain functional network and to investigate the potential altered intrinsic functional hubs. Methods Forty male patients with newly confirmed severe OSA on polysomnography, and well-matched good sleepers, participated in this study. All participants underwent a resting-state functional MRI scan and clinical and cognitive evaluation. Voxel-wise degree centrality (DC) was measured across the whole brain, and group difference in DC was compared. The relationship between the abnormal DC value and clinical variables was assessed using a linear correlation analysis. Results Remarkably similar spatial distributions of the functional hubs (high DC) were found in both groups. However, OSA patients exhibited a pattern of significantly reduced regional DC in the left middle occipital gyrus, posterior cingulate cortex, left superior frontal gyrus, and bilateral inferior parietal lobule, and DC was increased in the right orbital frontal cortex, bilateral cerebellum posterior lobes, and bilateral lentiform nucleus, including the putamen, extending to the hippocampus, and the inferior temporal gyrus, which overlapped with the functional hubs. Furthermore, a linear correlation analysis revealed that the DC value in the posterior cingulate cortex and left superior frontal gyrus were positively correlated with Montreal cognitive assessment scores, The DC value in the left middle occipital gyrus and bilateral inferior parietal lobule were negatively correlated with apnea-hypopnea index and arousal index in OSA patients. Conclusion Our findings suggest that OSA patients exhibited specific abnormal intrinsic functional hubs including relatively

  8. Functional Connectivity-Based Parcellation of Amygdala Using Self-Organized Mapping: A Data Driven Approach

    PubMed Central

    Mishra, Arabinda; Rogers, Baxter P.; Chen, Li Min; Gore, John C.

    2013-01-01

    The overall goal of this work is to demonstrate how resting state functional magnetic resonance imaging (fMRI) signals may be used to objectively parcellate functionally heterogeneous subregions of the human amygdala into structures characterized by similar patterns of functional connectivity. We hypothesize that similarity of functional connectivity of subregions with other parts of the brain can be a potential basis to segment and cluster voxels using data driven approaches. In this work, self-organizing map (SOM) was implemented to cluster the connectivity maps associated with each voxel of the human amygdala, thereby defining distinct subregions. The functional separation was optimized by evaluating the overall differences in functional connectivity between the subregions at group level. Analysis of 25 resting state fMRI data sets suggests that SOM can successfully identify functionally independent nuclei based on differences in their inter subregional functional connectivity, evaluated statistically at various confidence levels. Although amygdala contains several nuclei whose distinct roles are implicated in various functions, our objective approach discerns at least two functionally distinct volumes comparable to previous parcellation results obtained using probabilistic tractography and cytoarchitectonic analysis. Association of these nuclei with various known functions and a quantitative evaluation of their differences in overall functional connectivity with lateral orbital frontal cortex and temporal pole confirms the functional diversity of amygdala. The data driven approach adopted here may be used as a powerful indicator of structure–function relationships in the amygdala and other functionally heterogeneous structures as well. PMID:23418140

  9. Individual variation in functional brain connectivity: implications for personalized approaches to psychiatric disease

    PubMed Central

    Finn, Emily S.; Todd Constable, R.

    2016-01-01

    Functional brain connectivity measured with functional magnetic resonance imaging (fMRI) is a popular technique for investigating neural organization in both healthy subjects and patients with mental illness. Despite a rapidly growing body of literature, however, functional connectivity research has yet to deliver biomarkers that can aid psychiatric diagnosis or prognosis at the single-subject level. One impediment to developing such practical tools has been uncertainty regarding the ratio of intra- to interindividual variability in functional connectivity; in other words, how much variance is state- versus trait-related. Here, we review recent evidence that functional connectivity profiles are both reliable within subjects and unique across subjects, and that features of these profiles relate to behavioral phenotypes. Together, these results suggest the potential to discover reliable correlates of present and future illness and/or response to treatment in the strength of an individual's functional brain connections. Ultimately, this work could help develop personalized approaches to psychiatric illness. PMID:27757062

  10. Altered resting-state functional connectivity in cortical networks in psychopathy.

    PubMed

    Philippi, Carissa L; Pujara, Maia S; Motzkin, Julian C; Newman, Joseph; Kiehl, Kent A; Koenigs, Michael

    2015-04-15

    Psychopathy is a personality disorder characterized by callous antisocial behavior and criminal recidivism. Here we examine whether psychopathy is associated with alterations in functional connectivity in three large-scale cortical networks. Using fMRI in 142 adult male prison inmates, we computed resting-state functional connectivity using seeds from the default mode network, frontoparietal network, and cingulo-opercular network. To determine the specificity of our findings to these cortical networks, we also calculated functional connectivity using seeds from two comparison primary sensory networks: visual and auditory networks. Regression analyses related network connectivity to overall psychopathy scores and to subscores for the "factors" and "facets" of psychopathy: Factor 1, interpersonal/affective traits; Factor 2, lifestyle/antisocial traits; Facet 1, interpersonal; Facet 2, affective; Facet 3, lifestyle; Facet 4, antisocial. Overall psychopathy severity was associated with reduced functional connectivity between lateral parietal cortex and dorsal anterior cingulate cortex. The two factor scores exhibited contrasting relationships with functional connectivity: Factor 1 scores were associated with reduced functional connectivity in the three cortical networks, whereas Factor 2 scores were associated with heightened connectivity in the same networks. This dissociation was evident particularly in the functional connectivity between anterior insula and dorsal anterior cingulate cortex. The facet scores also demonstrated distinct patterns of connectivity. We found no associations between psychopathy scores and functional connectivity within visual or auditory networks. These findings provide novel evidence on the neural correlates of psychopathy and suggest that connectivity between cortical association hubs, such as the dorsal anterior cingulate cortex, may be a neurobiological marker of the disorder.

  11. Liver Function Test Abnormalities in Depressed Patients Treated with Antidepressants: A Real-World Systematic Observational Study in Psychiatric Settings

    PubMed Central

    Verstuyft, Céline; Corruble, Emmanuelle; Perlemuter, Gabriel; Colle, Romain

    2016-01-01

    Background Concerning the risk of antidepressant induced liver injury, it is not clear whether psychiatrists perform a liver function test (LFT) and whether an increase in aminotransferase levels should contraindicate antidepressant treatment. Aim To evaluate LFT availability, the prevalence of LFT abnormalities and the probable cause of an altered LFT in patients with a major depressive episode (MDE) requiring an antidepressant drug. Methods We studied LFT evaluation in a real world psychiatric setting, in a sample of 321 consecutive patients with a current major depressive episode (MDE) requiring an antidepressant drug treatment, but without current alcohol or drug dependence or unstable medical disease. Results An LFT is performed in 36.1% (116/321) of depressed patients. One fifth of antidepressant-treated patients who had an LFT evaluation had abnormal results. The most frequent causes of LFT abnormalities were: NAFLD (nonalcoholic fatty liver disease) (7/321; 2.1%), acute alcohol consumption (4/321; 1.2%), antidepressant-induced liver injury (3/321; 0.9%), hepatitis C virus infection (2/321; 0.6%) and heart failure (1/321; 0.3%). The cause of LFT abnormalities was unknown in 32% of patients (8/25) due to the absence of etiological investigations. Conclusion These results demonstrate that an LFT is infrequently performed by psychiatrists in depressed patients requiring an antidepressant drug. Baseline LFT assessment and observations during the first six months of antidepressant treatment may be useful for detection of patients with pre-existing liver disease such as NAFLD, and early identification of cases of antidepressant-induced liver injury. An increase in aminotransferase levels may be related to an underlying liver disease, but does not contraindicate antidepressant treatment. PMID:27171561

  12. Respiratory symptoms in rheumatoid arthritis: relation to pulmonary abnormalities detected by high-resolution CT and pulmonary functional testing.

    PubMed

    Youssef, Amir A; Machaly, Shereen A; El-Dosoky, Mohammed E; El-Maghraby, Nermeen M

    2012-07-01

    Pulmonary disease is the most frequent and among the most severe extra-articular manifestation of rheumatoid arthritis (RA). However, this issue has not been sufficiently studied in Egyptian patients. The objectives of the present study are to investigate the prevalence and types of pulmonary involvement using high-resolution computed tomography scan (HRCT) and pulmonary function tests (PFT) and evaluate the association between respiratory symptoms and RA-lung disease in a group of Egyptian RA patients. Thirty-six RA patients were recruited; 34 females (94.4%) and 2 males (5.6%) with median age of 48.5 years, and none of them was smoker. Detailed medical and drug histories were obtained. PFT, plain X-ray of the chest, and HRCT were performed to all subjects involved. Nearly 64% of RA patients demonstrated abnormalities in PFT and 47% in HRCT. Mixed restrictive and obstructive pattern was the commonest. Nearly two-thirds of our patients reported one or more pulmonary symptom whether dyspnea, cough, wheezing, or phlegm. Dyspnea was the most frequent symptom. Respiratory symptoms were statistically more common in patients with lung disease. The advanced age, high radiological score, and severity of rheumatoid disease were found to be predictive of lung involvement. Among respiratory symptoms, dyspnea and cough were associated with any pulmonary abnormalities. When specific pulmonary abnormalities were considered, only dyspnea was identified as predictor for restriction. For obstructive abnormality, both cough and wheezing provided valid prediction. We conclude that pulmonary involvement is a common manifestation in Egyptian RA patients, and the pattern of involvement is generally consistent with other studies that were performed worldwide. Specific respiratory symptoms could be used as practical, easy, and cost-effective method, especially in older and with more severe RA patients, to discriminate patients in need of subsequent PFT and HRCT imaging.

  13. Sex ratio of congenital abnormalities in the function of maternal age: a population-based study.

    PubMed

    Csermely, Gyula; Urbán, Robert; Czeizel, Andrew E; Veszprémi, Béla

    2015-05-01

    Maternal age effect is well-known in the origin of numerical chromosomal aberrations and some isolated congenital abnormalities (CAs). The sex ratio (SR), i.e. number of males divided by the number of males and females together, of most CAs deviates from the SR of newborn population (0.51). The objective of this analysis was to evaluate the possible association of maternal age with the SR of isolated CAs in a population-based large dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-1996. First, SR of 24 CA entities/groups was estimated in 21,494 patients with isolated CA. In the next step SR of different maternal age groups was compared to the mean SR of the given CA-groups. The SR of four CA-groups showed some deviation in certain maternal age groups. Cases with anencephaly had female excess in young mothers (<25 years). Cases with skull's CAs particularly craniosynostosis had a male excess in cases born to women over 30 years. Two other CA groups (cleft lip ± palate and valvar pulmonic stenosis within the group of right-sided obstructive defect of heart) had significant deviation in SR of certain maternal age groups from the mean SR, but these deviations were not harmonized with joining age groups and thus were considered as a chance effect due to multiple testing. In conclusion, our study did not suggest that in general SR of isolated CAs might be modified by certain maternal age groups with some exception such as anencephaly and craniosynostosis.

  14. Catechin averts experimental diabetes mellitus-induced vascular endothelial structural and functional abnormalities.

    PubMed

    Bhardwaj, Pooja; Khanna, Deepa; Balakumar, Pitchai

    2014-03-01

    Diabetes mellitus is associated with an induction of vascular endothelial dysfunction (VED), an initial event that could lead to the pathogenesis of atherosclerosis and hypertension. Previous studies showed that catechin, a key component of green tea, possesses vascular beneficial effects. We investigated the effect of catechin hydrate in diabetes mellitus-induced experimental vascular endothelial abnormalities (VEA). Streptozotocin (50 mg/kg, i.p., once) administration to rats produced diabetes mellitus, which subsequently induced VEA in 8 weeks by markedly attenuating acetylcholine-induced endothelium-dependent relaxation in the isolated aortic ring preparation, decreasing aortic and serum nitrite/nitrate concentrations and impairing aortic endothelial integrity. These abnormalities in diabetic rats were accompanied with elevated aortic superoxide anion generation and serum lipid peroxidation in addition to hyperglycemia. Catechin hydrate treatment (50 mg/kg/day p.o., 3 weeks) markedly prevented diabetes mellitus-induced VEA and vascular oxidative stress. Intriguingly, in vitro incubation of L-NAME (100 μM), an inhibitor of nitric oxide synthase, or Wortmannin (100 nM), a selective inhibitor of phosphatidylinositol 3-kinase (PI3K), markedly prevented catechin hydrate-induced improvement in acetylcholine-provoked endothelium-dependent relaxation in the diabetic rat aorta. Moreover, catechin hydrate treatment considerably reduced the elevated level of serum glucose in diabetic rats. In conclusion, catechin hydrate treatment prevents diabetes mellitus-induced VED through the activation of endothelial PI3K signal and subsequent activation of eNOS and generation of nitric oxide. In addition, reduction in high glucose, vascular oxidative stress, and lipid peroxidation might additionally contribute to catechin hydrate-associated prevention of diabetic VEA. PMID:24048981

  15. Sex ratio of congenital abnormalities in the function of maternal age: a population-based study.

    PubMed

    Csermely, Gyula; Urbán, Robert; Czeizel, Andrew E; Veszprémi, Béla

    2015-05-01

    Maternal age effect is well-known in the origin of numerical chromosomal aberrations and some isolated congenital abnormalities (CAs). The sex ratio (SR), i.e. number of males divided by the number of males and females together, of most CAs deviates from the SR of newborn population (0.51). The objective of this analysis was to evaluate the possible association of maternal age with the SR of isolated CAs in a population-based large dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-1996. First, SR of 24 CA entities/groups was estimated in 21,494 patients with isolated CA. In the next step SR of different maternal age groups was compared to the mean SR of the given CA-groups. The SR of four CA-groups showed some deviation in certain maternal age groups. Cases with anencephaly had female excess in young mothers (<25 years). Cases with skull's CAs particularly craniosynostosis had a male excess in cases born to women over 30 years. Two other CA groups (cleft lip ± palate and valvar pulmonic stenosis within the group of right-sided obstructive defect of heart) had significant deviation in SR of certain maternal age groups from the mean SR, but these deviations were not harmonized with joining age groups and thus were considered as a chance effect due to multiple testing. In conclusion, our study did not suggest that in general SR of isolated CAs might be modified by certain maternal age groups with some exception such as anencephaly and craniosynostosis. PMID:25354028

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

    ERIC Educational Resources Information Center

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

    2012-01-01

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

  17. Decoupling of structural and functional brain connectivity in older adults with white matter hyperintensities.

    PubMed

    Reijmer, Y D; Schultz, A P; Leemans, A; O'Sullivan, M J; Gurol, M E; Sperling, R; Greenberg, S M; Viswanathan, A; Hedden, T

    2015-08-15

    Age-related impairments in the default network (DN) have been related to disruptions in connecting white matter tracts. We hypothesized that the local correlation between DN structural and functional connectivity is negatively affected in the presence of global white matter injury. In 125 clinically normal older adults, we tested whether the relationship between structural connectivity (via diffusion imaging tractography) and functional connectivity (via resting-state functional MRI) of the posterior cingulate cortex (PCC) and medial prefrontal frontal cortex (MPFC) of the DN was altered in the presence of white matter hyperintensities (WMH). A significant correlation was observed between microstructural properties of the cingulum bundle and MPFC-PCC functional connectivity in individuals with low WMH load, but not with high WMH load. No correlation was observed between PCC-MPFC functional connectivity and microstructure of the inferior longitudinal fasciculus, a tract not passing through the PCC or MPFC. Decoupling of connectivity, measured as the absolute difference between structural and functional connectivity, in the high WMH group was related to poorer executive functioning and memory performance. These results suggest that such decoupling may reflect reorganization of functional networks in response to global white matter pathology and may provide an early marker of clinically relevant network alterations.

  18. Functional connectivity changes detected with magnetoencephalography after mild traumatic brain injury.

    PubMed

    Dimitriadis, Stavros I; Zouridakis, George; Rezaie, Roozbeh; Babajani-Feremi, Abbas; Papanicolaou, Andrew C

    2015-01-01

    Mild traumatic brain injury (mTBI) may affect normal cognition and behavior by disrupting the functional connectivity networks that mediate efficient communication among brain regions. In this study, we analyzed brain connectivity profiles from resting state Magnetoencephalographic (MEG) recordings obtained from 31 mTBI patients and 55 normal controls. We used phase-locking value estimates to compute functional connectivity graphs to quantify frequency-specific couplings between sensors at various frequency bands. Overall, normal controls showed a dense network of strong local connections and a limited number of long-range connections that accounted for approximately 20% of all connections, whereas mTBI patients showed networks characterized by weak local connections and strong long-range connections that accounted for more than 60% of all connections. Comparison of the two distinct general patterns at different frequencies using a tensor representation for the connectivity graphs and tensor subspace analysis for optimal feature extraction showed that mTBI patients could be separated from normal controls with 100% classification accuracy in the alpha band. These encouraging findings support the hypothesis that MEG-based functional connectivity patterns may be used as biomarkers that can provide more accurate diagnoses, help guide treatment, and monitor effectiveness of intervention in mTBI.

  19. Functional connectivity changes detected with magnetoencephalography after mild traumatic brain injury

    PubMed Central

    Dimitriadis, Stavros I.; Zouridakis, George; Rezaie, Roozbeh; Babajani-Feremi, Abbas; Papanicolaou, Andrew C.

    2015-01-01

    Mild traumatic brain injury (mTBI) may affect normal cognition and behavior by disrupting the functional connectivity networks that mediate efficient communication among brain regions. In this study, we analyzed brain connectivity profiles from resting state Magnetoencephalographic (MEG) recordings obtained from 31 mTBI patients and 55 normal controls. We used phase-locking value estimates to compute functional connectivity graphs to quantify frequency-specific couplings between sensors at various frequency bands. Overall, normal controls showed a dense network of strong local connections and a limited number of long-range connections that accounted for approximately 20% of all connections, whereas mTBI patients showed networks characterized by weak local connections and strong long-range connections that accounted for more than 60% of all connections. Comparison of the two distinct general patterns at different frequencies using a tensor representation for the connectivity graphs and tensor subspace analysis for optimal feature extraction showed that mTBI patients could be separated from normal controls with 100% classification accuracy in the alpha band. These encouraging findings support the hypothesis that MEG-based functional connectivity patterns may be used as biomarkers that can provide more accurate diagnoses, help guide treatment, and monitor effectiveness of intervention in mTBI. PMID:26640764

  20. Associations of Postural Knowledge and Basic Motor Skill with Dyspraxia in Autism: Implication for Abnormalities in Distributed Connectivity and Motor Learning

    PubMed Central

    Dowell, Lauren R.; Mahone, E. Mark; Mostofsky, Stewart H.

    2009-01-01

    Children with autism often have difficulty performing skilled movements. Praxis performance requires basic motor skill, knowledge of representations of the movement (mediated by parietal regions), and transcoding of these representations into movement plans (mediated by premotor circuits). The goals of this study were: (a) to determine whether dyspraxia in autism is associated with impaired representational (“postural”) knowledge, and (b) to examine the contributions of postural knowledge and basic motor skill to dyspraxia in autism. Thirty-seven children with autism spectrum disorder (ASD) and 50 typically developing (TD) children, ages 8–13, completed: (a) an examination of basic motor skills, (b) a postural knowledge test assessing praxis discrimination, and (c) a praxis examination. Children with ASD showed worse basic motor skill and postural knowledge than controls. The ASD group continued to show significantly poorer praxis than controls after accounting for age, IQ, basic motor skill, and postural knowledge. Dyspraxia in autism appears to be associated with impaired formation of spatial representations, as well as transcoding and execution. Distributed abnormality across parietal, premotor, and motor circuitry, as well as anomalous connectivity may be implicated. PMID:19702410

  1. State and Trait Components of Functional Connectivity: Individual Differences Vary with Mental State

    PubMed Central

    Rubinov, Mikail; Cam-CAN; Henson, Richard N.

    2015-01-01

    Resting-state functional connectivity, as measured by functional magnetic resonance imaging (fMRI), is often treated as a trait, used, for example, to draw inferences about individual differences in cognitive function, or differences between healthy or diseased populations. However, functional connectivity can also depend on the individual's mental state. In the present study, we examined the relative contribution of state and trait components in shaping an individual's functional architecture. We used fMRI data from a large, population-based human sample (N = 587, age 18–88 years), as part of the Cambridge Centre for Aging and Neuroscience (Cam-CAN), which were collected in three mental states: resting, performing a sensorimotor task, and watching a movie. Whereas previous studies have shown commonalities across mental states in the average functional connectivity across individuals, we focused on the effects of states on the pattern of individual differences in functional connectivity. We found that state effects were as important as trait effects in shaping individual functional connectivity patterns, each explaining an approximately equal amount of variance. This was true when we looked at aging, as one specific dimension of individual differences, as well as when we looked at generic aspects of individual variation. These results show that individual differences in functional connectivity consist of state-dependent aspects, as well as more stable, trait-like characteristics. Studying individual differences in functional connectivity across a wider range of mental states will therefore provide a more complete picture of the mechanisms underlying factors such as cognitive ability, aging, and disease. SIGNIFICANCE STATEMENT The brain's functional architecture is remarkably similar across different individuals and across different mental states, which is why many studies use functional connectivity as a trait measure. Despite these trait-like aspects, functional

  2. Abnormal Functional Lateralization and Activity of Language Brain Areas in Typical Specific Language Impairment (Developmental Dysphasia)

    ERIC Educational Resources Information Center

    de Guibert, Clement; Maumet, Camille; Jannin, Pierre; Ferre, Jean-Christophe; Treguier, Catherine; Barillot, Christian; Le Rumeur, Elisabeth; Allaire, Catherine; Biraben, Arnaud

    2011-01-01

    Atypical functional lateralization and specialization for language have been proposed to account for developmental language disorders, yet results from functional neuroimaging studies are sparse and inconsistent. This functional magnetic resonance imaging study compared children with a specific subtype of specific language impairment affecting…

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

    PubMed Central

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

    2015-01-01

    Background Resting brain spontaneous neural activities across cortical regions have been correlated with specific functional properties in psychiatric groups. Individuals with Internet gaming disorder (IGD) demonstrate impaired executive control. Thus, it is important to examine executive control networks (ECNs) during resting states and their relationships to executive control during task performance. Methods Thirty-five IGD and 36 healthy control participants underwent a resting-state fMRI scan and performed a Stroop task inside and outside of the MRI scanner. Correlations between Stroop effect and functional connectivity among ECN regions of interest (ROIs) were calculated within and between groups. Results IGD subjects show lower functional connectivity in ECNs than do HC participants during resting state; functional-connectivity measures in ECNs were negatively correlated with Stroop effect and positively correlated with brain activations in executive-control regions across groups. Within groups, negative trends were found between Stroop effect and functional connectivity in ECNs in IGD and HC groups, separately; positive trends were found between functional connectivity in ECNs and brain activations in Stroop task in IGD and HC groups, separately. Conclusions Higher functional connectivity in ECNs may underlie better executive control and may provide resilience with respect to IGD. Lower functional connectivity in ECNs may represent an important feature in understanding and treating IGD. PMID:25445475

  4. Preserved local but disrupted contextual figure-ground influences in an individual with abnormal function of intermediate visual areas.

    PubMed

    Brooks, Joseph L; Gilaie-Dotan, Sharon; Rees, Geraint; Bentin, Shlomo; Driver, Jon

    2012-06-01

    Visual perception depends not only on local stimulus features but also on their relationship to the surrounding stimulus context, as evident in both local and contextual influences on figure-ground segmentation. Intermediate visual areas may play a role in such contextual influences, as we tested here by examining LG, a rare case of developmental visual agnosia. LG has no evident abnormality of brain structure and functional neuroimaging showed relatively normal V1 function, but his intermediate visual areas (V2/V3) function abnormally. We found that contextual influences on figure-ground organization were selectively disrupted in LG, while local sources of figure-ground influences were preserved. Effects of object knowledge and familiarity on figure-ground organization were also significantly diminished. Our results suggest that the mechanisms mediating contextual and familiarity influences on figure-ground organization are dissociable from those mediating local influences on figure-ground assignment. The disruption of contextual processing in intermediate visual areas may play a role in the substantial object recognition difficulties experienced by LG.

  5. Resting-state functional connectivity between the dorsal anterior cingulate cortex and thalamus is associated with risky decision-making in nicotine addicts

    PubMed Central

    Wei, Zhengde; Yang, Nannan; Liu, Ying; Yang, Lizhuang; Wang, Ying; Han, Long; Zha, Rujing; Huang, Ruiqi; Zhang, Peng; Zhou, Yifeng; Zhang, Xiaochu

    2016-01-01

    Nicotine addiction is associated with risky behaviors and abnormalities in local brain areas related to risky decision-making such as the dorsal anterior cingulate cortex (dACC), anterior insula (AI), and thalamus. Although these brain abnormalities are anatomically separated, they may in fact belong to one neural network. However, it is unclear whether circuit-level abnormalities lead to risky decision-making in smokers. In the current study, we used task-based functional magnetic resonance imaging (fMRI) and examined resting-state functional connectivity (RSFC) to study how connectivity between the dACC, insula, and thalamus influence risky decision-making in nicotine addicts. We found that an increase in risky decision-making was associated with stronger nicotine dependence and stronger RSFC of the dACC-rAI (right AI), the dACC-thalamus, the dACC-lAI (left AI), and the rAI-lAI, but that risky decision-making was not associated with risk level-related activation. Furthermore, the severity of nicotine dependence positively correlated with RSFC of the dACC-thalamus but was not associated with risk level-related activation. Importantly, the dACC-thalamus coupling fully mediated the effect of nicotine-dependent severity on risky decision-making. These results suggest that circuit-level connectivity may be a critical neural link be