Altered default network resting-state functional connectivity in adolescents with Internet gaming addiction.

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Wei-na Ding

Full Text Available Excessive use of the Internet has been linked to a variety of negative psychosocial consequences. This study used resting-state functional magnetic resonance imaging (fMRI to investigate whether functional connectivity is altered in adolescents with Internet gaming addiction (IGA.Seventeen adolescents with IGA and 24 normal control adolescents underwent a 7.3 minute resting-state fMRI scan. Posterior cingulate cortex (PCC connectivity was determined in all subjects by investigating synchronized low-frequency fMRI signal fluctuations using a temporal correlation method. To assess the relationship between IGA symptom severity and PCC connectivity, contrast images representing areas correlated with PCC connectivity were correlated with the scores of the 17 subjects with IGA on the Chen Internet Addiction Scale (CIAS and Barratt Impulsiveness Scale-11 (BIS-11 and their hours of Internet use per week.There were no significant differences in the distributions of the age, gender, and years of education between the two groups. The subjects with IGA showed longer Internet use per week (hours (p<0.0001 and higher CIAS (p<0.0001 and BIS-11 (p = 0.01 scores than the controls. Compared with the control group, subjects with IGA exhibited increased functional connectivity in the bilateral cerebellum posterior lobe and middle temporal gyrus. The bilateral inferior parietal lobule and right inferior temporal gyrus exhibited decreased connectivity. Connectivity with the PCC was positively correlated with CIAS scores in the right precuneus, posterior cingulate gyrus, thalamus, caudate, nucleus accumbens, supplementary motor area, and lingual gyrus. It was negatively correlated with the right cerebellum anterior lobe and left superior parietal lobule.Our results suggest that adolescents with IGA exhibit different resting-state patterns of brain activity. As these alterations are partially consistent with those in patients with substance addiction, they support the

Altered functional connectivity differs in stroke survivors with impaired touch sensation following left and right hemisphere lesions

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Peter Goodin

Full Text Available One in two survivors experience impairment in touch sensation after stroke. The nature of this impairment is likely associated with changes associated with the functional somatosensory network of the brain; however few studies have examined this. In particular, the impact of lesioned hemisphere has not been investigated. We examined resting state functional connectivity in 28 stroke survivors, 14 with left hemisphere and 14 with right hemisphere lesion, and 14 healthy controls. Contra-lesional hands showed significantly decreased touch discrimination. Whole brain functional connectivity (FC data was extracted from four seed regions, i.e. primary (S1 and secondary (S2 somatosensory cortices in both hemispheres. Whole brain FC maps and Laterality Indices (LI were calculated for subgroups. Inter-hemispheric FC was greater in healthy controls compared to the combined stroke cohort from the left S1 seed and bilateral S2 seeds. The left lesion subgroup showed decreased FC, relative to controls, from left ipsi-lesional S1 to contra-lesional S1 and to distributed temporal, occipital and parietal regions. In comparison, the right lesion group showed decreased connectivity from contra-lesional left S1 and bilateral S2 to ipsi-lesional parietal operculum (S2, and to occipital and temporal regions. The right lesion group also showed increased intra-hemispheric FC from ipsi-lesional right S1 to inferior parietal regions compared to controls. In comparison to the left lesion group, those with right lesion showed greater intra-hemispheric connectivity from left S1 to left parietal and occipital regions and from right S1 to right angular and parietal regions. Laterality Indices were significantly greater for stroke subgroups relative to matched controls for contra-lesional S1 (left lesion group and contra-lesional S2 (both groups. We provide evidence of altered functional connectivity within the somatosensory network, across both hemispheres, and to other

Altered Insula Connectivity under MDMA.

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Walpola, Ishan C; Nest, Timothy; Roseman, Leor; Erritzoe, David; Feilding, Amanda; Nutt, David J; Carhart-Harris, Robin L

2017-10-01

Recent work with noninvasive human brain imaging has started to investigate the effects of 3,4-methylenedioxymethamphetamine (MDMA) on large-scale patterns of brain activity. MDMA, a potent monoamine-releaser with particularly pronounced serotonin- releasing properties, has unique subjective effects that include: marked positive mood, pleasant/unusual bodily sensations and pro-social, empathic feelings. However, the neurobiological basis for these effects is not properly understood, and the present analysis sought to address this knowledge gap. To do this, we administered MDMA-HCl (100 mg p.o.) and, separately, placebo (ascorbic acid) in a randomized, double-blind, repeated-measures design with twenty-five healthy volunteers undergoing fMRI scanning. We then employed a measure of global resting-state functional brain connectivity and follow-up seed-to-voxel analysis to the fMRI data we acquired. Results revealed decreased right insula/salience network functional connectivity under MDMA. Furthermore, these decreases in right insula/salience network connectivity correlated with baseline trait anxiety and acute experiences of altered bodily sensations under MDMA. The present findings highlight insular disintegration (ie, compromised salience network membership) as a neurobiological signature of the MDMA experience, and relate this brain effect to trait anxiety and acutely altered bodily sensations-both of which are known to be associated with insular functioning.

Altered frontal inter-hemispheric resting state functional connectivity is associated with bulimic symptoms among restrained eaters.

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Chen, Shuaiyu; Dong, Debo; Jackson, Todd; Su, Yanhua; Chen, Hong

2016-01-29

Theory and research have indicated that restrained eating (RE) increases risk for binge-eating and eating disorder symptoms. According to the goal conflict model, such risk may result from disrupted hedonic-feeding control and its interaction with reward-driven eating. However, RE-related alterations in functional interactions among associated underlying brain regions, especially between the cerebral hemispheres, have rarely been examined directly. Therefore, we investigated inter-hemispheric resting-state functional connectivity (RSFC) among female restrained eaters (REs) (n=23) and unrestrained eaters (UREs) (n=24) following food deprivation as well as its relation to overall bulimia nervosa (BN) symptoms using voxel-mirrored homotopic connectivity (VMHC). Seed-based RSFC associated with areas exhibiting significant VMHC differences was also assessed. Compared to UREs, REs showed reduced VMHC in the dorsal-lateral prefrontal cortex (DLPFC), an area involved in inhibiting hedonic overeating. REs also displayed decreased RSFC between the right DLPFC and regions associated with reward estimation--the ventromedial prefrontal cortex (VMPFC) and posterior cingulate cortex (PCC). Finally, bulimic tendencies had a negative correlation with VMHC in the DLPFC and a positive correlation with functional connectivity (DLPFC and VMPFC) among REs but not UREs. Findings suggested that reduced inter-hemispheric functional connectivity in appetite inhibition regions and altered functional connectivity in reward related regions may help to explain why some REs fail to control hedonically-motivated feeding and experience higher associated levels of BN symptomatology. Copyright © 2015 Elsevier Ltd. All rights reserved.

Convergent Findings of Altered Functional and Structural Brain Connectivity in Individuals with High Functioning Autism: A Multimodal MRI Study.

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Sophia Mueller

Full Text Available Brain tissue changes in autism spectrum disorders seem to be rather subtle and widespread than anatomically distinct. Therefore a multimodal, whole brain imaging technique appears to be an appropriate approach to investigate whether alterations in white and gray matter integrity relate to consistent changes in functional resting state connectivity in individuals with high functioning autism (HFA. We applied diffusion tensor imaging (DTI, voxel-based morphometry (VBM and resting state functional connectivity magnetic resonance imaging (fcMRI to assess differences in brain structure and function between 12 individuals with HFA (mean age 35.5, SD 11.4, 9 male and 12 healthy controls (mean age 33.3, SD 9.0, 8 male. Psychological measures of empathy and emotionality were obtained and correlated with the most significant DTI, VBM and fcMRI findings. We found three regions of convergent structural and functional differences between HFA participants and controls. The right temporo-parietal junction area and the left frontal lobe showed decreased fractional anisotropy (FA values along with decreased functional connectivity and a trend towards decreased gray matter volume. The bilateral superior temporal gyrus displayed significantly decreased functional connectivity that was accompanied by the strongest trend of gray matter volume decrease in the temporal lobe of HFA individuals. FA decrease in the right temporo-parietal region was correlated with psychological measurements of decreased emotionality. In conclusion, our results indicate common sites of structural and functional alterations in higher order association cortex areas and may therefore provide multimodal imaging support to the long-standing hypothesis of autism as a disorder of impaired higher-order multisensory integration.

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

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

2014-01-01

Patients with bilateral vestibular failure (BVF) suffer from gait unsteadiness, oscillopsia and impaired spatial orientation. Brain imaging studies applying caloric irrigation to patients with BVF have shown altered neural activity of cortical visual–vestibular interaction: decreased bilateral neural activity in the posterior insula and parietal operculum and decreased deactivations in the visual cortex. It is unknown how this affects functional connectivity in the resting brain and how chang...

Different alterations in brain functional networks according to direct and indirect topological connections in patients with schizophrenia.

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Park, Chang-Hyun; Lee, Seungyup; Kim, Taewon; Won, Wang Yeon; Lee, Kyoung-Uk

2017-10-01

Schizophrenia displays connectivity deficits in the brain, but the literature has shown inconsistent findings about alterations in global efficiency of brain functional networks. We supposed that such inconsistency at the whole brain level may be due to a mixture of different portions of global efficiency at sub-brain levels. Accordingly, we considered measuring portions of global efficiency in two aspects: spatial portions by considering sub-brain networks and topological portions by considering contributions to global efficiency according to direct and indirect topological connections. We proposed adjacency and indirect adjacency as new network parameters attributable to direct and indirect topological connections, respectively, and applied them to graph-theoretical analysis of brain functional networks constructed from resting state fMRI data of 22 patients with schizophrenia and 22 healthy controls. Group differences in the network parameters were observed not for whole brain and hemispheric networks, but for regional networks. Alterations in adjacency and indirect adjacency were in opposite directions, such that adjacency increased, but indirect adjacency decreased in patients with schizophrenia. Furthermore, over connections in frontal and parietal regions, increased adjacency was associated with more severe negative symptoms, while decreased adjacency was associated with more severe positive symptoms of schizophrenia. This finding indicates that connectivity deficits associated with positive and negative symptoms of schizophrenia may involve topologically different paths in the brain. In patients with schizophrenia, although changes in global efficiency may not be clearly shown, different alterations in brain functional networks according to direct and indirect topological connections could be revealed at the regional level. Copyright © 2017 Elsevier B.V. All rights reserved.

Altered functional connectivity differs in stroke survivors with impaired touch sensation following left and right hemisphere lesions.

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Goodin, Peter; Lamp, Gemma; Vidyasagar, Rishma; McArdle, David; Seitz, Rüdiger J; Carey, Leeanne M

2018-01-01

One in two survivors experience impairment in touch sensation after stroke. The nature of this impairment is likely associated with changes associated with the functional somatosensory network of the brain; however few studies have examined this. In particular, the impact of lesioned hemisphere has not been investigated. We examined resting state functional connectivity in 28 stroke survivors, 14 with left hemisphere and 14 with right hemisphere lesion, and 14 healthy controls. Contra-lesional hands showed significantly decreased touch discrimination. Whole brain functional connectivity (FC) data was extracted from four seed regions, i.e. primary (S1) and secondary (S2) somatosensory cortices in both hemispheres. Whole brain FC maps and Laterality Indices (LI) were calculated for subgroups. Inter-hemispheric FC was greater in healthy controls compared to the combined stroke cohort from the left S1 seed and bilateral S2 seeds. The left lesion subgroup showed decreased FC, relative to controls, from left ipsi-lesional S1 to contra-lesional S1 and to distributed temporal, occipital and parietal regions. In comparison, the right lesion group showed decreased connectivity from contra-lesional left S1 and bilateral S2 to ipsi-lesional parietal operculum (S2), and to occipital and temporal regions. The right lesion group also showed increased intra-hemispheric FC from ipsi-lesional right S1 to inferior parietal regions compared to controls. In comparison to the left lesion group, those with right lesion showed greater intra-hemispheric connectivity from left S1 to left parietal and occipital regions and from right S1 to right angular and parietal regions. Laterality Indices were significantly greater for stroke subgroups relative to matched controls for contra-lesional S1 (left lesion group) and contra-lesional S2 (both groups). We provide evidence of altered functional connectivity within the somatosensory network, across both hemispheres, and to other networks in stroke

Altered Brain Functional Connectivity in Betel Quid-Dependent Chewers

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Xiaojun Huang

2017-11-01

Full Text Available BackgroundBetel quid (BQ is a common psychoactive substance worldwide with particularly high usage in many Asian countries. This study aimed to explore the effect of BQ use on functional connectivity by comparing global functional brain networks and their subset between BQ chewers and healthy controls (HCs.MethodsResting-state functional magnetic resonance imaging (fMRI was obtained from 24 betel quid-dependent (BQD male chewers and 27 healthy male individuals on a 3.0T scanner. We used independent component analysis (ICA to determine components that represent the brain’s functional networks and their spatial aspects of functional connectivity. Two sample t-tests were used to identify the functional connectivity differences in each network between these two groups.ResultsSeventeen networks were identified by ICA. Nine of them showed connectivity differences between BQD and HCs (two sample t-tests, p < 0.001 uncorrected. We found increased functional connectivity in the orbitofrontal, bilateral frontoparietal, frontotemporal, occipital/parietal, frontotemporal/cerebellum, and temporal/limbic networks, and decreased connectivity in the parietal and medial frontal/anterior cingulate networks in the BQD compared to the HCs. The betel quid dependence scale scores were positively related to the increased functional connectivity in the orbitofrontal (r = 0.39, p = 0.03 while negatively related to the decreased functional connectivity in medial frontal/anterior cingulate networks (r = −0.35, p = 0.02.DiscussionOur findings provide further evidence that BQ chewing may lead to brain functional connectivity changes, which may play a key role in the psychological and physiological effects of BQ.

Altered Brain Functional Connectivity in Betel Quid-Dependent Chewers.

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Huang, Xiaojun; Pu, Weidan; Liu, Haihong; Li, Xinmin; Greenshaw, Andrew J; Dursun, Serdar M; Xue, Zhimin; Liu, Zhening

2017-01-01

Betel quid (BQ) is a common psychoactive substance worldwide with particularly high usage in many Asian countries. This study aimed to explore the effect of BQ use on functional connectivity by comparing global functional brain networks and their subset between BQ chewers and healthy controls (HCs). Resting-state functional magnetic resonance imaging (fMRI) was obtained from 24 betel quid-dependent (BQD) male chewers and 27 healthy male individuals on a 3.0T scanner. We used independent component analysis (ICA) to determine components that represent the brain's functional networks and their spatial aspects of functional connectivity. Two sample t -tests were used to identify the functional connectivity differences in each network between these two groups. Seventeen networks were identified by ICA. Nine of them showed connectivity differences between BQD and HCs (two sample t -tests, p  betel quid dependence scale scores were positively related to the increased functional connectivity in the orbitofrontal ( r  = 0.39, p  = 0.03) while negatively related to the decreased functional connectivity in medial frontal/anterior cingulate networks ( r  = -0.35, p  = 0.02). Our findings provide further evidence that BQ chewing may lead to brain functional connectivity changes, which may play a key role in the psychological and physiological effects of BQ.

Altered functional connectivity within the central reward network in overweight and obese women

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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, ingestive behaviors. PMID:25599560

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

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

2017-12-01

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

Altered Long- and Short-Range Functional Connectivity in Patients with Betel Quid Dependence: A Resting-State Functional MRI Study

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Tao Liu

2016-12-01

Full Text Available Objective: Addiction is a chronic relapsing brain disease. Brain structural abnormalities may constitute an abnormal neural network that underlies the risk of drug dependence. We hypothesized that individuals with Betel Quid Dependence (BQD have functional connectivity alterations that can be described by long- and short-range functional connectivity density(FCD maps. Methods: We tested this hypothesis using functional magnetic resonance imaging (fMRI data from subjects of the Han ethnic group in Hainan, China. Here, we examined BQD individuals (n = 33 and age-, sex-, and education-matched healthy controls (HCs (n = 32 in a rs-fMRI study to observe FCD alterations associated with the severity of BQD. Results: Compared with HCs, long-range FCD was decreased in the right anterior cingulate cortex (ACC and increased in the left cerebellum posterior lobe (CPL and bilateral inferior parietal lobule (IPL in the BQD group. Short-range FCD was reduced in the right ACC and left dorsolateral prefrontal cortex (dlPFC, and increased in the left CPL. The short-range FCD alteration in the right ACC displayed a negative correlation with the Betel Quid Dependence Scale (BQDS (r=-0.432, P=0.012, and the long-range FCD alteration of left IPL showed a positive correlation with the duration of BQD(r=0.519, P=0.002 in BQD individuals. Conclusions: fMRI revealed differences in long- and short- range FCD in BQD individuals, and these alterations might be due to BQ chewing, BQ dependency, or risk factors for developing BQD.

Altered default network resting-state functional connectivity in adolescents with Internet gaming addiction.

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Ding, Wei-na; Sun, Jin-hua; Sun, Ya-wen; Zhou, Yan; Li, Lei; Xu, Jian-rong; Du, Ya-song

2013-01-01

Excessive use of the Internet has been linked to a variety of negative psychosocial consequences. This study used resting-state functional magnetic resonance imaging (fMRI) to investigate whether functional connectivity is altered in adolescents with Internet gaming addiction (IGA). Seventeen adolescents with IGA and 24 normal control adolescents underwent a 7.3 minute resting-state fMRI scan. Posterior cingulate cortex (PCC) connectivity was determined in all subjects by investigating synchronized low-frequency fMRI signal fluctuations using a temporal correlation method. To assess the relationship between IGA symptom severity and PCC connectivity, contrast images representing areas correlated with PCC connectivity were correlated with the scores of the 17 subjects with IGA on the Chen Internet Addiction Scale (CIAS) and Barratt Impulsiveness Scale-11 (BIS-11) and their hours of Internet use per week. There were no significant differences in the distributions of the age, gender, and years of education between the two groups. The subjects with IGA showed longer Internet use per week (hours) (paddiction, they support the hypothesis that IGA as a behavioral addiction that may share similar neurobiological abnormalities with other addictive disorders.

Altered brain connectivity in sagittal craniosynostosis.

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Beckett, Joel S; Brooks, Eric D; Lacadie, Cheryl; Vander Wyk, Brent; Jou, Roger J; Steinbacher, Derek M; Constable, R Todd; Pelphrey, Kevin A; Persing, John A

2014-06-01

Sagittal nonsyndromic craniosynostosis (sNSC) is the most common form of NSC. The condition is associated with a high prevalence (> 50%) of deficits in executive function. The authors employed diffusion tensor imaging (DTI) and functional MRI to evaluate whether hypothesized structural and functional connectivity differences underlie the observed neurocognitive morbidity of sNSC. Using a 3-T Siemens Trio MRI system, the authors collected DTI and resting-state functional connectivity MRI data in 8 adolescent patients (mean age 12.3 years) with sNSC that had been previously corrected via total vault cranioplasty and 8 control children (mean age 12.3 years) without craniosynostosis. Data were analyzed using the FMRIB Software Library and BioImageSuite. Analyses of the DTI data revealed white matter alterations approaching statistical significance in all supratentorial lobes. Statistically significant group differences (sNSC right supramarginal gyrus. Analysis of the resting-state seed in relation to whole-brain data revealed significant increases in negative connectivity (anticorrelations) of Brodmann area 8 to the prefrontal cortex (Montreal Neurological Institute [MNI] center of mass coordinates [x, y, z]: -6, 53, 6) and anterior cingulate cortex (MNI coordinates 6, 43, 14) in the sNSC group relative to controls. Furthermore, in the sNSC patients versus controls, the Brodmann area 7, 39, and 40 seed had decreased connectivity to left angular gyrus (MNI coordinates -31, -61, 34), posterior cingulate cortex (MNI coordinates 13, -52, 18), precuneus (MNI coordinates 10, -55, 54), left and right parahippocampus (MNI coordinates -13, -52, 2 and MNI coordinates 11, -50, 2, respectively), lingual (MNI coordinates -11, -86, -10), and fusiform gyri (MNI coordinates -30, -79, -18). Intrinsic connectivity analysis also revealed altered connectivity between central nodes in the default mode network in sNSC relative to controls; the left and right posterior cingulate cortices

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

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Wang, Junkai; Fan, Yunli; 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

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. 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. 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. These findings suggest that chronic alcohol dependence could cause a complex neural changes linked to abnormal impulsivity.

Altered Coupling Between Resting-State Cerebral Blood Flow and Functional Connectivity in Schizophrenia.

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

2017-10-21

Respective changes in resting-state cerebral blood flow (CBF) and functional connectivity in schizophrenia have been reported. However, their coupling alterations in schizophrenia remain largely unknown. 89 schizophrenia patients and 90 sex- and age-matched healthy controls underwent resting-state functional MRI to calculate functional connectivity strength (FCS) and arterial spin labeling imaging to compute CBF. The CBF-FCS coupling of the whole gray matter and the CBF/FCS ratio (the amount of blood supply per unit of connectivity strength) of each voxel were compared between the 2 groups. Whole gray matter CBF-FCS coupling was decreased in schizophrenia patients relative to healthy controls. In schizophrenia patients, the decreased CBF/FCS ratio was predominantly located in cognitive- and emotional-related brain regions, including the dorsolateral prefrontal cortex, insula, hippocampus and thalamus, whereas an increased CBF/FCS ratio was mainly identified in the sensorimotor regions, including the putamen, and sensorimotor, mid-cingulate and visual cortices. These findings suggest that the neurovascular decoupling in the brain may be a possible neuropathological mechanism of schizophrenia. © The Author 2017. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com

Altered cerebro-cerebellum resting-state functional connectivity in HIV-infected male patients.

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Wang, Huijuan; Li, Ruili; Zhou, Yawen; Wang, Yanming; Cui, Jin; Nguchu, Benedictor Alexander; Qiu, Bensheng; Wang, Xiaoxiao; Li, Hongjun

2018-05-21

In addition to the role of planning and executing movement, the cerebellum greatly contributes to cognitive process. Numerous studies have reported structural and functional abnormalities in the cerebellum for HIV-infected patients, but little is known about the altered functional connectivity of particular cerebellar subregions and the cerebrum. Therefore, this study aimed to explore the resting-state functional connectivity (rsFC) changes of the cerebellum and further analyze the relationship between the rsFC changes and the neuropsychological evaluation. The experiment involved 26 HIV-infected men with asymptomatic neurocognitive impairment (ANI) and 28 healthy controls (HC). We selected bilateral hemispheric lobule VI and lobule IX as seed regions and mapped the whole-brain rsFC for each subregion. Results revealed that right lobule VI showed significant increased rsFC with the anterior cingulate cortex (ACC) in HIV-infected subjects. In addition, the correlation analysis on HIV-infected subjects illustrated the increased rsFC was negatively correlated with the attention/working memory score. Moreover, significantly increased cerebellar rsFCs were also observed in HIV-infected patients related to right inferior frontal gyrus (IFG) and right superior medial gyrus (SMG) while decreased rsFC was just found between right lobule VI and the left hippocampus (HIP). These findings suggested that, abnormalities of cerebro-cerebellar functional connectivity might be associated with cognitive dysfunction in HIV-infected men, particularly working memory impairment. It could also be the underlying mechanism of ANI, providing further evidence for early injury in the neural substrate of HIV-infected patients.

Connectivity and functional profiling of abnormal brain structures in pedophilia.

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

2015-06-01

Despite its 0.5-1% lifetime prevalence in men and its general societal relevance, neuroimaging investigations in pedophilia are scarce. Preliminary findings indicate abnormal brain structure and function. However, no study has yet linked structural alterations in pedophiles to both connectional and functional properties of the aberrant hotspots. The relationship between morphological alterations and brain function in pedophilia as well as their contribution to its psychopathology thus remain unclear. First, we assessed bimodal connectivity of structurally altered candidate regions using meta-analytic connectivity modeling (MACM) and resting-state correlations employing openly accessible data. We compared the ensuing connectivity maps to the activation likelihood estimation (ALE) maps of a recent quantitative meta-analysis of brain activity during processing of sexual stimuli. Second, we functionally characterized the structurally altered regions employing meta-data of a large-scale neuroimaging database. Candidate regions were functionally connected to key areas for processing of sexual stimuli. Moreover, we found that the functional role of structurally altered brain regions in pedophilia relates to nonsexual emotional as well as neurocognitive and executive functions, previously reported to be impaired in pedophiles. Our results suggest that structural brain alterations affect neural networks for sexual processing by way of disrupted functional connectivity, which may entail abnormal sexual arousal patterns. The findings moreover indicate that structural alterations account for common affective and neurocognitive impairments in pedophilia. The present multimodal integration of brain structure and function analyses links sexual and nonsexual psychopathology in pedophilia. © 2015 Wiley Periodicals, Inc.

Thermal Stimulation Alters Cervical Spinal Cord Functional Connectivity in Humans.

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Weber, Kenneth A; Sentis, Amy I; Bernadel-Huey, Olivia N; Chen, Yufen; Wang, Xue; Parrish, Todd B; Mackey, Sean

2018-01-15

The spinal cord has an active role in the modulation and transmission of the neural signals traveling between the body and the brain. Recent advancements in functional magnetic resonance imaging (fMRI) have made the in vivo examination of spinal cord function in humans now possible. This technology has been recently extended to the investigation of resting state functional networks in the spinal cord, leading to the identification of distinct patterns of spinal cord functional connectivity. In this study, we expand on the previous work and further investigate resting state cervical spinal cord functional connectivity in healthy participants (n = 15) using high resolution imaging coupled with both seed-based functional connectivity analyses and graph theory-based metrics. Within spinal cord segment functional connectivity was present between the left and right ventral horns (bilateral motor network), left and right dorsal horns (bilateral sensory network), and the ipsilateral ventral and dorsal horns (unilateral sensory-motor network). Functional connectivity between the spinal cord segments was less apparent with the connectivity centered at the region of interest and spanning spinal cord functional network was demonstrated to be state-dependent as thermal stimulation of the right ventrolateral forearm resulted in significant disruption of the bilateral sensory network, increased network global efficiency, and decreased network modularity. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

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

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

2017-07-01

Individuals with comorbid posttraumatic stress disorder and major depressive disorder (PTSD-MDD) often exhibit greater functional impairment and poorer treatment response than individuals with PTSD alone. Research has not determined whether PTSD-MDD is associated with different network connectivity abnormalities than PTSD alone. We used functional magnetic resonance imaging (fMRI) to measure resting state functional connectivity (rs-FC) patterns of brain regions involved in fear and reward processing in three groups: patients with PTSD-alone (n = 27), PTSD-MDD (n = 21), and trauma-exposed healthy controls (TEHCs, n = 34). Based on previous research, seeds included basolateral amygdala (BLA), centromedial amygdala (CMA), and nucleus accumbens (NAcc). Regardless of MDD comorbidity, PTSD was associated with decreased connectivity of BLA-orbitalfrontal cortex (OFC) and CMA-thalamus pathways, key to fear processing, and fear expression, respectively. PTSD-MDD, compared to PTSD-alone and TEHC, was associated with decreased connectivity across multiple amygdala and striatal-subcortical pathways: BLA-OFC, NAcc-thalamus, and NAcc-hippocampus. Further, while both the BLA-OFC and the NAcc-thalamus pathways were correlated with MDD symptoms, PTSD symptoms correlated with the amygdala pathways (BLA-OFC; CMA-thalamus) only. Comorbid PTSD-MDD may be associated with multifaceted functional connectivity alterations in both fear and reward systems. Clinical implications are discussed. © 2016 Wiley Periodicals, Inc.

Increased cortical thickness and altered functional connectivity of the right superior temporal gyrus in left-handers.

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Li, Meiling; Chen, Heng; Wang, Junping; Liu, Feng; Wang, Yifeng; Lu, Fengmei; Yu, Chunshui; Chen, Huafu

2015-01-01

Altered structure in the temporal cortex has been implicated in the variable language laterality of left-handers (LH). The neuroanatomy of language lateralization and the corresponding synchronous functional connectivity (FC) in handedness cohorts are not, however, fully understood. We used structural and resting-state functional magnetic resonance imaging (fMRI) data to investigate the effect of altered cortical thickness on FC in LH and right-handers (RH). Whole-brain cortical thickness was calculated and compared between the LH and RH. We observed increased cortical thickness in the right superior temporal gyrus (STG) in the LH. A further FC analysis was conducted between the right STG and the remaining voxels in the brain. Compared with RH, the LH showed significantly higher FC in the left STG, right occipital cortex, and lower FC in the left inferior frontal gyrus and supramarginal gyrus. Our findings suggest that LH have atypical connectivity in the language network, with an enhanced role of the STG, findings which provide novel insights into the structural and functional substrates underlying the atypical language development of left-handed individuals. Copyright © 2014 Elsevier Ltd. All rights reserved.

Altered intrinsic functional connectivity in the latent period of epileptogenesis in a temporal lobe epilepsy model.

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Lee, Hyoin; Jung, Seungmoon; Lee, Peter; Jeong, Yong

2017-10-01

The latent period, a seizure-free phase, is the duration between brain injury and the onset of spontaneous recurrent seizures (SRSs) during epileptogenesis. The latent period is thought to involve several progressive pathophysiological events that lead to the evolution of the chronic epilepsy phase. Hence, it is vital to investigate the changes in the latent period during epileptogenesis in order to better understand temporal lobe epilepsy (TLE), and to achieve early diagnosis and appropriate management of the condition. Accordingly, recent studies with patients with TLE using resting-state functional magnetic resonance imaging (rs-fMRI) have reported that alterations of resting-state functional connectivity (rsFC) during the chronic period are associated with some clinical manifestations, including learning and memory impairments, emotional instability, and social behavior deficits, in addition to repetitive seizure episodes. In contrast, the changes in the intrinsic rsFC during epileptogenesis, particularly during the latent period, remain unclear. In this study, we investigated the alterations in intrinsic rsFC during the latent and chronic periods in a pilocarpine-induced TLE mouse model using intrinsic optical signal imaging (IOSI). This technique can monitor the changes in the local hemoglobin concentration according to neuronal activity and can help investigate large-scale brain intrinsic networks. After seeding on the anatomical regions of interest (ROIs) and calculating the correlation coefficients between each ROI, we established and compared functional correlation matrices and functional connectivity maps during the latent and chronic periods of epilepsy. We found a decrease in the interhemispheric rsFC at the frontal and temporal regions during both the latent and chronic periods. Furthermore, a significant decrease in the interhemispheric rsFC was observed in the somatosensory area during the chronic period. Changes in network configurations during

Altered cerebellar functional connectivity with intrinsic connectivity networks in adults with major depressive disorder.

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Li Liu

Full Text Available BACKGROUND: Numerous studies have demonstrated the higher-order functions of the cerebellum, including emotion regulation and cognitive processing, and have indicated that the cerebellum should therefore be included in the pathophysiological models of major depressive disorder. The aim of this study was to compare the resting-state functional connectivity of the cerebellum in adults with major depression and healthy controls. METHODS: Twenty adults with major depression and 20 gender-, age-, and education-matched controls were investigated using seed-based resting-state functional connectivity magnetic resonance imaging. RESULTS: Compared with the controls, depressed patients showed significantly increased functional connectivity between the cerebellum and the temporal poles. However, significantly reduced cerebellar functional connectivity was observed in the patient group in relation to both the default-mode network, mainly including the ventromedial prefrontal cortex and the posterior cingulate cortex/precuneus, and the executive control network, mainly including the superior frontal cortex and orbitofrontal cortex. Moreover, the Hamilton Depression Rating Scale score was negatively correlated with the functional connectivity between the bilateral Lobule VIIb and the right superior frontal gyrus in depressed patients. CONCLUSIONS: This study demonstrated increased cerebellar coupling with the temporal poles and reduced coupling with the regions in the default-mode and executive control networks in adults with major depression. These differences between patients and controls could be associated with the emotional disturbances and cognitive control function deficits that accompany major depression. Aberrant cerebellar connectivity during major depression may also imply a substantial role for the cerebellum in the pathophysiological models of depression.

Altered dynamic functional connectivity in the default mode network in patients with cirrhosis and minimal hepatic encephalopathy

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Chen, Hua-Jun; Lin, Hai-Long; Chen, Qiu-Feng; Liu, Peng-Fei

2017-01-01

Abnormal brain intrinsic functional connectivity (FC) has been documented in minimal hepatic encephalopathy (MHE) by static connectivity analysis. However, changes in dynamic FC (dFC) remain unknown. We aimed to identify altered dFC within the default mode network (DMN) associated with MHE. Resting-state functional MRI data were acquired from 20 cirrhotic patients with MHE and 24 healthy controls. DMN seed regions were defined using seed-based FC analysis (centered on the posterior cingulate cortex (PCC)). Dynamic FC architecture was calculated using a sliding time-window method. K-means clustering (number of clusters = 2-4) was applied to estimate FC states. When the number of clusters was 2, MHE patients presented weaker connectivity strengths compared with controls in states 1 and 2. In state 1, decreased FC strength was found between the PCC/precuneus (PCUN) and right medial temporal lobe (MTL)/bilateral lateral temporal cortex (LTC); left inferior parietal lobule (IPL) and right MTL/left LTC; right IPL and right MTL/bilateral LTC; right MTL and right LTC; and medial prefrontal cortex (MPFC) and right MTL/bilateral LTC. In state 2, reduced FC strength was observed between the PCC/PCUN and bilateral MTL/bilateral LTC; left IPL and left MTL/bilateral LTC/MPFC; and left LTC and right LTC. Altered connectivities from state 1 were correlated with patient cognitive performance. Similar findings were observed when the number of clusters was set to 3 or 4. Aberrant dynamic DMN connectivity is an additional characteristic of MHE. Dynamic connectivity analysis offers a novel paradigm for understanding MHE-related mechanisms. (orig.)

Altered dynamic functional connectivity in the default mode network in patients with cirrhosis and minimal hepatic encephalopathy

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Chen, Hua-Jun; Lin, Hai-Long [Fujian Medical University Union Hospital, Department of Radiology, Fuzhou (China); Chen, Qiu-Feng; Liu, Peng-Fei [Central South University, School of Information Science and Engineering, Changsha (China)

2017-09-15

Abnormal brain intrinsic functional connectivity (FC) has been documented in minimal hepatic encephalopathy (MHE) by static connectivity analysis. However, changes in dynamic FC (dFC) remain unknown. We aimed to identify altered dFC within the default mode network (DMN) associated with MHE. Resting-state functional MRI data were acquired from 20 cirrhotic patients with MHE and 24 healthy controls. DMN seed regions were defined using seed-based FC analysis (centered on the posterior cingulate cortex (PCC)). Dynamic FC architecture was calculated using a sliding time-window method. K-means clustering (number of clusters = 2-4) was applied to estimate FC states. When the number of clusters was 2, MHE patients presented weaker connectivity strengths compared with controls in states 1 and 2. In state 1, decreased FC strength was found between the PCC/precuneus (PCUN) and right medial temporal lobe (MTL)/bilateral lateral temporal cortex (LTC); left inferior parietal lobule (IPL) and right MTL/left LTC; right IPL and right MTL/bilateral LTC; right MTL and right LTC; and medial prefrontal cortex (MPFC) and right MTL/bilateral LTC. In state 2, reduced FC strength was observed between the PCC/PCUN and bilateral MTL/bilateral LTC; left IPL and left MTL/bilateral LTC/MPFC; and left LTC and right LTC. Altered connectivities from state 1 were correlated with patient cognitive performance. Similar findings were observed when the number of clusters was set to 3 or 4. Aberrant dynamic DMN connectivity is an additional characteristic of MHE. Dynamic connectivity analysis offers a novel paradigm for understanding MHE-related mechanisms. (orig.)

Altered Functional Connectivity of Insular Subregions in Alzheimer’s Disease

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Xingyun Liu

2018-04-01

Full Text Available Recent researches have demonstrated that the insula is the crucial hub of the human brain networks and most vulnerable region of Alzheimer’s disease (AD. However, little is known about the changes of functional connectivity of insular subregions in the AD patients. In this study, we collected resting-state functional magnetic resonance imaging (fMRI data including 32 AD patients and 38 healthy controls (HCs. By defining three subregions of insula, we mapped whole-brain resting-state functional connectivity (RSFC and identified several distinct RSFC patterns of the insular subregions: For positive connectivity, three cognitive-related RSFC patterns were identified within insula that suggest anterior-to-posterior functional subdivisions: (1 an dorsal anterior zone of the insula that exhibits RSFC with executive control network (ECN; (2 a ventral anterior zone of insula, exhibits functional connectivity with the salience network (SN; (3 a posterior zone along the insula exhibits functional connectivity with the sensorimotor network (SMN. In addition, we found significant negative connectivities between the each insular subregion and several special default mode network (DMN regions. Compared with controls, the AD patients demonstrated distinct disruption of positive RSFCs in the different network (ECN and SMN, suggesting the impairment of the functional integrity. There were no differences of the positive RSFCs in the SN between the two groups. On the other hand, several DMN regions showed increased negative RSFCs to the sub-region of insula in the AD patients, indicating compensatory plasticity. Furthermore, these abnormal insular subregions RSFCs are closely correlated with cognitive performances in the AD patients. Our findings suggested that different insular subregions presented distinct RSFC patterns with various functional networks, which are differently affected in the AD patients.

Bilingualism alters brain functional connectivity between "control" regions and "language" regions: Evidence from bimodal bilinguals.

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Li, Le; Abutalebi, Jubin; Zou, Lijuan; Yan, Xin; Liu, Lanfang; Feng, Xiaoxia; Wang, Ruiming; Guo, Taomei; Ding, Guosheng

2015-05-01

Previous neuroimaging studies have revealed that bilingualism induces both structural and functional neuroplasticity in the dorsal anterior cingulate cortex (dACC) and the left caudate nucleus (LCN), both of which are associated with cognitive control. Since these "control" regions should work together with other language regions during language processing, we hypothesized that bilingualism may also alter the functional interaction between the dACC/LCN and language regions. Here we tested this hypothesis by exploring the functional connectivity (FC) in bimodal bilinguals and monolinguals using functional MRI when they either performed a picture naming task with spoken language or were in resting state. We found that for bimodal bilinguals who use spoken and sign languages, the FC of the dACC with regions involved in spoken language (e.g. the left superior temporal gyrus) was stronger in performing the task, but weaker in the resting state as compared to monolinguals. For the LCN, its intrinsic FC with sign language regions including the left inferior temporo-occipital part and right inferior and superior parietal lobules was increased in the bilinguals. These results demonstrate that bilingual experience may alter the brain functional interaction between "control" regions and "language" regions. For different control regions, the FC alters in different ways. The findings also deepen our understanding of the functional roles of the dACC and LCN in language processing. Copyright © 2015 Elsevier Ltd. All rights reserved.

Differential Functional Connectivity Alterations of Two Subdivisions within the Right dlPFC in Parkinson's Disease

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Julian Caspers

2017-05-01

Full Text Available Patients suffering from Parkinson's disease (PD often show impairments in executive function (EF like decision-making and action control. The right dorsolateral prefrontal cortex (dlPFC has been strongly implicated in EF in healthy subjects and has repeatedly been reported to show alterations related to EF impairment in PD. Recently, two key regions for cognitive action control have been identified within the right dlPFC by co-activation based parcellation. While the posterior region is engaged in rather basal EF like stimulus integration and working memory, the anterior region has a more abstract, supervisory function. To investigate whether these functionally distinct subdivisions of right dlPFC are differentially affected in PD, we analyzed resting-state functional connectivity (FC in 39 PD patients and 44 age- and gender-matched healthy controls. Patients were examined both after at least 12 h withdrawal of dopaminergic drugs (OFF and under their regular dopaminergic medication (ON. We found that only the posterior right dlPFC subdivision shows FC alterations in PD, while the anterior part remains unaffected. PD-related decreased FC with posterior right dlPFC was found in the bilateral medial posterior parietal cortex (mPPC and left dorsal premotor region (PMd in the OFF state. In the medical ON, FC with left PMd normalized, while decoupling with bilateral mPPC remained. Furthermore, we observed increased FC between posterior right dlPFC and the bilateral dorsomedial prefrontal cortex (dmPFC in PD in the ON state. Our findings point to differential disturbances of right dlPFC connectivity in PD, which relate to its hierarchical organization of EF processing by stronger affecting the functionally basal posterior aspect than the hierarchically higher anterior part.

Functional Connectivity Bias in the Prefrontal Cortex of Psychopaths.

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Contreras-Rodríguez, Oren; Pujol, Jesus; Batalla, Iolanda; Harrison, Ben J; Soriano-Mas, Carles; Deus, Joan; López-Solà, Marina; Macià, Dídac; Pera, Vanessa; Hernández-Ribas, Rosa; Pifarré, Josep; Menchón, José M; Cardoner, Narcís

2015-11-01

Psychopathy is characterized by a distinctive interpersonal style that combines callous-unemotional traits with inflexible and antisocial behavior. Traditional emotion-based perspectives link emotional impairment mostly to alterations in amygdala-ventromedial frontal circuits. However, these models alone cannot explain why individuals with psychopathy can regularly benefit from emotional information when placed on their focus of attention and why they are more resistant to interference from nonaffective contextual cues. The present study aimed to identify abnormal or distinctive functional links between and within emotional and cognitive brain systems in the psychopathic brain to characterize further the neural bases of psychopathy. High-resolution anatomic magnetic resonance imaging with a functional sequence acquired in the resting state was used to assess 22 subjects with psychopathy and 22 control subjects. Anatomic and functional connectivity alterations were investigated first using a whole-brain analysis. Brain regions showing overlapping anatomic and functional changes were examined further using seed-based functional connectivity mapping. Subjects with psychopathy showed gray matter reduction involving prefrontal cortex, paralimbic, and limbic structures. Anatomic changes overlapped with areas showing increased degree of functional connectivity at the medial-dorsal frontal cortex. Subsequent functional seed-based connectivity mapping revealed a pattern of reduced functional connectivity of prefrontal areas with limbic-paralimbic structures and enhanced connectivity within the dorsal frontal lobe in subjects with psychopathy. Our results suggest that a weakened link between emotional and cognitive domains in the psychopathic brain may combine with enhanced functional connections within frontal executive areas. The identified functional alterations are discussed in the context of potential contributors to the inflexible behavior displayed by individuals with

Altered intrinsic and extrinsic connectivity in schizophrenia.

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Zhou, Yuan; Zeidman, Peter; Wu, Shihao; Razi, Adeel; Chen, Cheng; Yang, Liuqing; Zou, Jilin; Wang, Gaohua; Wang, Huiling; Friston, Karl J

2018-01-01

Schizophrenia is a disorder characterized by functional dysconnectivity among distributed brain regions. However, it is unclear how causal influences among large-scale brain networks are disrupted in schizophrenia. In this study, we used dynamic causal modeling (DCM) to assess the hypothesis that there is aberrant directed (effective) connectivity within and between three key large-scale brain networks (the dorsal attention network, the salience network and the default mode network) in schizophrenia during a working memory task. Functional MRI data during an n-back task from 40 patients with schizophrenia and 62 healthy controls were analyzed. Using hierarchical modeling of between-subject effects in DCM with Parametric Empirical Bayes, we found that intrinsic (within-region) and extrinsic (between-region) effective connectivity involving prefrontal regions were abnormal in schizophrenia. Specifically, in patients (i) inhibitory self-connections in prefrontal regions of the dorsal attention network were decreased across task conditions; (ii) extrinsic connectivity between regions of the default mode network was increased; specifically, from posterior cingulate cortex to the medial prefrontal cortex; (iii) between-network extrinsic connections involving the prefrontal cortex were altered; (iv) connections within networks and between networks were correlated with the severity of clinical symptoms and impaired cognition beyond working memory. In short, this study revealed the predominance of reduced synaptic efficacy of prefrontal efferents and afferents in the pathophysiology of schizophrenia.

Altered network hub connectivity after acute LSD administration

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Felix Müller

Full Text Available LSD is an ambiguous substance, said to mimic psychosis and to improve mental health in people suffering from anxiety and depression. Little is known about the neuronal correlates of altered states of consciousness induced by this substance. Limited previous studies indicated profound changes in functional connectivity of resting state networks after the administration of LSD. The current investigation attempts to replicate and extend those findings in an independent sample. In a double-blind, randomized, cross-over study, 100 μg LSD and placebo were orally administered to 20 healthy participants. Resting state brain activity was assessed by functional magnetic resonance imaging. Within-network and between-network connectivity measures of ten established resting state networks were compared between drug conditions. Complementary analysis were conducted using resting state networks as sources in seed-to-voxel analyses. Acute LSD administration significantly decreased functional connectivity within visual, sensorimotor and auditory networks and the default mode network. While between-network connectivity was widely increased and all investigated networks were affected to some extent, seed-to-voxel analyses consistently indicated increased connectivity between networks and subcortical (thalamus, striatum and cortical (precuneus, anterior cingulate cortex hub structures. These latter observations are consistent with findings on the importance of hubs in psychopathological states, especially in psychosis, and could underlay therapeutic effects of hallucinogens as proposed by a recent model. Keywords: LSD, fMRI, Functional connectivity, Networks, Hubs

A whole-brain computational modeling approach to explain the alterations in resting-state functional connectivity during progression of Alzheimer's disease

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Murat Demirtaş

2017-01-01

Full Text Available Alzheimer's disease (AD is the most common dementia with dramatic consequences. The research in structural and functional neuroimaging showed altered brain connectivity in AD. In this study, we investigated the whole-brain resting state functional connectivity (FC of the subjects with preclinical Alzheimer's disease (PAD, mild cognitive impairment due to AD (MCI and mild dementia due to Alzheimer's disease (AD, the impact of APOE4 carriership, as well as in relation to variations in core AD CSF biomarkers. The synchronization in the whole-brain was monotonously decreasing during the course of the disease progression. Furthermore, in AD patients we found widespread significant decreases in functional connectivity (FC strengths particularly in the brain regions with high global connectivity. We employed a whole-brain computational modeling approach to study the mechanisms underlying these alterations. To characterize the causal interactions between brain regions, we estimated the effective connectivity (EC in the model. We found that the significant EC differences in AD were primarily located in left temporal lobe. Then, we systematically manipulated the underlying dynamics of the model to investigate simulated changes in FC based on the healthy control subjects. Furthermore, we found distinct patterns involving CSF biomarkers of amyloid-beta (Aβ1−42 total tau (t-tau and phosphorylated tau (p-tau. CSF Aβ1−42 was associated to the contrast between healthy control subjects and clinical groups. Nevertheless, tau CSF biomarkers were associated to the variability in whole-brain synchronization and sensory integration regions. These associations were robust across clinical groups, unlike the associations that were found for CSF Aβ1−42. APOE4 carriership showed no significant correlations with the connectivity measures.

Aberrant patterns of local and long-range functional connectivity densities in schizophrenia.

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Liu, Chuanxin; Zhang, Wei; Chen, Guangdong; Tian, Hongjun; Li, Jie; Qu, Hongru; Cheng, Langlang; Zhu, Jingjing; Zhuo, Chuanjun

2017-07-18

Schizophrenia is a disorder of brain dysconnectivity, and both the connection strength and connection number are disrupted in patients with schizophrenia. The functional connectivity density (FCD) can reflect alterations in the connection number. Alterations in the global FCD (gFCD) in schizophrenia were previously demonstrated; however, alterations in two other indices of the pathological characteristics of the brain, local FCD (lFCD) and long-range FCD (lrFCD), have not been revealed. To investigate lFCD and lrFCD alterations in patients with schizophrenia, 95 patients and 93 matched healthy controls were examined using structural and resting-state functional magnetic resonance imaging scanning. lFCD and lrFCD were measured using FCD mapping, and differences were identified using a two-sample t-test in a voxel-wise manner, with age and gender considered to increase variability. Multiple comparisons were performed using a false discovery rate method with a corrected threshold of Pschizophrenia is a disorder of brain dysconnectivity, particularly affecting the local functional connectivity network, and support the hypothesis that schizophrenia is associated with a widespread cortical functional connectivity/activity deficit, with hyper- and/or hypo-connectivity/activity coexisting in some cortical or subcortical regions.

Altered neural connectivity during response inhibition in adolescents with attention-deficit/hyperactivity disorder and their unaffected siblings.

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van Rooij, Daan; Hartman, Catharina A; Mennes, Maarten; Oosterlaan, Jaap; Franke, Barbara; Rommelse, Nanda; Heslenfeld, Dirk; Faraone, Stephen V; Buitelaar, Jan K; Hoekstra, Pieter J

2015-01-01

Response inhibition is one of the executive functions impaired in attention-deficit/hyperactivity disorder (ADHD). Increasing evidence indicates that altered functional and structural neural connectivity are part of the neurobiological basis of ADHD. Here, we investigated if adolescents with ADHD show altered functional connectivity during response inhibition compared to their unaffected siblings and healthy controls. Response inhibition was assessed using the stop signal paradigm. Functional connectivity was assessed using psycho-physiological interaction analyses applied to BOLD time courses from seed regions within inferior- and superior frontal nodes of the response inhibition network. Resulting networks were compared between adolescents with ADHD (N = 185), their unaffected siblings (N = 111), and controls (N = 125). Control subjects showed stronger functional connectivity than the other two groups within the response inhibition network, while subjects with ADHD showed relatively stronger connectivity between default mode network (DMN) nodes. Stronger connectivity within the response inhibition network was correlated with lower ADHD severity, while stronger connectivity with the DMN was correlated with increased ADHD severity. Siblings showed connectivity patterns similar to controls during successful inhibition and to ADHD subjects during failed inhibition. Additionally, siblings showed decreased connectivity with the primary motor areas as compared to both participants with ADHD and controls. Subjects with ADHD fail to integrate activation within the response inhibition network and to inhibit connectivity with task-irrelevant regions. Unaffected siblings show similar alterations only during failed stop trials, as well as unique suppression of motor areas, suggesting compensatory strategies. These findings support the role of altered functional connectivity in understanding the neurobiology and familial transmission of ADHD.

Differences in functional brain connectivity alterations associated with cerebral amyloid deposition in amnestic mild cognitive impairment

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Dahyun eYi

2015-02-01

Full Text Available Despite potential implications for the early detection of impending AD, very little is known about the differences of large scale brain networks between amnestic MCI (aMCI with high cerebral amyloid beta protein (Aβ deposition (i.e., aMCI+ and aMCI with no or very little Aβ deposition (i.e., aMCI-. We first aimed to extend the current literature on altering intrinsic functional connectivity (FC of the default mode network (DMN and salience network (SN from CN to AD dementia. Second, we further examined the differences of the DMN and the SN between aMCI-, aMCI+, and CN. Forty-three older adult (12 CN, 10 aMCI+, 10 aMCI-, and 11 AD dementia subjects were included. All participants received clinical and neuropsychological assessment, resting state functional MRI, structural MRI, and Pittsburgh compound-B-PET scans. FC data were preprocessed using Multivariate Exploratory Linear Optimized Decomposition into Independent Components of FSL. Group comparisons were carried out using the dual-regression approach. In addition, to verify presence of grey matter (GM volume changes with intrinsic functional network alterations, Voxel Based Morphometry was performed on the acquired T1-weighted data. As expected, AD dementia participants exhibited decreased FC in the DMN compared to CN (in precuneus and cingulate gyrus. The degree of alteration in the DMN in aMCI+ compared to CN was intermediate to that of AD. In contrast, aMCI- exhibited increased FC in the DMN compared to CN (in precuneus as well as aMCI+. In terms of the SN, aMCI- exhibited decreased FC compared to both CN and aMCI+ particularly in the inferior frontal gyrus. FC within the SN in aMCI+ and AD did not differ from CN. Compared to CN, aMCI- showed atrophy in bilateral superior temporal gyri whereas aMCI+ showed atrophy in right precuneus. The results indicate that despite of the similarity in cross-sectional cognitive features aMCI- has quite different functional brain connectivity compared to

Altered resting brain function and structure in professional badminton players.

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Di, Xin; Zhu, Senhua; Jin, Hua; Wang, Pin; Ye, Zhuoer; Zhou, Ke; Zhuo, Yan; Rao, Hengyi

2012-01-01

Neuroimaging studies of professional athletic or musical training have demonstrated considerable practice-dependent plasticity in various brain structures, which may reflect distinct training demands. In the present study, structural and functional brain alterations were examined in professional badminton players and compared with healthy controls using magnetic resonance imaging (MRI) and resting-state functional MRI. Gray matter concentration (GMC) was assessed using voxel-based morphometry (VBM), and resting-brain functions were measured by amplitude of low-frequency fluctuation (ALFF) and seed-based functional connectivity. Results showed that the athlete group had greater GMC and ALFF in the right and medial cerebellar regions, respectively. The athlete group also demonstrated smaller ALFF in the left superior parietal lobule and altered functional connectivity between the left superior parietal and frontal regions. These findings indicate that badminton expertise is associated with not only plastic structural changes in terms of enlarged gray matter density in the cerebellum, but also functional alterations in fronto-parietal connectivity. Such structural and functional alterations may reflect specific experiences of badminton training and practice, including high-capacity visuo-spatial processing and hand-eye coordination in addition to refined motor skills.

Altered Functional Connectivity of the Default Mode Network in Low-Empathy Subjects.

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Kim, Seung Jun; Kim, Sung Eun; Kim, Hyo Eun; Han, Kiwan; Jeong, Bumseok; Kim, Jae Jin; Namkoong, Kee; Kim, Ji Woong

2017-09-01

Empathy is the ability to identify with or make a vicariously experience of another person's feelings or thoughts based on memory and/or self-referential mental simulation. The default mode network in particular is related to self-referential empathy. In order to elucidate the possible neural mechanisms underlying empathy, we investigated the functional connectivity of the default mode network in subjects from a general population. Resting state functional magnetic resonance imaging data were acquired from 19 low-empathy subjects and 18 medium-empathy subjects. An independent component analysis was used to identify the default mode network, and differences in functional connectivity strength were compared between the two groups. The low-empathy group showed lower functional connectivity of the medial prefrontal cortex and anterior cingulate cortex (Brodmann areas 9 and 32) within the default mode network, compared to the medium-empathy group. The results of the present study suggest that empathy is related to functional connectivity of the medial prefrontal cortex/anterior cingulate cortex within the default mode network. Functional decreases in connectivity among low-empathy subjects may reflect an impairment of self-referential mental simulation. © Copyright: Yonsei University College of Medicine 2017.

Tinnitus alters resting state functional connectivity (RSFC) in human auditory and non-auditory brain regions as measured by functional near-infrared spectroscopy (fNIRS).

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San Juan, Juan; Hu, Xiao-Su; Issa, Mohamad; Bisconti, Silvia; Kovelman, Ioulia; Kileny, Paul; Basura, Gregory

2017-01-01

Tinnitus, or phantom sound perception, leads to increased spontaneous neural firing rates and enhanced synchrony in central auditory circuits in animal models. These putative physiologic correlates of tinnitus to date have not been well translated in the brain of the human tinnitus sufferer. Using functional near-infrared spectroscopy (fNIRS) we recently showed that tinnitus in humans leads to maintained hemodynamic activity in auditory and adjacent, non-auditory cortices. Here we used fNIRS technology to investigate changes in resting state functional connectivity between human auditory and non-auditory brain regions in normal-hearing, bilateral subjective tinnitus and controls before and after auditory stimulation. Hemodynamic activity was monitored over the region of interest (primary auditory cortex) and non-region of interest (adjacent non-auditory cortices) and functional brain connectivity was measured during a 60-second baseline/period of silence before and after a passive auditory challenge consisting of alternating pure tones (750 and 8000Hz), broadband noise and silence. Functional connectivity was measured between all channel-pairs. Prior to stimulation, connectivity of the region of interest to the temporal and fronto-temporal region was decreased in tinnitus participants compared to controls. Overall, connectivity in tinnitus was differentially altered as compared to controls following sound stimulation. Enhanced connectivity was seen in both auditory and non-auditory regions in the tinnitus brain, while controls showed a decrease in connectivity following sound stimulation. In tinnitus, the strength of connectivity was increased between auditory cortex and fronto-temporal, fronto-parietal, temporal, occipito-temporal and occipital cortices. Together these data suggest that central auditory and non-auditory brain regions are modified in tinnitus and that resting functional connectivity measured by fNIRS technology may contribute to conscious phantom

Tinnitus alters resting state functional connectivity (RSFC in human auditory and non-auditory brain regions as measured by functional near-infrared spectroscopy (fNIRS.

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Juan San Juan

Full Text Available Tinnitus, or phantom sound perception, leads to increased spontaneous neural firing rates and enhanced synchrony in central auditory circuits in animal models. These putative physiologic correlates of tinnitus to date have not been well translated in the brain of the human tinnitus sufferer. Using functional near-infrared spectroscopy (fNIRS we recently showed that tinnitus in humans leads to maintained hemodynamic activity in auditory and adjacent, non-auditory cortices. Here we used fNIRS technology to investigate changes in resting state functional connectivity between human auditory and non-auditory brain regions in normal-hearing, bilateral subjective tinnitus and controls before and after auditory stimulation. Hemodynamic activity was monitored over the region of interest (primary auditory cortex and non-region of interest (adjacent non-auditory cortices and functional brain connectivity was measured during a 60-second baseline/period of silence before and after a passive auditory challenge consisting of alternating pure tones (750 and 8000Hz, broadband noise and silence. Functional connectivity was measured between all channel-pairs. Prior to stimulation, connectivity of the region of interest to the temporal and fronto-temporal region was decreased in tinnitus participants compared to controls. Overall, connectivity in tinnitus was differentially altered as compared to controls following sound stimulation. Enhanced connectivity was seen in both auditory and non-auditory regions in the tinnitus brain, while controls showed a decrease in connectivity following sound stimulation. In tinnitus, the strength of connectivity was increased between auditory cortex and fronto-temporal, fronto-parietal, temporal, occipito-temporal and occipital cortices. Together these data suggest that central auditory and non-auditory brain regions are modified in tinnitus and that resting functional connectivity measured by fNIRS technology may contribute to

Altered intrinsic connectivity of the auditory cortex in congenital amusia.

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Leveque, Yohana; Fauvel, Baptiste; Groussard, Mathilde; Caclin, Anne; Albouy, Philippe; Platel, Hervé; Tillmann, Barbara

2016-07-01

Congenital amusia, a neurodevelopmental disorder of music perception and production, has been associated with abnormal anatomical and functional connectivity in a right frontotemporal pathway. To investigate whether spontaneous connectivity in brain networks involving the auditory cortex is altered in the amusic brain, we ran a seed-based connectivity analysis, contrasting at-rest functional MRI data of amusic and matched control participants. Our results reveal reduced frontotemporal connectivity in amusia during resting state, as well as an overconnectivity between the auditory cortex and the default mode network (DMN). The findings suggest that the auditory cortex is intrinsically more engaged toward internal processes and less available to external stimuli in amusics compared with controls. Beyond amusia, our findings provide new evidence for the link between cognitive deficits in pathology and abnormalities in the connectivity between sensory areas and the DMN at rest. Copyright © 2016 the American Physiological Society.

Group-ICA model order highlights patterns of functional brain connectivity

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Ahmed eAbou Elseoud

2011-06-01

Full Text Available Resting-state networks (RSNs can be reliably and reproducibly detected using independent component analysis (ICA at both individual subject and group levels. Altering ICA dimensionality (model order estimation can have a significant impact on the spatial characteristics of the RSNs as well as their parcellation into sub-networks. Recent evidence from several neuroimaging studies suggests that the human brain has a modular hierarchical organization which resembles the hierarchy depicted by different ICA model orders. We hypothesized that functional connectivity between-group differences measured with ICA might be affected by model order selection. We investigated differences in functional connectivity using so-called dual-regression as a function of ICA model order in a group of unmedicated seasonal affective disorder (SAD patients compared to normal healthy controls. The results showed that the detected disease-related differences in functional connectivity alter as a function of ICA model order. The volume of between-group differences altered significantly as a function of ICA model order reaching maximum at model order 70 (which seems to be an optimal point that conveys the largest between-group difference then stabilized afterwards. Our results show that fine-grained RSNs enable better detection of detailed disease-related functional connectivity changes. However, high model orders show an increased risk of false positives that needs to be overcome. Our findings suggest that multilevel ICA exploration of functional connectivity enables optimization of sensitivity to brain disorders.

Altered functional connectivity to stressful stimuli in prenatally cocaine-exposed adolescents.

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Zakiniaeiz, Yasmin; Yip, Sarah W; Balodis, Iris M; Lacadie, Cheryl M; Scheinost, Dustin; Constable, R Todd; Mayes, Linda C; Sinha, Rajita; Potenza, Marc N

2017-11-01

Prenatal cocaine exposure (PCE) is linked to addiction and obesity vulnerability. Neural responses to stressful and appetitive cues in adolescents with PCE versus those without have been differentially linked to substance-use initiation. However, no prior studies have assessed cue-reactivity responses among PCE adolescents using a connectivity-based approach. Twenty-two PCE and 22 non-prenatally drug-exposed (NDE) age-, sex-, IQ- and BMI-matched adolescents participated in individualized guided imagery with appetitive (favorite-food), stressful and neutral-relaxing cue scripts during functional magnetic resonance imaging. Subjective favorite-food craving scores were collected before and after script exposure. A data-driven voxel-wise intrinsic connectivity distribution analysis was used to identify between-group differences and examine relationships with craving scores. A group-by-cue interaction effect identified a parietal lobe cluster where PCE versus NDE adolescents showed less connectivity during stressful and more connectivity during neutral-relaxing conditions. Follow-up seed-based connectivity analyses revealed that, among PCE adolescents, the parietal seed was positively connected to inferior parietal and sensory areas and negatively connected to corticolimbic during both stress and neutral-relaxing conditions. For NDE, greater parietal connectivity to parietal, cingulate and sensory areas and lesser parietal connectivity to medial prefrontal areas were found during stress compared to neutral-relaxing cueing. Craving scores inversely correlated with corticolimbic connectivity in PCE, but not NDE adolescents, during the favorite-food condition. Findings from this first data-driven intrinsic connectivity analysis of PCE influences on adolescent brain function indicate differences relating to PCE status and craving. These findings provide insight into the developmental impact of in utero drug exposure. Copyright © 2017 Elsevier B.V. All rights reserved.

BDNF genotype modulates resting functional connectivity in children

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Moriah E Thomason

2009-11-01

Full Text Available A specific polymorphism of the brain-derived neurotrophic factor (BDNF gene is associated with alterations in brain anatomy and memory; its relevance to the functional connectivity of brain networks, however, is unclear. Given that altered hippocampal function and structure has been found in adults who carry the methionine (met allele of the BDNF gene and the molecular studies elucidating the role of BDNF in neurogenesis and synapse formation, we examined in the association between BDNF gene variants and neural resting connectivity in children and adolescents. We observed a reduction in hippocampal and parahippocampal to cortical connectivity in met-allele carriers within each of three resting networks: the default-mode, executive, and paralimbic networks. In contrast, we observed increased connectivity to amygdala, insula and striatal regions in met-carriers, within the paralimbic network. Because the BDNF met-allele has been linked to increased susceptibility to neuropsychiatric disorders, this latter finding of greater connectivity in circuits important for emotion processing may indicate a new neural mechanism through which these gene-related psychiatric differences are manifest. Here we show that the BDNF gene, known to regulate synaptic plasticity and connectivity in the brain, affects functional connectivity at the neural systems level. Additionally, we provide the first demonstration that the spatial topography of multiple high-level resting state networks in healthy children and adolescents is similar to that observed in adults.

Altered causal connectivity of resting state brain networks in amnesic MCI.

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Peipeng Liang

Full Text Available Most neuroimaging studies of resting state networks in amnesic mild cognitive impairment (aMCI have concentrated on functional connectivity (FC based on instantaneous correlation in a single network. The purpose of the current study was to investigate effective connectivity in aMCI patients based on Granger causality of four important networks at resting state derived from functional magnetic resonance imaging data--default mode network (DMN, hippocampal cortical memory network (HCMN, dorsal attention network (DAN and fronto-parietal control network (FPCN. Structural and functional MRI data were collected from 16 aMCI patients and 16 age, gender-matched healthy controls. Correlation-purged Granger causality analysis was used, taking gray matter atrophy as covariates, to compare the group difference between aMCI patients and healthy controls. We found that the causal connectivity between networks in aMCI patients was significantly altered with both increases and decreases in the aMCI group as compared to healthy controls. Some alterations were significantly correlated with the disease severity as measured by mini-mental state examination (MMSE, and California verbal learning test (CVLT scores. When the whole-brain signal averaged over the entire brain was used as a nuisance co-variate, the within-group maps were significantly altered while the between-group difference maps did not. These results suggest that the alterations in causal influences may be one of the possible underlying substrates of cognitive impairments in aMCI. The present study extends and complements previous FC studies and demonstrates the coexistence of causal disconnection and compensation in aMCI patients, and thus might provide insights into biological mechanism of the disease.

Alterations of White Matter Integrity and Hippocampal Functional Connectivity in Type 2 Diabetes Without Mild Cognitive Impairment

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Qian Sun

2018-03-01

Full Text Available Aims: To investigate the white matter (WM integrity and hippocampal functional connectivity (FC in type 2 diabetes mellitus (T2DM patients without mild cognitive impairment (MCI by using diffusion tensor imaging (DTI and resting-state functional magnetic resonance imaging (rs-fMRI, respectively.Methods: Twelve T2DM patients without MCI and 24 age, sex and education matched healthy controls (HC were recruited. DTI and rs-fMRI data were subsequently acquired on a 3.0T MR scanner. Tract-based spatial statistics (TBSS combining region of interests (ROIs analysis was used to investigate the alterations of DTI metrics (fractional anisotropy (FA, mean diffusivity (MD, λ1 and λ23 and FC measurement was performed to calculate hippocampal FC with other brain regions. Cognitive function was evaluated by using Mini-Mental State Examination (MMSE and Montreal Cognitive Assessment (MoCA. Brain volumes were also evaluated among these participants.Results: There were no difference of MMSE and MoCA scores between two groups. Neither whole brain nor regional brain volume decrease was revealed in T2DM patients without MCI. DTI analysis revealed extensive WM disruptions, especially in the body of corpus callosum (CC. Significant decreases of hippocampal FC with certain brain structures were revealed, especially with the bilateral frontal cortex. Furthermore, the decreased FA in left posterior thalamic radiation (PTR and increased MD in the splenium of CC were closely related with the decreased hippocampal FC to caudate nucleus and frontal cortex.Conclusions: T2DM patients without MCI showed extensive WM disruptions and abnormal hippocampal FC. Moreover, the WM disruptions and abnormal hippocampal FC were closely associated.Highlights-T2DM patients without MCI demonstrated no obvious brain volume decrease.-Extensive white matter disruptions, especially within the body of corpus callosum, were revealed with DTI analysis among the T2DM patients.-Despite no MCI in T2

Altered resting-state functional connectivity of the frontal-striatal reward system in social anxiety disorder.

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Manning, Joshua; Reynolds, Gretchen; Saygin, Zeynep M; Hofmann, Stefan G; Pollack, Mark; Gabrieli, John D E; Whitfield-Gabrieli, Susan

2015-01-01

We investigated differences in the intrinsic functional brain organization (functional connectivity) of the human reward system between healthy control participants and patients with social anxiety disorder. Functional connectivity was measured in the resting-state via functional magnetic resonance imaging (fMRI). 53 patients with social anxiety disorder and 33 healthy control participants underwent a 6-minute resting-state fMRI scan. Functional connectivity of the reward system was analyzed by calculating whole-brain temporal correlations with a bilateral nucleus accumbens seed and a ventromedial prefrontal cortex seed. Patients with social anxiety disorder, relative to the control group, had (1) decreased functional connectivity between the nucleus accumbens seed and other regions associated with reward, including ventromedial prefrontal cortex; (2) decreased functional connectivity between the ventromedial prefrontal cortex seed and lateral prefrontal regions, including the anterior and dorsolateral prefrontal cortices; and (3) increased functional connectivity between both the nucleus accumbens seed and the ventromedial prefrontal cortex seed with more posterior brain regions, including anterior cingulate cortex. Social anxiety disorder appears to be associated with widespread differences in the functional connectivity of the reward system, including markedly decreased functional connectivity between reward regions and between reward regions and lateral prefrontal cortices, and markedly increased functional connectivity between reward regions and posterior brain regions.

Hyperthermia-induced disruption of functional connectivity in the human brain network.

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Gang Sun

Full Text Available BACKGROUND: Passive hyperthermia is a potential risk factor to human cognitive performance and work behavior in many extreme work environments. Previous studies have demonstrated significant effects of passive hyperthermia on human cognitive performance and work behavior. However, there is a lack of a clear understanding of the exact affected brain regions and inter-regional connectivities. METHODOLOGY AND PRINCIPAL FINDINGS: We simulated 1 hour environmental heat exposure to thirty-six participants under two environmental temperature conditions (25 °C and 50 °C, and collected resting-state functional brain activity. The functional connectivities with a preselected region of interest (ROI in the posterior cingulate cortex and precuneus (PCC/PCu, furthermore, inter-regional connectivities throughout the entire brain using a prior Anatomical Automatic Labeling (AAL atlas were calculated. We identified decreased correlations of a set of regions with the PCC/PCu, including the medial orbitofrontal cortex (mOFC and bilateral medial temporal cortex, as well as increased correlations with the partial orbitofrontal cortex particularly in the bilateral orbital superior frontal gyrus. Compared with the normal control (NC group, the hyperthermia (HT group showed 65 disturbed functional connectivities with 50 of them being decreased and 15 of them being increased. While the decreased correlations mainly involved with the mOFC, temporal lobe and occipital lobe, increased correlations were mainly located within the limbic system. In consideration of physiological system changes, we explored the correlations of the number of significantly altered inter-regional connectivities with differential rectal temperatures and weight loss, but failed to obtain significant correlations. More importantly, during the attention network test (ANT we found that the number of significantly altered functional connectivities was positively correlated with an increase in

Assessment of the structural brain network reveals altered connectivity in children with unilateral cerebral palsy due to periventricular white matter lesions

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Kerstin Pannek

2014-01-01

Conclusion: This study shows that network-based analysis of structural connectivity can identify alterations in FA in unilateral CP, and that these alterations in FA are related to clinical function. Application of this connectome-based analysis to investigate alterations in connectivity following treatment may elucidate the neurological correlates of improved functioning due to intervention.

Altered resting state neuromotor connectivity in men with chronic prostatitis/chronic pelvic pain syndrome: A MAPP

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Jason J. Kutch

2015-01-01

Full Text Available Brain network activity associated with altered motor control in individuals with chronic pain is not well understood. Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS is a debilitating condition in which previous studies have revealed altered resting pelvic floor muscle activity in men with CP/CPPS compared to healthy controls. We hypothesized that the brain networks controlling pelvic floor muscles would also show altered resting state function in men with CP/CPPS. Here we describe the results of the first test of this hypothesis focusing on the motor cortical regions, termed pelvic-motor, that can directly activate pelvic floor muscles. A group of men with CP/CPPS (N = 28, as well as group of age-matched healthy male controls (N = 27, had resting state functional magnetic resonance imaging scans as part of the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP Research Network study. Brain maps of the functional connectivity of pelvic-motor were compared between groups. A significant group difference was observed in the functional connectivity between pelvic-motor and the right posterior insula. The effect size of this group difference was among the largest effect sizes in functional connectivity between all pairs of 165 anatomically-defined subregions of the brain. Interestingly, many of the atlas region pairs with large effect sizes also involved other subregions of the insular cortices. We conclude that functional connectivity between motor cortex and the posterior insula may be among the most important markers of altered brain function in men with CP/CPPS, and may represent changes in the integration of viscerosensory and motor processing.

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

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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.

Altered Functional Connectivity of the Default Mode Network in Patients With Schizo-obsessive Comorbidity: A Comparison Between Schizophrenia and Obsessive-compulsive Disorder

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Wang, Yongming; Zou, Lai-quan; Xie, Wen-lan

2018-01-01

increased rsFC between subregions of the DMN and the middle temporal gyrus, but the OCD group exhibited decreased rsFC between them. These findings highlight a specific alteration in functional connectivity in the DMN in patients with SOC, and provide new insights into the dysfunctional brain organization...

Altered functional connectivity of fusiform gyrus in subjects with amnestic mild cognitive impairment: a resting state fMRI study

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SuPing eCai

2015-08-01

Full Text Available Visual cognition such as face recognition requires a high level of functional interaction between distributed regions of a network. It has been reported that the fusiform gyrus (FG is an important brain area involved in facial cognition; altered connectivity of FG to some other regions may lead to a deficit in visual cognition especially face recognition. However, whether functional connectivity between the FG and other brain regions changes remains unclear during the resting state in amnestic mild cognitive impairment (aMCI subjects. Here, we employed a resting state functional MRI (fMRI to examine changes in functional connectivity of left/right FG comparing aMCI patients with age-matched control subjects. Forty-eight aMCI and thirty-eight control subjects from the Alzheimer’s disease Neuroimaging Initiative (ADNI were analyzed. We focused on the correlation between low frequency fMRI signal fluctuations in the FG and those in all other brain regions. Compared to the control group, we found some discrepant regions in the aMCI group which presented increased or decreased connectivity with the left/right FG including the left precuneus, left lingual gyrus, right thalamus, supramarginal gyrus, left supplementary motor area, left inferior temporal gyrus, and left parahippocampus. More importantly, we also obtained that both left and right FG have increased functional connections with the left middle occipital gyrus (MOG and right anterior cingulate gyrus (ACC in aMCI patients. That was not a coincidence and might imply that the MOG and ACC also play a critical role in visual cognition, especially face recognition. These findings in a large part supported our hypothesis and provided a new insight in understanding the important subtype of MCI.

Disturbed Interhemispheric Functional Connectivity Rather than Structural Connectivity in Irritable Bowel Syndrome

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Rongfeng Qi

2016-12-01

Full Text Available Neuroimaging studies have demonstrated that irritable bowel syndrome (IBS—a relapsing functional bowel disorder—presents with disrupted brain connections. However, little is known about the alterations of interhemispheric functional connectivity and underlying structural connectivity in IBS. This study combined resting-state functional magnetic resonance imaging (MRI and diffusion tensor imaging (DTI to investigate changes in interhemispheric coordination in IBS patients. Resting-state functional and structural magnetic resonance images were acquired from 65 IBS patients and 67 healthy controls (matched for age, sex and educational level. Interhemispheric voxel-mirrored homotopic connectivity (VMHC was calculated and compared between groups. Homotopic regions showing abnormal VMHC in patients were targeted as regions of interest for analysis of DTI tractography. The fractional anisotropy, fiber number, and fiber length were compared between groups. Statistical analysis was also performed by including anxiety and depression as covariates to evaluate their effect. A Pearson correlation analysis between abnormal interhemispheric connectivity and clinical indices of IBS patients was performed. Compared to healthy controls, IBS patients had higher interhemispheric functional connectivity between bilateral thalami, cuneus, posterior cingulate cortices, lingual gyri and inferior occipital/cerebellum lobes, as well as lower interhemispheric functional connectivity between bilateral ventral anterior cingulate cortices (vACC and inferior parietal lobules (IPL. The inclusion of anxiety and depression as covariates abolished VMHC difference in vACC. Microstructural features of white matter tracts connecting functionally abnormal regions did not reveal any differences between the groups. VMHC values in vACC negatively correlated with the quality of life scores of patients. In conclusion, this study provides preliminary evidence of the disrupted

Alteration and reorganization of functional networks: a new perspective in brain injury study

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Nazareth P. Castellanos

2011-09-01

Full Text Available Plasticity is the mechanism underlying brain’s potential capability to compensate injury. Recently several studies have shown that functional connections among brain areas are severely altered by brain injury and plasticity leading to a reorganization of the networks. This new approach studies the impact of brain injury by means of alteration of functional interactions. The concept of functional connectivity refers to the statistical interdependencies between physiological time series simultaneously recorded in various brain areas and it could be an essential tool for brain function studies, being its deviation from healthy reference an indicator for damage. In this article, we review studies investigating functional connectivity changes after brain injury and subsequent recovery, providing an accessible introduction to common mathematical methods to infer functional connectivity, exploring their capabilities, future perspectives and clinical uses in brain injury studies.

Altered functional connectivity density in patients with herpes zoster and postherpetic neuralgia

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Hong S

2018-04-01

Full Text Available Shunda Hong,1,* Lili Gu,2,* Fuqing Zhou,1 Jiaqi Liu,1 Muhua Huang,1 Jian Jiang,1 Laichang He,1 Honghan Gong,1 Xianjun Zeng1 1Department of Radiology, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Department of Pain, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi, People’s Republic of China *These authors contributed equally to this work Purpose: The aim of this study was to explore intrinsic functional connectivity patterns in patients with herpes zoster (HZ and postherpetic neuralgia (PHN. Patients and methods: Thirty-three right-handed HZ patients (13 males; mean age 57.15±9.30 years, 22 right-handed PHN patients (9 males; mean age 66.13±6.77 years, and 28 well-matched healthy controls (HC (9 males; mean age 54.21±7.72 years underwent resting-state functional magnetic resonance imaging for intrinsic functional connectivity analyses. Functional connectivity density (FCD was calculated and compared among the PHN, HZ, and HC groups. In addition, the Pearson correlation coefficient was calculated to compare various clinical indices in the regions with abnormal FCD values. Results: Compared with the HC, both HZ and PHN patients showed significantly decreased FCD in the precuneus, and patients with HZ displayed significantly increased FCD in the brainstem/limbic lobe/parahippocampalgyrus, whereas patients with PHN displayed significantly increased FCD in the hippocampus (correlation thresholds r=0.25, voxel level of P<0.01 and Gaussian random field theory at a cluster level of P<0.05. However, the FCD was not significantly different between the PHN and HZ patients. Furthermore, the decreased FCD in the precuneus was positively correlated with the visual analog scale score in the PHN group (r=0.672; P=0.001. Conclusion: Decreased connectivity of the precuneus occurred in both HZ and PHN patients, indicating a disrupted default-mode network. Furthermore, in the HZ

Default mode network connectivity as a function of familial and environmental risk for psychotic disorder.

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Peeters, Sanne C T; van de Ven, Vincent; Gronenschild, Ed H B M; Patel, Ameera X; Habets, Petra; Goebel, Rainer; van Os, Jim; Marcelis, Machteld

2015-01-01

Research suggests that altered interregional connectivity in specific networks, such as the default mode network (DMN), is associated with cognitive and psychotic symptoms in schizophrenia. In addition, frontal and limbic connectivity alterations have been associated with trauma, drug use and urban upbringing, though these environmental exposures have never been examined in relation to DMN functional connectivity in psychotic disorder. Resting-state functional MRI scans were obtained from 73 patients with psychotic disorder, 83 non-psychotic siblings of patients with psychotic disorder and 72 healthy controls. Posterior cingulate cortex (PCC) seed-based correlation analysis was used to estimate functional connectivity within the DMN. DMN functional connectivity was examined in relation to group (familial risk), group × environmental exposure (to cannabis, developmental trauma and urbanicity) and symptomatology. There was a significant association between group and PCC connectivity with the inferior parietal lobule (IPL), the precuneus (PCu) and the medial prefrontal cortex (MPFC). Compared to controls, patients and siblings had increased PCC connectivity with the IPL, PCu and MPFC. In the IPL and PCu, the functional connectivity of siblings was intermediate to that of controls and patients. No significant associations were found between DMN connectivity and (subclinical) psychotic/cognitive symptoms. In addition, there were no significant interactions between group and environmental exposures in the model of PCC functional connectivity. Increased functional connectivity in individuals with (increased risk for) psychotic disorder may reflect trait-related network alterations. The within-network "connectivity at rest" intermediate phenotype was not associated with (subclinical) psychotic or cognitive symptoms. The association between familial risk and DMN connectivity was not conditional on environmental exposure.

Altered caudate connectivity is associated with executive dysfunction after traumatic brain injury

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De Simoni, Sara; Jenkins, Peter O; Bourke, Niall J; Fleminger, Jessica J; Jolly, Amy E; Patel, Maneesh C; Leech, Robert; Sharp, David J

2018-01-01

Abstract Traumatic brain injury often produces executive dysfunction. This characteristic cognitive impairment often causes long-term problems with behaviour and personality. Frontal lobe injuries are associated with executive dysfunction, but it is unclear how these injuries relate to corticostriatal interactions that are known to play an important role in behavioural control. We hypothesized that executive dysfunction after traumatic brain injury would be associated with abnormal corticostriatal interactions, a question that has not previously been investigated. We used structural and functional MRI measures of connectivity to investigate this. Corticostriatal functional connectivity in healthy individuals was initially defined using a data-driven approach. A constrained independent component analysis approach was applied in 100 healthy adult dataset from the Human Connectome Project. Diffusion tractography was also performed to generate white matter tracts. The output of this analysis was used to compare corticostriatal functional connectivity and structural integrity between groups of 42 patients with traumatic brain injury and 21 age-matched controls. Subdivisions of the caudate and putamen had distinct patterns of functional connectivity. Traumatic brain injury patients showed disruption to functional connectivity between the caudate and a distributed set of cortical regions, including the anterior cingulate cortex. Cognitive impairments in the patients were mainly seen in processing speed and executive function, as well as increased levels of apathy and fatigue. Abnormalities of caudate functional connectivity correlated with these cognitive impairments, with reductions in right caudate connectivity associated with increased executive dysfunction, information processing speed and memory impairment. Structural connectivity, measured using diffusion tensor imaging between the caudate and anterior cingulate cortex was impaired and this also correlated with

Alterations in conflict monitoring are related to functional connectivity in Parkinson's disease.

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Rosenberg-Katz, Keren; Maidan, Inbal; Jacob, Yael; Giladi, Nir; Mirelman, Anat; Hausdorff, Jeffrey M

2016-09-01

Patients with Parkinson's disease (PD) have difficulties in executive functions including conflict monitoring. The neural mechanisms underlying these difficulties are not yet fully understood. In order to examine the neural mechanisms related to conflict monitoring in PD, we evaluated 35 patients with PD and 20 healthy older adults while they performed a word-color Stroop paradigm in the MRI. Specifically, we focused on changes between the groups in task-related functional connectivity using psycho-physiological interaction (PPI) analysis. The anterior cingulate cortex (ACC), which is a brain node previously associated with the Stroop paradigm, was selected as the seed region for this analysis. Patients with PD, as compared to healthy controls, had reduced task-related functional connectivity between the ACC and parietal regions including the precuneus and inferior parietal lobe. This was seen only in the incongruent Stroop condition. A higher level of connectivity between the ACC and precuneus was correlated with a lower error rate in the conflicting, incongruent Stroop condition in the healthy controls, but not in the patients with PD. Furthermore, the patients also had reduced functional connectivity between the ACC and the superior frontal gyrus which was present in both the incongruent and congruent task condition. The present findings shed light on brain mechanisms that are apparently associated with specific cognitive difficulties in patients with PD. Among patients with PD, impaired conflict monitoring processing within the ACC-based fronto-parietal network may contribute to difficulties under increased executive demands. Copyright © 2016 Elsevier Ltd. All rights reserved.

Altered thalamo-cortical resting state functional connectivity in smokers.

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Wang, Chaoyan; Bai, Jie; Wang, Caihong; von Deneen, Karen M; Yuan, Kai; Cheng, Jingliang

2017-07-13

The thalamus has widespread connections with the prefrontal cortex (PFC) and modulates communication between the striatum and PFC, which is crucial to the neural mechanisms of smoking. However, relatively few studies focused on the thalamic resting state functional connectivity (RSFC) patterns and their association with smoking behaviors in smokers. 24 young male smokers and 24 non-smokers were enrolled in our study. Fagerström Test for Nicotine Dependence (FTND) was used to assess the nicotine dependence level. The bilateral thalamic RSFC patterns were compared between smokers and non-smokers. The relationship between neuroimaging findings and smoking behaviors (FTND and pack-years) were also investigated in smokers. Relative to nonsmokers, smokers showed reduced RSFC strength between the left thalamus and several brain regions, i.e. the right dorsolateral prefrontal cortex (dlPFC), the anterior cingulate cortex (ACC) and the bilateral caudate. In addition, the right thalamus showed reduced RSFC with the right dlPFC as well as the bilateral insula in smokers. Therefore, the findings in the current study revealed the reduced RSFC of the thalamus with the dlPFC, the ACC, the insula and the caudate in smokers, which provided new insights into the roles of the thalamus in nicotine addiction from a function integration perspective. Copyright © 2017 Elsevier B.V. All rights reserved.

Altered activity and functional connectivity of superior temporal gyri in anxiety disorders: A functional magnetic resonance imaging study

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Zhao, Xiaohu; Xi, Qian; Wang, Peijun; Li, Chunbo [Tong Ji Hospital of Tong Ji University, Shanghai (China); He, Hongjian [Bio-X lab, Dept. of Physics, Zhe Jiang University, Hangzhou (China)

2014-08-15

The prior functional MRI studies have demonstrated significantly abnormal activity in the bilateral superior temporal gyrus (STG) of anxiety patients. The purpose of the current investigation was to determine whether the abnormal activity in these regions was related to a loss of functional connectivity between these regions. Ten healthy controls and 10 anxiety patients underwent noninvasive fMRI while actively listening to emotionally neutral words alternated by silence (Task 1) or threat-related words (Task 2). The participants were instructed to silently make a judgment of each word's valence (i.e., unpleasant, pleasant, or neutral). A coherence analysis was applied to the functional MRI data to examine the functional connectivity between the left and the right STG, which was selected as the primary region of interest on the basis of our prior results. The data demonstrated that the anxiety patients exhibited significantly increased activation in the bilateral STG than the normal controls. The functional connectivity analysis indicated that the patient group showed significantly decreased degree of connectivity between the bilateral STG during processing Task 2 compared to Task 1 (t = 2.588, p = 0.029). In addition, a significantly decreased connectivity was also observed in the patient group compared to the control group during processing Task 2 (t = 2.810, p = 0.012). Anxiety patients may exhibit increased activity of the STG but decreased functional connectivity between the left and right STG, which may reflect the underlying neural abnormality of anxiety disorder, and this will provide new insights into this disease.

Altered activity and functional connectivity of superior temporal gyri in anxiety disorders: A functional magnetic resonance imaging study

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Zhao, Xiaohu; Xi, Qian; Wang, Peijun; Li, Chunbo; He, Hongjian

2014-01-01

The prior functional MRI studies have demonstrated significantly abnormal activity in the bilateral superior temporal gyrus (STG) of anxiety patients. The purpose of the current investigation was to determine whether the abnormal activity in these regions was related to a loss of functional connectivity between these regions. Ten healthy controls and 10 anxiety patients underwent noninvasive fMRI while actively listening to emotionally neutral words alternated by silence (Task 1) or threat-related words (Task 2). The participants were instructed to silently make a judgment of each word's valence (i.e., unpleasant, pleasant, or neutral). A coherence analysis was applied to the functional MRI data to examine the functional connectivity between the left and the right STG, which was selected as the primary region of interest on the basis of our prior results. The data demonstrated that the anxiety patients exhibited significantly increased activation in the bilateral STG than the normal controls. The functional connectivity analysis indicated that the patient group showed significantly decreased degree of connectivity between the bilateral STG during processing Task 2 compared to Task 1 (t = 2.588, p = 0.029). In addition, a significantly decreased connectivity was also observed in the patient group compared to the control group during processing Task 2 (t = 2.810, p = 0.012). Anxiety patients may exhibit increased activity of the STG but decreased functional connectivity between the left and right STG, which may reflect the underlying neural abnormality of anxiety disorder, and this will provide new insights into this disease.

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

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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

2016-06-03

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. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Connectomics and neuroticism : an altered functional network organization

NARCIS (Netherlands)

Servaas, Michelle N; Geerligs, Linda; Renken, Remco J; Marsman, Jan-Bernard; Ormel, Johan; Riese, Harriëtte; Aleman, André

The personality trait neuroticism is a potent risk marker for psychopathology. Although the neurobiological basis remains unclear, studies have suggested that alterations in connectivity may underlie it. Therefore, the aim of the current study was to shed more light on the functional network

Bayesian network analysis reveals alterations to default mode network connectivity in individuals at risk for Alzheimer's disease.

Science.gov (United States)

Li, Rui; Yu, Jing; Zhang, Shouzi; Bao, Feng; Wang, Pengyun; Huang, Xin; Li, Juan

2013-01-01

Alzheimer's disease (AD) is associated with abnormal functioning of the default mode network (DMN). Functional connectivity (FC) changes to the DMN have been found in patients with amnestic mild cognitive impairment (aMCI), which is the prodromal stage of AD. However, whether or not aMCI also alters the effective connectivity (EC) of the DMN remains unknown. We employed a combined group independent component analysis (ICA) and Bayesian network (BN) learning approach to resting-state functional MRI (fMRI) data from 17 aMCI patients and 17 controls, in order to establish the EC pattern of DMN, and to evaluate changes occurring in aMCI. BN analysis demonstrated heterogeneous regional convergence degree across DMN regions, which were organized into two closely interacting subsystems. Compared to controls, the aMCI group showed altered directed connectivity weights between DMN regions in the fronto-parietal, temporo-frontal, and temporo-parietal pathways. The aMCI group also exhibited altered regional convergence degree in the right inferior parietal lobule. Moreover, we found EC changes in DMN regions in aMCI were correlated with regional FC levels, and the connectivity metrics were associated with patients' cognitive performance. This study provides novel sights into our understanding of the functional architecture of the DMN and adds to a growing body of work demonstrating the importance of the DMN as a mechanism of aMCI.

Altered functional connectivity of the default mode network in Williams syndrome: a multimodal approach.

Science.gov (United States)

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. © 2016 John Wiley & Sons Ltd.

Alteration in intrinsic and extrinsic functional connectivity of resting state networks associated with subclinical hypothyroid.

Science.gov (United States)

Kumar, Mukesh; Modi, Shilpi; Rana, Poonam; Kumar, Pawan; Kanwar, Ratnesh; Sekhri, Tarun; D'souza, Maria; Khushu, Subash

2018-03-05

Subclinical hypothyroidism (SCH) is characterized by mild elevation of thyroid stimulating hormone (TSH) (range 5-10 μIU/ml) and normal free triiodothyronine (FT3) and free thyroxine (FT4). The cognitive function impairment is well known in thyroid disorders such as hypothyroidism and hyperthyroidism, but little is known about deficits in brain functions in SCH subjects. Also, whether hormone-replacement treatment is necessary or not in SCH subjects is still debatable. In order to have an insight into the cognition of SCH subjects, intrinsic and extrinsic functional connectivity (FC) of the resting state networks (RSNs) was studied. For resting state data analysis we used an unbiased, data-driven approach based on Independent Component Analysis (ICA) and dual-regression that can emphasize widespread changes in FC without restricting to a set of predefined seeds. 28 SCH subjects and 28 matched healthy controls (HC) participated in the study. RSN analysis showed significantly decreased intrinsic FC in somato-motor network (SMN) and right fronto-parietal attention network (RAN) and increased intrinsic FC in default mode network (DMN) in SCH subjects as compared to control subjects. The reduced intrinsic FC in the SMN and RAN suggests neuro-cognitive alterations in SCH subjects in the corresponding functions which were also evident from the deficit in the neuropsychological performance of the SCH subjects on behavioural tests such as digit span, delayed recall, visual retention, recognition, Bender Gestalt and Mini-Mental State Examination (MMSE). We also found a significant reduction in extrinsic network FC between DMN and RAN; SMN and posterior default mode network (PDMN); and increased extrinsic FC between SMN and anterior default mode network (ADMN) in SCH subjects as compared to controls. An altered extrinsic FC in SCH suggests functional reorganization in response to neurological disruption. The partial correlation analysis between intrinsic and extrinsic RSNs

Multimodal Investigation of Network Level Effects Using Intrinsic Functional Connectivity, Anatomical Covariance, and Structure-to-Function Correlations in Unmedicated Major Depressive Disorder.

Science.gov (United States)

Scheinost, Dustin; Holmes, Sophie E; DellaGioia, Nicole; Schleifer, Charlie; Matuskey, David; Abdallah, Chadi G; Hampson, Michelle; Krystal, John H; Anticevic, Alan; Esterlis, Irina

2018-04-01

Converging evidence suggests that major depressive disorder (MDD) affects multiple large-scale brain networks. Analyses of the correlation or covariance of regional brain structure and function applied to structural and functional MRI data may provide insights into systems-level organization and structure-to-function correlations in the brain in MDD. This study applied tensor-based morphometry and intrinsic connectivity distribution to identify regions of altered volume and intrinsic functional connectivity in data from unmedicated individuals with MDD (n=17) and healthy comparison participants (HC, n=20). These regions were then used as seeds for exploratory anatomical covariance and connectivity analyses. Reduction in volume in the anterior cingulate cortex (ACC) and lower structural covariance between the ACC and the cerebellum were observed in the MDD group. Additionally, individuals with MDD had significantly lower whole-brain intrinsic functional connectivity in the medial prefrontal cortex (mPFC). This mPFC region showed altered connectivity to the ventral lateral PFC (vlPFC) and local circuitry in MDD. Global connectivity in the ACC was negatively correlated with reported depressive symptomatology. The mPFC-vlPFC connectivity was positively correlated with depressive symptoms. Finally, we observed increased structure-to-function correlation in the PFC/ACC in the MDD group. Although across all analysis methods and modalities alterations in the PFC/ACC were a common finding, each modality and method detected alterations in subregions belonging to distinct large-scale brain networks. These exploratory results support the hypothesis that MDD is a systems level disorder affecting multiple brain networks located in the PFC and provide new insights into the pathophysiology of this disorder.

Multimodal Investigation of Network Level Effects Using Intrinsic Functional Connectivity, Anatomical Covariance, and Structure-to-Function Correlations in Unmedicated Major Depressive Disorder

Science.gov (United States)

Scheinost, Dustin; Holmes, Sophie E; DellaGioia, Nicole; Schleifer, Charlie; Matuskey, David; Abdallah, Chadi G; Hampson, Michelle; Krystal, John H; Anticevic, Alan; Esterlis, Irina

2018-01-01

Converging evidence suggests that major depressive disorder (MDD) affects multiple large-scale brain networks. Analyses of the correlation or covariance of regional brain structure and function applied to structural and functional MRI data may provide insights into systems-level organization and structure-to-function correlations in the brain in MDD. This study applied tensor-based morphometry and intrinsic connectivity distribution to identify regions of altered volume and intrinsic functional connectivity in data from unmedicated individuals with MDD (n=17) and healthy comparison participants (HC, n=20). These regions were then used as seeds for exploratory anatomical covariance and connectivity analyses. Reduction in volume in the anterior cingulate cortex (ACC) and lower structural covariance between the ACC and the cerebellum were observed in the MDD group. Additionally, individuals with MDD had significantly lower whole-brain intrinsic functional connectivity in the medial prefrontal cortex (mPFC). This mPFC region showed altered connectivity to the ventral lateral PFC (vlPFC) and local circuitry in MDD. Global connectivity in the ACC was negatively correlated with reported depressive symptomatology. The mPFC–vlPFC connectivity was positively correlated with depressive symptoms. Finally, we observed increased structure-to-function correlation in the PFC/ACC in the MDD group. Although across all analysis methods and modalities alterations in the PFC/ACC were a common finding, each modality and method detected alterations in subregions belonging to distinct large-scale brain networks. These exploratory results support the hypothesis that MDD is a systems level disorder affecting multiple brain networks located in the PFC and provide new insights into the pathophysiology of this disorder. PMID:28944772

Amygdala Functional Connectivity is Reduced After the Cold Pressor Task

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Clewett, David; Schoeke, Andrej; Mather, Mara

2013-01-01

The amygdala forms a crucial link between central pain and stress systems. There is much evidence that psychological stress affects amygdala activity, but it is less clear how painful stressors influence subsequent amygdala functional connectivity. In the present study, we used pulsed arterial spin labeling (PASL) to investigate differences in healthy male adults’ resting-state amygdala functional connectivity following a cold pressor versus control task, with the stressor and control conditions conducted on different days. During the period of peak cortisol response to acute stress (approximately fifteen to thirty minutes after stressor onset), participants were asked to rest for six minutes with their eyes closed during a PASL scanning sequence. The cold pressor task led to reduced resting-state functional connectivity between the amygdalae and orbitofrontal cortex (OFC) and ventromedial prefrontal cortex (VMPFC), which occurred irrespective of cortisol release. The stressor also induced greater inverse connectivity between the left amygdala and dorsal anterior cingulate cortex (dACC), a brain region implicated in the down-regulation of amygdala responsivity. Furthermore, the degree of post-stressor left amygdala decoupling with the lateral OFC varied according to self-reported pain intensity during the cold pressor task. These findings indicate that the cold pressor task alters amygdala interactions with prefrontal and ACC regions 15–30 minutes after the stressor, and that these altered functional connectivity patterns are related to pain perception rather than cortisol feedback. PMID:23645370

Altered caudate connectivity is associated with executive dysfunction after traumatic brain injury.

Science.gov (United States)

De Simoni, Sara; Jenkins, Peter O; Bourke, Niall J; Fleminger, Jessica J; Hellyer, Peter J; Jolly, Amy E; Patel, Maneesh C; Cole, James H; Leech, Robert; Sharp, David J

2018-01-01

Traumatic brain injury often produces executive dysfunction. This characteristic cognitive impairment often causes long-term problems with behaviour and personality. Frontal lobe injuries are associated with executive dysfunction, but it is unclear how these injuries relate to corticostriatal interactions that are known to play an important role in behavioural control. We hypothesized that executive dysfunction after traumatic brain injury would be associated with abnormal corticostriatal interactions, a question that has not previously been investigated. We used structural and functional MRI measures of connectivity to investigate this. Corticostriatal functional connectivity in healthy individuals was initially defined using a data-driven approach. A constrained independent component analysis approach was applied in 100 healthy adult dataset from the Human Connectome Project. Diffusion tractography was also performed to generate white matter tracts. The output of this analysis was used to compare corticostriatal functional connectivity and structural integrity between groups of 42 patients with traumatic brain injury and 21 age-matched controls. Subdivisions of the caudate and putamen had distinct patterns of functional connectivity. Traumatic brain injury patients showed disruption to functional connectivity between the caudate and a distributed set of cortical regions, including the anterior cingulate cortex. Cognitive impairments in the patients were mainly seen in processing speed and executive function, as well as increased levels of apathy and fatigue. Abnormalities of caudate functional connectivity correlated with these cognitive impairments, with reductions in right caudate connectivity associated with increased executive dysfunction, information processing speed and memory impairment. Structural connectivity, measured using diffusion tensor imaging between the caudate and anterior cingulate cortex was impaired and this also correlated with measures of

Spatial working memory in neurofibromatosis 1: Altered neural activity and functional connectivity

Directory of Open Access Journals (Sweden)

Amira F.A. Ibrahim

2017-01-01

Conclusions: Dysfunctional engagement of WM circuitry, and aberrant functional connectivity of ‘task-negative’ regions in NF1 patients may underlie spatial WM difficulties characteristic of the disorder.

Mind-wandering and alterations to default mode network connectivity when listening to naturalistic versus artificial sounds.

Science.gov (United States)

Gould van Praag, Cassandra D; Garfinkel, Sarah N; Sparasci, Oliver; Mees, Alex; Philippides, Andrew O; Ware, Mark; Ottaviani, Cristina; Critchley, Hugo D

2017-03-27

Naturalistic environments have been demonstrated to promote relaxation and wellbeing. We assess opposing theoretical accounts for these effects through investigation of autonomic arousal and alterations of activation and functional connectivity within the default mode network (DMN) of the brain while participants listened to sounds from artificial and natural environments. We found no evidence for increased DMN activity in the naturalistic compared to artificial or control condition, however, seed based functional connectivity showed a shift from anterior to posterior midline functional coupling in the naturalistic condition. These changes were accompanied by an increase in peak high frequency heart rate variability, indicating an increase in parasympathetic activity in the naturalistic condition in line with the Stress Recovery Theory of nature exposure. Changes in heart rate and the peak high frequency were correlated with baseline functional connectivity within the DMN and baseline parasympathetic tone respectively, highlighting the importance of individual neural and autonomic differences in the response to nature exposure. Our findings may help explain reported health benefits of exposure to natural environments, through identification of alterations to autonomic activity and functional coupling within the DMN when listening to naturalistic sounds.

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

Science.gov (United States)

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

2014-01-01

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

State-Dependent Differences in Functional Connectivity in Young Children With Autism Spectrum Disorder

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Ashura W. Buckley

2015-12-01

Interpretation: Functional connectivity is distinctly different in children with autism compared to samples with typical development and developmental delay without autism. Differences in connectivity in autism are state and region related. In this study, children with autism were characterized by a dynamically evolving pattern of altered connectivity.

Decreased functional connectivity of the amygdala in Alzheimer's disease revealed by resting-state fMRI

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Yao, Hongxiang [Department of Radiology, Chinese PLA General Hospital, Beijing, 100853 (China); Liu, Yong, E-mail: yliu@nlpr.ia.ac.cn [Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190 (China); National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190 (China); Zhou, Bo; Zhang, Zengqiang [Department of Neurology, Institute of Geriatrics and Gerontology, Chinese PLA General Hospital, Beijing, 100853 (China); An, Ningyu [Department of Radiology, Chinese PLA General Hospital, Beijing, 100853 (China); Wang, Pan; Wang, Luning [Department of Neurology, Institute of Geriatrics and Gerontology, Chinese PLA General Hospital, Beijing, 100853 (China); Zhang, Xi, E-mail: zhangxi@301hospital.com.cn [Department of Neurology, Institute of Geriatrics and Gerontology, Chinese PLA General Hospital, Beijing, 100853 (China); Jiang, Tianzi [Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190 (China); National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190 (China); Key Laboratory for NeuroInformation of Ministry of Education, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, 610054 (China); The Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072 (Australia)

2013-09-15

Alzheimer's disease (AD), the most common cause of dementia, is thought to be a progressive neurodegenerative disease that is clinically characterised by a decline of memory and other cognitive functions. Mild cognitive impairment (MCI) is considered to be the prodromal stage of AD. However, the relationship between AD and MCI and the development process remains unclear. The amygdala is one of the most vulnerable structures in the early stages of AD. To our knowledge, this is the first report on the alteration of the functional connectivity of the amygdala in AD and MCI subjects. We hypothesised that the amygdala-cortical loop is impaired in AD and that these alterations relate to the disease severity. In our study, we used resting-state functional MRIs to investigate the altered amygdala connectivity patterns in 35 AD patients, 27 MCI patients and 27 age- and gender-matched normal controls (NC). Compared with the NC, the decreased functional connectivity found in the AD patients was mainly located between the amygdala and the regions that are included in the default mode, context conditioning and extinction networks. Importantly, the decreased functional connectivity between the amygdala and some of the identified regions was positively correlated with MMSE, which indicated that the cognitive function impairment is related to an altered functional connectivity pattern.

Decreased functional connectivity of the amygdala in Alzheimer's disease revealed by resting-state fMRI

International Nuclear Information System (INIS)

Yao, Hongxiang; Liu, Yong; Zhou, Bo; Zhang, Zengqiang; An, Ningyu; Wang, Pan; Wang, Luning; Zhang, Xi; Jiang, Tianzi

2013-01-01

Alzheimer's disease (AD), the most common cause of dementia, is thought to be a progressive neurodegenerative disease that is clinically characterised by a decline of memory and other cognitive functions. Mild cognitive impairment (MCI) is considered to be the prodromal stage of AD. However, the relationship between AD and MCI and the development process remains unclear. The amygdala is one of the most vulnerable structures in the early stages of AD. To our knowledge, this is the first report on the alteration of the functional connectivity of the amygdala in AD and MCI subjects. We hypothesised that the amygdala-cortical loop is impaired in AD and that these alterations relate to the disease severity. In our study, we used resting-state functional MRIs to investigate the altered amygdala connectivity patterns in 35 AD patients, 27 MCI patients and 27 age- and gender-matched normal controls (NC). Compared with the NC, the decreased functional connectivity found in the AD patients was mainly located between the amygdala and the regions that are included in the default mode, context conditioning and extinction networks. Importantly, the decreased functional connectivity between the amygdala and some of the identified regions was positively correlated with MMSE, which indicated that the cognitive function impairment is related to an altered functional connectivity pattern

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

Science.gov (United States)

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

2014-01-01

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

The brain functional connectome is robustly altered by lack of sleep.

Science.gov (United States)

Kaufmann, Tobias; Elvsåshagen, Torbjørn; Alnæs, Dag; Zak, Nathalia; Pedersen, Per Ø; Norbom, Linn B; Quraishi, Sophia H; Tagliazucchi, Enzo; Laufs, Helmut; Bjørnerud, Atle; Malt, Ulrik F; Andreassen, Ole A; Roussos, Evangelos; Duff, Eugene P; Smith, Stephen M; Groote, Inge R; Westlye, Lars T

2016-02-15

Sleep is a universal phenomenon necessary for maintaining homeostasis and function across a range of organs. Lack of sleep has severe health-related consequences affecting whole-body functioning, yet no other organ is as severely affected as the brain. The neurophysiological mechanisms underlying these deficits are poorly understood. Here, we characterize the dynamic changes in brain connectivity profiles inflicted by sleep deprivation and how they deviate from regular daily variability. To this end, we obtained functional magnetic resonance imaging data from 60 young, adult male participants, scanned in the morning and evening of the same day and again the following morning. 41 participants underwent total sleep deprivation before the third scan, whereas the remainder had another night of regular sleep. Sleep deprivation strongly altered the connectivity of several resting-state networks, including dorsal attention, default mode, and hippocampal networks. Multivariate classification based on connectivity profiles predicted deprivation state with high accuracy, corroborating the robustness of the findings on an individual level. Finally, correlation analysis suggested that morning-to-evening connectivity changes were reverted by sleep (control group)-a pattern which did not occur after deprivation. We conclude that both, a day of waking and a night of sleep deprivation dynamically alter the brain functional connectome. Copyright © 2015 Elsevier Inc. All rights reserved.

Altered neural connectivity during response inhibition in adolescents with attention-deficit/hyperactivity disorder and their unaffected siblings

NARCIS (Netherlands)

van Rooij, Daan; Hartman, Catharina A.; Mennes, Maarten; Oosterlaan, Jaap; Franke, Barbara; Rommelse, Nanda; Heslenfeld, Dirk; Faraone, Stephen V.; Buitelaar, Jan K.; Hoekstra, Pieter J.

2015-01-01

Introduction: Response inhibition is one of the executive functions impaired in attention-deficit/hyperactivity disorder (ADHD). Increasing evidence indicates that altered functional and structural neural connectivity are part of the neurobiological basis of ADHD. Here, we investigated if

Altered cortical hubs in functional brain networks in amyotrophic lateral sclerosis.

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Ma, Xujing; Zhang, Jiuquan; Zhang, Youxue; Chen, Heng; Li, Rong; Wang, Jian; Chen, Huafu

2015-11-01

Cortical hubs are highly connected nodes in functional brain networks that play vital roles in the efficient transfer of information across brain regions. Although altered functional connectivity has been found in amyotrophic lateral sclerosis (ALS), the changing pattern in functional network hubs in ALS remains unknown. In this study, we applied a voxel-wise method to investigate the changing pattern of cortical hubs in ALS. Through resting-state fMRI, we constructed whole-brain voxel-wise functional networks by measuring the temporal correlations of each pair of brain voxels and identified hubs using the graph theory method. Specifically, a functional connectivity strength (FCS) map was derived from the data on 20 patients with ALS and 20 healthy controls. The brain regions with high FCS values were regarded as functional network hubs. Functional hubs were found mainly in the bilateral precuneus, parietal cortex, medial prefrontal cortex, and in several visual regions and temporal areas in both groups. Within the hub regions, the ALS patients exhibited higher FCS in the prefrontal cortex compared with the healthy controls. The FCS value in the significantly abnormal hub regions was correlated with clinical variables. Results indicated the presence of altered cortical hubs in the ALS patients and could therefore shed light on the pathophysiology mechanisms underlying ALS.

Schizophrenia alters intra-network functional connectivity in the caudate for detecting speech under informational speech masking conditions.

Science.gov (United States)

Zheng, Yingjun; Wu, Chao; Li, Juanhua; Li, Ruikeng; Peng, Hongjun; She, Shenglin; Ning, Yuping; Li, Liang

2018-04-04

Speech recognition under noisy "cocktail-party" environments involves multiple perceptual/cognitive processes, including target detection, selective attention, irrelevant signal inhibition, sensory/working memory, and speech production. Compared to health listeners, people with schizophrenia are more vulnerable to masking stimuli and perform worse in speech recognition under speech-on-speech masking conditions. Although the schizophrenia-related speech-recognition impairment under "cocktail-party" conditions is associated with deficits of various perceptual/cognitive processes, it is crucial to know whether the brain substrates critically underlying speech detection against informational speech masking are impaired in people with schizophrenia. Using functional magnetic resonance imaging (fMRI), this study investigated differences between people with schizophrenia (n = 19, mean age = 33 ± 10 years) and their matched healthy controls (n = 15, mean age = 30 ± 9 years) in intra-network functional connectivity (FC) specifically associated with target-speech detection under speech-on-speech-masking conditions. The target-speech detection performance under the speech-on-speech-masking condition in participants with schizophrenia was significantly worse than that in matched healthy participants (healthy controls). Moreover, in healthy controls, but not participants with schizophrenia, the strength of intra-network FC within the bilateral caudate was positively correlated with the speech-detection performance under the speech-masking conditions. Compared to controls, patients showed altered spatial activity pattern and decreased intra-network FC in the caudate. In people with schizophrenia, the declined speech-detection performance under speech-on-speech masking conditions is associated with reduced intra-caudate functional connectivity, which normally contributes to detecting target speech against speech masking via its functions of suppressing masking-speech signals.

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

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Marjolein Verly

2014-01-01

Full Text Available 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.

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

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Xue Chen

2014-01-01

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

Alterations of parenchymal microstructure, neuronal connectivity and cerebrovascular resistance at adolescence following mild to moderate traumatic brain injury in early development.

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Parent, Maxime; Li, Ying; Santhakumar, Vijayalakshmi; Hyder, Fahmeed; Sanganahalli, Basavaraju G; Kannurpatti, Sridhar

2018-06-01

TBI is a leading cause of morbidity in children. To investigate outcome of early developmental TBI during adolescence, a rat model of fluid percussion injury was developed, where previous work reported deficits in sensorimotor behavior and cortical blood flow at adolescence. 1 Based on the non-localized outcome, we hypothesized that multiple neurophysiological components of brain function, namely neuronal connectivity, synapse/axonal microstructural integrity and neurovascular function are altered and magnetic resonance imaging (MRI) methods could be used to determine regional alterations. Adolescent outcomes of developmental TBI were studied 2-months after injury, using functional MRI (fMRI) and Diffusion Tensor Imaging (DTI). fMRI based resting state functional connectivity (RSFC), representing neural connectivity, was significantly altered between sham and TBI. RSFC strength decreased in the cortex, hippocampus and thalamus accompanied by decrease in the spatial extent of their corresponding RSFC networks and inter-hemispheric asymmetry. Cerebrovascular reactivity to arterial CO2 changes diminished after TBI across both hemispheres, with a more pronounced decrease in the ipsilateral hippocampus, thalamus and motor cortex. DTI measures of fractional anisotropy (FA) and apparent diffusion coefficient (ADC), reporting on axonal and microstructural integrity of the brain, indicated similar inter-hemispheric asymmetry, with highest change in the ipsilateral hippocampus and regions adjoining the ipsilateral thalamus, hypothalamus and amygdala. TBI-induced corpus callosal microstructural alterations indicated measurable changes in inter-hemispheric structural connectivity. Hippocampus, thalamus and select cortical regions were most consistently affected in multiple imaging markers. The multi-modal MRI results demonstrate cortical and subcortical alterations in neural connectivity, cerebrovascular resistance and parenchymal microstructure in the adolescent brain

Functional connectivity disruption in neonates with prenatal marijuana exposure

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Karen eGrewen

2015-11-01

Full Text Available 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 SSRI; -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 hypoconnectivity 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 hyperconnectivity of left amygdala seed with orbital frontal cortex and hypoconnectivity of posterior thalamus seed with hippocampus, suggesting vulnerability to multiple drugs in these circuits.

Functional Connectivity of the Amygdala Is Disrupted in Preschool-Aged Children With Autism Spectrum Disorder.

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Shen, Mark D; Li, Deana D; Keown, Christopher L; Lee, Aaron; Johnson, Ryan T; Angkustsiri, Kathleen; Rogers, Sally J; Müller, Ralph-Axel; Amaral, David G; Nordahl, Christine Wu

2016-09-01

The objective of this study was to determine whether functional connectivity of the amygdala is altered in preschool-age children with autism spectrum disorder (ASD) and to assess the clinical relevance of observed alterations in amygdala connectivity. A resting-state functional connectivity magnetic resonance imaging study of the amygdala (and a parallel study of primary visual cortex) was conducted in 72 boys (mean age 3.5 years; n = 43 with ASD; n = 29 age-matched controls). The ASD group showed significantly weaker connectivity between the amygdala and several brain regions involved in social communication and repetitive behaviors, including bilateral medial prefrontal cortex, temporal lobes, and striatum (p amygdala and frontal and temporal lobes was significantly correlated with increased autism severity in the ASD group (p amygdala and regions of the brain important for social communication and language, which might be clinically relevant because weaker connectivity was associated with increased autism severity. Moreover, although amygdala connectivity was associated with behavioral domains that are diagnostic of ASD, altered connectivity of primary visual cortex was related to sensory hypersensitivity. Copyright © 2016 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Non-concomitant cortical structural and functional alterations in sensorimotor areas following incomplete spinal cord injury

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Yu Pan

2017-01-01

Full Text Available Brain plasticity, including anatomical changes and functional reorganization, is the physiological basis of functional recovery after spinal cord injury (SCI. The correlation between brain anatomical changes and functional reorganization after SCI is unclear. This study aimed to explore whether alterations of cortical structure and network function are concomitant in sensorimotor areas after incomplete SCI. Eighteen patients with incomplete SCI (mean age 40.94 ± 14.10 years old; male:female, 7:11 and 18 healthy subjects (37.33 ± 11.79 years old; male:female, 7:11 were studied by resting state functional magnetic resonance imaging. Gray matter volume (GMV and functional connectivity were used to evaluate cortical structure and network function, respectively. There was no significant alteration of GMV in sensorimotor areas in patients with incomplete SCI compared with healthy subjects. Intra-hemispheric functional connectivity between left primary somatosensory cortex (BA1 and left primary motor cortex (BA4, and left BA1 and left somatosensory association cortex (BA5 was decreased, as well as inter-hemispheric functional connectivity between left BA1 and right BA4, left BA1 and right BA5, and left BA4 and right BA5 in patients with SCI. Functional connectivity between both BA4 areas was also decreased. The decreased functional connectivity between the left BA1 and the right BA4 positively correlated with American Spinal Injury Association sensory score in SCI patients. The results indicate that alterations of cortical anatomical structure and network functional connectivity in sensorimotor areas were non-concomitant in patients with incomplete SCI, indicating the network functional changes in sensorimotor areas may not be dependent on anatomic structure. The strength of functional connectivity within sensorimotor areas could serve as a potential imaging biomarker for assessment and prediction of sensory function in patients with incomplete SCI

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

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

2009-05-15

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

Altered amygdalar resting-state connectivity in depression is explained by both genes and environment.

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Córdova-Palomera, Aldo; Tornador, Cristian; Falcón, Carles; Bargalló, Nuria; Nenadic, Igor; Deco, Gustavo; Fañanás, Lourdes

2015-10-01

Recent findings indicate that alterations of the amygdalar resting-state fMRI connectivity play an important role in the etiology of depression. While both depression and resting-state brain activity are shaped by genes and environment, the relative contribution of genetic and environmental factors mediating the relationship between amygdalar resting-state connectivity and depression remain largely unexplored. Likewise, novel neuroimaging research indicates that different mathematical representations of resting-state fMRI activity patterns are able to embed distinct information relevant to brain health and disease. The present study analyzed the influence of genes and environment on amygdalar resting-state fMRI connectivity, in relation to depression risk. High-resolution resting-state fMRI scans were analyzed to estimate functional connectivity patterns in a sample of 48 twins (24 monozygotic pairs) informative for depressive psychopathology (6 concordant, 8 discordant and 10 healthy control pairs). A graph-theoretical framework was employed to construct brain networks using two methods: (i) the conventional approach of filtered BOLD fMRI time-series and (ii) analytic components of this fMRI activity. Results using both methods indicate that depression risk is increased by environmental factors altering amygdalar connectivity. When analyzing the analytic components of the BOLD fMRI time-series, genetic factors altering the amygdala neural activity at rest show an important contribution to depression risk. Overall, these findings show that both genes and environment modify different patterns the amygdala resting-state connectivity to increase depression risk. The genetic relationship between amygdalar connectivity and depression may be better elicited by examining analytic components of the brain resting-state BOLD fMRI signals. © 2015 Wiley Periodicals, Inc.

Altered brain functional connectivity and behaviour in a mouse model of maternal alcohol binge-drinking.

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Cantacorps, Lídia; González-Pardo, Héctor; Arias, Jorge L; Valverde, Olga; Conejo, Nélida M

2018-06-08

alcohol-exposed offspring, suggesting neuroadaptive effects due to early alcohol exposure. Our results demonstrate that maternal binge-like alcohol drinking causes long-lasting effects on motor and emotional-related behaviours associated with impaired neuronal metabolic capacity and altered functional brain connectivity. Copyright © 2018 Elsevier Inc. All rights reserved.

Mindfulness meditation training alters stress-related amygdala resting state functional connectivity: a randomized controlled trial.

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

2015-12-01

Recent studies indicate that mindfulness meditation training interventions reduce stress and improve stress-related health outcomes, but the neural pathways for these effects are unknown. The present research evaluates whether mindfulness meditation training alters resting state functional connectivity (rsFC) of the amygdala, a region known to coordinate stress processing and physiological stress responses. We show in an initial discovery study that higher perceived stress over the past month is associated with greater bilateral amygdala-subgenual anterior cingulate cortex (sgACC) rsFC in a sample of community adults (n = 130). A follow-up, single-blind randomized controlled trial shows that a 3-day intensive mindfulness meditation training intervention (relative to a well-matched 3-day relaxation training intervention without a mindfulness component) reduced right amygdala-sgACC rsFC in a sample of stressed unemployed community adults (n = 35). Although stress may increase amygdala-sgACC rsFC, brief training in mindfulness meditation could reverse these effects. This work provides an initial indication that mindfulness meditation training promotes functional neuroplastic changes, suggesting an amygdala-sgACC pathway for stress reduction effects. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Acupuncture induces divergent alterations of functional connectivity within conventional frequency bands: evidence from MEG recordings.

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Youbo You

Full Text Available As an ancient Chinese healing modality which has gained increasing popularity in modern society, acupuncture involves stimulation with fine needles inserted into acupoints. Both traditional literature and clinical data indicated that modulation effects largely depend on specific designated acupoints. However, scientific representations of acupoint specificity remain controversial. In the present study, considering the new findings on the sustained effects of acupuncture and its time-varied temporal characteristics, we employed an electrophysiological imaging modality namely magnetoencephalography with a temporal resolution on the order of milliseconds. Taken into account the differential band-limited signal modulations induced by acupuncture, we sought to explore whether or not stimulation at Stomach Meridian 36 (ST36 and a nearby non-meridian point (NAP would evoke divergent functional connectivity alterations within delta, theta, alpha, beta and gamma bands. Whole-head scanning was performed on 28 healthy participants during an eyes-closed no-task condition both preceding and following acupuncture. Data analysis involved calculation of band-limited power (BLP followed by pair-wise BLP correlations. Further averaging was conducted to obtain local and remote connectivity. Statistical analyses revealed the increased connection degree of the left temporal cortex within delta (0.5-4 Hz, beta (13-30 Hz and gamma (30-48 Hz bands following verum acupuncture. Moreover, we not only validated the closer linkage of the left temporal cortex with the prefrontal and frontal cortices, but further pinpointed that such patterns were more extensively distributed in the ST36 group in the delta and beta bands compared to the restriction only to the delta band for NAP. Psychophysical results for significant pain threshold elevation further confirmed the analgesic effect of acupuncture at ST36. In conclusion, our findings may provide a new perspective to lend

Connectomics and neuroticism: an altered functional network organization.

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Servaas, Michelle N; Geerligs, Linda; Renken, Remco J; Marsman, Jan-Bernard C; Ormel, Johan; Riese, Harriëtte; Aleman, André

2015-01-01

The personality trait neuroticism is a potent risk marker for psychopathology. Although the neurobiological basis remains unclear, studies have suggested that alterations in connectivity may underlie it. Therefore, the aim of the current study was to shed more light on the functional network organization in neuroticism. To this end, we applied graph theory on resting-state functional magnetic resonance imaging (fMRI) data in 120 women selected based on their neuroticism score. Binary and weighted brain-wide graphs were constructed to examine changes in the functional network structure and functional connectivity strength. Furthermore, graphs were partitioned into modules to specifically investigate connectivity within and between functional subnetworks related to emotion processing and cognitive control. Subsequently, complex network measures (ie, efficiency and modularity) were calculated on the brain-wide graphs and modules, and correlated with neuroticism scores. Compared with low neurotic individuals, high neurotic individuals exhibited a whole-brain network structure resembling more that of a random network and had overall weaker functional connections. Furthermore, in these high neurotic individuals, functional subnetworks could be delineated less clearly and the majority of these subnetworks showed lower efficiency, while the affective subnetwork showed higher efficiency. In addition, the cingulo-operculum subnetwork demonstrated more ties with other functional subnetworks in association with neuroticism. In conclusion, the 'neurotic brain' has a less than optimal functional network organization and shows signs of functional disconnectivity. Moreover, in high compared with low neurotic individuals, emotion and salience subnetworks have a more prominent role in the information exchange, while sensory(-motor) and cognitive control subnetworks have a less prominent role.

Preliminary findings of altered functional connectivity of the default mode network linked to functional outcomes one year after pediatric traumatic brain injury.

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Stephens, Jaclyn A; Salorio, Cynthia F; Barber, Anita D; Risen, Sarah R; Mostofsky, Stewart H; Suskauer, Stacy J

2017-07-10

This study examined functional connectivity of the default mode network (DMN) and examined brain-behavior relationships in a pilot cohort of children with chronic mild to moderate traumatic brain injury (TBI). Compared to uninjured peers, children with TBI demonstrated less anti-correlated functional connectivity between DMN and right Brodmann Area 40 (BA 40). In children with TBI, more anomalous less anti-correlated) connectivity between DMN and right BA 40 was linked to poorer performance on response inhibition tasks. Collectively, these preliminary findings suggest that functional connectivity between DMN and BA 40 may relate to longterm functional outcomes in chronic pediatric TBI.

Amygdala functional connectivity, HPA axis genetic variation, and life stress in children and relations to anxiety and emotion regulation

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Pagliaccio, David; Luby, Joan L.; Bogdan, Ryan; Agrawal, Arpana; Gaffrey, Michael S.; Belden, Andrew C.; Botteron, Kelly N.; Harms, Michael P.; Barch, Deanna M.

2015-01-01

Internalizing pathology is related to alterations in amygdala resting state functional connectivity, potentially implicating altered emotional reactivity and/or emotion regulation in the etiological pathway. Importantly, there is accumulating evidence that stress exposure and genetic vulnerability impact amygdala structure/function and risk for internalizing pathology. The present study examined whether early life stress and genetic profile scores (10 single nucleotide polymorphisms within four hypothalamic-pituitary-adrenal axis genes: CRHR1, NR3C2, NR3C1, and FKBP5) predicted individual differences in amygdala functional connectivity in school-age children (9–14 year olds; N=120). Whole-brain regression analyses indicated that increasing genetic ‘risk’ predicted alterations in amygdala connectivity to the caudate and postcentral gyrus. Experience of more stressful and traumatic life events predicted weakened amygdala-anterior cingulate cortex connectivity. Genetic ‘risk’ and stress exposure interacted to predict weakened connectivity between the amygdala and the inferior and middle frontal gyri, caudate, and parahippocampal gyrus in those children with the greatest genetic and environmental risk load. Furthermore, amygdala connectivity longitudinally predicted anxiety symptoms and emotion regulation skills at a later follow-up. Amygdala connectivity mediated effects of life stress on anxiety and of genetic variants on emotion regulation. The current results suggest that considering the unique and interacting effects of biological vulnerability and environmental risk factors may be key to understanding the development of altered amygdala functional connectivity, a potential factor in the risk trajectory for internalizing pathology. PMID:26595470

Amygdala functional connectivity, HPA axis genetic variation, and life stress in children and relations to anxiety and emotion regulation.

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Pagliaccio, David; Luby, Joan L; Bogdan, Ryan; Agrawal, Arpana; Gaffrey, Michael S; Belden, Andrew C; Botteron, Kelly N; Harms, Michael P; Barch, Deanna M

2015-11-01

Internalizing pathology is related to alterations in amygdala resting state functional connectivity, potentially implicating altered emotional reactivity and/or emotion regulation in the etiological pathway. Importantly, there is accumulating evidence that stress exposure and genetic vulnerability impact amygdala structure/function and risk for internalizing pathology. The present study examined whether early life stress and genetic profile scores (10 single nucleotide polymorphisms within 4 hypothalamic-pituitary-adrenal axis genes: CRHR1, NR3C2, NR3C1, and FKBP5) predicted individual differences in amygdala functional connectivity in school-age children (9- to 14-year-olds; N = 120). Whole-brain regression analyses indicated that increasing genetic "risk" predicted alterations in amygdala connectivity to the caudate and postcentral gyrus. Experience of more stressful and traumatic life events predicted weakened amygdala-anterior cingulate cortex connectivity. Genetic "risk" and stress exposure interacted to predict weakened connectivity between the amygdala and the inferior and middle frontal gyri, caudate, and parahippocampal gyrus in those children with the greatest genetic and environmental risk load. Furthermore, amygdala connectivity longitudinally predicted anxiety symptoms and emotion regulation skills at a later follow-up. Amygdala connectivity mediated effects of life stress on anxiety and of genetic variants on emotion regulation. The current results suggest that considering the unique and interacting effects of biological vulnerability and environmental risk factors may be key to understanding the development of altered amygdala functional connectivity, a potential factor in the risk trajectory for internalizing pathology. (c) 2015 APA, all rights reserved).

Altered Amygdala Resting-State Functional Connectivity and Hemispheric Asymmetry in Patients With Social Anxiety Disorder

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Ye-Ha Jung

2018-04-01

Full Text Available Background: The amygdala plays a key role in emotional hyperreactivity in response to social threat in patients with social anxiety disorder (SAD. We investigated resting-state functional connectivity (rs-FCN of the left and right amygdala with various brain regions and functional lateralization in patients with SAD.Methods: A total of 36 patients with SAD and 42 matched healthy controls underwent functional magnetic resonance imaging (fMRI at rest. Using the left and right amygdala as seed regions, we compared the strength of the rs-FCN in the patient and control groups. Furthermore, we investigated group differences in the hemispheric asymmetry of the functional connectivity maps of the left and right amygdala.Results: Compared with healthy controls, the rs-FCN between the left amygdala and the dorsolateral prefrontal cortex was reduced in patients with SAD, whereas left amygdala connectivity with the fusiform gyrus, anterior insula, supramarginal gyrus, and precuneus was increased or positively deflected in the patient group. Additionally, the strength rs-FCN between the left amygdala and anterior insula was positively associated with the severity of the fear of negative evaluation in patients with SAD (r = 0.338, p = 0.044. The rs-FCN between the right amygdala and medial frontal gyrus was decreased in patients with SAD compared with healthy controls, whereas connectivity with the parahippocampal gyrus was greater in the patient group than in the control group. The hemispheric asymmetry patterns in the anterior insula, intraparietal sulcus (IPS, and inferior frontal gyrus of the patient group were opposite those of the control group, and functional lateralization of the connectivity between the amygdala and the IPS was associated with the severity of social anxiety symptoms (r = 0.365, p = 0.037.Conclusion: Our findings suggest that in addition to impaired fronto-amygdala communication, the functional lateralization of amygdala function

Changes of functional connectivity in the left frontoparietal network following aphasic stroke

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Dan eZhu

2014-05-01

Full Text Available Language is an essential higher cognitive function supported by large-scale brain networks. In this study, we investigated functional connectivity changes in the left frontoparietal network (LFPN, a language-cognition related brain network in aphasic patients. We enrolled thirteen aphasic patients who had undergone a stroke in the left hemisphere and age-, gender-, educational level-matched controls and analyzed the data by integrating independent component analysis (ICA with a network connectivity analysis method. Resting state functional magnetic resonance imaging (fMRI and clinical evaluation of language function were assessed at two stages: one and two months after stroke onset. We found reduced functional connectivity between the LFPN and the right middle frontal cortex, medial frontal cortex and right inferior frontal cortex in aphasic patients as compared to controls. Correlation analysis showed that stronger functional connectivity between the LFPN and the right middle frontal cortex and medial frontal cortex coincided with more preserved language comprehension ability after stroke. Network connectivity analysis showed reduced LFPN connectivity as indicated by the mean network connectivity index of key regions in the LFPN of aphasic patients. The decreased LFPN connectivity in stroke patients was significantly associated with the impairment of language function in their comprehension ability. We also found significant association between recovery of comprehension ability and the mean changes in intrinsic LFPN connectivity. Our findings suggest that brain lesions may influence language comprehension by altering functional connectivity between regions and that the patterns of abnormal functional connectivity may contribute to the recovery of language deficits.

Structural connectivity in schizophrenia and its impact on the dynamics of spontaneous functional networks

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Cabral, Joana; Fernandes, Henrique M.; Van Hartevelt, Tim J.; Kringelbach, Morten L.; James, Anthony C.; Deco, Gustavo

2013-01-01

The neuropathology of schizophrenia remains unclear. Some insight has come from modern neuroimaging techniques, which offer an unparalleled opportunity to explore in vivo the structure and function of the brain. Using functional magnetic resonance imaging, it has been found that the large-scale resting-state functional connectivity (rsFC) in schizophrenia — measured as the temporal correlations of the blood-oxygen-level-dependent (BOLD) signal — exhibit altered network topology, with lower small-world index. The origin of these rsFC alterations and link with the underlying structural connectivity remain unclear. In this work, we used a computational model of spontaneous large-scale brain activity to explore the role of the structural connectivity in the large-scale dynamics of the brain in health and schizophrenia. The structural connectomes from 15 adolescent patients with early-onset schizophrenia and 15 age- and gender-matched controls were built from diffusion tensor imaging data to detect the white matter tracts between 90 brain areas. Brain areas, simulated using a reduced dynamic mean-field model, receive excitatory input from other areas in proportion to the number of fibre tracts between them. The simulated mean field activity was transformed into BOLD signal, and the properties of the simulated functional networks were analyzed. Our results suggest that the functional alterations observed in schizophrenia are not directly linked to alterations in the structural topology. Instead, subtly randomized and less small-world functional networks appear when the brain operates with lower global coupling, which shifts the dynamics from the optimal healthy regime

Structural connectivity in schizophrenia and its impact on the dynamics of spontaneous functional networks

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Cabral, Joana [Theoretical and Computational Neuroscience Group, Center of Brain and Cognition, Universitat Pompeu Fabra, Barcelona 08018 (Spain); Department of Psychiatry, University of Oxford, Oxford OX3 7JX (United Kingdom); Fernandes, Henrique M.; Van Hartevelt, Tim J.; Kringelbach, Morten L. [Department of Psychiatry, University of Oxford, Oxford OX3 7JX (United Kingdom); Center of Functionally Integrative Neuroscience (CFIN), Aarhus University, Aarhus (Denmark); James, Anthony C. [Department of Psychiatry, University of Oxford, Oxford OX3 7JX (United Kingdom); Highfield Unit, Warneford Hospital, Oxford OX3 7JX (United Kingdom); Deco, Gustavo [Theoretical and Computational Neuroscience Group, Center of Brain and Cognition, Universitat Pompeu Fabra, Barcelona 08018 (Spain); Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona 08010 (Spain)

2013-12-15

The neuropathology of schizophrenia remains unclear. Some insight has come from modern neuroimaging techniques, which offer an unparalleled opportunity to explore in vivo the structure and function of the brain. Using functional magnetic resonance imaging, it has been found that the large-scale resting-state functional connectivity (rsFC) in schizophrenia — measured as the temporal correlations of the blood-oxygen-level-dependent (BOLD) signal — exhibit altered network topology, with lower small-world index. The origin of these rsFC alterations and link with the underlying structural connectivity remain unclear. In this work, we used a computational model of spontaneous large-scale brain activity to explore the role of the structural connectivity in the large-scale dynamics of the brain in health and schizophrenia. The structural connectomes from 15 adolescent patients with early-onset schizophrenia and 15 age- and gender-matched controls were built from diffusion tensor imaging data to detect the white matter tracts between 90 brain areas. Brain areas, simulated using a reduced dynamic mean-field model, receive excitatory input from other areas in proportion to the number of fibre tracts between them. The simulated mean field activity was transformed into BOLD signal, and the properties of the simulated functional networks were analyzed. Our results suggest that the functional alterations observed in schizophrenia are not directly linked to alterations in the structural topology. Instead, subtly randomized and less small-world functional networks appear when the brain operates with lower global coupling, which shifts the dynamics from the optimal healthy regime.

Altered resting-state connectivity within default mode network associated with late chronotype.

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Horne, Charlotte Mary; Norbury, Ray

2018-04-20

Current evidence suggests late chronotype individuals have an increased risk of developing depression. However, the underlying neural mechanisms of this association are not fully understood. Forty-six healthy, right-handed individuals free of current or previous diagnosis of depression, family history of depression or sleep disorder underwent resting-state functional Magnetic Resonance Imaging (rsFMRI). Using an Independent Component Analysis (ICA) approach, the Default Mode Network (DMN) was identified based on a well validated template. Linear effects of chronotype on DMN connectivity were tested for significance using non-parametric permutation tests (applying 5000 permutations). Sleep quality, age, gender, measures of mood and anxiety, time of scan and cortical grey matter volume were included as covariates in the regression model. A significant positive correlation between chronotype and functional connectivity within nodes of the DMN was observed, including; bilateral PCC and precuneus, such that later chronotype (participants with lower rMEQ scores) was associated with decreased connectivity within these regions. The current results appear consistent with altered DMN connectivity in depressed patients and weighted evidence towards reduced DMN connectivity in other at-risk populations which may, in part, explain the increased vulnerability for depression in late chronotype individuals. The effect may be driven by self-critical thoughts associated with late chronotype although future studies are needed to directly investigate this. Copyright © 2018 Elsevier Ltd. All rights reserved.

Brain functional connectivity changes in children that differ in impulsivity temperamental trait

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Alberto eInuggi

2014-05-01

Full Text Available Impulsivity is a core personality trait forming part of normal behavior and contributing to adaptive functioning. However, in typically developing children, altered patterns of impulsivity constitute a risk factor for the development of behavioral problems. Since both pathological and non-pathological states are commonly characterized by continuous transitions, we used a correlative approach to investigate the potential link between personality and brain dynamics. We related brain functional connectivity of typically developing children, measured with magnetic resonance imaging at rest, with their impulsivity scores obtained from a questionnaire completed by their parents. We first looked for areas within the default mode network (DMN whose functional connectivity might be modulated by trait impulsivity. Then, we calculated the functional connectivity among these regions and the rest of the brain in order to assess if impulsivity trait altered their relationships. We found two DMN clusters located at the posterior cingulate cortex and the right angular gyrus which were negatively correlated with impulsivity scores. The whole-brain correlation analysis revealed the classic network of correlating and anti-correlating areas with respect to the DMN. The impulsivity trait modulated such pattern showing that the canonical anti-phasic relation between DMN and action-related network was reduced in high impulsive children. These results represent the first evidence that the impulsivity, measured as personality trait assessed through parents’ report, exerts a modulatory influence over the functional connectivity of resting state brain networks in typically developing children. The present study goes further to connect developmental approaches, mainly based on data collected through the use of questionnaires, and behavioral neuroscience, interested in how differences in brain structure and functions reflect in differences in behavior.

Brain functional connectivity changes in children that differ in impulsivity temperamental trait.

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Inuggi, Alberto; Sanz-Arigita, Ernesto; González-Salinas, Carmen; Valero-García, Ana V; García-Santos, Jose M; Fuentes, Luis J

2014-01-01

Impulsivity is a core personality trait forming part of normal behavior and contributing to adaptive functioning. However, in typically developing children, altered patterns of impulsivity constitute a risk factor for the development of behavioral problems. Since both pathological and non-pathological states are commonly characterized by continuous transitions, we used a correlative approach to investigate the potential link between personality and brain dynamics. We related brain functional connectivity of typically developing children, measured with magnetic resonance imaging at rest, with their impulsivity scores obtained from a questionnaire completed by their parents. We first looked for areas within the default mode network (DMN) whose functional connectivity might be modulated by trait impulsivity. Then, we calculated the functional connectivity among these regions and the rest of the brain in order to assess if impulsivity trait altered their relationships. We found two DMN clusters located at the posterior cingulate cortex and the right angular gyrus which were negatively correlated with impulsivity scores. The whole-brain correlation analysis revealed the classic network of correlating and anti-correlating areas with respect to the DMN. The impulsivity trait modulated such pattern showing that the canonical anti-phasic relation between DMN and action-related network was reduced in high impulsive children. These results represent the first evidence that the impulsivity, measured as personality trait assessed through parents' report, exerts a modulatory influence over the functional connectivity of resting state brain networks in typically developing children. The present study goes further to connect developmental approaches, mainly based on data collected through the use of questionnaires, and behavioral neuroscience, interested in how differences in brain structure and functions reflect in differences in behavior.

Intermittent Hypoxia Enhances Functional Connectivity of Midcervical Spinal Interneurons

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Streeter, Kristi A.; Sunshine, Michael D.; Patel, Shreya; Gonzalez-Rothi, Elisa J.; Reier, Paul J.

2017-01-01

Brief, intermittent oxygen reductions [acute intermittent hypoxia (AIH)] evokes spinal plasticity. Models of AIH-induced neuroplasticity have focused on motoneurons; however, most midcervical interneurons (C-INs) also respond to hypoxia. We hypothesized that AIH would alter the functional connectivity between C-INs and induce persistent changes in discharge. Bilateral phrenic nerve activity was recorded in anesthetized and ventilated adult male rats and a multielectrode array was used to record C4/5 spinal discharge before [baseline (BL)], during, and 15 min after three 5 min hypoxic episodes (11% O2, H1–H3). Most C-INs (94%) responded to hypoxia by either increasing or decreasing firing rate. Functional connectivity was examined by cross-correlating C-IN discharge. Correlograms with a peak or trough were taken as evidence for excitatory or inhibitory connectivity between C-IN pairs. A subset of C-IN pairs had increased excitatory cross-correlations during hypoxic episodes (34%) compared with BL (19%; p phrenic motoneurons and excitatory inputs to these “pre-phrenic” cells increased during AIH. We conclude that AIH alters connectivity of the midcervical spinal network. To our knowledge, this is the first demonstration that AIH induces plasticity within the propriospinal network. SIGNIFICANCE STATEMENT Acute intermittent hypoxia (AIH) can trigger spinal plasticity associated with sustained increases in respiratory, somatic, and/or autonomic motor output. The impact of AIH on cervical spinal interneuron (C-IN) discharge and connectivity is unknown. Our results demonstrate that AIH recruits excitatory C-INs into the spinal respiratory (phrenic) network. AIH also enhances excitatory and reduces inhibitory connections among the C-IN network. We conclude that C-INs are part of the respiratory, somatic, and/or autonomic response to AIH, and that propriospinal plasticity may contribute to sustained increases in motor output after AIH. PMID:28751456

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

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

2017-04-01

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

Assessment of cerebral perfusional and functional connectivity in schizophrenia using magnetic resonance imaging

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Oliveira, Ícaro A. F.; Guimarães, Tiago M.; Souza, Roberto M.; Santos, Antônio C. dos; Leoni, Renata F.; Machado-Sousa, João Paulo; Hallak, Jaime E.C.

2017-01-01

Schizophrenia is a significant mental disorder that compromises structural and functional aspects of the brain, with an extreme effect on the patient’s thoughts, feelings, and behavior. Physiologically, changes in neuronal activity are reported besides functional and structural abnormalities. Since the cerebral blood flow (CBF) is directly related to neuronal activity, the magnetic resonance imaging (MRI) technique called arterial spin labeling (ASL), which allows the quantification of CBF, is a useful tool in brain perfusional evaluation. In addition, ASL can be used to assess functional connectivity, which is efficient in investigating functional impairment between regions of the brain. Pseudo-continuous arterial spin labeling (pCASL) images were acquired from 28 schizophrenia patients in treatment and 28 age-matched healthy controls. Static CBF and connectivity patterns were assessed in both groups. Decreased CBF and functional connectivity were observed in regions that form two resting brain networks, default mode (DMN) and salience (SN), for schizophrenia patients. Previous studies related the features of this pathology with altered resting CBF and functional disconnections. Therefore, using a noninvasive technique, it was possible to find CBF deficits and altered functional organization of the brain in schizophrenia patients that are associated with the symptoms and characteristics of the disorder. (author)

Assessment of cerebral perfusional and functional connectivity in schizophrenia using magnetic resonance imaging

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Oliveira, Ícaro A. F.; Guimarães, Tiago M.; Souza, Roberto M.; Santos, Antônio C. dos; Leoni, Renata F.; Machado-Sousa, João Paulo; Hallak, Jaime E.C. [Universidade de Sao Paulo (USP), Ribeirao Preto, SP (Brazil)

2017-07-01

Schizophrenia is a significant mental disorder that compromises structural and functional aspects of the brain, with an extreme effect on the patient’s thoughts, feelings, and behavior. Physiologically, changes in neuronal activity are reported besides functional and structural abnormalities. Since the cerebral blood flow (CBF) is directly related to neuronal activity, the magnetic resonance imaging (MRI) technique called arterial spin labeling (ASL), which allows the quantification of CBF, is a useful tool in brain perfusional evaluation. In addition, ASL can be used to assess functional connectivity, which is efficient in investigating functional impairment between regions of the brain. Pseudo-continuous arterial spin labeling (pCASL) images were acquired from 28 schizophrenia patients in treatment and 28 age-matched healthy controls. Static CBF and connectivity patterns were assessed in both groups. Decreased CBF and functional connectivity were observed in regions that form two resting brain networks, default mode (DMN) and salience (SN), for schizophrenia patients. Previous studies related the features of this pathology with altered resting CBF and functional disconnections. Therefore, using a noninvasive technique, it was possible to find CBF deficits and altered functional organization of the brain in schizophrenia patients that are associated with the symptoms and characteristics of the disorder. (author)

Altered Interhemispheric Functional Coordination in Chronic Tinnitus Patients

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Yu-Chen Chen

2015-01-01

Full Text Available Purpose. Recent studies suggest that tinnitus may be due in part to aberrant callosal structure and interhemispheric interaction. To explore this hypothesis we use a novel method, voxel-mirrored homotopic connectivity (VMHC, to examine the resting-state interhemispheric functional connectivity and its relationships with clinical characteristics in chronic tinnitus patients. Materials and Methods. Twenty-eight chronic tinnitus patients with normal hearing thresholds and 30 age-, sex-, education-, and hearing threshold-matched healthy controls were included in this study and underwent the resting-state fMRI scanning. We computed the VMHC to analyze the interhemispheric functional coordination between homotopic points of the brain in both groups. Results. Compared to the controls, tinnitus patients showed significantly increased VMHC in the middle temporal gyrus, middle frontal gyrus, and superior occipital gyrus. In tinnitus patients, a positive correlation was found between tinnitus duration and VMHC of the uncus. Moreover, correlations between VMHC changes and tinnitus distress were observed in the transverse temporal gyrus, superior temporal pole, precentral gyrus, and calcarine cortex. Conclusions. These results show altered interhemispheric functional connectivity linked with specific tinnitus characteristics in chronic tinnitus patients, which may be implicated in the neuropathophysiology of tinnitus.

Functional connectivity in task-negative network of the Deaf: effects of sign language experience

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Evie Malaia

2014-06-01

Full Text Available Prior studies investigating cortical processing in Deaf signers suggest that life-long experience with sign language and/or auditory deprivation may alter the brain’s anatomical structure and the function of brain regions typically recruited for auditory processing (Emmorey et al., 2010; Pénicaud et al., 2013 inter alia. We report the first investigation of the task-negative network in Deaf signers and its functional connectivity—the temporal correlations among spatially remote neurophysiological events. We show that Deaf signers manifest increased functional connectivity between posterior cingulate/precuneus and left medial temporal gyrus (MTG, but also inferior parietal lobe and medial temporal gyrus in the right hemisphere- areas that have been found to show functional recruitment specifically during sign language processing. These findings suggest that the organization of the brain at the level of inter-network connectivity is likely affected by experience with processing visual language, although sensory deprivation could be another source of the difference. We hypothesize that connectivity alterations in the task negative network reflect predictive/automatized processing of the visual signal.

Age-related decline in functional connectivity of the vestibular cortical network.

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Cyran, Carolin Anna Maria; Boegle, Rainer; Stephan, Thomas; Dieterich, Marianne; Glasauer, Stefan

2016-04-01

In the elderly, major complaints include dizziness and an increasing number of falls, possibly related to an altered processing of vestibular sensory input. In this study, we therefore investigate age-related changes induced by processing of vestibular sensory stimulation. While previous functional imaging studies of healthy aging have investigated brain function during task performance or at rest, we used galvanic vestibular stimulation during functional MRI in a task-free sensory stimulation paradigm to study the effect of healthy aging on central vestibular processing, which might only become apparent during stimulation processing. Since aging may affect signatures of brain function beyond the BOLD-signal amplitude-such as functional connectivity or temporal signal variability--we employed independent component analysis and partial least squares analysis of temporal signal variability. We tested for age-associated changes unrelated to vestibular processing, using a motor paradigm, voxel-based morphometry and diffusion tensor imaging. This allows us to control for general age-related modifications, possibly originating from vascular, atrophic or structural connectivity changes. Age-correlated decreases of functional connectivity and increases of BOLD--signal variability were associated with multisensory vestibular networks. In contrast, no age-related functional connectivity changes were detected in somatosensory networks or during the motor paradigm. The functional connectivity decrease was not due to structural changes but to a decrease in response amplitude. In synopsis, our data suggest that both the age-dependent functional connectivity decrease and the variability increase may be due to deteriorating reciprocal cortico-cortical inhibition with age and related to multimodal vestibular integration of sensory inputs.

Altered temporal features of intrinsic connectivity networks in boys with combined type of attention deficit hyperactivity disorder

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Wang, Xun-Heng; Li, Lihua

2015-01-01

Highlights: • Temporal patterns within ICNs provide new way to investigate ADHD brains. • ADHD exhibits enhanced temporal activities within and between ICNs. • Network-wise ALFF influences functional connectivity between ICNs. • Univariate patterns within ICNs are correlated to behavior scores. - Abstract: Purpose: Investigating the altered temporal features within and between intrinsic connectivity networks (ICNs) for boys with attention-deficit/hyperactivity disorder (ADHD); and analyzing the relationships between altered temporal features within ICNs and behavior scores. Materials and methods: A cohort of boys with combined type of ADHD and a cohort of age-matched healthy boys were recruited from ADHD-200 Consortium. All resting-state fMRI datasets were preprocessed and normalized into standard brain space. Using general linear regression, 20 ICNs were taken as spatial templates to analyze the time-courses of ICNs for each subject. Amplitude of low frequency fluctuations (ALFFs) were computed as univariate temporal features within ICNs. Pearson correlation coefficients and node strengths were computed as bivariate temporal features between ICNs. Additional correlation analysis was performed between temporal features of ICNs and behavior scores. Results: ADHD exhibited more activated network-wise ALFF than normal controls in attention and default mode-related network. Enhanced functional connectivities between ICNs were found in ADHD. The network-wise ALFF within ICNs might influence the functional connectivity between ICNs. The temporal pattern within posterior default mode network (pDMN) was positively correlated to inattentive scores. The subcortical network, fusiform-related DMN and attention-related networks were negatively correlated to Intelligence Quotient (IQ) scores. Conclusion: The temporal low frequency oscillations of ICNs in boys with ADHD were more activated than normal controls during resting state; the temporal features within ICNs could

Altered temporal features of intrinsic connectivity networks in boys with combined type of attention deficit hyperactivity disorder

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Wang, Xun-Heng, E-mail: xhwang@hdu.edu.cn [College of Life Information Science and Instrument Engineering, Hangzhou Dianzi University, Hangzhou 310018 (China); School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096 (China); Li, Lihua [College of Life Information Science and Instrument Engineering, Hangzhou Dianzi University, Hangzhou 310018 (China)

2015-05-15

Highlights: • Temporal patterns within ICNs provide new way to investigate ADHD brains. • ADHD exhibits enhanced temporal activities within and between ICNs. • Network-wise ALFF influences functional connectivity between ICNs. • Univariate patterns within ICNs are correlated to behavior scores. - Abstract: Purpose: Investigating the altered temporal features within and between intrinsic connectivity networks (ICNs) for boys with attention-deficit/hyperactivity disorder (ADHD); and analyzing the relationships between altered temporal features within ICNs and behavior scores. Materials and methods: A cohort of boys with combined type of ADHD and a cohort of age-matched healthy boys were recruited from ADHD-200 Consortium. All resting-state fMRI datasets were preprocessed and normalized into standard brain space. Using general linear regression, 20 ICNs were taken as spatial templates to analyze the time-courses of ICNs for each subject. Amplitude of low frequency fluctuations (ALFFs) were computed as univariate temporal features within ICNs. Pearson correlation coefficients and node strengths were computed as bivariate temporal features between ICNs. Additional correlation analysis was performed between temporal features of ICNs and behavior scores. Results: ADHD exhibited more activated network-wise ALFF than normal controls in attention and default mode-related network. Enhanced functional connectivities between ICNs were found in ADHD. The network-wise ALFF within ICNs might influence the functional connectivity between ICNs. The temporal pattern within posterior default mode network (pDMN) was positively correlated to inattentive scores. The subcortical network, fusiform-related DMN and attention-related networks were negatively correlated to Intelligence Quotient (IQ) scores. Conclusion: The temporal low frequency oscillations of ICNs in boys with ADHD were more activated than normal controls during resting state; the temporal features within ICNs could

Altered brain activation and connectivity during anticipation of uncertain threat in trait anxiety.

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Geng, Haiyang; Wang, Yi; Gu, Ruolei; Luo, Yue-Jia; Xu, Pengfei; Huang, Yuxia; Li, Xuebing

2018-06-08

In the research field of anxiety, previous studies generally focus on emotional responses following threat. A recent model of anxiety proposes that altered anticipation prior to uncertain threat is related with the development of anxiety. Behavioral findings have built the relationship between anxiety and distinct anticipatory processes including attention, estimation of threat, and emotional responses. However, few studies have characterized the brain organization underlying anticipation of uncertain threat and its role in anxiety. In the present study, we used an emotional anticipation paradigm with functional magnetic resonance imaging (fMRI) to examine the aforementioned topics by employing brain activation and general psychophysiological interactions (gPPI) analysis. In the activation analysis, we found that high trait anxious individuals showed significantly increased activation in the thalamus, middle temporal gyrus (MTG), and dorsomedial prefrontal cortex (dmPFC), as well as decreased activation in the precuneus, during anticipation of uncertain threat compared to the certain condition. In the gPPI analysis, the key regions including the amygdala, dmPFC, and precuneus showed altered connections with distributed brain areas including the ventromedial prefrontal cortex (vmPFC), dorsolateral prefrontal cortex (dlPFC), inferior parietal sulcus (IPS), insula, para-hippocampus gyrus (PHA), thalamus, and MTG involved in anticipation of uncertain threat in anxious individuals. Taken together, our findings indicate that during the anticipation of uncertain threat, anxious individuals showed altered activations and functional connectivity in widely distributed brain areas, which may be critical for abnormal perception, estimation, and emotion reactions during the anticipation of uncertain threat. © 2018 Wiley Periodicals, Inc.

Aberrant functional connectivity for diagnosis of major depressive disorder: a discriminant analysis.

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Cao, Longlong; Guo, Shuixia; Xue, Zhimin; Hu, Yong; Liu, Haihong; Mwansisya, Tumbwene E; Pu, Weidan; Yang, Bo; Liu, Chang; Feng, Jianfeng; Chen, Eric Y H; Liu, Zhening

2014-02-01

Aberrant brain functional connectivity patterns have been reported in major depressive disorder (MDD). It is unknown whether they can be used in discriminant analysis for diagnosis of MDD. In the present study we examined the efficiency of discriminant analysis of MDD by individualized computer-assisted diagnosis. Based on resting-state functional magnetic resonance imaging data, a new approach was adopted to investigate functional connectivity changes in 39 MDD patients and 37 well-matched healthy controls. By using the proposed feature selection method, we identified significant altered functional connections in patients. They were subsequently applied to our analysis as discriminant features using a support vector machine classification method. Furthermore, the relative contribution of functional connectivity was estimated. After subset selection of high-dimension features, the support vector machine classifier reached up to approximately 84% with leave-one-out training during the discrimination process. Through summarizing the classification contribution of functional connectivities, we obtained four obvious contribution modules: inferior orbitofrontal module, supramarginal gyrus module, inferior parietal lobule-posterior cingulated gyrus module and middle temporal gyrus-inferior temporal gyrus module. The experimental results demonstrated that the proposed method is effective in discriminating MDD patients from healthy controls. Functional connectivities might be useful as new biomarkers to assist clinicians in computer auxiliary diagnosis of MDD. © 2013 The Authors. Psychiatry and Clinical Neurosciences © 2013 Japanese Society of Psychiatry and Neurology.

Aberrant resting-state corticostriatal functional connectivity in cirrhotic patients with hyperintense globus pallidus on T1-weighted MR imaging.

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Xi-Qi Zhu

Full Text Available Neurobiological and neuroimaging studies have emphasized the structural and functional alterations in the striatum of cirrhotic patients, but alterations in the functional connections between the striatum and other brain regions have not yet been explored. Of note, manganese accumulation in the nervous system, frequently reflected by hyperintensity at the bilateral globus pallidus (GP on T1-weighted imaging, has been considered a factor affecting the striatal and cortical functions in hepatic decompensation. We employed resting-state functional magnetic resonance imaging to analyze the temporal correlation between the striatum and the remaining brain regions using seed-based correlation analyses. The two-sample t-test was conducted to detect the differences in corticostriatal connectivity between 44 cirrhotic patients with hyperintensity at the bilateral GP and 20 healthy controls. Decreased connectivity of the caudate was detected in the anterior/middle cingulate gyrus, and increased connectivity of the caudate was found in the left motor cortex. A reduction in functional connectivity was found between the putamen and several regions, including the anterior cingulate gyrus, right insular lobe, inferior frontal gyrus, left parahippocampal gyrus, and anterior lobe of the right cerebellum; increased connectivity was detected between the putamen and right middle temporal gyrus. There were significant correlations between the corticostriatal connectivity and neuropsychological performances in the patient group, but not between the striatal connectivity and GP signal intensity. These alterations in the corticostriatal functional connectivity suggested the abnormalities in the intrinsic brain functional organiztion among the cirrhotic patients with manganese deposition, and may be associated with development of metabolic encephalopathy. The manganese deposition in nervous system, however, can not be an independent factor predicting the resting

Resting State Functional Connectivity in Early Blind Humans

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Harold eBurton

2014-04-01

Full Text Available 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.

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

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Seok, Ji-Woo; Sohn, Jin-Hun

2018-01-01

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

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

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Ji-Woo Seok

2018-03-01

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

Altered structural and functional thalamocortical networks in secondarily generalized extratemporal lobe seizures

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Syu-Jyun Peng

2017-01-01

Full Text Available Structural and functional abnormalities in the thalamocortical network in primary generalized epilepsies or mesial temporal lobe epilepsy have recently been identified by voxel-wise analyses of neuroimaging. However, evidence is needed regarding the profiles of the thalamocortical network in patients with secondarily generalized seizures from focal neocortical sources. We used high-resolution T1-weighted, diffusion-tensor and resting-state functional MR imaging (rs-fMRI to examine 16 patients with secondarily generalized extratemporal lobe seizures and 16 healthy controls. All the patients were medically effective and MRI-negative. Using whole brain voxel-based morphometry (VBM to compare the patients with the normal controls, we observed significantly decreased gray matter (GM density in the thalamus and 3 frontal gyri and significantly reduced white matter (WM fractional anisotropy (FA in the bilateral anterior corona radiata of the patients. Alterations in the thalamocortical functional connectivity with different cortices were identified by the rs-fMRI analysis seeding of the whole thalamus. The prefrontal gyri with the greatest functional connectivity were also traced by seeding a sub-thalamic region that is demarcated in an atlas, in which the thalamic parcellation is based on the WM connectivity to the cortices. This sub-thalamic region anatomically contains the mediodorsal thalamic nucleus where, concordantly, there was a significant decrease in thalamic GM density in the VBM study. In contrast to the negative correlation between the disease duration and reduced thalamic densities and subcortical FA values, the strength of the functional thalamocortical connectivity had a paradoxical correlation. Our results conclusively indicate that generalized seizures with a focal cortical source are associated with structural and functional alterations in the thalamocortical network.

Functional Connectivity Estimated from Resting-State fMRI Reveals Selective Alterations in Male Adolescents with Pure Conduct Disorder.

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Feng-Mei Lu

Full Text Available Conduct disorder (CD is characterized by a persistent pattern of antisocial behavior and aggression in childhood and adolescence. Previous task-based and resting-state functional magnetic resonance imaging (fMRI studies have revealed widespread brain regional abnormalities in adolescents with CD. However, whether the resting-state networks (RSNs are altered in adolescents with CD remains unknown. In this study, resting-state fMRI data were first acquired from eighteen male adolescents with pure CD and eighteen age- and gender-matched typically developing (TD individuals. Independent component analysis (ICA was implemented to extract nine representative RSNs, and the generated RSNs were then compared to show the differences between the CD and TD groups. Interestingly, it was observed from the brain mapping results that compared with the TD group, the CD group manifested decreased functional connectivity in four representative RSNs: the anterior default mode network (left middle frontal gyrus, which is considered to be correlated with impaired social cognition, the somatosensory network (bilateral supplementary motor area and right postcentral gyrus, the lateral visual network (left superior occipital gyrus, and the medial visual network (right fusiform, left lingual gyrus and right calcarine, which are expected to be relevant to the perceptual systems responsible for perceptual dysfunction in male adolescents with CD. Importantly, the novel findings suggested that male adolescents with pure CD were identified to have dysfunctions in both low-level perceptual networks (the somatosensory network and visual network and a high-order cognitive network (the default mode network. Revealing the changes in the functional connectivity of these RSNs enhances our understanding of the neural mechanisms underlying the modulation of emotion and social cognition and the regulation of perception in adolescents with CD.

Dynamic functional connectivity analysis reveals transient states of dysconnectivity in schizophrenia

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E. Damaraju

2014-01-01

. Group differences are weak or absent during other connectivity states. Dynamic analysis also revealed hypoconnectivity between the putamen and sensory networks during the same states of thalamic hyperconnectivity; notably, this finding cannot be observed in the static connectivity analysis. Finally, in post-hoc analyses we observed that the relationships between sub-cortical low frequency power and connectivity with sensory networks is altered in patients, suggesting different functional interactions between sub-cortical nuclei and sensorimotor cortex during specific connectivity states. While important differences between patients with schizophrenia and healthy controls have been identified, one should interpret the results with caution given the history of medication in patients. Taken together, our results support and expand current knowledge regarding dysconnectivity in schizophrenia, and strongly advocate the use of dynamic analyses to better account for and understand functional connectivity differences.

Two-stage decompositions for the analysis of functional connectivity for fMRI with application to Alzheimer’s disease risk

OpenAIRE

Caffo, Brian S.; Crainiceanu, Ciprian M.; Verduzco, Guillermo; Joel, Suresh; Mostofsky, Stewart H.; Bassett, Susan Spear; Pekar, James J.

2010-01-01

Functional connectivity is the study of correlations in measured neurophysiological signals. Altered functional connectivity has been shown to be associated with a variety of cognitive and memory impairments and dysfunction, including Alzheimer’s disease. In this manuscript we use a two-stage application of the singular value decomposition to obtain data driven population-level measures of functional connectivity in functional magnetic resonance imaging (fMRI). The method is computationally s...

More consistently altered connectivity patterns for cerebellum and medial temporal lobes than for amygdala and striatum in schizophrenia

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Henning ePeters

2016-02-01

Full Text Available Background: Brain architecture can be divided into a cortico-thalamic system and modulatory ‘subcortical-cerebellar’ systems containing key structures such as striatum, medial temporal lobes (MTLs, amygdala, and cerebellum. Subcortical-cerebellar systems are known to be altered in schizophrenia. In particular, intrinsic functional brain connectivity (iFC between these systems has been consistently demonstrated in patients. While altered connectivity is known for each subcortical-cerebellar system separately, it is unknown whether subcortical-cerebellar systems’ connectivity patterns with the cortico-thalamic system are comparably altered across systems, i.e., if separate subcortical-cerebellar systems’ connectivity patterns are consistent across patients. Methods: To investigate this question, 18 patients with schizophrenia (3 unmedicated, 15 medicated with atypical antipsychotics and 18 healthy controls were assessed by resting-state functional magnetic resonance imaging (fMRI. Independent component analysis of fMRI data revealed cortical intrinsic brain networks (NWs with time courses representing proxies for cortico-thalamic system activity. Subcortical-cerebellar systems’ activity was represented by fMRI-based time courses of selected regions-of-interest (ROIs (i.e., striatum, MTL, amygdala, cerebellum. Correlation analysis among ROI- and NWs-time courses yielded individual connectivity matrices (i.e. connectivity between NW and ROIs (allROIs-NW, separateROI-NW, only NWs (NWs-NWs, and only ROIs (allROIs-allROIs as main outcome measures, which were classified by support-vector-machine-based leave-one-out cross-validation. Differences in classification accuracy were statistically evaluated for consistency across subjects and systems. Results: Correlation matrices based on allROIs-NWs yielded 91% classification accuracy, which was significantly superior to allROIs-allROIs and NWs-NWs (56% and 74%, respectively. Considering separate

Altered Functional Connectivity of the Basal Nucleus of Meynert in Mild Cognitive Impairment: A Resting-State fMRI Study

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Hui Li

2017-05-01

Full Text Available Background: Cholinergic dysfunction plays an important role in mild cognitive impairment (MCI. The basal nucleus of Meynert (BNM provides the main source of cortical cholinergic innervation. Previous studies have characterized structural changes of the cholinergic basal forebrain in individuals at risk of developing Alzheimer’s disease (AD. However, whether and how functional connectivity of the BNM (BNM-FC is altered in MCI remains unknown.Objective: The aim of this study was to identify alterations in BNM-FC in individuals with MCI as compared to healthy controls (HCs, and to examine the relationship between these alterations with neuropsychological measures in individuals with MCI.Method: One-hundred-and-one MCI patients and 103 HCs underwent resting-state functional magnetic resonance imaging (rs-fMRI. Imaging data were processed with SPM8 and CONN software. BNM-FC was examined via correlation in low frequency fMRI signal fluctuations between the BNM and all other brain voxels. Group differences were examined with a covariance analysis with age, gender, education level, mean framewise displacement (FD and global correlation (GCOR as nuisance covariates. Pearson’s correlation was conducted to evaluate the relationship between the BNM-FC and clinical assessments.Result: Compared with HCs, individuals with MCI showed significantly decreased BNM-FC in the left insula extending into claustrum (insula/claustrum. Furthermore, greater decrease in BNM-FC with insula/claustrum was associated with more severe impairment in immediate recall during Auditory Verbal Learning Test (AVLT in MCI patients.Conclusion: MCI is associated with changes in BNM-FC to the insula/claustrum in relation to cognitive impairments. These new findings may advance research of the cholinergic bases of cognitive dysfunction during healthy aging and in individuals at risk of developing AD.

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

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Konova, Anna B.; Moeller, Scott J.; Tomasi, Dardo; Volkow, Nora D.; Goldstein, Rita Z.

2013-08-01

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

Altered whole-brain connectivity in albinism.

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Welton, Thomas; Ather, Sarim; Proudlock, Frank A; Gottlob, Irene; Dineen, Robert A

2017-02-01

Albinism is a group of congenital disorders of the melanin synthesis pathway. Multiple ocular, white matter and cortical abnormalities occur in albinism, including a greater decussation of nerve fibres at the optic chiasm, foveal hypoplasia and nystagmus. Despite this, visual perception is largely preserved. It was proposed that this may be attributable to reorganisation among cerebral networks, including an increased interhemispheric connectivity of the primary visual areas. A graph-theoretic model was applied to explore brain connectivity networks derived from resting-state functional and diffusion-tensor magnetic resonance imaging data in 23 people with albinism and 20 controls. They tested for group differences in connectivity between primary visual areas and in summary network organisation descriptors. Main findings were supplemented with analyses of control regions, brain volumes and white matter microstructure. Significant functional interhemispheric hyperconnectivity of the primary visual areas in the albinism group were found (P = 0.012). Tests of interhemispheric connectivity based on the diffusion-tensor data showed no significant group difference (P = 0.713). Second, it was found that a range of functional whole-brain network metrics were abnormal in people with albinism, including the clustering coefficient (P = 0.005), although this may have been driven partly by overall differences in connectivity, rather than reorganisation. Based on the results, it was suggested that changes occur in albinism at the whole-brain level, and not just within the visual processing pathways. It was proposed that their findings may reflect compensatory adaptations to increased chiasmic decussation, foveal hypoplasia and nystagmus. Hum Brain Mapp 38:740-752, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Altered Effective Connectivity of Hippocampus-Dependent Episodic Memory Network in mTBI Survivors

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Hao Yan

2016-01-01

Full Text Available Traumatic brain injuries (TBIs are generally recognized to affect episodic memory. However, less is known regarding how external force altered the way functionally connected brain structures of the episodic memory system interact. To address this issue, we adopted an effective connectivity based analysis, namely, multivariate Granger causality approach, to explore causal interactions within the brain network of interest. Results presented that TBI induced increased bilateral and decreased ipsilateral effective connectivity in the episodic memory network in comparison with that of normal controls. Moreover, the left anterior superior temporal gyrus (aSTG, the concept forming hub, left hippocampus (the personal experience binding hub, and left parahippocampal gyrus (the contextual association hub were no longer network hubs in TBI survivors, who compensated for hippocampal deficits by relying more on the right hippocampus (underlying perceptual memory and the right medial frontal gyrus (MeFG in the anterior prefrontal cortex (PFC. We postulated that the overrecruitment of the right anterior PFC caused dysfunction of the strategic component of episodic memory, which caused deteriorating episodic memory in mTBI survivors. Our findings also suggested that the pattern of brain network changes in TBI survivors presented similar functional consequences to normal aging.

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

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

2017-08-01

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

Alterations of Resting-State Static and Dynamic Functional Connectivity of the Dorsolateral Prefrontal Cortex in Subjects with Internet Gaming Disorder

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Xu Han

2018-02-01

Full Text Available Internet gaming disorder (IGD, a major behavior disorder, has gained increasing attention. Recent studies indicate altered resting-state static functional connectivity (FC of the dorsolateral prefrontal cortex (DLPFC in subjects with IGD. Whereas static FC often provides information on functional changes in subjects with IGD, investigations of temporal changes in FC between the DLPFC and the other brain regions may shed light on the dynamic characteristics of brain function associated with IGD. Thirty subjects with IGD and 30 healthy controls (HCs matched for age, gender and education status were recruited. Using the bilateral DLPFC as seeds, static FC and dynamic FC maps were calculated and compared between groups. Correlations between alterations in static FC and dynamic FC and clinical variables were also investigated within the IGD group. The IGD group showed significantly lower static FC between the right DLPFC and the left rolandic operculum while higher static FC between the right DLPFC and the left pars triangularis when compared to HCs. The IGD group also had significantly decreased dynamic FC between the right DLPFC and the left insula, right putamen and left precentral gyrus, and increased dynamic FC in the left precuneus. Moreover, the dynamic FC between the right DLPFC and the left insula was negatively correlated with the severity of IGD. Dynamic FC can be used as a powerful supplement to static FC, helping us obtain a more comprehensive understanding of large-scale brain network activity in IGD and put forward new ideas for behavioral intervention therapy for it.

Disrupted Olfactory Integration in Schizophrenia: Functional Connectivity Study.

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Kiparizoska, Sara; Ikuta, Toshikazu

2017-09-01

Evidence for olfactory dysfunction in schizophrenia has been firmly established. However, in the typical understanding of schizophrenia, olfaction is not recognized to contribute to or interact with the illness. Despite the solid presence of olfactory dysfunction in schizophrenia, its relation to the rest of the illness remains largely unclear. Here, we aimed to examine functional connectivity of the olfactory bulb, olfactory tract, and piriform cortices and isolate the network that would account for the altered olfaction in schizophrenia. We examined the functional connectivity of these specific olfactory regions in order to isolate other brain regions associated with olfactory processing in schizophrenia. Using the resting state functional MRI data from the Center for Biomedical Research Excellence in Brain Function and Mental Illness, we compared 84 patients of schizophrenia and 90 individuals without schizophrenia. The schizophrenia group showed disconnectivity between the anterior piriform cortex and the nucleus accumbens, between the posterior piriform cortex and the middle frontal gyrus, and between the olfactory tract and the visual cortices. The current results suggest functional disconnectivity of olfactory regions in schizophrenia, which may account for olfactory dysfunction and disrupted integration with other sensory modalities in schizophrenia. © The Author 2017. Published by Oxford University Press on behalf of CINP.

Ventral medial prefrontal functional connectivity and emotion regulation in chronic schizophrenia: A pilot study

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Feng-Mei Fan; Shu-Ping Tan; Fu-De Yang; Yun-Long Tan; Yan-Li Zhao; Nan Chen; Bin-Bin Li

2013-01-01

People with schizophrenia exhibit impaired social cognitive functions,particularly emotion regulation.Abnormal activations of the ventral medial prefrontal cortex (vMPFC) during emotional tasks have been demonstrated in schizophrenia,suggesting its important role in emotion processing in patients.We used the resting-state functional connectivity approach,setting a functionally relevant region,the vMPFC,as a seed region to examine the intrinsic functional interactions and communication between the vMPFC and other brain regions in schizophrenic patients.We found hypo-connectivity between the vMPFC and the medial frontal cortex,right middle temporal lobe (MTL),right hippocampus,parahippocampal cortex (PHC) and amygdala.Further,there was a decreased strength of the negative connectivity (or anticorrelation) between the vMPFC and the bilateral dorsal lateral prefrontal cortex (DLPFC) and pre-supplementary motor areas.Among these connectivity alterations,reduced vMPFCDLPFC connectivity was positively correlated with positive symptoms on the Positive and Negative Syndrome Scale,while vMPFC-right MTL/PHC/amygdala functional connectivity was positively correlated with the performance of emotional regulation in patients.These findings imply that communication and coordination throughout the brain networks are disrupted in schizophrenia.The emotional correlates of vMPFC connectivity suggest a role of the hypo-connectivity between these regions in the neuropathology of abnormal social cognition in chronic schizophrenia.

Data for default network reduced functional connectivity in meditators, negatively correlated with meditation expertise

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Aviva Berkovich-Ohana

2016-09-01

Full Text Available FMRI data described here was recorded during resting-state in Mindfulness Meditators (MM and control participants (see “Task-induced activity and resting-state fluctuations undergo similar alterations in visual and DMN areas of long-term meditators” Berkovich-Ohana et al. (2016 [1] for details. MM participants were also scanned during meditation. Analyses focused on functional connectivity within and between the default mode network (DMN and visual network (Vis. Here we show data demonstrating that: 1 Functional connectivity within the DMN and the Visual networks were higher in the control group than in the meditators; 2 Data show an increase for the functional connectivity between the DMN and the Visual networks in the meditators compared to controls; 3 Data demonstrate that functional connectivity both within and between networks reduces during meditation, compared to the resting-state; and 4 A significant negative correlation was found between DMN functional connectivity and meditation expertise. The reader is referred to Berkovich-Ohana et al. (2016 [1] for further interpretation and discussion.

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

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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.

Decreased resting functional connectivity after traumatic brain injury in the rat.

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Asht Mangal Mishra

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

Altered Functional Connectivity of Fronto-Cingulo-Striatal Circuits during Error Monitoring in Adolescents with a History of Childhood Abuse

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Heledd Hart

2018-01-01

Full Text Available Childhood maltreatment is associated with error hypersensitivity. We examined the effect of childhood abuse and abuse-by-gene (5-HTTLPR, MAOA interaction on functional brain connectivity during error processing in medication/drug-free adolescents. Functional connectivity was compared, using generalized psychophysiological interaction (gPPI analysis of functional magnetic resonance imaging (fMRI data, between 22 age- and gender-matched medication-naïve and substance abuse-free adolescents exposed to severe childhood abuse and 27 healthy controls, while they performed an individually adjusted tracking stop-signal task, designed to elicit 50% inhibition failures. During inhibition failures, abused participants relative to healthy controls exhibited reduced connectivity between right and left putamen, bilateral caudate and anterior cingulate cortex (ACC, and between right supplementary motor area (SMA and right inferior and dorsolateral prefrontal cortex. Abuse-related connectivity abnormalities were associated with longer abuse duration. No group differences in connectivity were observed for successful inhibition. The findings suggest that childhood abuse is associated with decreased functional connectivity in fronto-cingulo-striatal networks during error processing. Furthermore that the severity of connectivity abnormalities increases with abuse duration. Reduced connectivity of error detection networks in maltreated individuals may be linked to constant monitoring of errors in order to avoid mistakes which, in abusive contexts, are often associated with harsh punishment.

Abnormal brain functional connectivity leads to impaired mood and cognition in hyperthyroidism: a resting-state functional MRI study.

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Li, Ling; Zhi, Mengmeng; Hou, Zhenghua; Zhang, Yuqun; Yue, Yingying; Yuan, Yonggui

2017-01-24

Patients with hyperthyroidism frequently have neuropsychiatric complaints such as lack of concentration, poor memory, depression, anxiety, nervousness, and irritability, suggesting brain dysfunction. However, the underlying process of these symptoms remains unclear. Using resting-state functional magnetic resonance imaging (rs-fMRI), we depicted the altered graph theoretical metric degree centrality (DC) and seed-based resting-state functional connectivity (FC) in 33 hyperthyroid patients relative to 33 healthy controls. The peak points of significantly altered DC between the two groups were defined as the seed regions to calculate FC to the whole brain. Then, partial correlation analyses were performed between abnormal DC, FC and neuropsychological performances, as well as some clinical indexes. The decreased intrinsic functional connectivity in the posterior lobe of cerebellum (PLC) and medial frontal gyrus (MeFG), as well as the abnormal seed-based FC anchored in default mode network (DMN), attention network, visual network and cognitive network in this study, possibly constitutes the latent mechanism for emotional and cognitive changes in hyperthyroidism, including anxiety and impaired processing speed.

Abnormal brain functional connectivity leads to impaired mood and cognition in hyperthyroidism: a resting-state functional MRI study

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Li, Ling; Zhi, Mengmeng; Hou, Zhenghua; Zhang, Yuqun; Yue, Yingying; Yuan, Yonggui

2017-01-01

Patients with hyperthyroidism frequently have neuropsychiatric complaints such as lack of concentration, poor memory, depression, anxiety, nervousness, and irritability, suggesting brain dysfunction. However, the underlying process of these symptoms remains unclear. Using resting-state functional magnetic resonance imaging (rs-fMRI), we depicted the altered graph theoretical metric degree centrality (DC) and seed-based resting-state functional connectivity (FC) in 33 hyperthyroid patients relative to 33 healthy controls. The peak points of significantly altered DC between the two groups were defined as the seed regions to calculate FC to the whole brain. Then, partial correlation analyses were performed between abnormal DC, FC and neuropsychological performances, as well as some clinical indexes. The decreased intrinsic functional connectivity in the posterior lobe of cerebellum (PLC) and medial frontal gyrus (MeFG), as well as the abnormal seed-based FC anchored in default mode network (DMN), attention network, visual network and cognitive network in this study, possibly constitutes the latent mechanism for emotional and cognitive changes in hyperthyroidism, including anxiety and impaired processing speed. PMID:28009983

REORGANIZATION OF VISUAL CALLOSAL CONNECTIONS FOLLOWING ALTERATIONS OF RETINAL INPUT AND BRAIN DAMAGE

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LAURA RESTANI

2016-11-01

Full Text Available Vision is a very important sensory modality in humans. Visual disorders are numerous and arising from diverse and complex causes. Deficits in visual function are highly disabling from a social point of view and in addition cause a considerable economic burden. For all these reasons there is an intense effort by the scientific community to gather knowledge on visual deficit mechanisms and to find possible new strategies for recovery and treatment. In this review we focus on an important and sometimes neglected player of the visual function, the corpus callosum (CC. The CC is the major white matter structure in the brain and is involved in information processing between the two hemispheres. In particular, visual callosal connections interconnect homologous areas of visual cortices, binding together the two halves of the visual field. This interhemispheric communication plays a significant role in visual cortical output. Here, we will first review essential literature on the physiology of the callosal connections in normal vision. The available data support the view that the callosum contributes to both excitation and inhibition to the target hemisphere, with a dynamic adaptation to the strength of the incoming visual input. Next, we will focus on data showing how callosal connections may sense visual alterations and respond to the classical paradigm for the study of visual plasticity, i.e. monocular deprivation. This is a prototypical example of a model for the study of callosal plasticity in pathological conditions (e.g. strabismus and amblyopia characterized by unbalanced input from the two eyes. We will also discuss findings of callosal alterations in blind subjects. Noteworthy, we will discuss data showing that inter-hemispheric transfer mediates recovery of visual responsiveness following cortical damage. Finally, we will provide an overview of how callosal projections dysfunction could contribute to pathologies such as neglect and occipital

Reorganization of Visual Callosal Connections Following Alterations of Retinal Input and Brain Damage

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Restani, Laura; Caleo, Matteo

2016-01-01

Vision is a very important sensory modality in humans. Visual disorders are numerous and arising from diverse and complex causes. Deficits in visual function are highly disabling from a social point of view and in addition cause a considerable economic burden. For all these reasons there is an intense effort by the scientific community to gather knowledge on visual deficit mechanisms and to find possible new strategies for recovery and treatment. In this review, we focus on an important and sometimes neglected player of the visual function, the corpus callosum (CC). The CC is the major white matter structure in the brain and is involved in information processing between the two hemispheres. In particular, visual callosal connections interconnect homologous areas of visual cortices, binding together the two halves of the visual field. This interhemispheric communication plays a significant role in visual cortical output. Here, we will first review the essential literature on the physiology of the callosal connections in normal vision. The available data support the view that the callosum contributes to both excitation and inhibition to the target hemisphere, with a dynamic adaptation to the strength of the incoming visual input. Next, we will focus on data showing how callosal connections may sense visual alterations and respond to the classical paradigm for the study of visual plasticity, i.e., monocular deprivation (MD). This is a prototypical example of a model for the study of callosal plasticity in pathological conditions (e.g., strabismus and amblyopia) characterized by unbalanced input from the two eyes. We will also discuss the findings of callosal alterations in blind subjects. Noteworthy, we will discuss data showing that inter-hemispheric transfer mediates recovery of visual responsiveness following cortical damage. Finally, we will provide an overview of how callosal projections dysfunction could contribute to pathologies such as neglect and occipital

Exploring patterns of alteration in Alzheimer’s disease brain networks: a combined structural and functional connectomics analysis

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Fulvia Palesi

2016-09-01

Full Text Available Alzheimer’s disease (AD is a neurodegenerative disorder characterized by a severe derangement of cognitive functions, primarily memory, in elderly subjects. As far as the functional impairment is concerned, growing evidence supports the disconnection syndrome hypothesis. Recent investigations using fMRI have revealed a generalized alteration of resting state networks in patients affected by AD and mild cognitive impairment (MCI. However, it was unclear whether the changes in functional connectivity were accompanied by corresponding structural network changes. In this work, we have developed a novel structural/functional connectomic approach: resting state fMRI was used to identify the functional cortical network nodes and diffusion MRI to reconstruct the fiber tracts to give a weight to internodal subcortical connections. Then, local and global efficiency were determined for different networks, exploring specific alterations of integration and segregation patterns in AD and MCI patients compared to healthy controls (HC. In the default mode network (DMN, that was the most affected, axonal loss and reduced axonal integrity appeared to compromise both local and global efficiency along posterior-anterior connections. In the basal ganglia network (BGN, disruption of white matter integrity implied that main alterations occurred in local microstructure. In the anterior insular network (AIN, neuronal loss probably subtended a compromised communication with the insular cortex. Cognitive performance, evaluated by neuropsychological examinations, revealed a dependency on integration and segregation of brain networks. These findings are indicative of the fact that cognitive deficits in AD could be associated not only with cortical alterations (revealed by fMRI but also with subcortical alterations (revealed by diffusion MRI that extend beyond the areas primarily damaged by neurodegeneration, towards the support of an emerging concept of AD as a

Insight and psychosis: Functional and anatomical brain connectivity and self-reflection in Schizophrenia.

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Ćurčić-Blake, Branislava; van der Meer, Lisette; Pijnenborg, Gerdina H M; David, Anthony S; Aleman, André

2015-12-01

Impaired insight into illness, associated with worse treatment outcome, is common in schizophrenia. Insight has been related to the self-reflective processing, centred on the medial frontal cortex. We hypothesized that anatomical and functional routes to and from the ventromedial prefrontal cortex (vmPFC) would differ in patients according to their degree of impaired insight. Forty-five schizophrenia patients and 19 healthy subjects performed a self-reflection task during fMRI, and underwent diffusion tensor imaging. Using dynamic causal modelling we observed increased effective connectivity from the posterior cingulate cortex (PCC), inferior parietal lobule (IPL), and dorsal mPFC (dmPFC) towards the vmPFC with poorer insight and decrease from vmPFC to the IPL. Stronger connectivity from the PCC to vmPFC during judgment of traits related to self was associated with poorer insight. We found small-scale significant changes in white matter integrity associated with clinical insight. Self-reflection may be influenced by synaptic changes that lead to the observed alterations in functional connectivity accompanied by the small-scale but measurable alterations in anatomical connections. Our findings may point to a neural compensatory response to an impairment of connectivity between self-processing regions. Similarly, the observed hyper-connectivity might be a primary deficit linked to inefficiency in the component cognitive processes that lead to impaired insight. We suggest that the stronger cognitive demands placed on patients with poor insight is reflected in increased effective connectivity during the task in this study. © 2015 Wiley Periodicals, Inc.

Discriminative analysis of Parkinson's disease based on whole-brain functional connectivity.

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Yongbin Chen

Full Text Available Recently, there has been an increasing emphasis on applications of pattern recognition and neuroimaging techniques in the effective and accurate diagnosis of psychiatric or neurological disorders. In the present study, we investigated the whole-brain resting-state functional connectivity patterns of Parkinson's disease (PD, which are expected to provide additional information for the clinical diagnosis and treatment of this disease. First, we computed the functional connectivity between each pair of 116 regions of interest derived from a prior atlas. The most discriminative features based on Kendall tau correlation coefficient were then selected. A support vector machine classifier was employed to classify 21 PD patients with 26 demographically matched healthy controls. This method achieved a classification accuracy of 93.62% using leave-one-out cross-validation, with a sensitivity of 90.47% and a specificity of 96.15%. The majority of the most discriminative functional connections were located within or across the default mode, cingulo-opercular and frontal-parietal networks and the cerebellum. These disease-related resting-state network alterations might play important roles in the pathophysiology of this disease. Our results suggest that analyses of whole-brain resting-state functional connectivity patterns have the potential to improve the clinical diagnosis and treatment evaluation of PD.

The Effects of Long Duration Bed Rest on Brain Functional Connectivity and Sensorimotor Functioning

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Cassady, K.; Koppelmans, V.; De Dios, Y.; Stepanyan, V.; Szecsy, D.; Gadd, N.; Wood, S.; Reuter-Lorenz, P.; Castenada, R. Riascos; Kofman, I.;

Abnormal rich club organization and impaired correlation between structural and functional connectivity in migraine sufferers.

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Li, Kang; Liu, Lijun; Yin, Qin; Dun, Wanghuan; Xu, Xiaolin; Liu, Jixin; Zhang, Ming

2017-04-01

Because of the unique position of the topologically central role of densely interconnected brain hubs, our study aimed to investigate whether these regions and their related connections would be particularly vulnerable to migraine. In our study, we explored the rich club structure and its role in global functional dynamics in 30 patients with migraine without aura and 30 healthy controls. DTI and resting fMRI were used to construct structural connectivity (SC) and functional connectivity (FC) networks. An independent replication data set of 26 patients and 26 controls was included to replicate and validate significant findings. As compared with the controls, the structural networks of patients exhibited altered rich club organization with higher level of feeder connection density, abnormal small-world organization with increased global efficiency and decreased strength of SC-FC coupling. As these abnormal topological properties and headache attack duration exhibited a significant association with increased density of feeder connections, our results indicated that migraine may be characterized by a selective alteration of the structural connectivity of the rich club regions, tending to have higher 'bridgeness' with non-rich club regions, which may increase the integration among pain-related brain circuits with more excitability but less inhibition for the modulation of migraine.

Altered resting-state effective connectivity of fronto-parietal motor control systems on the primary motor network following stroke

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Inman, Cory S.; James, G. Andrew; Hamann, Stephan; Rajendra, Justin K.; Pagnoni, Giuseppe; Butler, Andrew J.

2011-01-01

Previous brain imaging work suggests that stroke alters the effective connectivity (the influence neural regions exert upon each other) of motor execution networks. The present study examines the intrinsic effective connectivity of top-down motor control in stroke survivors (n=13) relative to healthy participants (n=12). Stroke survivors exhibited significant deficits in motor function, as assessed by the Fugl-Meyer Motor Assessment. We used structural equation modeling (SEM) of resting-state fMRI data to investigate the relationship between motor deficits and the intrinsic effective connectivity between brain regions involved in motor control and motor execution. An exploratory adaptation of SEM determined the optimal model of motor execution effective connectivity in healthy participants, and confirmatory SEM assessed stroke survivors’ fit to that model. We observed alterations in spontaneous resting-state effective connectivity from fronto-parietal guidance systems to the motor network in stroke survivors. More specifically, diminished connectivity was found in connections from the superior parietal cortex to primary motor cortex and supplementary motor cortex. Furthermore, the paths demonstrated large individual variance in stroke survivors but less variance in healthy participants. These findings suggest that characterizing the deficits in resting-state connectivity of top-down processes in stroke survivors may help optimize cognitive and physical rehabilitation therapies by individually targeting specific neural pathway. PMID:21839174

Increased functional connectivity between prefrontal cortex and reward system in pathological gambling.

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Saskia Koehler

Full Text Available Pathological gambling (PG shares clinical characteristics with substance-use disorders and is thus discussed as a behavioral addiction. Recent neuroimaging studies on PG report functional changes in prefrontal structures and the mesolimbic reward system. While an imbalance between these structures has been related to addictive behavior, whether their dysfunction in PG is reflected in the interaction between them remains unclear. We addressed this question using functional connectivity resting-state fMRI in male subjects with PG and controls. Seed-based functional connectivity was computed using two regions-of-interest, based on the results of a previous voxel-based morphometry study, located in the prefrontal cortex and the mesolimbic reward system (right middle frontal gyrus and right ventral striatum. PG patients demonstrated increased connectivity from the right middle frontal gyrus to the right striatum as compared to controls, which was also positively correlated with nonplanning aspect of impulsiveness, smoking and craving scores in the PG group. Moreover, PG patients demonstrated decreased connectivity from the right middle frontal gyrus to other prefrontal areas as compared to controls. The right ventral striatum demonstrated increased connectivity to the right superior and middle frontal gyrus and left cerebellum in PG patients as compared to controls. The increased connectivity to the cerebellum was positively correlated with smoking in the PG group. Our results provide further evidence for alterations in functional connectivity in PG with increased connectivity between prefrontal regions and the reward system, similar to connectivity changes reported in substance use disorder.

Connectivity and tissue microstructural alterations in right and left temporal lobe epilepsy revealed by diffusion spectrum imaging.

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Lemkaddem, Alia; Daducci, Alessandro; Kunz, Nicolas; Lazeyras, François; Seeck, Margitta; Thiran, Jean-Philippe; Vulliémoz, Serge

2014-01-01

Focal epilepsy is increasingly recognized as the result of an altered brain network, both on the structural and functional levels and the characterization of these widespread brain alterations is crucial for our understanding of the clinical manifestation of seizure and cognitive deficits as well as for the management of candidates to epilepsy surgery. Tractography based on Diffusion Tensor Imaging allows non-invasive mapping of white matter tracts in vivo. Recently, diffusion spectrum imaging (DSI), based on an increased number of diffusion directions and intensities, has improved the sensitivity of tractography, notably with respect to the problem of fiber crossing and recent developments allow acquisition times compatible with clinical application. We used DSI and parcellation of the gray matter in regions of interest to build whole-brain connectivity matrices describing the mutual connections between cortical and subcortical regions in patients with focal epilepsy and healthy controls. In addition, the high angular and radial resolution of DSI allowed us to evaluate also some of the biophysical compartment models, to better understand the cause of the changes in diffusion anisotropy. Global connectivity, hub architecture and regional connectivity patterns were altered in TLE patients and showed different characteristics in RTLE vs LTLE with stronger abnormalities in RTLE. The microstructural analysis suggested that disturbed axonal density contributed more than fiber orientation to the connectivity changes affecting the temporal lobes whereas fiber orientation changes were more involved in extratemporal lobe changes. Our study provides further structural evidence that RTLE and LTLE are not symmetrical entities and DSI-based imaging could help investigate the microstructural correlate of these imaging abnormalities.

Functional Connectivity During Exposure to Favorite-Food, Stress, and Neutral-Relaxing Imagery Differs Between Smokers and Nonsmokers.

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Garrison, Kathleen A; Sinha, Rajita; Lacadie, Cheryl M; Scheinost, Dustin; Jastreboff, Ania M; Constable, R Todd; Potenza, Marc N

2016-09-01

Tobacco-use disorder is a complex condition involving multiple brain networks and presenting with multiple behavioral correlates including changes in diet and stress. In a previous functional magnetic resonance imaging (fMRI) study of neural responses to favorite-food, stress, and neutral-relaxing imagery, smokers versus nonsmokers demonstrated blunted corticostriatal-limbic responses to favorite-food cues. Based on other recent reports of alterations in functional brain networks in smokers, the current study examined functional connectivity during exposure to favorite-food, stress, and neutral-relaxing imagery in smokers and nonsmokers, using the same dataset. The intrinsic connectivity distribution was measured to identify brain regions that differed in degree of functional connectivity between groups during each imagery condition. Resulting clusters were evaluated for seed-to-voxel connectivity to identify the specific connections that differed between groups during each imagery condition. During exposure to favorite-food imagery, smokers versus nonsmokers showed lower connectivity in the supramarginal gyrus, and differences in connectivity between the supramarginal gyrus and the corticostriatal-limbic system. During exposure to neutral-relaxing imagery, smokers versus nonsmokers showed greater connectivity in the precuneus, and greater connectivity between the precuneus and the posterior insula and rolandic operculum. During exposure to stress imagery, smokers versus nonsmokers showed lower connectivity in the cerebellum. These findings provide data-driven insights into smoking-related alterations in brain functional connectivity patterns related to appetitive, relaxing, and stressful states. This study uses a data-driven approach to demonstrate that smokers and nonsmokers show differential patterns of functional connectivity during guided imagery related to personalized favorite-food, stress, and neutral-relaxing cues, in brain regions implicated in attention

Functional Connectivity of Human Chewing

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Quintero, A.; Ichesco, E.; Schutt, R.; Myers, C.; Peltier, S.; Gerstner, G.E.

2013-01-01

Mastication is one of the most important orofacial functions. The neurobiological mechanisms of masticatory control have been investigated in animal models, but less so in humans. This project used functional connectivity magnetic resonance imaging (fcMRI) to assess the positive temporal correlations among activated brain areas during a gum-chewing task. Twenty-nine healthy young-adults underwent an fcMRI scanning protocol while they chewed gum. Seed-based fcMRI analyses were performed with the motor cortex and cerebellum as regions of interest. Both left and right motor cortices were reciprocally functionally connected and functionally connected with the post-central gyrus, cerebellum, cingulate cortex, and precuneus. The cerebellar seeds showed functional connections with the contralateral cerebellar hemispheres, bilateral sensorimotor cortices, left superior temporal gyrus, and left cingulate cortex. These results are the first to identify functional central networks engaged during mastication. PMID:23355525

Progressively Disrupted Brain Functional Connectivity Network in Subcortical Ischemic Vascular Cognitive Impairment Patients.

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Sang, Linqiong; Chen, Lin; Wang, Li; Zhang, Jingna; Zhang, Ye; Li, Pengyue; Li, Chuanming; Qiu, Mingguo

2018-01-01

Cognitive impairment caused by subcortical ischemic vascular disease (SIVD) has been elucidated by many neuroimaging studies. However, little is known regarding the changes in brain functional connectivity networks in relation to the severity of cognitive impairment in SIVD. In the present study, 20 subcortical ischemic vascular cognitive impairment no dementia patients (SIVCIND) and 20 dementia patients (SIVaD) were enrolled; additionally, 19 normal controls were recruited. Each participant underwent a resting-state functional MRI scan. Whole-brain functional networks were analyzed with graph theory and network-based statistics (NBS) to study the functional organization of networks and find alterations in functional connectivity among brain regions. After adjustments for age, gender, and duration of formal education, there were significant group differences for two network functional organization indices, global efficiency and local efficiency, which decreased (NC > SIVCIND > SIVaD) as cognitive impairment worsened. Between-group differences in functional connectivity (NBS corrected, p  impairment worsened, with an increased number of decreased connections between brain regions. We also observed more reductions in nodal efficiency in the prefrontal and temporal cortices for SIVaD than for SIVCIND. These findings indicated a progressively disrupted pattern of the brain functional connectivity network with increased cognitive impairment and showed promise for the development of reliable biomarkers of network metric changes related to cognitive impairment caused by SIVD.

Functional connectivity of the rodent brain using optical imaging

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Guevara Codina, Edgar

showed a decreasing trend of homologous correlation in the motor and cingulate cortices. Graph analyses showed a randomization of the cortex functional networks, suggesting a loss of connectivity, more specifically in the motor cortex ipsilateral to the treated carotid; however these changes are not reflected in differentiated metabolic estimates. Confounds remain due to the fact that carotid rigidification gives rise to neural decline in the hippocampus as well as unilateral alteration of vascular pulsatility; however the results support the need to look at several hemodynamic parameters when imaging the brain after arterial remodeling. The third article of this thesis studies a model of inflammatory injury on the newborn rat. Oxygen saturation and functional connectivity were assessed with photoacoustic tomography. Oxygen saturation was decreased in the site of the lesion and on the cortex ipsilateral to the injury; however this decrease is not fully explained by hypovascularization revealed by histology. Seed-based functional connectivity analysis showed that inter-hemispheric connectivity is not affected by inflammatory injury.

Abnormal Functional Connectivity Between Default and Salience Networks in Pediatric Bipolar Disorder.

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Lopez-Larson, Melissa P; Shah, Lubdha M; Weeks, Howard R; King, Jace B; Mallik, Atul K; Yurgelun-Todd, Deborah A; Anderson, Jeffrey S

2017-01-01

Pediatric bipolar disorder (PBD) (occurring prior to 18 years of age) is a developmental brain disorder that is among the most severe and disabling psychiatric conditions affecting youth. Despite increasing evidence that brain connectivity is atypical in adults with bipolar disorder, it is not clear how brain connectivity may be altered in youths with PBD. This cross-sectional resting-state functional magnetic resonance imaging study included 80 participants recruited over 4 years: 32 youths with PBD, currently euthymic (13 males; 15.1 years old), and 48 healthy control (HC) subjects (27 males; 14.5 years old). Functional connectivity between eight major intrinsic connectivity networks, along with connectivity measurements between 333 brain regions, was compared between PBD and HC subjects. Additionally, connectivity differences were evaluated between PBD and HC samples in negatively correlated connections, as defined by 839 subjects of the Human Connectome Project dataset. We found increased inter- but not intranetwork functional connectivity in PBD between the default mode and salience networks (p = .0017). Throughout the brain, atypical connections showed failure to develop anticorrelation with age during adolescence in PBD but not HC samples among connections that exhibit negative correlation in adulthood. Youths with PBD demonstrate reduced anticorrelation between default mode and salience networks. Further evaluation of the interaction between these networks is needed in development and with other mood states such as depression and mania to clarify if this atypical connectivity is a PBD trait biomarker. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Altered Functional Connectivity of Cognitive-Related Cerebellar Subregions in Alzheimer’s Disease

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Weimin Zheng

2017-05-01

Full Text Available Alzheimer’s disease (AD is the most common cause of dementia. Previous studies have found disrupted resting state functional connectivities (rsFCs in various brain networks in the AD patients. However, few studies have focused on the rsFCs of the cerebellum and its sub-regions in the AD patients. In this study, we collected resting-state functional magnetic resonance imaging (rs-fMRI data including 32 AD patients and 38 healthy controls (HCs. We selected two cognitive-related subregions of the cerebellum as seed region and mapped the whole-brain rsFCs for each subregion. We identified several distinct rsFC patterns of the two cognitive-related cerebellar subregions: default-mode network (DMN, frontoparietal network (FPN, visual network (VN and sensorimotor network (SMN. Compared with the controls, the AD patients showed disrupted rsFCs in several different networks (DMN, VN and SMN, predicting the impairment of the functional integration in the cerebellum. Notably, these abnormal rsFCs of the two cerebellar subregions were closely associated with cognitive performance. Collectively, we demonstrated the distinct rsFCs patterns of cerebellar sub-regions with various functional networks, which were differentially impaired in the AD patients.

Independent functional connectivity networks underpin food and monetary reward sensitivity in excess weight.

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Verdejo-Román, Juan; Fornito, Alex; Soriano-Mas, Carles; Vilar-López, Raquel; Verdejo-García, Antonio

2017-02-01

Overvaluation of palatable food is a primary driver of obesity, and is associated with brain regions of the reward system. However, it remains unclear if this network is specialized in food reward, or generally involved in reward processing. We used functional magnetic resonance imaging (fMRI) to characterize functional connectivity during processing of food and monetary rewards. Thirty-nine adults with excess weight and 37 adults with normal weight performed the Willingness to Pay for Food task and the Monetary Incentive Delay task in the fMRI scanner. A data-driven graph approach was applied to compare whole-brain, task-related functional connectivity between groups. Excess weight was associated with decreased functional connectivity during the processing of food rewards in a network involving primarily frontal and striatal areas, and increased functional connectivity during the processing of monetary rewards in a network involving principally frontal and parietal areas. These two networks were topologically and anatomically distinct, and were independently associated with BMI. The processing of food and monetary rewards involve segregated neural networks, and both are altered in individuals with excess weight. Copyright © 2016 Elsevier Inc. All rights reserved.

Mind-wandering and alterations to default mode network connectivity when listening to naturalistic versus artificial sounds

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Gould van Praag, CD; Garfinkel, SN; Sparasci, O; Mees, A; Philippides, AO; Ware, M; Ottaviani, C; Critchley, HD

2017-01-01

Naturalistic environments have been demonstrated to promote relaxation and wellbeing. We assess opposing theoretical accounts for these effects through investigation of autonomic arousal and alterations of activation and functional connectivity within the default mode network (DMN) of the brain while participants listened to sounds from artificial and natural environments. We found no evidence for increased DMN activity in the naturalistic compared to artificial or control condition, however,...

Altered resting state functional connectivity of the cognitive control network in fibromyalgia and the modulation effect of mind-body intervention.

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Kong, Jian; Wolcott, Emily; Wang, Zengjian; Jorgenson, Kristen; Harvey, William F; Tao, Jing; Rones, Ramel; Wang, Chenchen

2018-05-02

This study examines altered resting state functional connectivity (rsFC) of the cognitive control network (CCN) in fibromyalgia patients as compared to healthy controls, as well as how an effective mind-body intervention, Tai Chi, can modulate the altered rsFC of the CCN. Patients with fibromyalgia and matched healthy subjects were recruited in this study. Fibromyalgia patients were scanned 12 weeks before and after intervention. The bilateral dorsolateral prefrontal cortex (DLPFC) was used as a seed to explore the rsFC of the CCN. Data analysis was conducted with 21 patients and 20 healthy subjects. Compared to healthy subjects, fibromyalgia patients exhibited increased rsFC between the DLPFC and the bilateral rostral anterior cingulate cortex (rACC) and medial prefrontal cortex (MPFC) at baseline. The rsFC between the CCN and rACC/MPFC further increased after Tai Chi intervention, and this increase was accompanied by clinical improvements. This rsFC change was also significantly associated with corresponding changes in the Overall Impact domain of the Revised Fibromyalgia Impact Questionnaire (FIQR). Further analysis showed that the rACC/MPFC rsFC with both the PAG and hippocampus significantly decreased following Tai Chi intervention. Our study suggests that fibromyalgia is associated with altered CCN rsFC and that effective mind-body treatment may elicit clinical improvements by further increasing this altered rsFC. Elucidating this mechanism of enhancing the allostasis process will deepen our understanding of the mechanisms underlying mind-body interventions in fibromyalgia patients and facilitate the development of new pain management methods.

Cognitive Behavioral Therapy Lowers Elevated Functional Connectivity in Depressed Adolescents

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Shayanti Chattopadhyay

2017-03-01

Full Text Available Imaging studies have implicated altered functional connectivity in adults with major depressive disorder (MDD. Whether similar dysfunction is present in adolescent patients is unclear. The degree of resting-state functional connectivity (rsFC may reflect abnormalities within emotional (‘hot’ and cognitive control (‘cold’ neural systems. Here, we investigate rsFC of these systems in adolescent patients and changes following cognitive behavioral therapy (CBT. Functional Magnetic Resonance Imaging (fMRI was acquired from adolescent patients before CBT, and 24-weeks later following completed therapy. Similar data were obtained from control participants. Cross-sectional Cohort: From 82 patients and 34 controls at baseline, rsFC of the amygdala, anterior cingulate cortex (ACC, and pre-frontal cortex (PFC was calculated for comparison. Longitudinal Cohort: From 17 patients and 30 controls with longitudinal data, treatment effects were tested on rsFC. Patients demonstrated significantly greater rsFC to left amygdala, bilateral supragenual ACC, but not with PFC. Treatment effects were observed in right insula connected to left supragenual ACC, with baseline case-control differences reduced. rsFC changes were significantly correlated with changes in depression severity. Depressed adolescents exhibited heightened connectivity in regions of ‘hot’ emotional processing, known to be associated with depression, where treatment exposure exerted positive effects, without concomitant differences in areas of ‘cold’ cognition.

Functional connectivity of emotional processing in depression.

LENUS (Irish Health Repository)

Carballedo, Angela

2012-02-01

OBJECTIVES: The aim of the study is to map a neural network of emotion processing and to identify differences in major depression compared to healthy controls. It is hypothesized that intentional perception of emotional faces activates connections between amygdala (Demir et al.), orbitofrontal cortex (OFC), anterior cingulate cortex (ACC) and prefrontal cortex (PFC) and that frontal-amygdala connections are altered in major depressive disorder (MDD). METHODS: Fifteen medication-free patients with MDD and fifteen healthy controls were enrolled. All subjects were assessed using the same face-matching functional Magnetic Resonance Imaging (fMRI) task, known to involve those areas. Brain activations were obtained using Statistical Parametric Mapping version 5 (SPM5) for data analysis and MARSBAR for extracting of fMRI time series. Then data was analyzed using structural equation modeling (SEM). RESULTS: A valid model was established for the left and the right hemispheres showing a circuit involving ACC, OFC, PFC and AMY. The left hemisphere shows significant lower connectivity strengths in patients than controls, for the pathway that goes from AMY to the OF11, and a trend of higher connectivity in patients for the path that goes from the PF9 to the OF11. In the right hemisphere, patients show lower connectivity coefficients in the paths from the AMY to OF11, from the AMY to ACC, and from the ACC to PF9. By the contrary, controls show lower connectivity strengths for the path that goes from ACC to AMY. CONCLUSIONS: Functional disconnection between limbic and frontal brain regions could be demonstrated using structural equation modeling. The interpretation of these findings could be that there is an emotional processing bias with disconnection bilaterally between amygdala to orbitofrontal cortices and in addition a right disconnection between amygdala and ACC as well as between ACC and prefrontal cortex possibly in line with a more prominent role for the right hemisphere

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

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Tanaka, Shoji; Kirino, Eiji

2016-01-01

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

Motor and cortico-striatal-thalamic connectivity alterations in intrauterine growth restriction.

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Eixarch, Elisenda; Muñoz-Moreno, Emma; Bargallo, Nuria; Batalle, Dafnis; Gratacos, Eduard

2016-06-01

.409 ± 0.046; P = .016) in both networks were observed in the intrauterine growth restriction group, with no differences in number of streamlines. More importantly, strong specific correlation was found between tractography-related metrics and its relative function in both networks in intrauterine growth restricted children. Motor network metrics were correlated specifically with motor scale results (fractional anisotropy: rho = 0.857; integrity: rho = 0.740); cortico-striatal-thalamic network metrics were correlated with cognitive (fractional anisotropy: rho = 0.793; integrity, rho = 0.762) and socioemotional scale (fractional anisotropy: rho = 0.850; integrity: rho = 0.877). These results support the existence of altered brain connectivity in intrauterine growth restriction demonstrated by altered connectivity in motor and cortico-striatal-thalamic networks, with reduced fractional anisotropy and integrity. The specific correlation between tractography-related metrics and neurodevelopmental outcomes in intrauterine growth restriction shows the potential to use this approach to develop imaging biomarkers to predict specific neurodevelopmental outcome in infants who are at risk because of intrauterine growth restriction and other prenatal diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

Perceived social isolation is associated with altered functional connectivity in neural networks associated with tonic alertness and executive control.

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Layden, Elliot A; Cacioppo, John T; Cacioppo, Stephanie; Cappa, Stefano F; Dodich, Alessandra; Falini, Andrea; Canessa, Nicola

2017-01-15

Perceived social isolation (PSI), colloquially known as loneliness, is associated with selectively altered attentional, cognitive, and affective processes in humans, but the neural mechanisms underlying these adjustments remain largely unexplored. Behavioral, eye tracking, and neuroimaging research has identified associations between PSI and implicit hypervigilance for social threats. Additionally, selective executive dysfunction has been evidenced by reduced prepotent response inhibition in social Stroop and dichotic listening tasks. Given that PSI is associated with pre-attentional processes, PSI may also be related to altered resting-state functional connectivity (FC) in the brain. Therefore, we conducted the first resting-state fMRI FC study of PSI in healthy young adults. Five-minute resting-state scans were obtained from 55 participants (31 females). Analyses revealed robust associations between PSI and increased brain-wide FC in areas encompassing the right central operculum and right supramarginal gyrus, and these associations were not explained by depressive symptomatology, objective isolation, or demographics. Further analyses revealed that PSI was associated with increased FC between several nodes of the cingulo-opercular network, a network known to underlie the maintenance of tonic alertness. These regions encompassed the bilateral insula/frontoparietal opercula and ACC/pre-SMA. In contrast, FC between the cingulo-opercular network and right middle/superior frontal gyrus was reduced, a finding associated with diminished executive function in prior literature. We suggest that, in PSI, increased within-network cingulo-opercular FC may be associated with hypervigilance to social threat, whereas reduced right middle/superior frontal gyrus FC to the cingulo-opercular network may be associated with diminished impulse control. Copyright © 2016 Elsevier Inc. All rights reserved.

Disconnection and hyper-connectivity underlie reorganization after TBI: A rodent functional connectomic analysis.

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Harris, N G; Verley, D R; Gutman, B A; Thompson, P M; Yeh, H J; Brown, J A

2016-03-01

While past neuroimaging methods have contributed greatly to our understanding of brain function after traumatic brain injury (TBI), resting state functional MRI (rsfMRI) connectivity methods have more recently provided a far more unbiased approach with which to monitor brain circuitry compared to task-based approaches. However, current knowledge on the physiologic underpinnings of the correlated blood oxygen level dependent signal, and how changes in functional connectivity relate to reorganizational processes that occur following injury is limited. The degree and extent of this relationship remain to be determined in order that rsfMRI methods can be fully adapted for determining the optimal timing and type of rehabilitative interventions that can be used post-TBI to achieve the best outcome. Very few rsfMRI studies exist after experimental TBI and therefore we chose to acquire rsfMRI data before and at 7, 14 and 28 days after experimental TBI using a well-known, clinically-relevant, unilateral controlled cortical impact injury (CCI) adult rat model of TBI. This model was chosen since it has widespread axonal injury, a well-defined time-course of reorganization including spine, dendrite, axonal and cortical map changes, as well as spontaneous recovery of sensorimotor function by 28 d post-injury from which to interpret alterations in functional connectivity. Data were co-registered to a parcellated rat template to generate adjacency matrices for network analysis by graph theory. Making no assumptions about direction of change, we used two-tailed statistical analysis over multiple brain regions in a data-driven approach to access global and regional changes in network topology in order to assess brain connectivity in an unbiased way. Our main hypothesis was that deficits in functional connectivity would become apparent in regions known to be structurally altered or deficient in axonal connectivity in this model. The data show the loss of functional connectivity

Altered functional connectivity during self- and close other-reflection in patients with bipolar disorder with past psychosis and patients with schizophrenia.

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Zhang, Liwen; Vander Meer, Lisette; Opmeer, Esther M; Marsman, Jan-Bernard C; Ruhé, Henricus G; Aleman, André

2016-12-01

Disturbances in implicit self-processing have been reported both in psychotic patients with bipolar disorder (BD) and schizophrenia. It remains unclear whether these two psychotic disorders show disturbed functional connectivity during explicit self-reflection, which is associated with social functioning and illness symptoms. Therefore, we investigated functional connectivity during explicit self-reflection in BD with past psychosis and schizophrenia. Twenty-three BD-patients, 17 schizophrenia-patients and 21 health controls (HC) performed a self-reflection task, including the conditions self-reflection, close other-reflection and semantic control. Functional connectivity was investigated with generalized psycho-physiological interaction (gPPI). During self-reflection compared to semantic, BD-patients had decreased connectivity between several cortical-midline structures (CMS) nodes (i.e., anterior cingulate cortex, ventromedial prefrontal cortex), the insula and the head of the caudate while HC showed increased connectivities. Schizophrenia-patients, during close other-reflection compared to semantic, demonstrated reduced ventral-anterior insula-precuneus/posterior cingulate cortex (PCC) functional connectivity, whereas this was increased in HC. There were no differences between BD and schizophrenia during self- and close other-reflection. We propose that decreased functional connectivity between the CMS nodes/insula and head of the caudate in BD-patients may imply a reduced involvement of the motivational system during self-reflection; and the reduced functional connectivity between the ventral-anterior insula and precuneus/PCC during close other-reflection in schizophrenia-patients may subserve difficulties in information integration of autobiographical memory and emotional awareness in relation to close others. These distinctive impaired patterns of functional connectivity in BD and schizophrenia (compared to HC) deserve further investigation to determine their

Altered structure-function relations of semantic processing in youths with high-functioning autism: a combined diffusion and functional MRI study.

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Lo, Yu-Chun; Chou, Tai-Li; Fan, Li-Ying; Gau, Susan Shur-Fen; Chiu, Yen-Nan; Tseng, Wen-Yih Isaac

2013-12-01

Deficits in language and communication are among the core symptoms of autism, a common neurodevelopmental disorder with long-term impairment. Despite the striking nature of the autistic language impairment, knowledge about its corresponding alterations in the brain is still evolving. We hypothesized that the dual stream language network is altered in autism, and that this alteration could be revealed by changes in the relationships between microstructural integrity and functional activation. The study recruited 20 right-handed male youths with autism and 20 carefully matched individually, typically developing (TD) youths. Microstructural integrity of the left dorsal and left ventral pathways responsible for language processing and the functional activation of the connected brain regions were investigated by using diffusion spectrum imaging and functional magnetic resonance imaging of a semantic task, respectively. Youths with autism had significantly poorer language function, and lower functional activation in left dorsal and left ventral regions of the language network, compared with TD youths. The TD group showed a significant correlation of the functional activation of the left dorsal region with microstructural integrity of the left ventral pathway, whereas the autism group showed a significant correlation of the functional activation of the left ventral region with microstructural integrity of the left dorsal pathway, and moreover verbal comprehension index was correlated with microstructural integrity of the left ventral pathway. These altered structure-function relationships in autism suggest possible involvement of the dual pathways in supporting deficient semantic processing. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.

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

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

2018-05-01

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

Aberrant Functional Connectivity of the Amygdala Complexes in PTSD during Conscious and Subconscious Processing of Trauma-Related Stimuli.

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Daniela Rabellino

Full Text Available Post-traumatic stress disorder (PTSD is characterized by altered functional connectivity of the amygdala complexes at rest. However, amygdala complex connectivity during conscious and subconscious threat processing remains to be elucidated. Here, we investigate specific connectivity of the centromedial amygdala (CMA and basolateral amygdala (BLA during conscious and subconscious processing of trauma-related words among individuals with PTSD (n = 26 as compared to non-trauma-exposed controls (n = 20. Psycho-physiological interaction analyses were performed using the right and left amygdala complexes as regions of interest during conscious and subconscious trauma word processing. These analyses revealed a differential, context-dependent responses by each amygdala seed during trauma processing in PTSD. Specifically, relative to controls, during subconscious processing, individuals with PTSD demonstrated increased connectivity of the CMA with the superior frontal gyrus, accompanied by a pattern of decreased connectivity between the BLA and the superior colliculus. During conscious processing, relative to controls, individuals with PTSD showed increased connectivity between the CMA and the pulvinar. These findings demonstrate alterations in amygdala subregion functional connectivity in PTSD and highlight the disruption of the innate alarm network during both conscious and subconscious trauma processing in this disorder.

Co-altered functional networks and brain structure in unmedicated patients with bipolar and major depressive disorders.

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He, Hao; Sui, Jing; Du, Yuhui; Yu, Qingbao; Lin, Dongdong; Drevets, Wayne C; Savitz, Jonathan B; Yang, Jian; Victor, Teresa A; Calhoun, Vince D

2017-12-01

Bipolar disorder (BD) and major depressive disorder (MDD) share similar clinical characteristics that often obscure the diagnostic distinctions between their depressive conditions. Both functional and structural brain abnormalities have been reported in these two disorders. However, the direct link between altered functioning and structure in these two diseases is unknown. To elucidate this relationship, we conducted a multimodal fusion analysis on the functional network connectivity (FNC) and gray matter density from MRI data from 13 BD, 40 MDD, and 33 matched healthy controls (HC). A data-driven fusion method called mCCA+jICA was used to identify the co-altered FNC and gray matter components. Comparing to HC, BD exhibited reduced gray matter density in the parietal and occipital cortices, which correlated with attenuated functional connectivity within sensory and motor networks, as well as hyper-connectivity in regions that are putatively engaged in cognitive control. In addition, lower gray matter density was found in MDD in the amygdala and cerebellum. High accuracy in discriminating across groups was also achieved by trained classification models, implying that features extracted from the fusion analysis hold the potential to ultimately serve as diagnostic biomarkers for mood disorders.

Atypical functional connectivity in autism spectrum disorder is associated with disrupted white matter microstructural organisation

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Jane eMcGrath

2013-09-01

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

Changes of intranetwork and internetwork functional connectivity in Alzheimer’s disease and mild cognitive impairment

Science.gov (United States)

Zhu, Haoze; Zhou, Peng; Alcauter, Sarael; Chen, Yuanyuan; Cao, Hongbao; Tian, Miao; Ming, Dong; Qi, Hongzhi; Wang, Xuemin; Zhao, Xin; He, Feng; Ni, Hongyan; Gao, Wei

2016-08-01

Objective. Alzheimer’s disease (AD) is a serious neurodegenerative disorder characterized by deficits of working memory, attention, language and many other cognitive functions. Although different stages of the disease are relatively well characterized by clinical criteria, stage-specific pathological changes in the brain remain relatively poorly understood, especially at the level of large-scale functional networks. In this study, we aimed to characterize the potential disruptions of large-scale functional brain networks based on a sample including amnestic mild cognition impairment (aMCI) and AD patients to help delineate the underlying stage-dependent AD pathology. Approach. We sought to identify the neural connectivity mechanisms of aMCI and AD through examination of both intranetwork and internetwork interactions among four of the brain’s key networks, namely dorsal attention network (DAN), default mode network (DMN), executive control network (ECN) and salience network (SAL). We analyzed functional connectivity based on resting-state functional magnetic resonance imaging (rs-fMRI) data from 25 Alzheimer’s disease patients, 20 aMCI patients and 35 elderly normal controls (NC). Main results. Intranetwork functional disruptions within the DAN and ECN were detected in both aMCI and AD patients. Disrupted intranetwork connectivity of DMN and anti-correlation between DAN and DMN were observed in AD patients. Moreover, aMCI-specific alterations in the internetwork functional connectivity of SAL were observed. Significance. Our results confirmed previous findings that AD pathology was related to dysconnectivity both within and between resting-state networks but revealed more spatial details. Moreover, the SAL network, reportedly flexibly coupling either with the DAN or DMN networks during different brain states, demonstrated interesting alterations specifically in the early stage of the disease.

Early brain connectivity alterations and cognitive impairment in a rat model of Alzheimer's disease.

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Muñoz-Moreno, Emma; Tudela, Raúl; López-Gil, Xavier; Soria, Guadalupe

2018-02-07

Animal models of Alzheimer's disease (AD) are essential to understanding the disease progression and to development of early biomarkers. Because AD has been described as a disconnection syndrome, magnetic resonance imaging (MRI)-based connectomics provides a highly translational approach to characterizing the disruption in connectivity associated with the disease. In this study, a transgenic rat model of AD (TgF344-AD) was analyzed to describe both cognitive performance and brain connectivity at an early stage (5 months of age) before a significant concentration of β-amyloid plaques is present. Cognitive abilities were assessed by a delayed nonmatch-to-sample (DNMS) task preceded by a training phase where the animals learned the task. The number of training sessions required to achieve a learning criterion was recorded and evaluated. After DNMS, MRI acquisition was performed, including diffusion-weighted MRI and resting-state functional MRI, which were processed to obtain the structural and functional connectomes, respectively. Global and regional graph metrics were computed to evaluate network organization in both transgenic and control rats. The results pointed to a delay in learning the working memory-related task in the AD rats, which also completed a lower number of trials in the DNMS task. Regarding connectivity properties, less efficient organization of the structural brain networks of the transgenic rats with respect to controls was observed. Specific regional differences in connectivity were identified in both structural and functional networks. In addition, a strong correlation was observed between cognitive performance and brain networks, including whole-brain structural connectivity as well as functional and structural network metrics of regions related to memory and reward processes. In this study, connectivity and neurocognitive impairments were identified in TgF344-AD rats at a very early stage of the disease when most of the pathological hallmarks

Mesial temporal lobe epilepsy diminishes functional connectivity during emotion perception.

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Steiger, Bettina K; Muller, Angela M; Spirig, Esther; Toller, Gianina; Jokeit, Hennric

2017-08-01

Unilateral mesial temporal lobe epilepsy (MTLE) has been associated with impaired recognition of emotional facial expressions. Correspondingly, imaging studies showed decreased activity of the amygdala and cortical face processing regions in response to emotional faces. However, functional connectivity among regions involved in emotion perception has not been studied so far. To address this, we examined intrinsic functional connectivity (FC) modulated by the perception of dynamic fearful faces among the amygdala and limbic, frontal, temporal and brainstem regions. Regions of interest were identified in an activation analysis by presenting a block-design with dynamic fearful faces and dynamic landscapes to 15 healthy individuals. This led to 10 predominately right-hemispheric regions. Functional connectivity between these regions during the perception of fearful faces was examined in drug-refractory patients with left- (n=16) or right-sided (n=17) MTLE, epilepsy patients with extratemporal seizure onset (n=15) and a second group of 15 healthy controls. Healthy controls showed a widespread functional network modulated by the perception of fearful faces that encompassed bilateral amygdalae, limbic, cortical, subcortical and brainstem regions. In patients with left MTLE, a downsized network of frontal and temporal regions centered on the right amygdala was present. Patients with right MTLE showed almost no significant functional connectivity. A maintained network in the epilepsy control group indicates that findings in mesial temporal lobe epilepsy could not be explained by clinical factors such as seizures and antiepileptic medication. Functional networks underlying facial emotion perception are considerably changed in left and right MTLE. Alterations are present for both hemispheres in either MTLE group, but are more pronounced in right MTLE. Disruption of the functional network architecture possibly contributes to deficits in facial emotion recognition frequently

Altered amygdala-prefrontal connectivity during emotion perception in schizophrenia.

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Bjorkquist, Olivia A; Olsen, Emily K; Nelson, Brady D; Herbener, Ellen S

2016-08-01

Individuals with schizophrenia evidence impaired emotional functioning. Abnormal amygdala activity has been identified as an etiological factor underlying affective impairment in this population, but the exact nature remains unclear. The current study utilized psychophysiological interaction analyses to examine functional connectivity between the amygdala and medial prefrontal cortex (mPFC) during an emotion perception task. Participants with schizophrenia (SZ) and healthy controls (HC) viewed and rated positive, negative, and neutral images while undergoing functional neuroimaging. Results revealed a significant group difference in right amygdala-mPFC connectivity during perception of negative versus neutral images. Specifically, HC participants demonstrated positive functional coupling between the amygdala and mPFC, consistent with co-active processing of salient information. In contrast, SZ participants evidenced negative functional coupling, consistent with top-down inhibition of the amygdala by the mPFC. A significant positive correlation between connectivity strength during negative image perception and clinician-rated social functioning was also observed in SZ participants, such that weaker right amygdala-mPFC coupling during negative compared to neutral image perception was associated with poorer social functioning. Overall, results suggest that emotional dysfunction and associated deficits in functional outcome in schizophrenia may relate to abnormal interactions between the amygdala and mPFC during perception of emotional stimuli. This study adds to the growing literature on abnormal functional connections in schizophrenia and supports the functional disconnection hypothesis of schizophrenia. Copyright © 2016 Elsevier B.V. All rights reserved.

Altered thalamic connectivity during spontaneous attacks of migraine without aura

DEFF Research Database (Denmark)

Amin, Faisal Mohammad; Hougaard, Anders; Magon, Stefano

2017-01-01

,-58,-30) and cerebellum lobule VI (right, 34,-42,-36 and left, -32,-42,-36). Results We found increased functional connectivity between the right thalamus and several contralateral brain regions (superior parietal lobule, insular cortex, primary motor cortex, supplementary motor area and orbitofrontal cortex...... and the headache-free days. Functional connectivity was assessed in four different networks using seed-based analysis. The chosen seeds were in the thalamus (MNI coordinates x,y,z: right, 22,-24,0 and left, -22,-28,6), pons (right, 8,-24,-32 and left, -8,-24,-32), cerebellum crus I (right, 46,-58,-30 and left, -46......). There was decreased functional connectivity between the right thalamus and three ipsilateral brain areas (primary somatosensory cortex and premotor cortex). We found no change in functional connectivity in the pontine or the cerebellar networks. Conclusions The study indicates that network connectivity between...

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

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

2013-09-01

Resting state networks are proposed to reflect the neuronal connectivity that underlies cognitive processes. Consequently, abnormal behaviour of these networks due to disease or altered development may predict poor cognitive outcome. To understand how very preterm birth may affect the development of resting state connectivity, we followed a cohort of very preterm-born infants from birth through to 4 years of age using resting state functional MRI. From a larger longitudinal cohort of infants born very preterm (regions and left and right temporal lobes, we investigated local and inter-region connectivity as a function of group and age. We found strong local connectivity during the preterm period, which matured into inter-hemispheric and preliminary default-mode network correlations by 4 years of age. This development is comparable to the resting state networks found in term-born infants of equivalent age. The results of this study suggest that differences in developmental trajectory between preterm-born and term-born infants are small and, if present, would require a large sample from both populations to be detected.

Resting-State Functional Connectivity in Individuals with Down Syndrome and Williams Syndrome Compared with Typically Developing Controls.

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Vega, Jennifer N; Hohman, Timothy J; Pryweller, Jennifer R; Dykens, Elisabeth M; Thornton-Wells, Tricia A

2015-10-01

The emergence of resting-state functional connectivity (rsFC) analysis, which examines temporal correlations of low-frequency (syndrome (DS) compared with another neurodevelopmental disorder, Williams syndrome (WS), and TD. Ten subjects with DS, 18 subjects with WS, and 40 subjects with TD each participated in a 3-Tesla MRI scan. We tested for group differences (DS vs. TD, DS vs. WS, and WS vs. TD) in between- and within-network rsFC connectivity for seven functional networks. For the DS group, we also examined associations between rsFC and other cognitive and genetic risk factors. In DS compared with TD, we observed higher levels of between-network connectivity in 6 out 21 network pairs but no differences in within-network connectivity. Participants with WS showed lower levels of within-network connectivity and no significant differences in between-network connectivity relative to DS. Finally, our comparison between WS and TD controls revealed lower within-network connectivity in multiple networks and higher between-network connectivity in one network pair relative to TD controls. While preliminary due to modest sample sizes, our findings suggest a global difference in between-network connectivity in individuals with neurodevelopmental disorders compared with controls and that such a difference is exacerbated across many brain regions in DS. However, this alteration in DS does not appear to extend to within-network connections, and therefore, the altered between-network connectivity must be interpreted within the framework of an intact intra-network pattern of activity. In contrast, WS shows markedly lower levels of within-network connectivity in the default mode network and somatomotor network relative to controls. These findings warrant further investigation using a task-based procedure that may help disentangle the relationship between brain function and cognitive performance across the spectrum of neurodevelopmental disorders.

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

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

2014-05-01

biological evidence that DM1 is a clinical condition that also involves an alteration of functional connectivity of the brain. We speculate that these functional brain abnormalities, similarly to frank psychiatric disorders, may account for the atypical personality traits observed in patients with DM1.

EEG resting state functional connectivity analysis in children with benign epilepsy with centrotemporal spikes

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Azeez eAdebimpe

2016-03-01

Full Text Available In this study, we investigated changes in functional connectivity of the brain networks in patients with benign epilepsy with centrotemporal spikes compared to healthy controls using high-density EEG data collected under eyes-closed resting state condition. EEG source reconstruction was performed with exact Low Resolution Electromagnetic Tomography (eLORETA. We investigated functional connectivity (FC between 84 Brodmann areas using lagged phase synchronization (LPS in four frequency bands (δ, θ, α, and β. We further computed the network degree, clustering coefficient and efficiency. Compared to controls, patients displayed higher θ and α and lower β lagged phase synchronization values. In these frequency bands, patients were also characterized by less well ordered brain networks exhibiting higher global degrees and efficiencies and lower clustering coefficients. In the beta band, patients exhibited reduced functional segregation and integration due to loss of both local and long-distance functional connections. These findings suggest that benign epileptic brain networks might be functionally disrupted due to their altered functional organization especially in the α and β frequency bands.

Increased functional connectivity strength of right inferior temporal gyrus in first-episode, drug-naive somatization disorder.

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Su, Qinji; Yao, Dapeng; Jiang, Muliang; Liu, Feng; Jiang, Jiajing; Xu, Chunxing; Dai, Yi; Yu, Miaoyu; Long, Liling; Li, Hongzheng; Liu, Jianrong; Zhang, Zhikun; Zhang, Jian; Xiao, Changqing; Guo, Wenbin

2015-01-01

Evidence of brain structural and functional alterations have been implicated in patients with somatization disorder (SD). However, little is known about brain functional connectivity in SD. In the present study, resting-state functional magnetic resonance imaging (fMRI) and graph theory were used to obtain a comprehensive view of whole-brain functional connectivity and to investigate the changes of voxel-wise functional networks in patients with SD. Twenty-five first-episode, medication-naive patients with SD and 28 age-, sex- and education-matched healthy controls (HCs) underwent resting-state fMRI. The graph theory approach was employed to analyze the data. Compared to the HCs, patients with SD showed significantly increased functional connectivity strength in the right inferior temporal gyrus (ITG). There is a significant positive correlation between the z-values of the cluster in the right ITG and Hamilton Anxiety Scale scores. Our findings indicate that there is a disruption of the functional connectivity pattern in the right ITG in first-episode, treatment-naive patients with SD, which bears clinical significance. © The Royal Australian and New Zealand College of Psychiatrists 2014.

Conflict-related anterior cingulate functional connectivity is associated with past suicidal ideation and behavior in recent-onset schizophrenia.

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Minzenberg, Michael J; Lesh, Tyler; Niendam, Tara; Yoon, Jong H; Cheng, Yaoan; Rhoades, Remy; Carter, Cameron S

2015-06-01

Suicide is highly prevalent in schizophrenia (SZ), yet it remains unclear how suicide risk factors such as past suicidal ideation or behavior relate to brain function. Circuits modulated by the prefrontal cortex (PFC) are altered in SZ, including in dorsal anterior cingulate cortex (dACC) during conflict-monitoring (an important component of cognitive control), and dACC changes are observed in post-mortem studies of heterogeneous suicide victims. We tested whether conflict-related dACC functional connectivity is associated with past suicidal ideation and behavior in SZ. 32 patients with recent-onset of DSM-IV-TR-defined SZ were evaluated with the Columbia Suicide Severity Rating Scale and functional MRI during cognitive control (AX-CPT) task performance. Group-level regression models relating past history of suicidal ideation or behavior to dACC-seeded functional connectivity during conflict-monitoring controlled for severity of depression, psychosis and impulsivity. Past suicidal ideation was associated with relatively higher functional connectivity of the dACC with the precuneus during conflict-monitoring. Intensity of worst-point past suicidal ideation was associated with relatively higher dACC functional connectivity in medial parietal lobe and striato-thalamic nuclei. In contrast, among those with past suicidal ideation (n = 17), past suicidal behavior was associated with lower conflict-related dACC connectivity with multiple lateral and medial PFC regions, parietal and temporal cortical regions. This study provides unique evidence that recent-onset schizophrenia patients with past suicidal ideation or behavior show altered dACC-based circuit function during conflict-monitoring. Suicidal ideation and suicidal behavior have divergent patterns of associated dACC functional connectivity, suggesting a differing pattern of conflict-related brain dysfunction with these two distinct features of suicide phenomenology. Published by Elsevier Ltd.

Altered contralateral sensorimotor system organization after experimental hemispherectomy: a structural and functional connectivity study.

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Otte, Willem M; van der Marel, Kajo; van Meer, Maurits P A; van Rijen, Peter C; Gosselaar, Peter H; Braun, Kees P J; Dijkhuizen, Rick M

2015-08-01

Hemispherectomy is often followed by remarkable recovery of cognitive and motor functions. This reflects plastic capacities of the remaining hemisphere, involving large-scale structural and functional adaptations. Better understanding of these adaptations may (1) provide new insights in the neuronal configuration and rewiring that underlies sensorimotor outcome restoration, and (2) guide development of rehabilitation strategies to enhance recovery after hemispheric lesioning. We assessed brain structure and function in a hemispherectomy model. With MRI we mapped changes in white matter structural integrity and gray matter functional connectivity in eight hemispherectomized rats, compared with 12 controls. Behavioral testing involved sensorimotor performance scoring. Diffusion tensor imaging and resting-state functional magnetic resonance imaging were acquired 7 and 49 days post surgery. Hemispherectomy caused significant sensorimotor deficits that largely recovered within 2 weeks. During the recovery period, fractional anisotropy was maintained and white matter volume and axial diffusivity increased in the contralateral cerebral peduncle, suggestive of preserved or improved white matter integrity despite overall reduced white matter volume. This was accompanied by functional adaptations in the contralateral sensorimotor network. The observed white matter modifications and reorganization of functional network regions may provide handles for rehabilitation strategies improving functional recovery following large lesions.

Resting state functional connectivity changes in adults with developmental stuttering: an initial sLORETA study.

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Kathleen eJoos

2014-10-01

Full Text Available Introduction: Stuttering is defined as speech characterized by verbal dysfluencies, but should not be seen as an isolated speech disorder, but as a generalized sensorimotor timing deficit due to impaired communication between speech related brain areas. Therefore we focused on resting state brain activity and functional connectivity.Method: We included 11 patients with developmental stuttering and 11 age matched controls. To objectify stuttering severity and the impact on the quality of life (QoL, we used the Dutch validated Test for Stuttering Severity-Readers (TSS-R and the Overall Assessment of the Speaker’s Experience of Stuttering (OASES, respectively. Furthermore, we used standardized low resolution brain electromagnetic tomography (sLORETA analyses to look at resting state activity and functional connectivity differences and their correlations with the TSS-R and OASES.Results: No resting state activity differences were identified in comparison to fluently speaking controls or in correlation with stuttering severity or QoL measures. Significant alterations in resting state functional connectivity were found, predominantly interhemispheric, i.e. a decreased functional connectivity for high frequency oscillations (beta and gamma between motor speech areas (BA44 and 45 and the contralateral premotor (BA 6 and motor (BA 4 areas. A positive correlation was found between functional connectivity at low frequency oscillations (theta and alpha and stuttering severity, while a mixed increased and decreased functional connectivity at low and high frequency oscillations correlated with QoL.Discussion: PWS are characterized by decreased high frequency interhemispheric functional connectivity between motor speech, premotor and motor areas in the resting state, while higher functional connectivity in the low frequency bands indicates more severe speech disturbances, suggesting that increased interhemispheric and right sided functional connectivity is

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

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

2014-01-01

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

Resting state functional connectivity of the anterior cingulate cortex in veterans with and without post-traumatic stress disorder

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Kennis, Mitzy; Rademaker, Arthur R.; van Rooij, Sanne J H; Kahn, René S.; Geuze, Elbert

2015-01-01

Post-traumatic stress disorder (PTSD) is an anxiety disorder that is associated with structural and functional alterations in several brain areas, including the anterior cingulate cortex (ACC). Here, we examine resting state functional connectivity of ACC subdivisions in PTSD, using a seed-based

Altered Cortico-Striatal Connectivity in Offspring of Schizophrenia Patients Relative to Offspring of Bipolar Patients and Controls.

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Cristina Solé-Padullés

Full Text Available Schizophrenia (SZ and bipolar disorder (BD share clinical features, genetic risk factors and neuroimaging abnormalities. There is evidence of disrupted connectivity in resting state networks in patients with SZ and BD and their unaffected relatives. Resting state networks are known to undergo reorganization during youth coinciding with the period of increased incidence for both disorders. We therefore focused on characterizing resting state network connectivity in youth at familial risk for SZ or BD to identify alterations arising during this period. We measured resting-state functional connectivity in a sample of 106 youth, aged 7-19 years, comprising offspring of patients with SZ (N = 27, offspring of patients with BD (N = 39 and offspring of community control parents (N = 40. We used Independent Component Analysis to assess functional connectivity within the default mode, executive control, salience and basal ganglia networks and define their relationship to grey matter volume, clinical and cognitive measures. There was no difference in connectivity within any of the networks examined between offspring of patients with BD and offspring of community controls. In contrast, offspring of patients with SZ showed reduced connectivity within the left basal ganglia network compared to control offspring, and they showed a positive correlation between connectivity in this network and grey matter volume in the left caudate. Our findings suggest that dysconnectivity in the basal ganglia network is a robust correlate of familial risk for SZ and can be detected during childhood and adolescence.

Staging of cortical and deep grey matter functional connectivity changes in multiple sclerosis.

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Meijer, Kim A; Eijlers, Anand J C; Geurts, Jeroen J G; Schoonheim, Menno M

2018-02-01

Functional connectivity is known to increase as well as decrease throughout the brain in multiple sclerosis (MS), which could represent different stages of the disease. In addition, functional connectivity changes could follow the atrophy pattern observed with disease progression, that is, moving from the deep grey matter towards the cortex. This study investigated when and where connectivity changes develop and explored their clinical and cognitive relevance across different MS stages. A cohort of 121 patients with early relapsing-remitting MS (RRMS), 122 with late RRMS and 53 with secondary progressive MS (SPMS) as well as 96 healthy controls underwent MRI and neuropsychological testing. Functional connectivity changes were investigated for (1) within deep grey matter connectivity, (2) connectivity between the deep grey matter and cortex and (3) within-cortex connectivity. A post hoc regional analysis was performed to identify which regions were driving the connectivity changes. Patients with late RRMS and SPMS showed increased connectivity of the deep grey matter, especially of the putamen and palladium, with other deep grey matter structures and with the cortex. Within-cortex connectivity was decreased, especially for temporal, occipital and frontal regions, but only in SPMS relative to early RRMS. Deep grey matter connectivity alterations were related to cognition and disability, whereas within-cortex connectivity was only related to disability. Increased connectivity of the deep grey matter became apparent in late RRMS and further increased in SPMS. The additive effect of cortical network degeneration, which was only seen in SPMS, may explain the sudden clinical deterioration characteristic to this phase of the disease. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

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

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

2018-01-01

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

Functional connectivity change as shared signal dynamics

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Cole, Michael W.; Yang, Genevieve J.; Murray, John D.; Repovš, Grega; Anticevic, Alan

2015-01-01

Background An increasing number of neuroscientific studies gain insights by focusing on differences in functional connectivity – between groups, individuals, temporal windows, or task conditions. We found using simulations that additional insights into such differences can be gained by forgoing variance normalization, a procedure used by most functional connectivity measures. Simulations indicated that these functional connectivity measures are sensitive to increases in independent fluctuations (unshared signal) in time series, consistently reducing functional connectivity estimates (e.g., correlations) even though such changes are unrelated to corresponding fluctuations (shared signal) between those time series. This is inconsistent with the common notion of functional connectivity as the amount of inter-region interaction. New Method Simulations revealed that a version of correlation without variance normalization – covariance – was able to isolate differences in shared signal, increasing interpretability of observed functional connectivity change. Simulations also revealed cases problematic for non-normalized methods, leading to a “covariance conjunction” method combining the benefits of both normalized and non-normalized approaches. Results We found that covariance and covariance conjunction methods can detect functional connectivity changes across a variety of tasks and rest in both clinical and non-clinical functional MRI datasets. Comparison with Existing Method(s) We verified using a variety of tasks and rest in both clinical and non-clinical functional MRI datasets that it matters in practice whether correlation, covariance, or covariance conjunction methods are used. Conclusions These results demonstrate the practical and theoretical utility of isolating changes in shared signal, improving the ability to interpret observed functional connectivity change. PMID:26642966

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

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

2017-01-01

. Homotopic GCaMP6 functional connectivity maps at 0.4-4.0Hz in the anesthetized states show a striking correlated and anti-correlated structure along the anterior to posterior axis. This structure is potentially explained in part by observed propagation of delta-band activity from frontal somatomotor regions to visuoparietal areas. During awake imaging, this spatio-temporal quality is altered, and a more complex and detailed functional connectivity structure is observed. The combined calcium/hemoglobin imaging technique described here will enable the dissociation of changes in ionic and hemodynamic functional structure and neurovascular coupling and provide a framework for subsequent studies of neurological disease such as stroke.

The effects of hemorrhagic parenchymal infarction on the establishment of sensori-motor structural and functional connectivity in early infancy

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Arichi, T.; Edwards, A.D.; Counsell, S.J.; Mondi, V.; Tusor, N.; Merchant, N.; Allievi, A.G.; Burdet, E.; Chew, A.T.; Martinez-Biarge, M.; Cowan, F.M.

2014-01-01

The objective of the study was to characterize alterations of structural and functional connectivity within the developing sensori-motor system in infants with focal perinatal brain injury and at high risk of cerebral palsy. Functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) data were used to study the developing functional and structural connectivity framework in six infants born prematurely at term equivalent age. This was first characterised in three infants without focal pathology, which was then compared to that derived from three infants with unilateral haemorrhagic parenchymal infarction and a subsequent focal periventricular white matter lesion who developed later haemiparesis. Functional responses to passive hand movement were in the contralateral perirolandic cortex, regardless of focal pathology. In infants with unilateral periventricular injury, afferent thalamo-cortical tracts appeared to have developed compensatory trajectories which circumvented areas of damage. In contrast, efferent corticospinal tracts showed marked asymmetry at term equivalent age following focal brain injury. Sensori-motor network analysis suggested that inter-hemispheric functional connectivity is largely preserved despite pathology and that impairment may be associated with adverse neurodevelopmental outcome. Following focal perinatal brain injury, altered structural and functional connectivity is already present and can be characterized with MRI at term equivalent age. The results of this small case series suggest that these techniques may provide valuable new information about prognosis and the pathophysiology underlying cerebral palsy. (orig.)

The effects of hemorrhagic parenchymal infarction on the establishment of sensori-motor structural and functional connectivity in early infancy

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Arichi, T.; Edwards, A.D. [Kings College London, St Thomas' Hospital, Department of Perinatal Imaging and Health, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); Imperial College London, Department of Bioengineering, London (United Kingdom); Counsell, S.J.; Mondi, V.; Tusor, N.; Merchant, N. [Kings College London, St Thomas' Hospital, Department of Perinatal Imaging and Health, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); Allievi, A.G.; Burdet, E. [Imperial College London, Department of Bioengineering, London (United Kingdom); Chew, A.T. [Kings College London, St Thomas' Hospital, Department of Perinatal Imaging and Health, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); Imperial College Healthcare NHS Trust, Department of Paediatrics, London (United Kingdom); Martinez-Biarge, M.; Cowan, F.M. [Imperial College Healthcare NHS Trust, Department of Paediatrics, London (United Kingdom)

2014-11-15

The objective of the study was to characterize alterations of structural and functional connectivity within the developing sensori-motor system in infants with focal perinatal brain injury and at high risk of cerebral palsy. Functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) data were used to study the developing functional and structural connectivity framework in six infants born prematurely at term equivalent age. This was first characterised in three infants without focal pathology, which was then compared to that derived from three infants with unilateral haemorrhagic parenchymal infarction and a subsequent focal periventricular white matter lesion who developed later haemiparesis. Functional responses to passive hand movement were in the contralateral perirolandic cortex, regardless of focal pathology. In infants with unilateral periventricular injury, afferent thalamo-cortical tracts appeared to have developed compensatory trajectories which circumvented areas of damage. In contrast, efferent corticospinal tracts showed marked asymmetry at term equivalent age following focal brain injury. Sensori-motor network analysis suggested that inter-hemispheric functional connectivity is largely preserved despite pathology and that impairment may be associated with adverse neurodevelopmental outcome. Following focal perinatal brain injury, altered structural and functional connectivity is already present and can be characterized with MRI at term equivalent age. The results of this small case series suggest that these techniques may provide valuable new information about prognosis and the pathophysiology underlying cerebral palsy. (orig.)

Altered cortico-striatal-thalamic connectivity in relation to spatial working memory capacity in children with ADHD

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Kathryn L. Mills

2012-01-01

Full Text Available Introduction: Attention deficit hyperactivity disorder (ADHD captures a heterogeneous group of children, who are characterized by a range of cognitive and behavioral symptoms. Previous resting state functional connectivity (rs-fcMRI studies have sought to understand the neural correlates of ADHD by comparing connectivity measurements between those with and without the disorder, focusing primarily on cortical-striatal circuits mediated by the thalamus. To integrate the multiple phenotypic features associated with ADHD and help resolve its heterogeneity, it is helpful to determine how specific circuits relate to unique cognitive domains of the ADHD syndrome. Spatial working memory has been proposed as a key mechanism in the pathophysiology of ADHD.Methods: We correlated the rs-fcMRI of five thalamic regions of interest with spatial span working memory scores in a sample of 67 children aged 7-11 years (ADHD and typically developing children; TDC. In an independent dataset, we then examined group differences in thalamo-striatal functional connectivity between 70 ADHD and 89 TDC (7-11 years from the ADHD-200 dataset. Thalamic regions of interest were created based on previous methods that utilize known thalamo-cortical loops and rs-fcMRI to identify functional boundaries in the thalamus.Results/Conclusions: Using these thalamic regions, we found atypical rs-fcMRI between specific thalamic groupings with the basal ganglia. To identify the thalamic connections that relate to spatial working memory in ADHD, only connections identified in both the correlational and comparative analyses were considered. Multiple connections between the thalamus and basal ganglia, particularly between medial and anterior dorsal thalamus and the putamen, were related to spatial working memory and also altered in ADHD. These thalamo-striatal disruptions may be one of multiple atypical neural and cognitive mechanisms that relate to the ADHD clinical phenotype.

Reduced resting state functional connectivity of the somatosensory cortex predicts psychopathological symptoms in women with bulimia nervosa

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Luca eLavagnino

2014-08-01

Full Text Available BackgroundAlterations in the resting state functional connectivity (rs-FC of several brain networks have been demonstrated in eating disorders. However, very few studies are currently available on brain network dysfunctions in bulimia nervosa (BN. The somatosensory network is central in processing body-related stimuli and it may be altered in BN. The present study therefore aimed to investigate rs-FC in the somatosensory network in bulimic women. MethodsSixteen medication-free women with BN (age=23±5 years and 18 matched controls (age=23±3 years underwent a functional magnetic resonance resting state scan and assessment of eating disorder symptoms. Within-network and seed-based functional connectivity analyses were conducted to assess rs-FC within the somatosensory network and to other areas of the brain. ResultsBN patients showed a decreased resting state functional connectivity both within the somatosensory network (t=9.0, df=1, P=0.005 and with posterior cingulate cortex (PCC and two visual areas (the right middle occipital gyrus and the right cuneus(P=0.05 corrected for multiple comparison. The region in the right middle occipital gyrus is implicated in body processing and is known as extrastriate body area, or EBA. The rs-FC of the left paracentral lobule with the EBA correlated with psychopathology measures like bulimia (r=-0.4; P=0.02 and interoceptive awareness (r=-0.4; P=0.01. Analyses were conducted using age, BMI (body mass index and depressive symptoms as covariates. ConclusionsOur findings show a specific alteration of the rs-FC of the somatosensory cortex in BN patients, which correlates with eating disorder symptoms. The connectivity between the somatosensory cortex and the EBA might be related to dysfunctions in body image processing. The results should be considered preliminary due to the small sample size.

Insular subdivisions functional connectivity dysfunction within major depressive disorder.

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Peng, Xiaolong; Lin, Pan; Wu, Xiaoping; Gong, Ruxue; Yang, Rui; Wang, Jue

2018-02-01

Major depressive disorder (MDD) is a mental disorder characterized by cognitive and affective deficits. Previous studies suggested that insula is a crucial node of the salience network for initiating network switching, and dysfunctional connection to this region may be related to the mechanism of MDD. In this study, we systematically investigated and quantified the altered functional connectivity (FC) of the specific insular subdivisions and its relationship to psychopathology of MDD. Resting-state FC of insular subdivisions, including bilateral ventral/dorsal anterior insula and posterior insula, were estimated in 19 MDD patients and 19 healthy controls. Abnormal FC was quantified between groups. Additionally, we investigated the relationships between insular connectivity and depressive symptom severity. MDD patients demonstrated aberrant FC for insular subdivisions to superior temporal sulcus, inferior prefrontal gyrus, amygdala and posterior parietal cortex. Moreover, depression symptoms (Hamilton Depression Rating Scale and Hamilton Anxiety Rating Scale scorers) were associated with the FC values of insular subdivisions. First, the sample size of our current study is relatively small, which may affect the statistic power. Second, using standardized insular subdivision seeds for FC analyses may neglect subtle natural differences in size and location of functional area across individuals and may thus affect connectivity maps. Abnormal FC of insular subdivisions to default network and central executive network may represent impaired intrinsic networks switching which may affect the underlying emotional and sensory disturbances in MDD. And our findings can help to understand the pathophysiology and underlying neural mechanisms of MDD. Copyright © 2017 Elsevier B.V. All rights reserved.

The effect of criticism on functional brain connectivity and associations with neuroticism.

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Michelle Nadine Servaas

Full Text Available Neuroticism is a robust personality trait that constitutes a risk factor for psychopathology, especially anxiety disorders and depression. High neurotic individuals tend to be more self-critical and are overly sensitive to criticism by others. Hence, we used a novel resting-state paradigm to investigate the effect of criticism on functional brain connectivity and associations with neuroticism. Forty-eight participants completed the NEO Personality Inventory Revised (NEO-PI-R to assess neuroticism. Next, we recorded resting state functional magnetic resonance imaging (rsfMRI during two sessions. We manipulated the second session before scanning by presenting three standardized critical remarks through headphones, in which the subject was urged to please lie still in the scanner. A seed-based functional connectivity method and subsequent clustering were used to analyse the resting state data. Based on the reviewed literature related to criticism, we selected brain regions associated with self-reflective processing and stress-regulation as regions of interest. The findings showed enhanced functional connectivity between the clustered seed regions and brain areas involved in emotion processing and social cognition during the processing of criticism. Concurrently, functional connectivity was reduced between these clusters and brain structures related to the default mode network and higher-order cognitive control. Furthermore, individuals scoring higher on neuroticism showed altered functional connectivity between the clustered seed regions and brain areas involved in the appraisal, expression and regulation of negative emotions. These results may suggest that the criticized person is attempting to understand the beliefs, perceptions and feelings of the critic in order to facilitate flexible and adaptive social behavior. Furthermore, multiple aspects of emotion processing were found to be affected in individuals scoring higher on neuroticism during

Analyses of functional brain connectivity; Untersuchungen zur funktionellen Konnektivitaet des Gehirns

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Stephan, K.E.

2003-03-01

This dissertation includes two independent studies that investigate two complementary aspects of functional connectivity in the Macaque and the human brain. In the first study, a computational meta-analysis of published electrophysiological data on context-independent functional brain connectivity was conducted by means of three independent methods. The second study investigated the effects of the atypical antipsychotic substance olanzapine on the functional connectivity of the cerebellum during a simple motor task (self-paced finger tapping). Six schizophrenic patients and six control subjects matched for age and sex were investigated by functional magnetic resonance imaging (fMRI) twice. This study provided the first experimental data on the effects of atypical antipsychotic agents on functional brain connectivity and demonstrated pronounced olanzapine-dependent changes of functional couplings between cerebellum, thalamus, and prefrontal cortex. (orig.) [German] In der hier vorgelegten Arbeit werden zwei komplementaere Aspekte der funktionellen Konnektivitaet - im Gehirn des Makaken und Menschen anhand zweier separater Studien untersucht. In der ersten Studie wurde mittels dreier unabhaengiger Methoden eine Metaanalyse publizierter elektrophysiologischer Daten zur kontextunabhaengigen funktionellen Konnektivitaet des Makakenkortex durchgefuehrt. Diese Studie erbrachte damit zum ersten Mal den Nachweis einer funktionellen Small World-Netzwerkstruktur des Primatenkortex. In der zweiten Studie wurde der Effekt des atypischen Neuroleptikums Olanzapin auf die funktionelle Konnektivitaet des Zerebellums im Kontext einer einfachen motorischen Aufgabe (selbstgesteuertes Fingertrapping) untersucht. Sechs schizophrene Patienten, die Neuroleptika-naiv bzw. -entwoehnt waren, sowie sechs alters- und geschlechtsentprechende Kontrollprobanden wurden im Abstand von jeweils drei Wochen mit funktioneller Magnetresonanztomografie (fMRT) untersucht. Diese Studie lieferte die ersten

Effective artifact removal in resting state fMRI data improves detection of DMN functional connectivity alteration in Alzheimer’s disease

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Ludovica eGriffanti

2015-08-01

Full Text Available Artefact removal from resting state fMRI data is an essential step for a better identification of the resting state networks and the evaluation of their functional connectivity (FC, especially in pathological conditions. There is growing interest in the development of cleaning procedures, especially those not requiring external recordings (data-driven, which are able to remove multiple sources of artefacts. It is important that only inter-subject variability due to the artefacts is removed, preserving the between-subject variability of interest - crucial in clinical applications using clinical scanners to discriminate different pathologies and monitor their staging. In Alzheimer’s disease (AD patients, decreased FC is usually observed in the posterior cingulate cortex within the default mode network (DMN, and this is becoming a possible biomarker for AD. The aim of this study was to compare four different data-driven cleaning procedures (regression of motion parameters; regression of motion parameters, mean white matter and cerebrospinal fluid signal; FMRIB's ICA-based X-noiseifier –FIX- cleanup with soft and aggressive options on data acquired at 1.5T. The approaches were compared using data from 20 elderly healthy subjects and 21 AD patients in a mild stage, in terms of their impact on within-group consistency in FC and ability to detect the typical FC alteration of the DMN in AD patients. Despite an increased within-group consistency across subjects after applying any of the cleaning approaches, only after cleaning with FIX the expected DMN FC alteration in AD was detectable. Our study validates the efficacy of artefact removal even in a relatively small clinical population, and supports the importance of cleaning fMRI data for sensitive detection of FC alterations in a clinical environment.

Selective augmentation of striatal functional connectivity following NMDA receptor antagonism: implications for psychosis.

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Dandash, Orwa; Harrison, Ben J; Adapa, Ram; Gaillard, Raphael; Giorlando, Francesco; Wood, Stephen J; Fletcher, Paul C; Fornito, Alex

2015-02-01

The psychotomimetic effect of the N-methyl-D-aspartate receptor (NMDAR) antagonist ketamine is thought to arise from a functional modulation of the brain's fronto-striato-thalamic (FST) circuits. Animal models suggest a pronounced effect on ventral 'limbic' FST systems, although recent work in patients with psychosis and high-risk individuals suggests specific alterations of dorsal 'associative' FST circuits. Here, we used functional magnetic resonance imaging to investigate the effects of a subanesthetic dose of ketamine on measures of functional connectivity as indexed by the temporal coherence of spontaneous neural activity in both dorsal and ventral FST circuits, as well as their symptom correlates. We adopted a placebo-controlled, double-blind, randomized, repeated-measures design in which 19 healthy participants received either an intravenous saline infusion or a racemic mixture of ketamine (100 ng/ml) separated by at least 1 week. Compared with placebo, ketamine increased functional connectivity between the dorsal caudate and both the thalamus and midbrain bilaterally. Ketamine additionally increased functional connectivity of the ventral striatum/nucleus accumbens and ventromedial prefrontal cortex. Both connectivity increases significantly correlated with the psychosis-like and dissociative symptoms under ketamine. Importantly, dorsal caudate connectivity with the ventrolateral thalamus and subthalamic nucleus showed inverse correlation with ketamine-induced symptomatology, pointing to a possible resilience role to disturbances in FST circuits. Although consistent with the role of FST in mediating psychosis, these findings contrast with previous research in clinical samples by suggesting that acute NMDAR antagonism may lead to psychosis-like experiences via a mechanism that is distinct from that implicated in frank psychotic illness.

Hippocampal Atrophy Is Associated with Altered Hippocampus-Posterior Cingulate Cortex Connectivity in Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis.

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Shih, Y C; Tseng, C E; Lin, F-H; Liou, H H; Tseng, W Y I

2017-03-01

Unilateral mesial temporal lobe epilepsy and hippocampal sclerosis have structural and functional abnormalities in the mesial temporal regions. To gain insight into the pathophysiology of the epileptic network in mesial temporal lobe epilepsy with hippocampal sclerosis, we aimed to clarify the relationships between hippocampal atrophy and the altered connection between the hippocampus and the posterior cingulate cortex in patients with mesial temporal lobe epilepsy with hippocampal sclerosis. Fifteen patients with left mesial temporal lobe epilepsy with hippocampal sclerosis and 15 healthy controls were included in the study. Multicontrast MR imaging, including high-resolution T1WI, diffusion spectrum imaging, and resting-state fMRI, was performed to measure the hippocampal volume, structural connectivity of the inferior cingulum bundle, and intrinsic functional connectivity between the hippocampus and the posterior cingulate cortex, respectively. Compared with controls, patients had decreased left hippocampal volume (volume ratio of the hippocampus and controls, 0.366% ± 0.029%; patients, 0.277% ± 0.063%, corrected P = .002), structural connectivity of the bilateral inferior cingulum bundle (generalized fractional anisotropy, left: controls, 0.234 ± 0.020; patients, 0.193 ± 0.022, corrected P = .0001, right: controls, 0.226 ± 0.022; patients, 0.208 ± 0.017, corrected P = .047), and intrinsic functional connectivity between the left hippocampus and the left posterior cingulate cortex (averaged z-value: controls, 0.314 ± 0.152; patients, 0.166 ± 0.062). The left hippocampal volume correlated with structural connectivity positively (standardized β = 0.864, P = .001), but it had little correlation with intrinsic functional connectivity (standardized β = -0.329, P = .113). On the contralesional side, the hippocampal volume did not show any significant correlation with structural connectivity or intrinsic functional connectivity ( F 2,12 = 0.284, P = .757, R 2

Atypical within- and between-hemisphere motor network functional connections in children with developmental coordination disorder and attention-deficit/hyperactivity disorder

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Kevin R. McLeod

2016-01-01

Full Text Available Developmental coordination disorder (DCD and attention-deficit hyperactivity disorder (ADHD are highly comorbid neurodevelopmental disorders; however, the neural mechanisms of this comorbidity are poorly understood. Previous research has demonstrated that children with DCD and ADHD have altered brain region communication, particularly within the motor network. The structure and function of the motor network in a typically developing brain exhibits hemispheric dominance. It is plausible that functional deficits observed in children with DCD and ADHD are associated with neurodevelopmental alterations in within- and between-hemisphere motor network functional connection strength that disrupt this hemispheric dominance. We used resting-state functional magnetic resonance imaging to examine functional connections of the left and right primary and sensory motor (SM1 cortices in children with DCD, ADHD and DCD + ADHD, relative to typically developing children. Our findings revealed that children with DCD, ADHD and DCD + ADHD exhibit atypical within- and between-hemisphere functional connection strength between SM1 and regions of the basal ganglia, as well as the cerebellum. Our findings further support the assertion that development of atypical motor network connections represents common and distinct neural mechanisms underlying DCD and ADHD. In children with DCD and DCD + ADHD (but not ADHD, a significant correlation was observed between clinical assessment of motor function and the strength of functional connections between right SM1 and anterior cingulate cortex, supplementary motor area, and regions involved in visuospatial processing. This latter finding suggests that behavioral phenotypes associated with atypical motor network development differ between individuals with DCD and those with ADHD.

Glucocorticoid Mechanisms of Functional Connectivity Changes in Stress-Related Neuropsychiatric Disorders.

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Hall, Baila S; Moda, Rachel N; Liston, Conor

2015-01-01

Stress-especially chronic, uncontrollable stress-is an important risk factor for many neuropsychiatric disorders. The underlying mechanisms are complex and multifactorial, but they involve correlated changes in structural and functional measures of neuronal connectivity within cortical microcircuits and across neuroanatomically distributed brain networks. Here, we review evidence from animal models and human neuroimaging studies implicating stress-associated changes in functional connectivity in the pathogenesis of PTSD, depression, and other neuropsychiatric conditions. Changes in fMRI measures of corticocortical connectivity across distributed networks may be caused by specific structural alterations that have been observed in the prefrontal cortex, hippocampus, and other vulnerable brain regions. These effects are mediated in part by glucocorticoids, which are released from the adrenal gland in response to a stressor and also oscillate in synchrony with diurnal rhythms. Recent work indicates that circadian glucocorticoid oscillations act to balance synapse formation and pruning after learning and during development, and chronic stress disrupts this balance. We conclude by considering how disrupted glucocorticoid oscillations may contribute to the pathophysiology of depression and PTSD in vulnerable individuals, and how circadian rhythm disturbances may affect non-psychiatric populations, including frequent travelers, shift workers, and patients undergoing treatment for autoimmune disorders.

Towards mapping the brain connectome in depression: functional connectivity by perfusion SPECT.

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Gardner, Ann; Åstrand, Disa; Öberg, Johanna; Jacobsson, Hans; Jonsson, Cathrine; Larsson, Stig; Pagani, Marco

2014-08-30

Several studies have demonstrated altered brain functional connectivity in the resting state in depression. However, no study has investigated interregional networking in patients with persistent depressive disorder (PDD). The aim of this study was to assess differences in brain perfusion distribution and connectivity between large groups of patients and healthy controls. Participants comprised 91 patients with PDD and 65 age- and sex-matched healthy controls. Resting state perfusion was investigated by single photon emission computed tomography, and group differences were assessed by Statistical Parametric Mapping. Brain connectivity was explored through a voxel-wise interregional correlation analysis using as covariate of interest the normalized values of clusters of voxels in which perfusion differences were found in group analysis. Significantly increased regional brain perfusion distribution covering a large part of the cerebellum was observed in patients as compared with controls. Patients showed a significant negative functional connectivity between the cerebellar cluster and caudate, bilaterally. This study demonstrated inverse relative perfusion between the cerebellum and the caudate in PDD. Functional uncoupling may be associated with a dysregulation between the role of the cerebellum in action control and of the caudate in action selection, initiation and decision making in the patients. The potential impact of the resting state condition and the possibility of mitochondrial impairment are discussed. Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Neuromorphological and wiring pattern alterations effects on brain function: a mixed experimental and computational approach.

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Linus Manubens-Gil

2015-04-01

In addition, the study of fixed intact brains (by means of the state of the art CLARITY technique brings us closer to biologically and medically relevant situations, allowing not only to confirm whether the functional links in neuronal cultures are also present in vivo, but also enabling the introduction of functional information (like behavioral studies and functional imaging and another layer of structural alterations such as brain region morphology, neuronal density, and long-range connectivity. Taking together the experimental information from these systems we want to feed self-developed computational models that allow us to understand what are the fundamental characteristics of the observed connectivity patterns and the impact of each of the alterations on neuronal network function. These models will also provide a framework able to account for the emergent properties that bridge the gap between spontaneous electrical activity arousal/transmission and higher order information processing and memory storage capacities in the brain. As an additional part of the project we are now working on the application of the clearing, labeling and imaging protocols to human biopsy samples. Our aim is to obtain neuronal architecture and connectivity information from focal cortical dysplasia microcircuits using samples from intractable temporal lobe epilepsy patients that undergo deep-brain electrode recording diagnosis and posterior surgical extraction of the tissue. Our computational models can allow us to discern the contributions of the observed abnormalities to neuronal hyperactivity and epileptic seizure generation.

Interictal functional connectivity of human epileptic networks assessed by intracerebral EEG and BOLD signal fluctuations.

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Gaelle Bettus

Full Text Available In this study, we aimed to demonstrate whether spontaneous fluctuations in the blood oxygen level dependent (BOLD signal derived from resting state functional magnetic resonance imaging (fMRI reflect spontaneous neuronal activity in pathological brain regions as well as in regions spared by epileptiform discharges. This is a crucial issue as coherent fluctuations of fMRI signals between remote brain areas are now widely used to define functional connectivity in physiology and in pathophysiology. We quantified functional connectivity using non-linear measures of cross-correlation between signals obtained from intracerebral EEG (iEEG and resting-state functional MRI (fMRI in 5 patients suffering from intractable temporal lobe epilepsy (TLE. Functional connectivity was quantified with both modalities in areas exhibiting different electrophysiological states (epileptic and non affected regions during the interictal period. Functional connectivity as measured from the iEEG signal was higher in regions affected by electrical epileptiform abnormalities relative to non-affected areas, whereas an opposite pattern was found for functional connectivity measured from the BOLD signal. Significant negative correlations were found between the functional connectivities of iEEG and BOLD signal when considering all pairs of signals (theta, alpha, beta and broadband and when considering pairs of signals in regions spared by epileptiform discharges (in broadband signal. This suggests differential effects of epileptic phenomena on electrophysiological and hemodynamic signals and/or an alteration of the neurovascular coupling secondary to pathological plasticity in TLE even in regions spared by epileptiform discharges. In addition, indices of directionality calculated from both modalities were consistent showing that the epileptogenic regions exert a significant influence onto the non epileptic areas during the interictal period. This study shows that functional

Frontal dysconnectivity in 22q11.2 deletion syndrome: an atlas-based functional connectivity analysis.

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Mattiaccio, Leah M; Coman, Ioana L; Thompson, Carlie A; Fremont, Wanda P; Antshel, Kevin M; Kates, Wendy R

2018-01-20

22q11.2 deletion syndrome (22q11DS) is a neurodevelopmental syndrome associated with deficits in cognitive and emotional processing. This syndrome represents one of the highest risk factors for the development of schizophrenia. Previous studies of functional connectivity (FC) in 22q11DS report aberrant connectivity patterns in large-scale networks that are associated with the development of psychotic symptoms. In this study, we performed a functional connectivity analysis using the CONN toolbox to test for differential connectivity patterns between 54 individuals with 22q11DS and 30 healthy controls, between the ages of 17-25 years old. We mapped resting-state fMRI data onto 68 atlas-based regions of interest (ROIs) generated by the Desikan-Killany atlas in FreeSurfer, resulting in 2278 ROI-to-ROI connections for which we determined total linear temporal associations between each. Within the group with 22q11DS only, we further tested the association between prodromal symptoms of psychosis and FC. We observed that relative to controls, individuals with 22q11DS displayed increased FC in lobar networks involving the frontal-frontal, frontal-parietal, and frontal-occipital ROIs. In contrast, FC between ROIs in the parietal-temporal and occipital lobes was reduced in the 22q11DS group relative to healthy controls. Moreover, positive psychotic symptoms were positively associated with increased functional connections between the left precuneus and right superior frontal gyrus, as well as reduced functional connectivity between the bilateral pericalcarine. Positive symptoms were negatively associated with increased functional connectivity between the right pericalcarine and right postcentral gyrus. Our results suggest that functional organization may be altered in 22q11DS, leading to disruption in connectivity between frontal and other lobar substructures, and potentially increasing risk for prodromal psychosis.

Altered resting state connectivity in right side frontoparietal network in primary insomnia patients

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Li, Shumei; Tian, Junzhang; Li, Meng; Wang, Tianyue; Lin, Chulan; Yin, Yi; Jiang, Guihua [Guangdong Second Provincial General Hospital, Department of Medical Imaging, Guangzhou (China); Zeng, Luxian [Guangdong Second Provincial General Hospital, Department of Science and Education, Guangzhou (China); Li, Cheng [Guangdong Second Provincial General Hospital, Department of Renal Transplantation, Guangzhou (China)

2018-02-15

This study investigated alterations of resting-state networks (RSNs) in primary insomnia patients as well as relationships between these changes and clinical features. Fifty-nine primary insomnia patients and 53 healthy control subjects underwent a resting-state fMRI scan (rs-fMRI). Ten RSNs were identified using independent component analysis of rs-fMRI data. To assess significant differences between the two groups, voxel-wise analysis of ten RSNs was conducted using dual regression with FSL randomised non-parametric permutation testing and a threshold-free cluster enhanced technique to control for multiple comparisons. Relationships between abnormal functional connectivity and clinical variables were then investigated with Pearson's correlation analysis. Primary insomnia patients showed decreased connectivity in regions of the right frontoparietal network (FPN), including the superior parietal lobule and superior frontal gyrus. Moreover, decreased connectivity in the right middle temporal gyrus and right lateral occipital cortex with the FPN showed significant positive correlations with disease duration and self-rated anxiety, respectively. Our study suggests that primary insomnia patients are characterised by abnormal organisation of the right FPN, and dysfunction of the FPN is correlated with disease duration and anxiety. The results enhance our understanding of neural substrates underlying symptoms of primary insomnia from the viewpoint of resting-state networks. (orig.)

Altered resting state connectivity in right side frontoparietal network in primary insomnia patients

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Li, Shumei; Tian, Junzhang; Li, Meng; Wang, Tianyue; Lin, Chulan; Yin, Yi; Jiang, Guihua; Zeng, Luxian; Li, Cheng

2018-01-01

This study investigated alterations of resting-state networks (RSNs) in primary insomnia patients as well as relationships between these changes and clinical features. Fifty-nine primary insomnia patients and 53 healthy control subjects underwent a resting-state fMRI scan (rs-fMRI). Ten RSNs were identified using independent component analysis of rs-fMRI data. To assess significant differences between the two groups, voxel-wise analysis of ten RSNs was conducted using dual regression with FSL randomised non-parametric permutation testing and a threshold-free cluster enhanced technique to control for multiple comparisons. Relationships between abnormal functional connectivity and clinical variables were then investigated with Pearson's correlation analysis. Primary insomnia patients showed decreased connectivity in regions of the right frontoparietal network (FPN), including the superior parietal lobule and superior frontal gyrus. Moreover, decreased connectivity in the right middle temporal gyrus and right lateral occipital cortex with the FPN showed significant positive correlations with disease duration and self-rated anxiety, respectively. Our study suggests that primary insomnia patients are characterised by abnormal organisation of the right FPN, and dysfunction of the FPN is correlated with disease duration and anxiety. The results enhance our understanding of neural substrates underlying symptoms of primary insomnia from the viewpoint of resting-state networks. (orig.)

Training for Micrographia Alters Neural Connectivity in Parkinson's Disease

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Evelien Nackaerts

2018-01-01

Full Text Available Despite recent advances in clarifying the neural networks underlying rehabilitation in Parkinson's disease (PD, the impact of prolonged motor learning interventions on brain connectivity in people with PD is currently unknown. Therefore, the objective of this study was to compare cortical network changes after 6 weeks of visually cued handwriting training (= experimental with a placebo intervention to address micrographia, a common problem in PD. Twenty seven early Parkinson's patients on dopaminergic medication performed a pre-writing task in both the presence and absence of visual cues during behavioral tests and during fMRI. Subsequently, patients were randomized to the experimental (N = 13 or placebo intervention (N = 14 both lasting 6 weeks, after which they underwent the same testing procedure. We used dynamic causal modeling to compare the neural network dynamics in both groups before and after training. Most importantly, intensive writing training propagated connectivity via the left hemispheric visuomotor stream to an increased coupling with the supplementary motor area, not witnessed in the placebo group. Training enhanced communication in the left visuomotor integration system in line with the learned visually steered training. Notably, this pattern was apparent irrespective of the presence of cues, suggesting transfer from cued to uncued handwriting. We conclude that in early PD intensive motor skill learning, which led to clinical improvement, alters cortical network functioning. We showed for the first time in a placebo-controlled design that it remains possible to enhance the drive to the supplementary motor area through motor learning.

Aberrant Resting-State Functional Connectivity in the Salience Network of Adolescent Chronic Fatigue Syndrome.

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Laura Anne Wortinger

Full Text Available Neural network investigations are currently absent in adolescent chronic fatigue syndrome (CFS. In this study, we examine whether the core intrinsic connectivity networks (ICNs are altered in adolescent CFS patients. Eighteen adolescent patients with CFS and 18 aged matched healthy adolescent control subjects underwent resting-state functional magnetic resonance imaging (rfMRI. Data was analyzed using dual-regression independent components analysis, which is a data-driven approach for the identification of independent brain networks. Intrinsic connectivity was evaluated in the default mode network (DMN, salience network (SN, and central executive network (CEN. Associations between network characteristics and symptoms of CFS were also explored. Adolescent CFS patients displayed a significant decrease in SN functional connectivity to the right posterior insula compared to healthy comparison participants, which was related to fatigue symptoms. Additionally, there was an association between pain intensity and SN functional connectivity to the left middle insula and caudate that differed between adolescent patients and healthy comparison participants. Our findings of insula dysfunction and its association with fatigue severity and pain intensity in adolescent CFS demonstrate an aberration of the salience network which might play a role in CFS pathophysiology.

Altered Intrinsic Functional Connectivity in Language-Related Brain Regions in Association with Verbal Memory Performance in Euthymic Bipolar Patients

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David E. J. Linden

2013-09-01

Full Text Available Potential abnormalities in the structure and function of the temporal lobes have been studied much less in bipolar disorder than in schizophrenia. This may not be justified because language-related symptoms, such as pressured speech and flight of ideas, and cognitive deficits in the domain of verbal memory are amongst the hallmark of bipolar disorder (BD, and contribution of temporal lobe dysfunction is therefore likely. In the current study, we examined resting-state functional connectivity (FC between the auditory cortex (Heschl’s gyrus [HG], planum temporale [PT] and whole brain using seed correlation analysis in n = 21 BD euthymic patients and n = 20 matched healthy controls and associated it with verbal memory performance. In comparison to controls BD patients showed decreased functional connectivity between Heschl’s gyrus and planum temporale and the left superior and middle temporal gyrus. Additionally, fronto-temporal functional connectivity with the right inferior frontal/precentral gyrus and the insula was increased in patients. Verbal episodic memory deficits in the investigated sample of BD patients and language-related symptoms might therefore be associated with a diminished FC within the auditory/temporal gyrus and a compensatory fronto-temporal pathway.

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

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

2015-11-18

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

Short-term memory deficits correlate with hippocampal-thalamic functional connectivity alterations following acute sleep restriction.

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Chengyang, Li; Daqing, Huang; Jianlin, Qi; Haisheng, Chang; Qingqing, Meng; Jin, Wang; Jiajia, Liu; Enmao, Ye; Yongcong, Shao; Xi, Zhang

2017-08-01

Acute sleep restriction heavily influences cognitive function, affecting executive processes such as attention, response inhibition, and memory. Previous neuroimaging studies have suggested a link between hippocampal activity and short-term memory function. However, the specific contribution of the hippocampus to the decline of short-term memory following sleep restriction has yet to be established. In the current study, we utilized resting-state functional magnetic resonance imaging (fMRI) to examine the association between hippocampal functional connectivity (FC) and the decline of short-term memory following total sleep deprivation (TSD). Twenty healthy adult males aged 20.9 ± 2.3 years (age range, 18-24 years) were enrolled in a within-subject crossover study. Short-term memory and FC were assessed using a Delay-matching short-term memory test and a resting-state fMRI scan before and after TSD. Seed-based correlation analysis was performed using fMRI data for the left and right hippocampus to identify differences in hippocampal FC following TSD. Subjects demonstrated reduced alertness and a decline in short-term memory performance following TSD. Moreover, fMRI analysis identified reduced hippocampal FC with the superior frontal gyrus (SFG), temporal regions, and supplementary motor area. In addition, an increase in FC between the hippocampus and bilateral thalamus was observed, the extent of which correlated with short-term memory performance following TSD. Our findings indicate that the disruption of hippocampal-cortical connectivity is linked to the decline in short-term memory observed after acute sleep restriction. Such results provide further evidence that support the cognitive impairment model of sleep deprivation.

Altered resting-state whole-brain functional networks of neonates with intrauterine growth restriction.

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Batalle, Dafnis; Muñoz-Moreno, Emma; Tornador, Cristian; Bargallo, Nuria; Deco, Gustavo; Eixarch, Elisenda; Gratacos, Eduard

2016-04-01

The feasibility to use functional MRI (fMRI) during natural sleep to assess low-frequency basal brain activity fluctuations in human neonates has been demonstrated, although its potential to characterise pathologies of prenatal origin has not yet been exploited. In the present study, we used intrauterine growth restriction (IUGR) as a model of altered neurodevelopment due to prenatal condition to show the suitability of brain networks to characterise functional brain organisation at neonatal age. Particularly, we analysed resting-state fMRI signal of 20 neonates with IUGR and 13 controls, obtaining whole-brain functional networks based on correlations of blood oxygen level-dependent (BOLD) signal in 90 grey matter regions of an anatomical atlas (AAL). Characterisation of the networks obtained with graph theoretical features showed increased network infrastructure and raw efficiencies but reduced efficiency after normalisation, demonstrating hyper-connected but sub-optimally organised IUGR functional brain networks. Significant association of network features with neurobehavioral scores was also found. Further assessment of spatiotemporal dynamics displayed alterations into features associated to frontal, cingulate and lingual cortices. These findings show the capacity of functional brain networks to characterise brain reorganisation from an early age, and their potential to develop biomarkers of altered neurodevelopment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Altered brain activation and functional connectivity in working memory related networks in patients with type 2 diabetes: An ICA-based analysis

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Zhang, Yang; Lu, Shan; Liu, Chunlei; Zhang, Huimei; Zhou, Xuanhe; Ni, Changlin; Qin, Wen; Zhang, Quan

2016-01-01

Type 2 diabetes mellitus (T2DM) can cause multidimensional cognitive deficits, among which working memory (WM) is usually involved at an early stage. However, the neural substrates underlying impaired WM in T2DM patients are still unclear. To clarify this issue, we utilized functional magnetic resonance imaging (fMRI) and independent component analysis to evaluate T2DM patients for alterations in brain activation and functional connectivity (FC) in WM networks and to determine their associations with cognitive and clinical variables. Twenty complication-free T2DM patients and 19 matched healthy controls (HCs) were enrolled, and fMRI data were acquired during a block-designed 1-back WM task. The WM metrics of the T2DM patients showed no differences compared with those of the HCs, except for a slightly lower accuracy rate in the T2DM patients. Compared with the HCs, the T2DM patients demonstrated increased activation within their WM fronto-parietal networks, and activation strength was significantly correlated with WM performance. The T2DM patients also showed decreased FC within and between their WM networks. Our results indicate that the functional integration of WM sub-networks was disrupted in the complication-free T2DM patients and that strengthened regional activity in fronto-parietal networks may compensate for the WM impairment caused by T2DM. PMID:27021340

Whole brain functional connectivity in clinically isolated syndrome without conventional brain MRI lesions

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Liu, Yaou; Dai, Zhengjia; Duan, Yunyun; Huang, Jing; Ren, Zhuoqiong; Li, Kuncheng; Liu, Zheng; Dong, Huiqing; Shu, Ni; He, Yong; Vrenken, Hugo; Wattjes, Mike P.; Barkhof, Frederik

2016-01-01

To investigate brain functional connectivity (FC) alterations in patients with clinically isolated syndromes (CIS) presenting without conventional brain MRI lesions, and to identify the FC differences between the CIS patients who converted to multiple sclerosis (MS) and those not converted during a 5-year follow-up. We recruited 20 CIS patients without conventional brain lesions, 28 patients with MS and 28 healthy controls (HC). Normalized voxel-based functional connectivity strength (nFCS) was determined using resting-state fMRI (R-fMRI) and compared among groups. Furthermore, 5-years clinical follow-up of the CIS patients was performed to examine the differences in nFCS between converters and non-converters. Compared to HC, CIS patients showed significantly decreased nFCS in the visual areas and increased nFCS in several brain regions predominately in the temporal lobes. MS patients revealed more widespread higher nFCS especially in deep grey matter (DGM), compared to CIS and HC. In the four CIS patients converting to MS, significantly higher nFCS was found in right anterior cingulate gyrus (ACC) and fusiform gyrus (FG), compared to non-converted patients. We demonstrated both functional impairment and compensation in CIS by R-fMRI. nFCS alteration in ACC and FG seems to occur in CIS patients at risk of developing MS. (orig.)

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

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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.

Random geometric graphs with general connection functions

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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.

Structure-function relationships during segregated and integrated network states of human brain functional connectivity.

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Fukushima, Makoto; Betzel, Richard F; He, Ye; van den Heuvel, Martijn P; Zuo, Xi-Nian; Sporns, Olaf

2018-04-01

Structural white matter connections are thought to facilitate integration of neural information across functionally segregated systems. Recent studies have demonstrated that changes in the balance between segregation and integration in brain networks can be tracked by time-resolved functional connectivity derived from resting-state functional magnetic resonance imaging (rs-fMRI) data and that fluctuations between segregated and integrated network states are related to human behavior. However, how these network states relate to structural connectivity is largely unknown. To obtain a better understanding of structural substrates for these network states, we investigated how the relationship between structural connectivity, derived from diffusion tractography, and functional connectivity, as measured by rs-fMRI, changes with fluctuations between segregated and integrated states in the human brain. We found that the similarity of edge weights between structural and functional connectivity was greater in the integrated state, especially at edges connecting the default mode and the dorsal attention networks. We also demonstrated that the similarity of network partitions, evaluated between structural and functional connectivity, increased and the density of direct structural connections within modules in functional networks was elevated during the integrated state. These results suggest that, when functional connectivity exhibited an integrated network topology, structural connectivity and functional connectivity were more closely linked to each other and direct structural connections mediated a larger proportion of neural communication within functional modules. Our findings point out the possibility of significant contributions of structural connections to integrative neural processes underlying human behavior.

Changed hub and corresponding functional connectivity of subgenual anterior cingulate cortex in major depressive disorder

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Huawang Wu

2016-12-01

Full Text Available Major depressive disorder (MDD is one of the most prevalent mental disorders. In the brain, the hubs of the brain network play a key role in integrating and transferring information between different functional modules. However, whether the changed pattern in functional network hubs contributes to the onset of MDD remains unclear. Using resting-state functional magnetic resonance imaging and graph theory methods, we investigated whether alterations of hubs can be detected in MDD. First, we constructed the whole-brain voxel-wise functional networks and calculated a functional connectivity strength (FCS map in each subject in 34 MDD patients and 34 gender-, age-, and education level-matched healthy controls (HC. Next, the two-sample t-test was applied to compare the FCS maps between HC and MDD patients and identified significant decreased FCS in subgenual anterior cingulate cortex (sgACC in MDD patients. Subsequent functional connectivity analyses of sgACC showed disruptions in functional connectivity with posterior insula, middle and inferior temporal gyrus, lingual gyrus, and cerebellum in MDD patients. Furthermore, the changed FCS of sgACC and functional connections to sgACC were significantly correlated with the Hamilton Depression Rating Scale (HDRS scores in MDD patients. The results of the present study revealed the abnormal hub of sgACC and its corresponding disrupted frontal-limbic-visual cognitive-cerebellum functional networks in MDD. These findings may provide a new insight for the diagnosis and treatment of MDD.

Connectivity Neurofeedback Training Can Differentially Change Functional Connectivity and Cognitive Performance.

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Yamashita, Ayumu; Hayasaka, Shunsuke; Kawato, Mitsuo; Imamizu, Hiroshi

2017-10-01

Advances in functional magnetic resonance imaging have made it possible to provide real-time feedback on brain activity. Neurofeedback has been applied to therapeutic interventions for psychiatric disorders. Since many studies have shown that most psychiatric disorders exhibit abnormal brain networks, a novel experimental paradigm named connectivity neurofeedback, which can directly modulate a brain network, has emerged as a promising approach to treat psychiatric disorders. Here, we investigated the hypothesis that connectivity neurofeedback can induce the aimed direction of change in functional connectivity, and the differential change in cognitive performance according to the direction of change in connectivity. We selected the connectivity between the left primary motor cortex and the left lateral parietal cortex as the target. Subjects were divided into 2 groups, in which only the direction of change (an increase or a decrease in correlation) in the experimentally manipulated connectivity differed between the groups. As a result, subjects successfully induced the expected connectivity changes in either of the 2 directions. Furthermore, cognitive performance significantly and differentially changed from preneurofeedback to postneurofeedback training between the 2 groups. These findings indicate that connectivity neurofeedback can induce the aimed direction of change in connectivity and also a differential change in cognitive performance. © The Author 2017. Published by Oxford University Press.

Functional Connectivity Alterations between Networks and Associations with Infant Immune Health within Networks in HIV Infected Children on Early Treatment: A Study at 7 Years

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Jadrana T. F. Toich

2018-01-01

Full Text Available Although HIV has been shown to impact brain connectivity in adults and youth, it is not yet known to what extent long-term early antiretroviral therapy (ART may alter these effects, especially during rapid brain development in early childhood. Using both independent component analysis (ICA and seed-based correlation analysis (SCA, we examine the effects of HIV infection in conjunction with early ART on resting state functional connectivity (FC in 7 year old children. HIV infected (HIV+ children were from the Children with HIV Early Antiretroviral Therapy (CHER trial and all initiated ART before 18 months; uninfected children were recruited from an interlinking vaccine trial. To better understand the effects of current and early immune health on the developing brain, we also investigated among HIV+ children the association of FC at 7 years with CD4 count and CD4%, both in infancy (6–8 weeks and at scan. Although we found no differences within any ICA-generated resting state networks (RSNs between HIV+ and uninfected children (27 HIV+, 18 uninfected, whole brain connectivity to seeds located at RSN connectivity peaks revealed several loci of FC differences, predominantly from seeds in midline regions (posterior cingulate cortex, paracentral lobule, cuneus, and anterior cingulate. Reduced long-range connectivity and increased short-range connectivity suggest developmental delay. Within the HIV+ children, clinical measures at age 7 years were not associated with FC values in any of the RSNs; however, poor immune health during infancy was associated with localized FC increases in the somatosensory, salience and basal ganglia networks. Together these findings suggest that HIV may affect brain development from its earliest stages and persist into childhood, despite early ART.

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

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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…

Glucocorticoid mechanisms of functional connectivity changes in stress-related neuropsychiatric disorders

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Baila S. Hall

2015-01-01

Full Text Available Stress—especially chronic, uncontrollable stress—is an important risk factor for many neuropsychiatric disorders. The underlying mechanisms are complex and multifactorial, but they involve correlated changes in structural and functional measures of neuronal connectivity within cortical microcircuits and across neuroanatomically distributed brain networks. Here, we review evidence from animal models and human neuroimaging studies implicating stress-associated changes in functional connectivity in the pathogenesis of PTSD, depression, and other neuropsychiatric conditions. Changes in fMRI measures of corticocortical connectivity across distributed networks may be caused by specific structural alterations that have been observed in the prefrontal cortex, hippocampus, and other vulnerable brain regions. These effects are mediated in part by glucocorticoids, which are released from the adrenal gland in response to a stressor and also oscillate in synchrony with diurnal rhythms. Recent work indicates that circadian glucocorticoid oscillations act to balance synapse formation and pruning after learning and during development, and chronic stress disrupts this balance. We conclude by considering how disrupted glucocorticoid oscillations may contribute to the pathophysiology of depression and PTSD in vulnerable individuals, and how circadian rhythm disturbances may affect non-psychiatric populations, including frequent travelers, shift workers, and patients undergoing treatment for autoimmune disorders.

Aberrant brain regional homogeneity and functional connectivity in middle-aged T2DM patients: a resting-state functional MRI study

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Daihong Liu

2016-09-01

Full Text Available Type 2 diabetes mellitus (T2DM has been associated with cognitive impairment. However, its neurological mechanism remains elusive. Combining regional homogeneity (ReHo and functional connectivity (FC analyses, the present study aimed to investigate brain functional alterations in middle-aged T2DM patients, which could provide complementary information for the neural substrates underlying T2DM-associated brain dysfunction. Twenty-five T2DM patients and 25 healthy controls were involved in neuropsychological testing and structural and resting-state functional magnetic resonance imaging data acquisition. ReHo analysis was conducted to determine the peak coordinates of brain regions with abnormal local brain activity synchronization. Then, the identified brain regions were considered as seeds, and FC between these brain regions and global voxels was computed. Finally, the potential correlations between the imaging indices and neuropsychological data were also explored. Compared with healthy controls, T2DM patients exhibited higher ReHo values in the anterior cingulate gyrus and lower ReHo in right fusiform gyrus, right precentral gyrus and right medial orbit of the superior frontal gyrus. Considering these areas as seed regions, T2DM patients displayed aberrant FC, mainly in the frontal and parietal lobes. The pattern of FC alterations in T2DM patients was characterized by decreased connectivity and positive to negative or negative to positive converted connectivity. Digital Span Test forward scores revealed significant correlations with the ReHo values of the right precentral gyrus (ρ = 0.527, p = 0.014 and FC between the right fusiform gyrus and middle temporal gyrus (ρ = -0.437, p = 0.048. Our findings suggest that T2DM patients suffer from cognitive dysfunction related to spatially local and remote brain activity synchronization impairment. The patterns of ReHo and FC alterations shed light on the mechanisms underlying T2DM-associated brain

Enhanced limbic/impaired cortical-loop connection onto the hippocampus of NHE rats: Application of resting-state functional connectivity in a preclinical ADHD model.

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Zoratto, F; Palombelli, G M; Ruocco, L A; Carboni, E; Laviola, G; Sadile, A G; Adriani, W; Canese, R

2017-08-30

Due to a hyperfunctioning mesocorticolimbic system, Naples-High-Excitability (NHE) rats have been proposed to model for the meso-cortical variant of attention deficit/hyperactivity disorder (ADHD). Compared to Naples Random-Bred (NRB) controls, NHE rats show hyperactivity, impaired non-selective attention (Aspide et al., 1998), and impaired selective spatial attention (Ruocco et al., 2009a, 2014). Alteration in limbic functions has been proposed; however, resulting unbalance among forebrain areas has not been assessed yet. By resting-state functional Magnetic-Resonance Imaging (fMRI) in vivo, we investigated the connectivity of neuronal networks belonging to limbic vs. cortical loops in NHE and NRB rats (n=10 each). Notably, resting-state fMRI was applied using a multi-slice sagittal, gradient-echo sequence. Voxel-wise connectivity maps at rest, based on temporal correlation among fMRI time-series, were computed by seeding the hippocampus (Hip), nucleus accumbens (NAcc), dorsal striatum (dStr), amygdala (Amy) and dorsal/medial prefrontal cortex (PFC), both hemispheres. To summarize patterns of altered connection, clearly directional connectivity was evident within the cortical loop: bilaterally and specularly, from orbital and dorsal PFCs through dStr and hence towards Hip. Such network communication was reduced in NHE rats (also, with less mesencephalic/pontine innervation). Conversely, enhanced network activity emerged within the limbic loop of NHE rats: from left PFC, both through the NAcc and directly, to the Hip (all of which received greater ventral tegmental innervation, likely dopamine). Together with tuned-down cortical loop, this potentiated limbic loop may serve a major role in controlling ADHD-like behavioral symptoms in NHE rats. Copyright © 2017 Elsevier B.V. All rights reserved.

Mapping functional connectivity

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Peter Vogt; Joseph R. Ferrari; Todd R. Lookingbill; Robert H. Gardner; Kurt H. Riitters; Katarzyna Ostapowicz

2009-01-01

An objective and reliable assessment of wildlife movement is important in theoretical and applied ecology. The identification and mapping of landscape elements that may enhance functional connectivity is usually a subjective process based on visual interpretations of species movement patterns. New methods based on mathematical morphology provide a generic, flexible,...

Abnormal resting-state functional connectivity study in unilateral pulsatile tinnitus patients with single etiology: A seed-based functional connectivity study

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Lv, Han [Department of Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050 (China); Neuroradiology Division, Department of Radiology, Stanford University, CA, 94305 (United States); Zhao, Pengfei [Department of Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050 (China); Liu, Zhaohui [Department of Radiology, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730 (China); Li, Rui; Zhang, Ling; Wang, Peng [Department of Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050 (China); Yan, Fei [Department of Radiology, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730 (China); Liu, Liheng [Department of Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050 (China); Wang, Guopeng; Zeng, Rong [Department of Otolaryngology Head and Neck Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing 100050 (China); Li, Ting [Department of Radiology, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730 (China); Dong, Cheng [Department of Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050 (China); Gong, Shusheng, E-mail: gongss@ccmu.edu.cn [Department of Otolaryngology Head and Neck Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing 100050 (China); Wang, Zhenchang, E-mail: cjr.wzhch@vip.163.com [Department of Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050 (China)

2016-11-15

Objective: Previous studies demonstrated altered regional neural activations in several brain areas in patients with pulsatile tinnitus (PT), especially indicating an important role of posterior cingulate cortex (PCC). However, few studies focused on the degree of functional connectivity (FC) of this area in PT patients. In this study, we will compare the FC of PCC in patients affected with this condition and normal controls by using resting-state functional magnetic resonance imaging (fMRI). Methods: Structural and functional MRI data were obtained from 36 unilateral PT patients with single etiology and 36 matched healthy controls. FC feature of the region of interest (PCC) were characterized using a seed-based correlation method with the voxels in the whole-brain. Results: Compared with healthy controls, patients showed significant decreased FC to the right middle temporal gyrus (MTG), right thalamus and bilateral insula. By contrast, PCC demonstrated increased functional connectivity between the precuneus, bilateral inferior parietal lobule and middle occipital gyrus. We also found correlations between the disease duration of PT and FC of PCC-right MTG (r = −0.616, p < 0.001). Conclusions: Unilateral PT patients could have abnormal FC to the PCC bilaterally in the brain. PCC, as a highly integrated brain area, is an example of nucleus that was involved in mediation between different neural networks. It might be a modulation core between visual network and auditory network. The decreased FC of MTG to PCC may indicate a down regulation of activity between PCC and auditory associated brain cortex. Decreased FC between limbic system (bilateral AI) and PCC may reflect the emotional message control in patient group. This study facilitated understanding of the underlying neuropathological process in patients with pulsatile tinnitus.

Abnormal resting-state functional connectivity study in unilateral pulsatile tinnitus patients with single etiology: A seed-based functional connectivity study

International Nuclear Information System (INIS)

Lv, Han; Zhao, Pengfei; Liu, Zhaohui; Li, Rui; Zhang, Ling; Wang, Peng; Yan, Fei; Liu, Liheng; Wang, Guopeng; Zeng, Rong; Li, Ting; Dong, Cheng; Gong, Shusheng; Wang, Zhenchang

2016-01-01

Objective: Previous studies demonstrated altered regional neural activations in several brain areas in patients with pulsatile tinnitus (PT), especially indicating an important role of posterior cingulate cortex (PCC). However, few studies focused on the degree of functional connectivity (FC) of this area in PT patients. In this study, we will compare the FC of PCC in patients affected with this condition and normal controls by using resting-state functional magnetic resonance imaging (fMRI). Methods: Structural and functional MRI data were obtained from 36 unilateral PT patients with single etiology and 36 matched healthy controls. FC feature of the region of interest (PCC) were characterized using a seed-based correlation method with the voxels in the whole-brain. Results: Compared with healthy controls, patients showed significant decreased FC to the right middle temporal gyrus (MTG), right thalamus and bilateral insula. By contrast, PCC demonstrated increased functional connectivity between the precuneus, bilateral inferior parietal lobule and middle occipital gyrus. We also found correlations between the disease duration of PT and FC of PCC-right MTG (r = −0.616, p < 0.001). Conclusions: Unilateral PT patients could have abnormal FC to the PCC bilaterally in the brain. PCC, as a highly integrated brain area, is an example of nucleus that was involved in mediation between different neural networks. It might be a modulation core between visual network and auditory network. The decreased FC of MTG to PCC may indicate a down regulation of activity between PCC and auditory associated brain cortex. Decreased FC between limbic system (bilateral AI) and PCC may reflect the emotional message control in patient group. This study facilitated understanding of the underlying neuropathological process in patients with pulsatile tinnitus.

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

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Martin Göttlich

2014-01-01

Using whole brain resting-state connectivity analysis in BVF patients we show that enduring bilateral deficient or missing vestibular input leads to changes in resting-state connectivity of the brain. These changes in the resting brain are robust and task-independent as they were found in the absence of sensory stimulation and without a region-related a priori hypothesis. Therefore they may indicate a fundamental disease-related change in the resting brain. They may account for the patients' persistent deficits in visuo-spatial attention, spatial orientation and unsteadiness. The relation of increasing connectivity in the inferior parietal lobe, specifically SMG, to improvement of VOR during active head movements reflects cortical plasticity in BVF and may play a clinical role in vestibular rehabilitation.

Laterality patterns of brain functional connectivity: gender effects.

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Tomasi, Dardo; Volkow, Nora D

2012-06-01

Lateralization of brain connectivity may be essential for normal brain function and may be sexually dimorphic. Here, we study the laterality patterns of short-range (implicated in functional specialization) and long-range (implicated in functional integration) connectivity and the gender effects on these laterality patterns. Parallel computing was used to quantify short- and long-range functional connectivity densities in 913 healthy subjects. Short-range connectivity was rightward lateralized and most asymmetrical in areas around the lateral sulcus, whereas long-range connectivity was rightward lateralized in lateral sulcus and leftward lateralizated in inferior prefrontal cortex and angular gyrus. The posterior inferior occipital cortex was leftward lateralized (short- and long-range connectivity). Males had greater rightward lateralization of brain connectivity in superior temporal (short- and long-range), inferior frontal, and inferior occipital cortices (short-range), whereas females had greater leftward lateralization of long-range connectivity in the inferior frontal cortex. The greater lateralization of the male's brain (rightward and predominantly short-range) may underlie their greater vulnerability to disorders with disrupted brain asymmetries (schizophrenia, autism).

Income change alters default mode network connectivity for adolescents in poverty

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David G. Weissman

2018-04-01

Full Text Available Experiencing poverty during childhood and adolescence may affect brain function. However, income is dynamic, and studies have not addressed whether income change relates to brain function. In the present study, we investigated whether intrinsic functional connectivity of default mode network (DMN regions was influenced by mean family income and family income change. Parents of 68 Mexican-origin adolescents (35 females reported family income annually when adolescents were 10–16 years old. Intercept and slope of income at each of these ages were calculated for each participant. At age 16 years, adolescents completed a resting state functional neuroimaging scan. Adolescents from high and low income families did not differ in their functional connectivity, but for adolescents in families with lower incomes, their connectivity patterns depended on their income slope. Low-income adolescents whose income increased demonstrated greater connectivity between the posterior cingulate cortex (PCC and the medial prefrontal cortex (mPFC, both DMN regions, and between the PCC and the right inferior frontal gyrus. Increases in income were associated with greater connectivity of the mPFC with the right inferior frontal gyrus and the left superior parietal lobule regardless of mean income. Increases in income, especially among adolescents in poverty, may alleviate stressors, influencing the development of brain networks. Keywords: Adversity, Brain, fMRI, Resting state, Socio-economic status, Youth

Income change alters default mode network connectivity for adolescents in poverty.

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Weissman, David G; Conger, Rand D; Robins, Richard W; Hastings, Paul D; Guyer, Amanda E

2018-04-01

Experiencing poverty during childhood and adolescence may affect brain function. However, income is dynamic, and studies have not addressed whether income change relates to brain function. In the present study, we investigated whether intrinsic functional connectivity of default mode network (DMN) regions was influenced by mean family income and family income change. Parents of 68 Mexican-origin adolescents (35 females) reported family income annually when adolescents were 10-16 years old. Intercept and slope of income at each of these ages were calculated for each participant. At age 16 years, adolescents completed a resting state functional neuroimaging scan. Adolescents from high and low income families did not differ in their functional connectivity, but for adolescents in families with lower incomes, their connectivity patterns depended on their income slope. Low-income adolescents whose income increased demonstrated greater connectivity between the posterior cingulate cortex (PCC) and the medial prefrontal cortex (mPFC), both DMN regions, and between the PCC and the right inferior frontal gyrus. Increases in income were associated with greater connectivity of the mPFC with the right inferior frontal gyrus and the left superior parietal lobule regardless of mean income. Increases in income, especially among adolescents in poverty, may alleviate stressors, influencing the development of brain networks. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Network-based analysis reveals functional connectivity related to internet addiction tendency

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Tanya eWen

2016-02-01

Full Text Available IntroductionPreoccupation and compulsive use of the internet can have negative psychological effects, such that it is increasingly being recognized as a mental disorder. The present study employed network-based statistics to explore how whole-brain functional connections at rest is related to the extent of individual’s level of internet addiction, indexed by a self-rated questionnaire. We identified two topologically significant networks, one with connections that are positively correlated with internet addiction tendency, and one with connections negatively correlated with internet addiction tendency. The two networks are interconnected mostly at frontal regions, which might reflect alterations in the frontal region for different aspects of cognitive control (i.e., for control of internet usage and gaming skills. Next, we categorized the brain into several large regional subgroupings, and found that the majority of proportions of connections in the two networks correspond to the cerebellar model of addiction which encompasses the four-circuit model. Lastly, we observed that the brain regions with the most inter-regional connections associated with internet addiction tendency replicate those often seen in addiction literature, and is corroborated by our meta-analysis of internet addiction studies. This research provides a better understanding of large-scale networks involved in internet addiction tendency and shows that pre-clinical levels of internet addiction are associated with similar regions and connections as clinical cases of addiction.

Amodal brain activation and functional connectivity in response to high-energy-density food cues in obesity.

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Carnell, Susan; Benson, Leora; Pantazatos, Spiro P; Hirsch, Joy; Geliebter, Allan

2014-11-01

The obesogenic environment is pervasive, yet only some people become obese. The aim was to investigate whether obese individuals show differential neural responses to visual and auditory food cues, independent of cue modality. Obese (BMI 29-41, n = 10) and lean (BMI 20-24, n = 10) females underwent fMRI scanning during presentation of auditory (spoken word) and visual (photograph) cues representing high-energy-density (ED) and low-ED foods. The effect of obesity on whole-brain activation, and on functional connectivity with the midbrain/VTA, was examined. Obese compared with lean women showed greater modality-independent activation of the midbrain/VTA and putamen in response to high-ED (vs. low-ED) cues, as well as relatively greater functional connectivity between the midbrain/VTA and cerebellum (P food cues within the midbrain/VTA and putamen, and altered functional connectivity between the midbrain/VTA and cerebellum, could contribute to excessive food intake in obese individuals. © 2014 The Obesity Society.

A systematic framework for functional connectivity measures

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Huifang Elizabeth Wang

2014-12-01

Full Text Available 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.

Whole-brain functional connectivity predicted by indirect structural connections

DEFF Research Database (Denmark)

Røge, Rasmus; Ambrosen, Karen Marie Sandø; Albers, Kristoffer Jon

2017-01-01

Modern functional and diffusion magnetic resonance imaging (fMRI and dMRI) provide data from which macro-scale networks of functional and structural whole brain connectivity can be estimated. Although networks derived from these two modalities describe different properties of the human brain, the...

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

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

2014-07-01

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

Migraine classification using magnetic resonance imaging resting-state functional connectivity data.

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Chong, Catherine D; Gaw, Nathan; Fu, Yinlin; Li, Jing; Wu, Teresa; Schwedt, Todd J

2017-08-01

Background This study used machine-learning techniques to develop discriminative brain-connectivity biomarkers from resting-state functional magnetic resonance neuroimaging ( rs-fMRI) data that distinguish between individual migraine patients and healthy controls. Methods This study included 58 migraine patients (mean age = 36.3 years; SD = 11.5) and 50 healthy controls (mean age = 35.9 years; SD = 11.0). The functional connections of 33 seeded pain-related regions were used as input for a brain classification algorithm that tested the accuracy of determining whether an individual brain MRI belongs to someone with migraine or to a healthy control. Results The best classification accuracy using a 10-fold cross-validation method was 86.1%. Resting functional connectivity of the right middle temporal, posterior insula, middle cingulate, left ventromedial prefrontal and bilateral amygdala regions best discriminated the migraine brain from that of a healthy control. Migraineurs with longer disease durations were classified more accurately (>14 years; 96.7% accuracy) compared to migraineurs with shorter disease durations (≤14 years; 82.1% accuracy). Conclusions Classification of migraine using rs-fMRI provides insights into pain circuits that are altered in migraine and could potentially contribute to the development of a new, noninvasive migraine biomarker. Migraineurs with longer disease burden were classified more accurately than migraineurs with shorter disease burden, potentially indicating that disease duration leads to reorganization of brain circuitry.

Embryonic exposure to an aqueous coal dust extract results in gene expression alterations associated with the development and function of connective tissue and the hematological system, immunological and inflammatory disease, and cancer in zebrafish.

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Caballero-Gallardo, Karina; Wirbisky-Hershberger, Sara E; Olivero-Verbel, Jesus; de la Rosa, Jesus; Freeman, Jennifer L

2018-03-01

Coal mining is one of the economic activities with the greatest impact on environmental quality. At all stages contaminants are released as particulates such as coal dust. The first aim of this study was to obtain an aqueous coal dust extract and characterize its composition in terms of trace elements by ICP-MS. In addition, the developmental toxicity of the aqueous coal extract was evaluated using zebrafish (Danio rerio) after exposure to different concentrations (0-1000 ppm; μg mL -1 ) to establish acute toxicity, morphology and transcriptome changes. Trace elements within the aqueous coal dust extract present at the highest concentrations (>10 ppb) included Sr, Zn, Ba, As, Cu and Se. In addition, Cd and Pb were found in lower concentrations. No significant difference in mortality was observed (p > 0.05), but a delay in hatching was found at 0.1 and 1000 ppm (p 0.05). Transcriptomic results of zebrafish larvae revealed alterations in 77, 61 and 1376 genes in the 1, 10, and 100 ppm groups, respectively. Gene ontology analysis identified gene alterations associated with the development and function of connective tissue and the hematological system, as well as pathways associated with apoptosis, the cell cycle, transcription, and oxidative stress including the MAPK signaling pathway. In addition, altered genes were associated with cancer; connective tissue, muscular, and skeletal disorders; and immunological and inflammatory diseases. Overall, this is the first study to characterize gene expression alterations in response to developmental exposure to aqueous coal dust residue from coal mining with transcriptome results signifying functions and systems to target in future studies.

Replicated landscape genetic and network analyses reveal wide variation in functional connectivity for American pikas.

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Castillo, Jessica A; Epps, Clinton W; Jeffress, Mackenzie R; Ray, Chris; Rodhouse, Thomas J; Schwalm, Donelle

2016-09-01

. We concluded that climate change, besides influencing patch occupancy as predicted by other studies, may alter landscape resistance for pikas, thereby influencing functional connectivity through multiple pathways simultaneously. Spatial autocorrelation among genotypes varied across study sites and was largest where habitat was most dispersed, suggesting that dispersal distances increased with habitat fragmentation, up to a point. This study demonstrates how landscape features linked to climate can affect functional connectivity for species with naturally fragmented distributions, and reinforces the importance of replicating studies across landscapes. © 2016 by the Ecological Society of America.

Identifying the Alteration Patterns of Brain Functional Connectivity in Progressive Mild Cognitive Impairment Patients: A Longitudinal Whole-Brain Voxel-Wise Degree Analysis.

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Deng, Yanjia; Liu, Kai; Shi, Lin; Lei, Yi; Liang, Peipeng; Li, Kuncheng; Chu, Winnie C W; Wang, Defeng

2016-01-01

Patients with mild cognitive impairment (MCI) are at high risk for developing Alzheimer's disease (AD), while some of them may remain stable over decades. The underlying mechanism is still not fully understood. In this study, we aimed to explore the connectivity differences between progressive MCI (PMCI) and stable MCI (SMCI) individuals on a whole-brain scale and on a voxel-wise basis, and we also aimed to reveal the differential dynamic alteration patterns between these two disease subtypes. The resting-state functional magnetic resonance images of PMCI and SMCI patients at baseline and year-one were obtained from the Alzheimer's Disease Neuroimaging Initiative dataset, and the progression was determined based on a 3-year follow-up. A whole-brain voxel-wise degree map that was calculated based on graph-theory was constructed for each subject, and then the cross-sectional and longitudinal analyses on the degree maps were performed between PMCI and SMCI patients. In longitudinal analyses, compared with SMCI group, PMCI group showed decreased long-range degree in the left middle occipital/supramarginal gyrus, while the short-range degree was increased in the left supplementary motor area and middle frontal gyrus and decreased in the right middle temporal pole. A significant longitudinal alteration of decreased short-range degree in the right middle occipital was found in PMCI group. Taken together with previous evidence, our current findings may suggest that PMCI, compared with SMCI, might be a "severe" presentation of disease along the AD continuum, and the rapidly reduced degree in the right middle occipital gyrus may have indicative value for the disease progression. Moreover, the cross-sectional comparison results and corresponding receiver-operator characteristic-curves analyses may indicate that the baseline degree difference is not a good predictor of disease progression in MCI patients. Overall, these findings may provide objective evidence and an indicator

Advanced Connectivity Analysis (ACA): a Large Scale Functional Connectivity Data Mining Environment.

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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.

Multisite Reliability of MR-Based Functional Connectivity

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Noble, Stephanie; Scheinost, Dustin; Finn, Emily S.; Shen, Xilin; Papademetris, Xenophon; McEwen, Sarah C.; Bearden, Carrie E.; Addington, Jean; Goodyear, Bradley; Cadenhead, Kristin S.; Mirzakhanian, Heline; Cornblatt, Barbara A.; Olvet, Doreen M.; Mathalon, Daniel H.; McGlashan, Thomas H.; Perkins, Diana O.; Belger, Aysenil; Seidman, Larry J.; Thermenos, Heidi; Tsuang, Ming T.; van Erp, Theo G.M.; Walker, Elaine F.; Hamann, Stephan; Woods, Scott W.; Cannon, Tyrone D.; Constable, R. Todd

2016-01-01

Recent years have witnessed an increasing number of multisite MRI functional connectivity (fcMRI) studies. While multisite studies are an efficient way to speed up data collection and increase sample sizes, especially for rare clinical populations, any effects of site or MRI scanner could ultimately limit power and weaken results. Little data exists on the stability of functional connectivity measurements across sites and sessions. In this study, we assess the influence of site and session on resting state functional connectivity measurements in a healthy cohort of traveling subjects (8 subjects scanned twice at each of 8 sites) scanned as part of the North American Prodrome Longitudinal Study (NAPLS). Reliability was investigated in three types of connectivity analyses: (1) seed-based connectivity with posterior cingulate cortex (PCC), right motor cortex (RMC), and left thalamus (LT) as seeds; (2) the intrinsic connectivity distribution (ICD), a voxel-wise connectivity measure; and (3) matrix connectivity, a whole-brain, atlas-based approach assessing connectivity between nodes. Contributions to variability in connectivity due to subject, site, and day-of-scan were quantified and used to assess between-session (test-retest) reliability in accordance with Generalizability Theory. Overall, no major site, scanner manufacturer, or day-of-scan effects were found for the univariate connectivity analyses; instead, subject effects dominated relative to the other measured factors. However, summaries of voxel-wise connectivity were found to be sensitive to site and scanner manufacturer effects. For all connectivity measures, although subject variance was three times the site variance, the residual represented 60–80% of the variance, indicating that connectivity differed greatly from scan to scan independent of any of the measured factors (i.e., subject, site, and day-of-scan). Thus, for a single 5 min scan, reliability across connectivity measures was poor (ICC=0.07–0

Sustained NMDA receptor hypofunction induces compromised neural systems integration and schizophrenia-like alterations in functional brain networks.

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Dawson, Neil; Xiao, Xiaolin; McDonald, Martin; Higham, Desmond J; Morris, Brian J; Pratt, Judith A

2014-02-01

Compromised functional integration between cerebral subsystems and dysfunctional brain network organization may underlie the neurocognitive deficits seen in psychiatric disorders. Applying topological measures from network science to brain imaging data allows the quantification of complex brain network connectivity. While this approach has recently been used to further elucidate the nature of brain dysfunction in schizophrenia, the value of applying this approach in preclinical models of psychiatric disease has not been recognized. For the first time, we apply both established and recently derived algorithms from network science (graph theory) to functional brain imaging data from rats treated subchronically with the N-methyl-D-aspartic acid (NMDA) receptor antagonist phencyclidine (PCP). We show that subchronic PCP treatment induces alterations in the global properties of functional brain networks akin to those reported in schizophrenia. Furthermore, we show that subchronic PCP treatment induces compromised functional integration between distributed neural systems, including between the prefrontal cortex and hippocampus, that have established roles in cognition through, in part, the promotion of thalamic dysconnectivity. We also show that subchronic PCP treatment promotes the functional disintegration of discrete cerebral subsystems and also alters the connectivity of neurotransmitter systems strongly implicated in schizophrenia. Therefore, we propose that sustained NMDA receptor hypofunction contributes to the pathophysiology of dysfunctional brain network organization in schizophrenia.

Disrupted intrinsic and remote functional connectivity in heterotopia-related epilepsy.

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Liu, W; Hu, X; An, D; Gong, Q; Zhou, D

2018-01-01

Several neuroimaging studies have examined neural interactions in patients with periventricular nodular heterotopia (PNH). However, features of the underlying functional network remain poorly understood. In this study, we examined alterations in the local (regional) and remote (interregional) cerebral networks in this disorder. Twenty-eight subjects all having suffered from PNH with epilepsy, as well as 28 age- and sex- matched healthy controls, were enrolled in this study. Amplitude of low-frequency fluctuation (ALFF) and seed-based functional connectivity (FC) were calculated to detect regional neural function and functional network integration, respectively. Compared with healthy controls, patients with PNH-related epilepsy showed decreased ALFF in the ventromedial prefrontal cortex (vmPFC) and precuneus areas. ALFF values in both areas were negative correlated with epilepsy duration (P < .05, Bonferroni-corrected). Furthermore, patients with PNH-related epilepsy had increased remote interregional FC mainly in bilateral prefrontal and parietal cortices, supramarginal gyrus, dorsal cingulate gyrus, and right insula; lower FC was found in posterior brain regions including bilateral parahippocampal gyrus and inferior temporal gyrus. Focal spontaneous hypofunction, as assessed by ALFF, correlates with epilepsy duration in patients with PNH-related epilepsy. Abnormalities existed both within the default-mode network and then across the whole brain, demonstrating that intrinsic brain dysfunction may be related to specific network interactions. Our findings provide novel understanding of the connectivity-based pathophysiological mechanisms of PNH. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Brain structure and functional connectivity associated with pornography consumption: the brain on porn.

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Kühn, Simone; Gallinat, Jürgen

2014-07-01

Since pornography appeared on the Internet, the accessibility, affordability, and anonymity of consuming visual sexual stimuli have increased and attracted millions of users. Based on the assumption that pornography consumption bears resemblance with reward-seeking behavior, novelty-seeking behavior, and addictive behavior, we hypothesized alterations of the frontostriatal network in frequent users. To determine whether frequent pornography consumption is associated with the frontostriatal network. In a study conducted at the Max Planck Institute for Human Development in Berlin, Germany, 64 healthy male adults covering a wide range of pornography consumption reported hours of pornography consumption per week. Pornography consumption was associated with neural structure, task-related activation, and functional resting-state connectivity. Gray matter volume of the brain was measured by voxel-based morphometry and resting state functional connectivity was measured on 3-T magnetic resonance imaging scans. We found a significant negative association between reported pornography hours per week and gray matter volume in the right caudate (P < .001, corrected for multiple comparisons) as well as with functional activity during a sexual cue-reactivity paradigm in the left putamen (P < .001). Functional connectivity of the right caudate to the left dorsolateral prefrontal cortex was negatively associated with hours of pornography consumption. The negative association of self-reported pornography consumption with the right striatum (caudate) volume, left striatum (putamen) activation during cue reactivity, and lower functional connectivity of the right caudate to the left dorsolateral prefrontal cortex could reflect change in neural plasticity as a consequence of an intense stimulation of the reward system, together with a lower top-down modulation of prefrontal cortical areas. Alternatively, it could be a precondition that makes pornography consumption more rewarding.

How functional connectivity between emotion regulation structures can be disrupted: preliminary evidence from adolescents with moderate to severe traumatic brain injury.

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Newsome, Mary R; Scheibel, Randall S; Mayer, Andrew R; Chu, Zili D; Wilde, Elisabeth A; Hanten, Gerri; Steinberg, Joel L; Lin, Xiaodi; Li, Xiaoqi; Merkley, Tricia L; Hunter, Jill V; Vasquez, Ana C; Cook, Lori; Lu, Hanzhang; Vinton, Kami; Levin, Harvey S

2013-09-01

Outcome of moderate to severe traumatic brain injury (TBI) includes impaired emotion regulation. Emotion regulation has been associated with amygdala and rostral anterior cingulate (rACC). However, functional connectivity between the two structures after injury has not been reported. A preliminary examination of functional connectivity of rACC and right amygdala was conducted in adolescents 2 to 3 years after moderate to severe TBI and in typically developing (TD)control adolescents, with the hypothesis that the TBI adolescents would demonstrate altered functional connectivity in the two regions. Functional connectivity was determined by correlating fluctuations in the blood oxygen level dependent(BOLD) signal of the rACC and right amygdala with that of other brain regions. In the TBI adolescents, the rACC was found to be significantly less functionally connected to medial prefrontal cortices and to right temporal regions near the amygdala (height threshold T = 2.5, cluster level p functional connectivity with the rACC (height threshold T = 2.5, cluster level p = .06, FDR corrected). Data suggest disrupted functional connectivity in emotion regulation regions. Limitations include small sample sizes. Studies with larger sample sizes are necessary to characterize the persistent neural damage resulting from moderate to severe TBI during development.

Maternal Immune Activation During the Third Trimester Is Associated with Neonatal Functional Connectivity of the Salience Network and Fetal to Toddler Behavior.

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Spann, Marisa N; Monk, Catherine; Scheinost, Dustin; Peterson, Bradley S

2018-03-14

Prenatal maternal immune activation (MIA) is associated with altered brain development and risk of psychiatric disorders in offspring. Translational human studies of MIA are few in number. Alterations of the salience network have been implicated in the pathogenesis of the same psychiatric disorders associated with MIA. If MIA is pathogenic, then associated abnormalities in the salience network should be detectable in neonates immediately after birth. We tested the hypothesis that third trimester MIA of adolescent women who are at risk for high stress and inflammation is associated with the strength of functional connectivity in the salience network of their neonate. Thirty-six women underwent blood draws to measure interleukin-6 (IL-6) and C-reactive protein (CRP) and electrocardiograms to measure fetal heart rate variability (FHRV) at 34-37 weeks gestation. Resting-state imaging data were acquired in the infants at 40-44 weeks postmenstrual age (PMA). Functional connectivity was measured from seeds placed in the anterior cingulate cortex and insula. Measures of cognitive development were obtained at 14 months PMA using the Bayley Scales of Infant and Toddler Development-Third Edition (BSID-III). Both sexes were studied. Regions in which the strength of the salience network correlated with maternal IL-6 or CRP levels included the medial prefrontal cortex, temporoparietal junction, and basal ganglia. Maternal CRP level correlated inversely with FHRV acquired at the same gestational age. Maternal CRP and IL-6 levels correlated positively with measures of cognitive development on the BSID-III. These results suggest that MIA is associated with short- and long-term influences on offspring brain and behavior. SIGNIFICANCE STATEMENT Preclinical studies in rodents and nonhuman primates and epidemiological studies in humans suggest that maternal immune activation (MIA) alters the development of brain circuitry and associated behaviors, placing offspring at risk for

Corticolimbic functional connectivity in adolescents with bipolar disorder.

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Fei Wang

Full Text Available Convergent evidence supports regional dysfunction within a corticolimbic neural system that subserves emotional processing and regulation in adolescents and adults with bipolar disorder (BD, with abnormalities prominent within the amygdala and its major anterior paralimbic cortical connection sites including ventral anterior cingulate, orbitofrontal, insular and temporopolar cortices. Recent studies of adults with BD demonstrate abnormalities in the functional connectivity between the amygdala and anterior paralimbic regions suggesting an important role for the connections between these regions in the development of the disorder. This study tests the hypothesis that these functional connectivity abnormalities are present in adolescents with BD. Fifty-seven adolescents, twenty-one with BD and thirty-six healthy comparison (HC adolescents, participated in functional magnetic resonance imaging while processing emotional face stimuli. The BD and HC groups were compared in the strength of functional connectivity from amygdala to the anterior paralimbic cortical regions, and explored in remaining brain regions. Functional connectivity was decreased in the BD group, compared to the HC group, during processing of emotional faces in ventral anterior cingulate (VACC, orbitofrontal, insular and temporopolar cortices (p<0.005. Orbitofrontal and VACC findings for the happy condition, and additionally right insula for the neutral condition, survived multiple comparison correction. Exploratory analyses did not reveal additional regions of group differences. This study provides evidence for decreased functional connectivity between the amygdala and anterior paralimbic cortices in adolescents with BD. This suggests that amygdala-anterior paralimbic connectivity abnormalities are early features of BD that emerge at least by adolescence in the disorder.

Altered resting brain connectivity in persistent cancer related fatigue

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Johnson P. Hampson

2015-01-01

Full Text Available There is an estimated 3 million women in the US living as breast cancer survivors and persistent cancer related fatigue (PCRF disrupts the lives of an estimated 30% of these women. PCRF is associated with decreased quality of life, decreased sleep quality, impaired cognition and depression. The mechanisms of cancer related fatigue are not well understood; however, preliminary findings indicate dysfunctional activity in the brain as a potential factor. Here we investigate the relationship between PCRF on intrinsic resting state connectivity in this population. Twenty-three age matched breast cancer survivors (15 fatigued and 8 non-fatigued who completed all cancer-related treatments at least 12 weeks prior to the study, were recruited to undergo functional connectivity magnetic resonance imaging (fcMRI. Intrinsic resting state networks were examined with both seed based and independent component analysis methods. Comparisons of brain connectivity patterns between groups as well as correlations with self-reported fatigue symptoms were performed. Fatigued patients displayed greater left inferior parietal lobule to superior frontal gyrus connectivity as compared to non-fatigued patients (P < 0.05 FDR corrected. This enhanced connectivity was associated with increased physical fatigue (P = 0.04, r = 0.52 and poor sleep quality (P = 0.04, r = 0.52 in the fatigued group. In contrast greater connectivity in the non-fatigued group was found between the right precuneus to the periaqueductal gray as well as the left IPL to subgenual cortex (P < 0.05 FDR corrected. Mental fatigue scores were associated with greater default mode network (DMN connectivity to the superior frontal gyrus (P = 0.05 FDR corrected among fatigued subjects (r = 0.82 and less connectivity in the non-fatigued group (r = −0.88. These findings indicate that there is enhanced intrinsic DMN connectivity to the frontal gyrus in breast cancer survivors with persistent

Obesity is marked by distinct functional connectivity in brain networks involved in food reward and salience.

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Wijngaarden, M A; Veer, I M; Rombouts, S A R B; van Buchem, M A; Willems van Dijk, K; Pijl, H; van der Grond, J

2015-01-01

We hypothesized that brain circuits involved in reward and salience respond differently to fasting in obese versus lean individuals. We compared functional connectivity networks related to food reward and saliency after an overnight fast (baseline) and after a prolonged fast of 48 h in lean versus obese subjects. We included 13 obese (2 males, 11 females, BMI 35.4 ± 1.2 kg/m(2), age 31 ± 3 years) and 11 lean subjects (2 males, 9 females, BMI 23.2 ± 0.5 kg/m(2), age 28 ± 3 years). Resting-state functional magnetic resonance imaging scans were made after an overnight fast (baseline) and after a prolonged 48 h fast. Functional connectivity of the amygdala, hypothalamus and posterior cingulate cortex (default-mode) networks was assessed using seed-based correlations. At baseline, we found a stronger connectivity between hypothalamus and left insula in the obese subjects. This effect diminished upon the prolonged fast. After prolonged fasting, connectivity of the hypothalamus with the dorsal anterior cingulate cortex (dACC) increased in lean subjects and decreased in obese subjects. Amygdala connectivity with the ventromedial prefrontal cortex was stronger in lean subjects at baseline, which did not change upon the prolonged fast. No differences in posterior cingulate cortex connectivity were observed. In conclusion, obesity is marked by alterations in functional connectivity networks involved in food reward and salience. Prolonged fasting differentially affected hypothalamic connections with the dACC and the insula between obese and lean subjects. Our data support the idea that food reward and nutrient deprivation are differently perceived and/or processed in obesity. Copyright © 2015 Elsevier B.V. All rights reserved.

Network structure shapes spontaneous functional connectivity dynamics.

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Shen, Kelly; Hutchison, R Matthew; Bezgin, Gleb; Everling, Stefan; McIntosh, Anthony R

2015-04-08

The structural organization of the brain constrains the range of interactions between different regions and shapes ongoing information processing. Therefore, it is expected that large-scale dynamic functional connectivity (FC) patterns, a surrogate measure of coordination between brain regions, will be closely tied to the fiber pathways that form the underlying structural network. Here, we empirically examined the influence of network structure on FC dynamics by comparing resting-state FC (rsFC) obtained using BOLD-fMRI in macaques (Macaca fascicularis) to structural connectivity derived from macaque axonal tract tracing studies. Consistent with predictions from simulation studies, the correspondence between rsFC and structural connectivity increased as the sample duration increased. Regions with reciprocal structural connections showed the most stable rsFC across time. The data suggest that the transient nature of FC is in part dependent on direct underlying structural connections, but also that dynamic coordination can occur via polysynaptic pathways. Temporal stability was found to be dependent on structural topology, with functional connections within the rich-club core exhibiting the greatest stability over time. We discuss these findings in light of highly variable functional hubs. The results further elucidate how large-scale dynamic functional coordination exists within a fixed structural architecture. Copyright © 2015 the authors 0270-6474/15/355579-10$15.00/0.

Disruption of functional networks in dyslexia: A whole-brain, data-driven analysis of connectivity

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Finn, Emily S.; Shen, Xilin; Holahan, John M.; Scheinost, Dustin; Lacadie, Cheryl; Papademetris, Xenophon; Shaywitz, Sally E.; Shaywitz, Bennett A.; Constable, R. Todd

2013-01-01

Background Functional connectivity analyses of fMRI data are a powerful tool for characterizing brain networks and how they are disrupted in neural disorders. However, many such analyses examine only one or a small number of a priori seed regions. Studies that consider the whole brain frequently rely on anatomic atlases to define network nodes, which may result in mixing distinct activation timecourses within a single node. Here, we improve upon previous methods by using a data-driven brain parcellation to compare connectivity profiles of dyslexic (DYS) versus non-impaired (NI) readers in the first whole-brain functional connectivity analysis of dyslexia. Methods Whole-brain connectivity was assessed in children (n = 75; 43 NI, 32 DYS) and adult (n = 104; 64 NI, 40 DYS) readers. Results Compared to NI readers, DYS readers showed divergent connectivity within the visual pathway and between visual association areas and prefrontal attention areas; increased right-hemisphere connectivity; reduced connectivity in the visual word-form area (part of the left fusiform gyrus specialized for printed words); and persistent connectivity to anterior language regions around the inferior frontal gyrus. Conclusions Together, findings suggest that NI readers are better able to integrate visual information and modulate their attention to visual stimuli, allowing them to recognize words based on their visual properties, while DYS readers recruit altered reading circuits and rely on laborious phonology-based “sounding out” strategies into adulthood. These results deepen our understanding of the neural basis of dyslexia and highlight the importance of synchrony between diverse brain regions for successful reading. PMID:24124929

Brain Functional Connectivity Is Modified by a Hypocaloric Mediterranean Diet and Physical Activity in Obese Women.

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García-Casares, Natalia; Bernal-López, María R; Roé-Vellvé, Nuria; Gutiérrez-Bedmar, Mario; Fernández-García, Jose C; García-Arnés, Juan A; Ramos-Rodriguez, José R; Alfaro, Francisco; Santamaria-Fernández, Sonia; Steward, Trevor; Jiménez-Murcia, Susana; Garcia-Garcia, Isabel; Valdivielso, Pedro; Fernández-Aranda, Fernando; Tinahones, Francisco J; Gómez-Huelgas, Ricardo

2017-07-01

Functional magnetic resonance imaging (fMRI) in the resting state has shown altered brain connectivity networks in obese individuals. However, the impact of a Mediterranean diet on cerebral connectivity in obese patients when losing weight has not been previously explored. The aim of this study was to examine the connectivity between brain structures before and six months after following a hypocaloric Mediterranean diet and physical activity program in a group of sixteen obese women aged 46.31 ± 4.07 years. Before and after the intervention program, the body mass index (BMI) (kg/m²) was 38.15 ± 4.7 vs. 34.18 ± 4.5 ( p diet and physical exercise.

Altered Structural and Functional Connectivity of Juvenile Myoclonic Epilepsy: An fMRI Study

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Chengqing Zhong

2018-01-01

Full Text Available The aim of this study was to investigate the structural and functional connectivity (FC of juvenile myoclonic epilepsy (JME using resting state functional magnetic resonance imaging (rs-fMRI. High-resolution T1-weighted magnetic resonance imaging (MRI and rs-fMRI data were collected in 25 patients with JME and in 24 control subjects. A FC analysis was subsequently performed, with seeding at the regions that demonstrated between-group differences in gray matter volume (GMV. Then, the observed structural and FCs were associated with the clinical manifestations. The decreased GMV regions were found in the bilateral anterior cerebellum, the right orbital superior frontal gyrus, the left middle temporal gyrus, the left putamen, the right hippocampus, the bilateral caudate, and the right thalamus. The changed FCs were mainly observed in the motor-related areas and the cognitive-related areas. The significant findings of this study revealed an important role for the cerebellum in motor control and cognitive regulation in JME patients, which also have an effect on the activity of the occipital lobe. In addition, the changed FCs were related to the clinical features of JME patients. The current observations may contribute to the understanding of the pathogenesis of JME.

Postoperative seizure freedom does not normalize altered connectivity in temporal lobe epilepsy.

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Maccotta, Luigi; Lopez, Mayra A; Adeyemo, Babatunde; Ances, Beau M; Day, Brian K; Eisenman, Lawrence N; Dowling, Joshua L; Leuthardt, Eric C; Schlaggar, Bradley L; Hogan, Robert Edward

2017-11-01

Specific changes in the functional connectivity of brain networks occur in patients with epilepsy. Yet whether such changes reflect a stable disease effect or one that is a function of active seizure burden remains unclear. Here, we longitudinally assessed the connectivity of canonical cognitive functional networks in patients with intractable temporal lobe epilepsy (TLE), both before and after patients underwent epilepsy surgery and achieved seizure freedom. Seventeen patients with intractable TLE who underwent epilepsy surgery with Engel class I outcome and 17 matched healthy controls took part in the study. The functional connectivity of a set of cognitive functional networks derived from typical cognitive tasks was assessed in patients, preoperatively and postoperatively, as well as in controls, using stringent methods of artifact reduction. Preoperatively, functional networks in TLE patients differed significantly from healthy controls, with differences that largely, but not exclusively, involved the default mode and temporal/auditory subnetworks. However, undergoing epilepsy surgery and achieving seizure freedom did not lead to significant changes in network connectivity, with postoperative functional network abnormalities closely mirroring the preoperative state. This result argues for a stable chronic effect of the disease on brain connectivity, with changes that are largely "burned in" by the time a patient with intractable TLE undergoes epilepsy surgery, which typically occurs years after the initial diagnosis. The result has potential implications for the treatment of intractable epilepsy, suggesting that delaying surgical intervention that may achieve seizure freedom may lead to functional network changes that are no longer reversible by the time of epilepsy surgery. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

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

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

2016-03-29

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

Multivariate Heteroscedasticity Models for Functional Brain Connectivity

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Christof Seiler

2017-12-01

Full Text Available Functional brain connectivity is the co-occurrence of brain activity in different areas during resting and while doing tasks. The data of interest are multivariate timeseries measured simultaneously across brain parcels using resting-state fMRI (rfMRI. We analyze functional connectivity using two heteroscedasticity models. Our first model is low-dimensional and scales linearly in the number of brain parcels. Our second model scales quadratically. We apply both models to data from the Human Connectome Project (HCP comparing connectivity between short and conventional sleepers. We find stronger functional connectivity in short than conventional sleepers in brain areas consistent with previous findings. This might be due to subjects falling asleep in the scanner. Consequently, we recommend the inclusion of average sleep duration as a covariate to remove unwanted variation in rfMRI studies. A power analysis using the HCP data shows that a sample size of 40 detects 50% of the connectivity at a false discovery rate of 20%. We provide implementations using R and the probabilistic programming language Stan.

Association Between Brain Activation and Functional Connectivity.

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Tomasi, Dardo; Volkow, Nora D

2018-04-13

The origin of the "resting-state" brain activity recorded with functional magnetic resonance imaging (fMRI) is still uncertain. Here we provide evidence for the neurovascular origins of the amplitude of the low-frequency fluctuations (ALFF) and the local functional connectivity density (lFCD) by comparing them with task-induced blood-oxygen level dependent (BOLD) responses, which are considered a proxy for neuronal activation. Using fMRI data for 2 different tasks (Relational and Social) collected by the Human Connectome Project in 426 healthy adults, we show that ALFF and lFCD have linear associations with the BOLD response. This association was significantly attenuated by a novel task signal regression (TSR) procedure, indicating that task performance enhances lFCD and ALFF in activated regions. We also show that lFCD predicts BOLD activation patterns, as was recently shown for other functional connectivity metrics, which corroborates that resting functional connectivity architecture impacts brain activation responses. Thus, our findings indicate a common source for BOLD responses, ALFF and lFCD, which is consistent with the neurovascular origin of local hemodynamic synchrony presumably reflecting coordinated fluctuations in neuronal activity. This study also supports the development of task-evoked functional connectivity density mapping.

Evidence for altered basal ganglia-brainstem connections in cervical dystonia.

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Anne J Blood

Full Text Available There has been increasing interest in the interaction of the basal ganglia with the cerebellum and the brainstem in motor control and movement disorders. In addition, it has been suggested that these subcortical connections with the basal ganglia may help to coordinate a network of regions involved in mediating posture and stabilization. While studies in animal models support a role for this circuitry in the pathophysiology of the movement disorder dystonia, thus far, there is only indirect evidence for this in humans with dystonia.In the current study we investigated probabilistic diffusion tractography in DYT1-negative patients with cervical dystonia and matched healthy control subjects, with the goal of showing that patients exhibit altered microstructure in the connectivity between the pallidum and brainstem. The brainstem regions investigated included nuclei that are known to exhibit strong connections with the cerebellum. We observed large clusters of tractography differences in patients relative to healthy controls, between the pallidum and the brainstem. Tractography was decreased in the left hemisphere and increased in the right hemisphere in patients, suggesting a potential basis for the left/right white matter asymmetry we previously observed in focal dystonia patients.These findings support the hypothesis that connections between the basal ganglia and brainstem play a role in the pathophysiology of dystonia.

Reduced resting-state functional connectivity of the somatosensory cortex predicts psychopathological symptoms in women with bulimia nervosa.

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Lavagnino, Luca; Amianto, Federico; D'Agata, Federico; Huang, Zirui; Mortara, Paolo; Abbate-Daga, Giovanni; Marzola, Enrica; Spalatro, Angela; Fassino, Secondo; Northoff, Georg

2014-01-01

Alterations in the resting-state functional connectivity (rs-FC) of several brain networks have been demonstrated in eating disorders. However, very few studies are currently available on brain network dysfunctions in bulimia nervosa (BN). The somatosensory network is central in processing body-related stimuli and it may be altered in BN. The present study therefore aimed to investigate rs-FC in the somatosensory network in bulimic women. Sixteen medication-free women with BN (age = 23 ± 5 years) and 18 matched controls (age = 23 ± 3 years) underwent a functional magnetic resonance resting-state scan and assessment of eating disorder symptoms. Within-network and seed-based functional connectivity analyses were conducted to assess rs-FC within the somatosensory network and to other areas of the brain. Bulimia nervosa patients showed a decreased rs-FC both within the somatosensory network (t = 9.0, df = 1, P = 0.005) and with posterior cingulate cortex and two visual areas (the right middle occipital gyrus and the right cuneus) (P = 0.05 corrected for multiple comparison). The rs-FC of the left paracentral lobule with the right middle occipital gyrus correlated with psychopathology measures like bulimia (r = -0.4; P = 0.02) and interoceptive awareness (r = -0.4; P = 0.01). Analyses were conducted using age, BMI (body mass index), and depressive symptoms as covariates. Our findings show a specific alteration of the rs-FC of the somatosensory cortex in BN patients, which correlates with eating disorder symptoms. The region in the right middle occipital gyrus is implicated in body processing and is known as extrastriate body area (EBA). The connectivity between the somatosensory cortex and the EBA might be related to dysfunctions in body image processing. The results should be considered preliminary due to the small sample size.

Functional connectivity of motor cortical network in patients with brachial plexus avulsion injury after contralateral cervical nerve transfer: a resting-state fMRI study

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Yu, Aihong; Cheng, Xiaoguang; Liang, Wei; Bai, Rongjie [The 4th Medical College of Peking University, Department of Radiology, Beijing Jishuitan Hospital, Xicheng Qu, Beijing (China); Wang, Shufeng; Xue, Yunhao; Li, Wenjun [The 4th Medical College of Peking University, Department of Hand Surgery, Beijing Jishuitan Hospital, Beijing (China)

2017-03-15

The purpose of this study is to assess the functional connectivity of the motor cortical network in patients with brachial plexus avulsion injury (BPAI) after contralateral C7 nerve transfer, using resting-state functional magnetic resonance imaging (RS-fMRI). Twelve patients with total brachial plexus root avulsion underwent RS-fMRI after contralateral C7 nerve transfer. Seventeen healthy volunteers were also included in this fMRI study as controls. The hand motor seed regions were defined as region of interests in the bilateral hemispheres. The seed-based functional connectivity was calculated in all the subjects. Differences in functional connectivity of the motor cortical network between patients and healthy controls were compared. The inter-hemispheric functional connectivity of the M1 areas was increased in patients with BPAI compared with the controls. The inter-hemispheric functional connectivity between the supplementary motor areas was reduced bilaterally. The resting-state inter-hemispheric functional connectivity of the bilateral M1 areas is altered in patients after contralateral C7 nerve transfer, suggesting a functional reorganization of cerebral cortex. (orig.)

Functional connectivity of motor cortical network in patients with brachial plexus avulsion injury after contralateral cervical nerve transfer: a resting-state fMRI study

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Yu, Aihong; Cheng, Xiaoguang; Liang, Wei; Bai, Rongjie; Wang, Shufeng; Xue, Yunhao; Li, Wenjun

2017-01-01

The purpose of this study is to assess the functional connectivity of the motor cortical network in patients with brachial plexus avulsion injury (BPAI) after contralateral C7 nerve transfer, using resting-state functional magnetic resonance imaging (RS-fMRI). Twelve patients with total brachial plexus root avulsion underwent RS-fMRI after contralateral C7 nerve transfer. Seventeen healthy volunteers were also included in this fMRI study as controls. The hand motor seed regions were defined as region of interests in the bilateral hemispheres. The seed-based functional connectivity was calculated in all the subjects. Differences in functional connectivity of the motor cortical network between patients and healthy controls were compared. The inter-hemispheric functional connectivity of the M1 areas was increased in patients with BPAI compared with the controls. The inter-hemispheric functional connectivity between the supplementary motor areas was reduced bilaterally. The resting-state inter-hemispheric functional connectivity of the bilateral M1 areas is altered in patients after contralateral C7 nerve transfer, suggesting a functional reorganization of cerebral cortex. (orig.)

Progressively Disrupted Intrinsic Functional Connectivity of Basolateral Amygdala in Very Early Alzheimer’s Disease

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Marion Ortner

2016-09-01

Full Text Available Abstract:Very early Alzheimer’s disease (AD - i.e., AD at stages of mild cognitive impairment (MCI and mild dementia - is characterized by progressive structural and neuropathologic changes such as atrophy or tangle deposition in medial temporal lobes, including hippocampus and entorhinal cortex but also adjacent amygdala. While progressively disrupted intrinsic connectivity of hippocampus with other brain areas has been demonstrated by many studies, amygdala connectivity was rarely investigated in AD, notwithstanding its known relevance for emotion processing and mood disturbances, which are both important in early AD. Intrinsic functional connectivity (iFC patterns of hippocampus and amygdala overlap in healthy persons. Thus, we hypothesized that increased alteration of iFC patterns along AD is not limited to the hippocampus but also concerns the amygdala, independent from atrophy. To address this hypothesis, we applied structural and functional resting-state MRI in healthy controls (CON, n=33 and patients with AD in the stages of MCI (AD-MCI, n=38 and mild dementia (AD-D, n=36. Outcome measures were voxel-based morphometry (VBM values and region of interest-based intrinsic functional connectivity maps (iFC of basolateral amygdala, which has extended cortical connectivity. Amygdala VBM values were progressively reduced in patients (CON > AD-MCI and AD-D. Amygdala iFC was progressively reduced along impairment severity (CON > AD-MCI > AD-D, particularly for hippocampus, temporal lobes, and fronto-parietal areas. Notably, decreased iFC was independent of amygdala atrophy. Results demonstrate progressively impaired amygdala intrinsic connectivity in temporal and fronto-parietal lobes independent from increasing amygdala atrophy in very early AD. Data suggest that early AD disrupts intrinsic connectivity of medial temporal lobe key regions including that of amygdala.

Empirical validation of directed functional connectivity.

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Mill, Ravi D; Bagic, Anto; Bostan, Andreea; Schneider, Walter; Cole, Michael W

2017-02-01

Mapping directions of influence in the human brain connectome represents the next phase in understanding its functional architecture. However, a host of methodological uncertainties have impeded the application of directed connectivity methods, which have primarily been validated via "ground truth" connectivity patterns embedded in simulated functional MRI (fMRI) and magneto-/electro-encephalography (MEG/EEG) datasets. Such simulations rely on many generative assumptions, and we hence utilized a different strategy involving empirical data in which a ground truth directed connectivity pattern could be anticipated with confidence. Specifically, we exploited the established "sensory reactivation" effect in episodic memory, in which retrieval of sensory information reactivates regions involved in perceiving that sensory modality. Subjects performed a paired associate task in separate fMRI and MEG sessions, in which a ground truth reversal in directed connectivity between auditory and visual sensory regions was instantiated across task conditions. This directed connectivity reversal was successfully recovered across different algorithms, including Granger causality and Bayes network (IMAGES) approaches, and across fMRI ("raw" and deconvolved) and source-modeled MEG. These results extend simulation studies of directed connectivity, and offer practical guidelines for the use of such methods in clarifying causal mechanisms of neural processing. Copyright © 2016 Elsevier Inc. All rights reserved.

Sex-related differences in amygdala functional connectivity during resting conditions.

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Kilpatrick, L A; Zald, D H; Pardo, J V; Cahill, L F

2006-04-01

Recent neuroimaging studies have established a sex-related hemispheric lateralization of amygdala involvement in memory for emotionally arousing material. Here, we examine the possibility that sex-related differences in amygdala involvement in memory for emotional material develop from differential patterns of amygdala functional connectivity evident in the resting brain. Seed voxel partial least square analyses of regional cerebral blood flow data revealed significant sex-related differences in amygdala functional connectivity during resting conditions. The right amygdala was associated with greater functional connectivity in men than in women. In contrast, the left amygdala was associated with greater functional connectivity in women than in men. Furthermore, the regions displaying stronger functional connectivity with the right amygdala in males (sensorimotor cortex, striatum, pulvinar) differed from those displaying stronger functional connectivity with the left amygdala in females (subgenual cortex, hypothalamus). These differences in functional connectivity at rest may link to sex-related differences in medical and psychiatric disorders.

Detecting altered connectivity patterns in HIV associated neurocognitive impairment using mutual connectivity analysis

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

2016-03-01

The use of functional Magnetic Resonance Imaging (fMRI) has provided interesting insights into our understanding of the brain. In clinical setups these scans have been used to detect and study changes in the brain network properties in various neurological disorders. A large percentage of subjects infected with HIV present cognitive deficits, which are known as HIV associated neurocognitive disorder (HAND). In this study we propose to use our novel technique named Mutual Connectivity Analysis (MCA) to detect differences in brain networks in subjects with and without HIV infection. Resting state functional MRI scans acquired from 10 subjects (5 HIV+ and 5 HIV-) were subject to standard preprocessing routines. Subsequently, the average time-series for each brain region of the Automated Anatomic Labeling (AAL) atlas are extracted and used with the MCA framework to obtain a graph characterizing the interactions between them. The network graphs obtained for different subjects are then compared using Network-Based Statistics (NBS), which is an approach to detect differences between graphs edges while controlling for the family-wise error rate when mass univariate testing is performed. Applying this approach on the graphs obtained yields a single network encompassing 42 nodes and 65 edges, which is significantly different between the two subject groups. Specifically connections to the regions in and around the basal ganglia are significantly decreased. Also some nodes corresponding to the posterior cingulate cortex are affected. These results are inline with our current understanding of pathophysiological mechanisms of HIV associated neurocognitive disease (HAND) and other HIV based fMRI connectivity studies. Hence, we illustrate the applicability of our novel approach with network-based statistics in a clinical case-control study to detect differences connectivity patterns.

Functional network connectivity underlying food processing: disturbed salience and visual processing in overweight and obese adults.

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Kullmann, Stephanie; Pape, Anna-Antonia; Heni, Martin; Ketterer, Caroline; Schick, Fritz; Häring, Hans-Ulrich; Fritsche, Andreas; Preissl, Hubert; Veit, Ralf

2013-05-01

In order to adequately explore the neurobiological basis of eating behavior of humans and their changes with body weight, interactions between brain areas or networks need to be investigated. In the current functional magnetic resonance imaging study, we examined the modulating effects of stimulus category (food vs. nonfood), caloric content of food, and body weight on the time course and functional connectivity of 5 brain networks by means of independent component analysis in healthy lean and overweight/obese adults. These functional networks included motor sensory, default-mode, extrastriate visual, temporal visual association, and salience networks. We found an extensive modulation elicited by food stimuli in the 2 visual and salience networks, with a dissociable pattern in the time course and functional connectivity between lean and overweight/obese subjects. Specifically, only in lean subjects, the temporal visual association network was modulated by the stimulus category and the salience network by caloric content, whereas overweight and obese subjects showed a generalized augmented response in the salience network. Furthermore, overweight/obese subjects showed changes in functional connectivity in networks important for object recognition, motivational salience, and executive control. These alterations could potentially lead to top-down deficiencies driving the overconsumption of food in the obese population.

EEG sensorimotor rhythms' variation and functional connectivity measures during motor imagery: linear relations and classification approaches.

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Stefano Filho, Carlos A; Attux, Romis; Castellano, Gabriela

2017-01-01

Hands motor imagery (MI) has been reported to alter synchronization patterns amongst neurons, yielding variations in the mu and beta bands' power spectral density (PSD) of the electroencephalography (EEG) signal. These alterations have been used in the field of brain-computer interfaces (BCI), in an attempt to assign distinct MI tasks to commands of such a system. Recent studies have highlighted that information may be missing if knowledge about brain functional connectivity is not considered. In this work, we modeled the brain as a graph in which each EEG electrode represents a node. Our goal was to understand if there exists any linear correlation between variations in the synchronization patterns-that is, variations in the PSD of mu and beta bands-induced by MI and alterations in the corresponding functional networks. Moreover, we (1) explored the feasibility of using functional connectivity parameters as features for a classifier in the context of an MI-BCI; (2) investigated three different types of feature selection (FS) techniques; and (3) compared our approach to a more traditional method using the signal PSD as classifier inputs. Ten healthy subjects participated in this study. We observed significant correlations ( p  < 0.05) with values ranging from 0.4 to 0.9 between PSD variations and functional network alterations for some electrodes, prominently in the beta band. The PSD method performed better for data classification, with mean accuracies of (90 ± 8)% and (87 ± 7)% for the mu and beta band, respectively, versus (83 ± 8)% and (83 ± 7)% for the same bands for the graph method. Moreover, the number of features for the graph method was considerably larger. However, results for both methods were relatively close, and even overlapped when the uncertainties of the accuracy rates were considered. Further investigation regarding a careful exploration of other graph metrics may provide better alternatives.

Local functional connectivity suggests functional immaturity in children with attention-deficit/hyperactivity disorder.

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Marcos-Vidal, Luis; Martínez-García, Magdalena; Pretus, Clara; Garcia-Garcia, David; Martínez, Kenia; Janssen, Joost; Vilarroya, Oscar; Castellanos, Francisco X; Desco, Manuel; Sepulcre, Jorge; Carmona, Susanna

2018-06-01

Previous studies have associated Attention-Deficit/Hyperactivity Disorder (ADHD) with a maturational lag of brain functional networks. Functional connectivity of the human brain changes from primarily local to more distant connectivity patterns during typical development. Under the maturational lag hypothesis, we expect children with ADHD to exhibit increased local connectivity and decreased distant connectivity compared with neurotypically developing (ND) children. We applied a graph-theory method to compute local and distant connectivity levels and cross-sectionally compared them in a sample of 120 children with ADHD and 120 age-matched ND children (age range = 7-17 years). In addition, we measured if potential group differences in local and distant connectivity were stable across the age range considered. Finally, we assessed the clinical relevance of observed group differences by correlating the connectivity levels and ADHD symptoms severity separately for each group. Children with ADHD exhibited more local connectivity than age-matched ND children in multiple brain regions, mainly overlapping with default mode, fronto-parietal and ventral attentional functional networks (p attentional networks, the severity of clinical symptoms is related to atypical functional connectivity within somatomotor areas. Additionally, our findings are in line with the view of ADHD as a disorder of deviated maturational trajectories, mainly affecting somatomotor areas, rather than delays that normalize with age. © 2018 Wiley Periodicals, Inc.

Alterations of White Matter Connectivity in Preschool Children with Autism Spectrum Disorder.

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Li, Shi-Jun; Wang, Yi; Qian, Long; Liu, Gang; Liu, Shuang-Feng; Zou, Li-Ping; Zhang, Ji-Shui; Hu, Nan; Chen, Xiao-Qiao; Yu, Sheng-Yuan; Guo, Sheng-Li; Li, Ke; He, Mian-Wang; Wu, Hai-Tao; Qiu, Jiang-Xia; Zhang, Lei; Wang, Yu-Lin; Lou, Xin; Ma, Lin

2018-03-27

Purpose To investigate the topologic architecture of white matter connectivity networks in preschool-aged children with a diagnosis of autism spectrum disorder (ASD) versus typical development (TD). Materials and Methods Forty-two participants were enrolled, including 21 preschool children with ASD (14 male children and seven female children; mean age, 4.56 years ± 0.97 [standard deviation]) and 21 children with TD (11 males and 10 females; mean age, 5.13 years ± 0.82). The diagnosis of ASD was determined according to the Diagnostic and Statistical Manual of Mental Disorders Global Assessment of Functioning scores (mean score, 8.00 ± 0.50). All participants underwent diffusion-tensor imaging (DTI) and T2-weighted imaging on a 3-T magnetic resonance system. A graph theoretical analysis was applied to investigate the topologic organization of the brain network including global and local topologic parameters. Statistical analysis was then performed for the comparison between the groups. Results Compared with the TD group, children with ASD demonstrated shortened characteristic path length (t 1 = 0.536, t 2 = 0.534, t 3 = 0.523, t 4 = 0.510, and t 5 = 0.501; P < .05) and increased global efficiency (t 1 = 0.499, t 2 = 0.497, t 3 = 0.486, t 4 = 0.473, and t 5 = 0.465; P < .05) and clustering coefficient (t 1 = 0.673, t 2 = 0.750, t 3 = 0.757, t 4 = 0.738, and t 5 = 0.741; P < .05). Significant increases in nodal efficiency were mainly found in left pallidum (0.037 vs 0.032, respectively; P < .01) and right caudate nucleus (0.037 vs 0.032, respectively; P < .01) of the basal ganglia network. Conclusion Significantly altered patterns of global and local brain network topography may underlie the abnormal brain development in preschool children with ASD compared with those who have TD. The identification of altered structural connectivity in basal ganglia and paralimbic-limbic networks may point toward potential imaging biomarkers for preschool-age patients with ASD. �

Alterations of Brain Functional Architecture Associated with Psychopathic Traits in Male Adolescents with Conduct Disorder.

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Pu, Weidan; Luo, Qiang; Jiang, Yali; Gao, Yidian; Ming, Qingsen; Yao, Shuqiao

2017-09-12

Psychopathic traits of conduct disorder (CD) have a core callous-unemotional (CU) component and an impulsive-antisocial component. Previous task-driven fMRI studies have suggested that psychopathic traits are associated with dysfunction of several brain areas involved in different cognitive functions (e.g., empathy, reward, and response inhibition etc.), but the relationship between psychopathic traits and intrinsic brain functional architecture has not yet been explored in CD. Using a holistic brain-wide functional connectivity analysis, this study delineated the alterations in brain functional networks in patients with conduct disorder. Compared with matched healthy controls, we found decreased anti-synchronization between the fronto-parietal network (FPN) and default mode network (DMN), and increased intra-network synchronization within the frontothalamic-basal ganglia, right frontoparietal, and temporal/limbic/visual networks in CD patients. Correlation analysis showed that the weakened FPN-DMN interaction was associated with CU traits, while the heightened intra-network functional connectivity was related to impulsivity traits in CD patients. Our findings suggest that decoupling of cognitive control (FPN) with social understanding of others (DMN) is associated with the CU traits, and hyper-functions of the reward and motor inhibition systems elevate impulsiveness in CD.

Brain Functional Connectivity Is Modified by a Hypocaloric Mediterranean Diet and Physical Activity in Obese Women

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Natalia García-Casares

2017-07-01

Full Text Available Functional magnetic resonance imaging (fMRI in the resting state has shown altered brain connectivity networks in obese individuals. However, the impact of a Mediterranean diet on cerebral connectivity in obese patients when losing weight has not been previously explored. The aim of this study was to examine the connectivity between brain structures before and six months after following a hypocaloric Mediterranean diet and physical activity program in a group of sixteen obese women aged 46.31 ± 4.07 years. Before and after the intervention program, the body mass index (BMI (kg/m2 was 38.15 ± 4.7 vs. 34.18 ± 4.5 (p < 0.02, and body weight (kg was 98.5 ± 13.1 vs. 88.28 ± 12.2 (p < 0.03. All subjects underwent a pre- and post-intervention fMRI under fasting conditions. Functional connectivity was assessed using seed-based correlations. After the intervention, we found decreased connectivity between the left inferior parietal cortex and the right temporal cortex (p < 0.001, left posterior cingulate (p < 0.001, and right posterior cingulate (p < 0.03; decreased connectivity between the left superior frontal gyrus and the right temporal cortex (p < 0.01; decreased connectivity between the prefrontal cortex and the somatosensory cortex (p < 0.025; and decreased connectivity between the left and right posterior cingulate (p < 0.04. Results were considered significant at a voxel-wise threshold of p ≤ 0.05, and a cluster-level family-wise error correction for multiple comparisons of p ≤ 0.05. In conclusion, functional connectivity between brain structures involved in the pathophysiology of obesity (the inferior parietal lobe, posterior cingulate, temporo-insular cortex, prefrontal cortex may be modified by a weight loss program including a Mediterranean diet and physical exercise.

Long-term oil contamination alters the molecular ecological networks of soil microbial functional genes

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Yuting eLiang

2016-02-01

Full Text Available With knowledge on microbial composition and diversity, investigation of within-community interactions is a further step to elucidate microbial ecological functions, such as the biodegradation of hazardous contaminants. In this work, microbial functional molecular ecological networks were studied in both contaminated and uncontaminated soils to determine the possible influences of oil contamination on microbial interactions and potential functions. Soil samples were obtained from an oil-exploring site located in South China, and the microbial functional genes were analyzed with GeoChip, a high-throughput functional microarray. By building random networks based on null model, we demonstrated that overall network structures and properties were significantly different between contaminated and uncontaminated soils (P < 0.001. Network connectivity, module numbers, and modularity were all reduced with contamination. Moreover, the topological roles of the genes (module hub and connectors were altered with oil contamination. Subnetworks of genes involved in alkane and polycyclic aromatic hydrocarbon degradation were also constructed. Negative co-occurrence patterns prevailed among functional genes, thereby indicating probable competition relationships. The potential keystone genes, defined as either hubs or genes with highest connectivities in the network, were further identified. The network constructed in this study predicted the potential effects of anthropogenic contamination on microbial community co-occurrence interactions.

The functional connectivity landscape of the human brain.

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Bratislav Mišić

Full Text Available 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.

Cerebro-cerebellar connectivity is increased in primary lateral sclerosis.

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

2015-01-01

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

Altered Functional Subnetwork During Emotional Face Processing: A Potential Intermediate Phenotype for Schizophrenia.

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Cao, Hengyi; Bertolino, Alessandro; Walter, Henrik; Schneider, Michael; Schäfer, Axel; Taurisano, Paolo; Blasi, Giuseppe; Haddad, Leila; Grimm, Oliver; Otto, Kristina; Dixson, Luanna; Erk, Susanne; Mohnke, Sebastian; Heinz, Andreas; Romanczuk-Seiferth, Nina; Mühleisen, Thomas W; Mattheisen, Manuel; Witt, Stephanie H; Cichon, Sven; Noethen, Markus; Rietschel, Marcella; Tost, Heike; Meyer-Lindenberg, Andreas

2016-06-01

Although deficits in emotional processing are prominent in schizophrenia, it has been difficult to identify neural mechanisms related to the genetic risk for this highly heritable illness. Prior studies have not found consistent regional activation or connectivity alterations in first-degree relatives compared with healthy controls, suggesting that a more comprehensive search for connectomic biomarkers is warranted. To identify a potential systems-level intermediate phenotype linked to emotion processing in schizophrenia and to examine the psychological association, task specificity, test-retest reliability, and clinical validity of the identified phenotype. The study was performed in university research hospitals from June 1, 2008, through December 31, 2013. We examined 58 unaffected first-degree relatives of patients with schizophrenia and 94 healthy controls with an emotional face-matching functional magnetic resonance imaging paradigm. Test-retest reliability was analyzed with an independent sample of 26 healthy participants. A clinical association study was performed in 31 patients with schizophrenia and 45 healthy controls. Data analysis was performed from January 1 to September 30, 2014. Conventional amygdala activity and seeded connectivity measures, graph-based global and local network connectivity measures, Spearman rank correlation, intraclass correlation, and gray matter volumes. Among the 152 volunteers included in the relative-control sample, 58 were unaffected first-degree relatives of patients with schizophrenia (mean [SD] age, 33.29 [12.56]; 38 were women), and 94 were healthy controls without a first-degree relative with mental illness (mean [SD] age, 32.69 [10.09] years; 55 were women). A graph-theoretical connectivity approach identified significantly decreased connectivity in a subnetwork that primarily included the limbic cortex, visual cortex, and subcortex during emotional face processing (cluster-level P corrected for familywise error =�

Altered resting state brain networks in Parkinson's disease.

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Martin Göttlich

Full Text Available Parkinson's disease (PD is a neurodegenerative disorder affecting dopaminergic neurons in the substantia nigra leading to dysfunctional cortico-striato-thalamic-cortical loops. In addition to the characteristic motor symptoms, PD patients often show cognitive impairments, affective changes and other non-motor symptoms, suggesting system-wide effects on brain function. Here, we used functional magnetic resonance imaging and graph-theory based analysis methods to investigate altered whole-brain intrinsic functional connectivity in PD patients (n = 37 compared to healthy controls (n = 20. Global network properties indicated less efficient processing in PD. Analysis of brain network modules pointed to increased connectivity within the sensorimotor network, but decreased interaction of the visual network with other brain modules. We found lower connectivity mainly between the cuneus and the ventral caudate, medial orbitofrontal cortex and the temporal lobe. To identify regions of altered connectivity, we mapped the degree of intrinsic functional connectivity both on ROI- and on voxel-level across the brain. Compared to healthy controls, PD patients showed lower connectedness in the medial and middle orbitofrontal cortex. The degree of connectivity was also decreased in the occipital lobe (cuneus and calcarine, but increased in the superior parietal cortex, posterior cingulate gyrus, supramarginal gyrus and supplementary motor area. Our results on global network and module properties indicated that PD manifests as a disconnection syndrome. This was most apparent in the visual network module. The higher connectedness within the sensorimotor module in PD patients may be related to compensation mechanism in order to overcome the functional deficit of the striato-cortical motor loops or to loss of mutual inhibition between brain networks. Abnormal connectivity in the visual network may be related to adaptation and compensation processes as a consequence

Functional Imaging and Migraine: New Connections?

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Schwedt, Todd J.; Chong, Catherine D.

2015-01-01

Purpose of Review Over the last several years, a growing number of brain functional imaging studies have provided insights into mechanisms underlying migraine. This manuscript reviews the recent migraine functional neuroimaging literature and provides recommendations for future studies that will help fill knowledge gaps. Recent Findings Positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) studies have identified brain regions that might be responsible for mediating the onset of a migraine attack and those associated with migraine symptoms. Enhanced activation of brain regions that facilitate processing of sensory stimuli suggests a mechanism by which migraineurs are hypersensitive to visual, olfactory, and cutaneous stimuli. Resting state functional connectivity MRI studies have identified numerous brain regions and functional networks with atypical functional connectivity in migraineurs, suggesting that migraine is associated with aberrant brain functional organization. Summary fMRI and PET studies that have identified brain regions and brain networks that are atypical in migraine have helped to describe the neurofunctional basis for migraine symptoms. Future studies should compare functional imaging findings in migraine to other headache and pain disorders and should explore the utility of functional imaging data as biomarkers for diagnostic and treatment purposes. PMID:25887764

Aberrant whole-brain functional connectivity and intelligence structure in children with primary nocturnal enuresis.

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Bing Yu

Full Text Available AIM: To assess the potential relationship between intelligence structure abnormalities and whole-brain functional connectivity in children with primary nocturnal enuresis (PNE with resting-state functional magnetic resonance imaging (fMRI to provide insights into the association between these two seemingly unrelated conditions. METHODS: Intelligence testing and fMRI data were obtained from 133 right-handed children, including 67 PNE children (M/F, 39:28; age, 10.5 ± 1.2 y and 66 age-matched healthy controls (M/F, 37:29; age, 10.1 ± 1.1 y. All intelligence tests were performed using the China-Wechsler Intelligence Scale for Children (C-WISC. Each subject's full intelligence quotient (FIQ, verbal IQ (VIQ, performance IQ (PIQ, and memory/caution (M/C factor was measured and recorded. Resting state fMRI scans were performed on a 3.0-T MR scanner and post-processed using REST software. Comparisons of z-score correlation coefficients between distinct cerebral regions were used to identify altered functional connectivity in PNE children. RESULTS: The PNE group had normal FIQ, VIQ, and PIQ values, indicating no significant variation from the control group. However, the M/C factor was significantly lower in the PNE group. Compared to the control group, PNE children exhibited overall lower levels of functional connectivity that were most apparent in the cerebello-thalamo-frontal pathway. The M/C factor significantly correlated with z-scores representing connectivity between Cerebellum_Crus1_L and Frontal_Mid_R. CONCLUSION: PNE children exhibit intelligence structure imbalance and attention deficits. Our findings suggest that cerebello-thalamo-frontal circuit abnormalities are likely to be involved in the onset and progression of attention impairment in PNE children.

Increased Gray Matter Volume and Resting-State Functional Connectivity in Somatosensory Cortex and their Relationship with Autistic Symptoms in Young Boys with Autism Spectrum Disorder.

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Wang, Jia; Fu, Kuang; Chen, Lei; Duan, Xujun; Guo, Xiaonan; Chen, Heng; Wu, Qiong; Xia, Wei; Wu, Lijie; Chen, Huafu

2017-01-01

Autism spectrum disorder (ASD) has been widely recognized as a complex neurodevelopmental disorder. A large number of neuroimaging studies suggest abnormalities in brain structure and function of patients with ASD, but there is still no consistent conclusion. We sought to investigate both of the structural and functional brain changes in 3-7-year-old children with ASD compared with typically developing controls (TDs), and to assess whether these alterations are associated with autistic behavioral symptoms. Firstly, we applied an optimized method of voxel-based morphometry (VBM) analysis on structural magnetic resonance imaging (sMRI) data to assess the differences of gray matter volume (GMV) between 31 autistic boys aged 3-7 and 31 age- and handness-matched male TDs. Secondly, we used clusters with between-group differences as seed regions to generate intrinsic functional connectivity maps based on resting-state functional connectivity magnetic resonance imaging (rs-fcMRI) in order to evaluate the functional impairments induced by structural alterations. Brain-behavior correlations were assessed among GMV, functional connectivity and symptom severity in children with ASD. VBM analyses revealed increased GMV in left superior temporal gyrus (STG) and left postcentral gyrus (PCG) in ASD children, comparing with TDs. Using left PCG as a seed region, ASD children displayed significantly higher positive connectivity with right angular gyrus (AG) and greater negative connectivity with right superior parietal gyrus (SPG) and right superior occipital gyrus (SOG), which were associated with the severity of symptoms in social interaction, communication and self-care ability. We suggest that stronger functional connectivity between left PCG and right AG, SPG, and SOG detected in young boys with ASD may serve as important indicators of disease severity. Our study provided preliminary functional evidence that may underlie impaired higher-order multisensory integration in ASD

Increased Gray Matter Volume and Resting-State Functional Connectivity in Somatosensory Cortex and their Relationship with Autistic Symptoms in Young Boys with Autism Spectrum Disorder

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Jia Wang

2017-08-01

Full Text Available Autism spectrum disorder (ASD has been widely recognized as a complex neurodevelopmental disorder. A large number of neuroimaging studies suggest abnormalities in brain structure and function of patients with ASD, but there is still no consistent conclusion. We sought to investigate both of the structural and functional brain changes in 3–7-year-old children with ASD compared with typically developing controls (TDs, and to assess whether these alterations are associated with autistic behavioral symptoms. Firstly, we applied an optimized method of voxel-based morphometry (VBM analysis on structural magnetic resonance imaging (sMRI data to assess the differences of gray matter volume (GMV between 31 autistic boys aged 3–7 and 31 age- and handness-matched male TDs. Secondly, we used clusters with between-group differences as seed regions to generate intrinsic functional connectivity maps based on resting-state functional connectivity magnetic resonance imaging (rs-fcMRI in order to evaluate the functional impairments induced by structural alterations. Brain-behavior correlations were assessed among GMV, functional connectivity and symptom severity in children with ASD. VBM analyses revealed increased GMV in left superior temporal gyrus (STG and left postcentral gyrus (PCG in ASD children, comparing with TDs. Using left PCG as a seed region, ASD children displayed significantly higher positive connectivity with right angular gyrus (AG and greater negative connectivity with right superior parietal gyrus (SPG and right superior occipital gyrus (SOG, which were associated with the severity of symptoms in social interaction, communication and self-care ability. We suggest that stronger functional connectivity between left PCG and right AG, SPG, and SOG detected in young boys with ASD may serve as important indicators of disease severity. Our study provided preliminary functional evidence that may underlie impaired higher-order multisensory

Joint brain connectivity estimation from diffusion and functional MRI data

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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

Alterations in Cortical Sensorimotor Connectivity following Complete Cervical Spinal Cord Injury: A Prospective Resting-State fMRI Study.

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Akinwunmi Oni-Orisan

Full Text Available Functional magnetic resonance imaging (fMRI studies have demonstrated alterations during task-induced brain activation in spinal cord injury (SCI patients. The interruption to structural integrity of the spinal cord and the resultant disrupted flow of bidirectional communication between the brain and the spinal cord might contribute to the observed dynamic reorganization (neural plasticity. However, the effect of SCI on brain resting-state connectivity patterns remains unclear. We undertook a prospective resting-state fMRI (rs-fMRI study to explore changes to cortical activation patterns following SCI. With institutional review board approval, rs-fMRI data was obtained in eleven patients with complete cervical SCI (>2 years post injury and nine age-matched controls. The data was processed using the Analysis of Functional Neuroimages software. Region of interest (ROI based analysis was performed to study changes in the sensorimotor network using pre- and post-central gyri as seed regions. Two-sampled t-test was carried out to check for significant differences between the two groups. SCI patients showed decreased functional connectivity in motor and sensory cortical regions when compared to controls. The decrease was noted in ipsilateral, contralateral, and interhemispheric regions for left and right precentral ROIs. Additionally, the left postcentral ROI demonstrated increased connectivity with the thalamus bilaterally in SCI patients. Our results suggest that cortical activation patterns in the sensorimotor network undergo dynamic reorganization following SCI. The presence of these changes in chronic spinal cord injury patients is suggestive of the inherent neural plasticity within the central nervous system.

Altered Behavioral and Autonomic Pain Responses in Alzheimer’s Disease Are Associated with Dysfunctional Affective, Self-Reflective and Salience Network Resting-State Connectivity

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Paul A. Beach

2017-09-01

Full Text Available While pain behaviors are increased in Alzheimer’s disease (AD patients compared to healthy seniors (HS across multiple disease stages, autonomic responses are reduced with advancing AD. To better understand the neural mechanisms underlying these phenomena, we undertook a controlled cross-sectional study examining behavioral (Pain Assessment in Advanced Dementia, PAINAD scores and autonomic (heart rate, HR pain responses in 24 HS and 20 AD subjects using acute pressure stimuli. Resting-state fMRI was utilized to investigate how group connectivity differences were related to altered pain responses. Pain behaviors (slope of PAINAD score change and mean PAINAD score were increased in patients vs. controls. Autonomic measures (HR change intercept and mean HR change were reduced in severe vs. mildly affected AD patients. Group functional connectivity differences associated with greater pain behavior reactivity in patients included: connectivity within a temporal limbic network (TLN and between the TLN and ventromedial prefrontal cortex (vmPFC; between default mode network (DMN subcomponents; between the DMN and ventral salience network (vSN. Reduced HR responses within the AD group were associated with connectivity changes within the DMN and vSN—specifically the precuneus and vmPFC. Discriminant classification indicated HR-related connectivity within the vSN to the vmPFC best distinguished AD severity. Thus, altered behavioral and autonomic pain responses in AD reflects dysfunction of networks and structures subserving affective, self-reflective, salience and autonomic regulation.

Remodeling of Sensorimotor Brain Connectivity in Gpr88-Deficient Mice.

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Arefin, Tanzil Mahmud; Mechling, Anna E; Meirsman, Aura Carole; Bienert, Thomas; Hübner, Neele Saskia; Lee, Hsu-Lei; Ben Hamida, Sami; Ehrlich, Aliza; Roquet, Dan; Hennig, Jürgen; von Elverfeldt, Dominik; Kieffer, Brigitte Lina; Harsan, Laura-Adela

2017-10-01

Recent studies have demonstrated that orchestrated gene activity and expression support synchronous activity of brain networks. However, there is a paucity of information on the consequences of single gene function on overall brain functional organization and connectivity and how this translates at the behavioral level. In this study, we combined mouse mutagenesis with functional and structural magnetic resonance imaging (MRI) to determine whether targeted inactivation of a single gene would modify whole-brain connectivity in live animals. The targeted gene encodes GPR88 (G protein-coupled receptor 88), an orphan G protein-coupled receptor enriched in the striatum and previously linked to behavioral traits relevant to neuropsychiatric disorders. Connectivity analysis of Gpr88-deficient mice revealed extensive remodeling of intracortical and cortico-subcortical networks. Most prominent modifications were observed at the level of retrosplenial cortex connectivity, central to the default mode network (DMN) whose alteration is considered a hallmark of many psychiatric conditions. Next, somatosensory and motor cortical networks were most affected. These modifications directly relate to sensorimotor gating deficiency reported in mutant animals and also likely underlie their hyperactivity phenotype. Finally, we identified alterations within hippocampal and dorsal striatum functional connectivity, most relevant to a specific learning deficit that we previously reported in Gpr88 -/- animals. In addition, amygdala connectivity with cortex and striatum was weakened, perhaps underlying the risk-taking behavior of these animals. This is the first evidence demonstrating that GPR88 activity shapes the mouse brain functional and structural connectome. The concordance between connectivity alterations and behavior deficits observed in Gpr88-deficient mice suggests a role for GPR88 in brain communication.

Altered intrahemispheric structural connectivity in Gilles de la Tourette syndrome

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Bastian Cheng

2014-01-01

Full Text Available Gilles de la Tourette syndrome (GTS is a common developmental neuropsychiatric disorder characterized by tics and frequent psychiatric comorbidities, often causing significant disability. Tic generation has been linked to disturbed networks of brain areas involved in planning, controlling and execution of actions, particularly structural and functional disorders in the striatum and cortico–striato–thalamo–cortical loops. We therefore applied structural diffusion tensor imaging (DTI to characterize changes in intrahemispheric white matter connectivity in cortico-subcortical circuits engaged in motor control in 15 GTS patients without psychiatric comorbidities. White matter connectivity was analyzed by probabilistic fiber tractography between 12 predefined cortical and subcortical regions of interest. Connectivity values were combined with measures of clinical severity rated by the Yale Global Tic Severity Scale (YGTSS. GTS patients showed widespread structural connectivity deficits. Lower connectivity values were found specifically in tracts connecting the supplementary motor areas (SMA with basal ganglia (pre-SMA–putamen, SMA–putamen and in frontal cortico-cortical circuits. There was an overall trend towards negative correlations between structural connectivity in these tracts and YGTSS scores. Structural connectivity of frontal brain networks involved in planning, controlling and executing actions is reduced in adult GTS patients which is associated with tic severity. These findings are in line with the concept of GTS as a neurodevelopmental disorder of brain immaturity.

The cerebellum after trauma: Resting-state functional connectivity of the cerebellum in posttraumatic stress disorder and its dissociative subtype.

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

2018-04-17

The cerebellum plays a key role not only in motor function but also in affect and cognition. Although several psychopathological disorders have been associated with overall cerebellar dysfunction, it remains unclear whether different regions of the cerebellum contribute uniquely to psychopathology. Accordingly, we compared seed-based resting-state functional connectivity of the anterior cerebellum (lobule IV-V), of the posterior cerebellum (Crus I), and of the anterior vermis across posttraumatic stress disorder (PTSD; n = 65), its dissociative subtype (PTSD + DS; n = 37), and non-trauma-exposed healthy controls (HC; n = 47). Here, we observed decreased functional connectivity of the anterior cerebellum and anterior vermis with brain regions involved in somatosensory processing, multisensory integration, and bodily self-consciousness (temporo-parietal junction, postcentral gyrus, and superior parietal lobule) in PTSD + DS as compared to PTSD and HC. Moreover, the PTSD + DS group showed increased functional connectivity of the posterior cerebellum with cortical areas related to emotion regulation (ventromedial prefrontal and orbito-frontal cortex, subgenual anterior cingulum) as compared to PTSD. By contrast, PTSD showed increased functional connectivity of the anterior cerebellum with cortical areas associated with visual processing (fusiform gyrus), interoceptive awareness (posterior insula), memory retrieval, and contextual processing (hippocampus) as compared to HC. Finally, we observed decreased functional connectivity between the posterior cerebellum and prefrontal regions involved in emotion regulation, in PTSD as compared to HC. These findings not only highlight the crucial role of each cerebellar region examined in the psychopathology of PTSD but also reveal unique alterations in functional connectivity distinguishing the dissociative subtype of PTSD versus PTSD. © 2018 Wiley Periodicals, Inc.

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

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

2015-01-01

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

Abnormal Functional Connectivity of Anterior Cingulate Cortex in Patients With Primary Insomnia: A Resting-State Functional Magnetic Resonance Imaging Study

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Chao-Qun Yan

2018-06-01

Full Text Available Background: Recently, there have been many reports about abnormalities regarding structural and functional brain connectivity of the patients with primary insomnia. However, the alterations in functional interaction between the left and right cerebral hemispheres have not been well understood. The resting-state fMRI approach, which reveals spontaneous neural fluctuations in blood-oxygen-level-dependent signals, offers a method to quantify functional interactions between the hemispheres directly.Methods: We compared interhemispheric functional connectivity (FC between 26 patients with primary insomnia (48.85 ± 12.02 years and 28 healthy controls (49.07 ± 11.81 years using a voxel-mirrored homotopic connectivity (VMHC method. The patients with primary insomnia and healthy controls were matched for age, gender, and education. Brain regions, which had significant differences in VMHC maps between the primary insomnia and healthy control groups, were defined as seed region of interests. A seed-based approach was further used to reveal significant differences of FC between the seeds and the whole contralateral hemisphere.Results: The patients with primary insomnia showed higher VMHC than healthy controls in the anterior cingulate cortex (ACC bilaterally. The seed-based analyses demonstrated increased FC between the left ACC and right thalamus (and the right ACC and left orbitofrontal cortex in patients with primary insomnia, revealing abnormal connectivity between the two cerebral hemispheres. The VMHC values in the ACC were positively correlated with the time to fall asleep and Self-Rating Depression Scale scores (SDS.Conclusions: The results demonstrate that there is abnormal interhemispheric resting-state FC in the brain regions of patients with primary insomnia, especially in the ACC. Our finding demonstrates valid evidence that the ACC is an area of interest in the neurobiology of primary insomnia.

Function-specific and Enhanced Brain Structural Connectivity Mapping via Joint Modeling of Diffusion and Functional MRI.

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

2018-03-16

A joint structural-functional brain network model is presented, which enables the discovery of function-specific brain circuits, and recovers structural connections that are under-estimated by diffusion MRI (dMRI). Incorporating information from functional MRI (fMRI) into diffusion MRI to estimate brain circuits is a challenging task. Usually, seed regions for tractography are selected from fMRI activation maps to extract the white matter pathways of interest. The proposed method jointly analyzes whole brain dMRI and fMRI data, allowing the estimation of complete function-specific structural networks instead of interactively investigating the connectivity of individual cortical/sub-cortical areas. Additionally, tractography techniques are prone to limitations, which can result in erroneous pathways. The proposed framework explicitly models the interactions between structural and functional connectivity measures thereby improving anatomical circuit estimation. Results on Human Connectome Project (HCP) data demonstrate the benefits of the approach by successfully identifying function-specific anatomical circuits, such as the language and resting-state networks. In contrast to correlation-based or independent component analysis (ICA) functional connectivity mapping, detailed anatomical connectivity patterns are revealed for each functional module. Results on a phantom (Fibercup) also indicate improvements in structural connectivity mapping by rejecting false-positive connections with insufficient support from fMRI, and enhancing under-estimated connectivity with strong functional correlation.

Prefrontal-Thalamic Anatomical Connectivity and Executive Cognitive Function in Schizophrenia.

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Giraldo-Chica, Monica; Rogers, Baxter P; Damon, Stephen M; Landman, Bennett A; Woodward, Neil D

2018-03-15

Executive cognitive functions, including working memory, cognitive flexibility, and inhibition, are impaired in schizophrenia. Executive functions rely on coordinated information processing between the prefrontal cortex (PFC) and thalamus, particularly the mediodorsal nucleus. This raises the possibility that anatomical connectivity between the PFC and mediodorsal thalamus may be 1) reduced in schizophrenia and 2) related to deficits in executive function. The current investigation tested these hypotheses. Forty-five healthy subjects and 62 patients with a schizophrenia spectrum disorder completed a battery of tests of executive function and underwent diffusion-weighted imaging. Probabilistic tractography was used to quantify anatomical connectivity between six cortical regions, including PFC, and the thalamus. Thalamocortical anatomical connectivity was compared between healthy subjects and patients with schizophrenia using region-of-interest and voxelwise approaches, and the association between PFC-thalamic anatomical connectivity and severity of executive function impairment was examined in patients. Anatomical connectivity between the thalamus and PFC was reduced in schizophrenia. Voxelwise analysis localized the reduction to areas of the mediodorsal thalamus connected to lateral PFC. Reduced PFC-thalamic connectivity in schizophrenia correlated with impaired working memory but not cognitive flexibility and inhibition. In contrast to reduced PFC-thalamic connectivity, thalamic connectivity with somatosensory and occipital cortices was increased in schizophrenia. The results are consistent with models implicating disrupted PFC-thalamic connectivity in the pathophysiology of schizophrenia and mechanisms of cognitive impairment. PFC-thalamic anatomical connectivity may be an important target for procognitive interventions. Further work is needed to determine the implications of increased thalamic connectivity with sensory cortex. Copyright © 2017 Society of

Decreased prefrontal lobe interhemispheric functional connectivity in adolescents with internet gaming disorder: a primary study using resting-state FMRI.

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Yao Wang

Full Text Available Recent neuroimaging studies have shown that people with Internet gaming disorder (IGD have structural and functional abnormalities in specific brain areas and connections. However, little is known about the alterations of the interhemispheric resting-state functional connectivity (rsFC in participants with IGD. In the present study, we used a newly developed voxel-mirrored homotopic connectivity (VMHC method to investigate the interhemispheric rsFC of the whole brain in participants with IGD.We compared interhemispheric rsFC between 17 participants with IGD and 24 healthy controls, group-matched on age, gender, and education status. All participants were provided written informed consent. Resting-state functional and structural magnetic resonance images were acquired for all participants. The rsFC between bilateral homotopic voxels was calculated. Regions showing abnormal VMHC in IGD participants were adopted as regions of interest for correlation analyses.Compared to healthy controls, IGD participants showed decreased VMHC between the left and right superior frontal gyrus (orbital part, inferior frontal gyrus (orbital part, middle frontal gyrus and superior frontal gyrus. Further analyses showed Chen Internet Addiction Scale (CIAS-related VMHC in superior frontal gyrus (orbital part and CIAS (r = -0.55, p = 0.02, uncorrected.Our findings implicate the important role of altered interhemispheric rsFC in the bilateral prefrontal lobe in the neuropathological mechanism of IGD, and provide further supportive evidence for the reclassification of IGD as a behavioral addiction.

Detecting Brain State Changes via Fiber-Centered Functional Connectivity Analysis

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Li, Xiang; Lim, Chulwoo; Li, Kaiming; Guo, Lei; Liu, Tianming

2013-01-01

Diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI) have been widely used to study structural and functional brain connectivity in recent years. A common assumption used in many previous functional brain connectivity studies is the temporal stationarity. However, accumulating literature evidence has suggested that functional brain connectivity is under temporal dynamic changes in different time scales. In this paper, a novel and intuitive approach is proposed to model and detect dynamic changes of functional brain states based on multimodal fMRI/DTI data. The basic idea is that functional connectivity patterns of all fiber-connected cortical voxels are concatenated into a descriptive functional feature vector to represent the brain’s state, and the temporal change points of brain states are decided by detecting the abrupt changes of the functional vector patterns via the sliding window approach. Our extensive experimental results have shown that meaningful brain state change points can be detected in task-based fMRI/DTI, resting state fMRI/DTI, and natural stimulus fMRI/DTI data sets. Particularly, the detected change points of functional brain states in task-based fMRI corresponded well to the external stimulus paradigm administered to the participating subjects, thus partially validating the proposed brain state change detection approach. The work in this paper provides novel perspective on the dynamic behaviors of functional brain connectivity and offers a starting point for future elucidation of the complex patterns of functional brain interactions and dynamics. PMID:22941508

Impairments of thalamic resting-state functional connectivity in patients with chronic tinnitus

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Zhang, Jian [Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing (China); Chen, Yu-Chen [Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing (China); Center for Hearing and Deafness, University at Buffalo, State University of New York, Buffalo, NY (United States); Feng, Xu [Department of Otolaryngology, Zhongda Hospital, Medical School, Southeast University, Nanjing (China); Yang, Ming; Liu, Bin; Qian, Cheng [Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing (China); Wang, Jian [Department of Physiology, Southeast University, Nanjing (China); School of Human Communication Disorders, Dalhousie University, Halifax, NS (Canada); Salvi, Richard [Center for Hearing and Deafness, University at Buffalo, State University of New York, Buffalo, NY (United States); Teng, Gao-Jun, E-mail: gjteng@vip.sina.com [Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing (China)

2015-07-15

Highlights: • Tinnitus patients have aberrant thalamic connectivity to many brain regions. • Decreased thalamic connectivity is linked with tinnitus characteristics. • Thalamocortical connectivity disturbances can reflect tinnitus-related networks. - Abstract: Purpose: The phantom sound of tinnitus is believed to arise from abnormal functional coupling between the thalamus and cerebral cortex. To explore this hypothesis, we used resting-state functional magnetic resonance imaging (fMRI) to compare the degree of thalamocortical functional connectivity in chronic tinnitus patients and controls. Materials and methods: Resting-state fMRI scans were obtained from 31 chronic tinnitus patients and 33 well-matched healthy controls. Thalamocortical functional connectivity was characterized using a seed-based whole-brain correlation method. The resulting thalamic functional connectivity measures were correlated with other clinical data. Results: We found decreased functional connectivity between the seed region in left thalamus and right middle temporal gyrus (MTG), right middle orbitofrontal cortex, left middle frontal gyrus, right precentral gyrus, and bilateral calcarine cortex. Decreased functional connectivity was detected between the seed in the right thalamus and the left superior temporal gyrus (STG), left amygdala, right superior frontal gyrus, left precentral gyrus, and left middle occipital gyrus. Tinnitus distress correlated negatively with thalamic functional connectivity in right MTG; tinnitus duration correlated negatively with thalamic functional connectivity in left STG. Increased functional connectivity between the bilateral thalamus and a set of regions were also observed. Conclusions: Chronic tinnitus patients have disrupted thalamocortical functional connectivity to selected brain regions which is associated with specific tinnitus characteristics. Resting-state thalamic functional connectivity disturbances may play an important role in

Impairments of thalamic resting-state functional connectivity in patients with chronic tinnitus

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Zhang, Jian; Chen, Yu-Chen; Feng, Xu; Yang, Ming; Liu, Bin; Qian, Cheng; Wang, Jian; Salvi, Richard; Teng, Gao-Jun

2015-01-01

Highlights: • Tinnitus patients have aberrant thalamic connectivity to many brain regions. • Decreased thalamic connectivity is linked with tinnitus characteristics. • Thalamocortical connectivity disturbances can reflect tinnitus-related networks. - Abstract: Purpose: The phantom sound of tinnitus is believed to arise from abnormal functional coupling between the thalamus and cerebral cortex. To explore this hypothesis, we used resting-state functional magnetic resonance imaging (fMRI) to compare the degree of thalamocortical functional connectivity in chronic tinnitus patients and controls. Materials and methods: Resting-state fMRI scans were obtained from 31 chronic tinnitus patients and 33 well-matched healthy controls. Thalamocortical functional connectivity was characterized using a seed-based whole-brain correlation method. The resulting thalamic functional connectivity measures were correlated with other clinical data. Results: We found decreased functional connectivity between the seed region in left thalamus and right middle temporal gyrus (MTG), right middle orbitofrontal cortex, left middle frontal gyrus, right precentral gyrus, and bilateral calcarine cortex. Decreased functional connectivity was detected between the seed in the right thalamus and the left superior temporal gyrus (STG), left amygdala, right superior frontal gyrus, left precentral gyrus, and left middle occipital gyrus. Tinnitus distress correlated negatively with thalamic functional connectivity in right MTG; tinnitus duration correlated negatively with thalamic functional connectivity in left STG. Increased functional connectivity between the bilateral thalamus and a set of regions were also observed. Conclusions: Chronic tinnitus patients have disrupted thalamocortical functional connectivity to selected brain regions which is associated with specific tinnitus characteristics. Resting-state thalamic functional connectivity disturbances may play an important role in

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

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

2014-04-16

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

A Tensor Statistical Model for Quantifying Dynamic Functional Connectivity.

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Zhu, Yingying; Zhu, Xiaofeng; Kim, Minjeong; Yan, Jin; Wu, Guorong

2017-06-01

Functional connectivity (FC) has been widely investigated in many imaging-based neuroscience and clinical studies. Since functional Magnetic Resonance Image (MRI) signal is just an indirect reflection of brain activity, it is difficult to accurately quantify the FC strength only based on signal correlation. To address this limitation, we propose a learning-based tensor model to derive high sensitivity and specificity connectome biomarkers at the individual level from resting-state fMRI images. First, we propose a learning-based approach to estimate the intrinsic functional connectivity. In addition to the low level region-to-region signal correlation, latent module-to-module connection is also estimated and used to provide high level heuristics for measuring connectivity strength. Furthermore, sparsity constraint is employed to automatically remove the spurious connections, thus alleviating the issue of searching for optimal threshold. Second, we integrate our learning-based approach with the sliding-window technique to further reveal the dynamics of functional connectivity. Specifically, we stack the functional connectivity matrix within each sliding window and form a 3D tensor where the third dimension denotes for time. Then we obtain dynamic functional connectivity (dFC) for each individual subject by simultaneously estimating the within-sliding-window functional connectivity and characterizing the across-sliding-window temporal dynamics. Third, in order to enhance the robustness of the connectome patterns extracted from dFC, we extend the individual-based 3D tensors to a population-based 4D tensor (with the fourth dimension stands for the training subjects) and learn the statistics of connectome patterns via 4D tensor analysis. Since our 4D tensor model jointly (1) optimizes dFC for each training subject and (2) captures the principle connectome patterns, our statistical model gains more statistical power of representing new subject than current state

PCB 136 Atropselectively Alters Morphometric and Functional Parameters of Neuronal Connectivity in Cultured Rat Hippocampal Neurons via Ryanodine Receptor-Dependent Mechanisms

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Yang, Dongren; Kania-Korwel, Izabela; Ghogha, Atefeh; Chen, Hao; Stamou, Marianna; Bose, Diptiman D.; Pessah, Isaac N.; Lehmler, Hans-Joachim; Lein, Pamela J.

2014-01-01

We recently demonstrated that polychlorinated biphenyl (PCB) congeners with multiple ortho chlorine substitutions sensitize ryanodine receptors (RyRs), and this activity promotes Ca2+-dependent dendritic growth in cultured neurons. Many ortho-substituted congeners display axial chirality, and we previously reported that the chiral congener PCB 136 (2,2′,3,3′,6,6′-hexachlorobiphenyl) atropselectively sensitizes RyRs. Here, we test the hypothesis that PCB 136 atropisomers differentially alter dendritic growth and other parameters of neuronal connectivity influenced by RyR activity. (−)-PCB 136, which potently sensitizes RyRs, enhances dendritic growth in primary cultures of rat hippocampal neurons, whereas (+)-PCB 136, which lacks RyR activity, has no effect on dendritic growth. The dendrite-promoting activity of (−)-PCB 136 is observed at concentrations ranging from 0.1 to 100nM and is blocked by pharmacologic RyR antagonism. Neither atropisomer alters axonal growth or cell viability. Quantification of PCB 136 atropisomers in hippocampal cultures indicates that atropselective effects on dendritic growth are not due to differential partitioning of atropisomers into cultured cells. Imaging of hippocampal neurons loaded with Ca2+-sensitive dye demonstrates that (−)-PCB 136 but not (+)-PCB 136 increases the frequency of spontaneous Ca2+ oscillations. Similarly, (−)-PCB 136 but not (+)-PCB 136 increases the activity of hippocampal neurons plated on microelectrode arrays. These data support the hypothesis that atropselective effects on RyR activity translate into atropselective effects of PCB 136 atropisomers on neuronal connectivity, and suggest that the variable atropisomeric enrichment of chiral PCBs observed in the human population may be a significant determinant of individual susceptibility for adverse neurodevelopmental outcomes following PCB exposure. PMID:24385416

Decreased functional connectivity and structural deficit in alertness network with right-sided temporal lobe epilepsy.

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Gao, Yujun; Zheng, Jinou; Li, Yaping; Guo, Danni; Wang, Mingli; Cui, Xiangxiang; Ye, Wei

2018-04-01

Patients with temporal lobe epilepsy (TLE) often suffer from alertness alterations. However, specific regions connected with alertness remain controversial, and whether these regions have structural impairment is also elusive. This study aimed to investigate the characteristics and neural mechanisms underlying the functions and structures of alertness network in patients with right-sided temporal lobe epilepsy (rTLE) by performing the attentional network test (ANT), resting-state functional magnetic resonance imaging (R-SfMRI), and diffusion tensor imaging (DTI).A total of 47 patients with rTLE and 34 healthy controls underwent ANT, R-SfMRI, and DTI scan. The seed-based functional connectivity (FC) method and deterministic tractography were used to analyze the data.Patients with rTLE had longer reaction times in the no-cue and double-cue conditions. However, no differences were noted in the alertness effect between the 2 groups. The patient group had lower FC compared with the control group in the right inferior parietal lobe (IPL), amygdala, and insula. Structural deficits were found in the right parahippocampal gyrus, superior temporal pole, insula, and amygdala in the patient group compared with the control group. Also significantly negative correlations were observed between abnormal fractional anisotropy (between the right insula and the superior temporal pole) and illness duration in the patients with rTLE.The findings of this study suggested abnormal intrinsic and phasic alertness, decreased FC, and structural deficits within the alerting network in the rTLE. This study provided new insights into the mechanisms of alertness alterations in rTLE.

Modular organization of functional network connectivity in healthy controls and patients with schizophrenia during the resting state

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Qingbao eYu

2012-01-01

Full Text Available Neuroimaging studies have shown that functional brain networks composed from select regions of interest (ROIs have a modular community structure. However, the organization of functional network connectivity (FNC, comprising a purely data-driven network built from spatially independent brain components, is not yet clear. The aim of this study is to explore the modular organization of FNC in both healthy controls (HCs and patients with schizophrenia (SZs. Resting state functional magnetic resonance imaging (R-fMRI data of HCs and SZs were decomposed into independent components (ICs by group independent component analysis (ICA. Then weighted brain networks (in which nodes are brain components were built based on correlations among of ICA time courses. Clustering coefficients and connectivity strength of the networks were computed. A dynamic branch cutting algorithm was used to identify modules of the FNC in HCs and SZs. Results show stronger connectivity strength and higher clustering coefficient in HCs with more and smaller modules in SZs. In addition, HCs and SZs had some different hubs. Our findings demonstrate altered modular architecture of the FNC in schizophrenia and provide insights into abnormal topological organization of intrinsic brain networks in this mental illness.

Precentral gyrus functional connectivity signatures of autism

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Mary Beth eNebel

2014-05-01

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

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

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

2017-05-01

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

Connectivity and tissue microstructural alterations in right and left temporal lobe epilepsy revealed by diffusion spectrum imaging

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Alia Lemkaddem

2014-01-01

Global connectivity, hub architecture and regional connectivity patterns were altered in TLE patients and showed different characteristics in RTLE vs LTLE with stronger abnormalities in RTLE. The microstructural analysis suggested that disturbed axonal density contributed more than fiber orientation to the connectivity changes affecting the temporal lobes whereas fiber orientation changes were more involved in extratemporal lobe changes. Our study provides further structural evidence that RTLE and LTLE are not symmetrical entities and DSI-based imaging could help investigate the microstructural correlate of these imaging abnormalities.

Habenula functional resting-state connectivity in pediatric CRPS.

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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.

Hyper-connectivity of functional networks for brain disease diagnosis.

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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

Adrenergic Blockade Bi-directionally and Asymmetrically Alters Functional Brain-Heart Communication and Prolongs Electrical Activities of the Brain and Heart during Asphyxic Cardiac Arrest

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Tian, Fangyun; Liu, Tiecheng; Xu, Gang; Li, Duan; Ghazi, Talha; Shick, Trevor; Sajjad, Azeem; Wang, Michael M.; Farrehi, Peter; Borjigin, Jimo

2018-01-01

Sudden cardiac arrest is a leading cause of death in the United States. The neurophysiological mechanism underlying sudden death is not well understood. Previously we have shown that the brain is highly stimulated in dying animals and that asphyxia-induced death could be delayed by blocking the intact brain-heart neuronal connection. These studies suggest that the autonomic nervous system plays an important role in mediating sudden cardiac arrest. In this study, we tested the effectiveness of phentolamine and atenolol, individually or combined, in prolonging functionality of the vital organs in CO2-mediated asphyxic cardiac arrest model. Rats received either saline, phentolamine, atenolol, or phentolamine plus atenolol, 30 min before the onset of asphyxia. Electrocardiogram (ECG) and electroencephalogram (EEG) signals were simultaneously collected from each rat during the entire process and investigated for cardiac and brain functions using a battery of analytic tools. We found that adrenergic blockade significantly suppressed the initial decline of cardiac output, prolonged electrical activities of both brain and heart, asymmetrically altered functional connectivity within the brain, and altered, bi-directionally and asymmetrically, functional, and effective connectivity between the brain and heart. The protective effects of adrenergic blockers paralleled the suppression of brain and heart connectivity, especially in the right hemisphere associated with central regulation of sympathetic function. Collectively, our results demonstrate that blockade of brain-heart connection via alpha- and beta-adrenergic blockers significantly prolonged the detectable activities of both the heart and the brain in asphyxic rat. The beneficial effects of combined alpha and beta blockers may help extend the survival of cardiac arrest patients. PMID:29487541

Adrenergic Blockade Bi-directionally and Asymmetrically Alters Functional Brain-Heart Communication and Prolongs Electrical Activities of the Brain and Heart during Asphyxic Cardiac Arrest

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Fangyun Tian

2018-02-01

Full Text Available Sudden cardiac arrest is a leading cause of death in the United States. The neurophysiological mechanism underlying sudden death is not well understood. Previously we have shown that the brain is highly stimulated in dying animals and that asphyxia-induced death could be delayed by blocking the intact brain-heart neuronal connection. These studies suggest that the autonomic nervous system plays an important role in mediating sudden cardiac arrest. In this study, we tested the effectiveness of phentolamine and atenolol, individually or combined, in prolonging functionality of the vital organs in CO2-mediated asphyxic cardiac arrest model. Rats received either saline, phentolamine, atenolol, or phentolamine plus atenolol, 30 min before the onset of asphyxia. Electrocardiogram (ECG and electroencephalogram (EEG signals were simultaneously collected from each rat during the entire process and investigated for cardiac and brain functions using a battery of analytic tools. We found that adrenergic blockade significantly suppressed the initial decline of cardiac output, prolonged electrical activities of both brain and heart, asymmetrically altered functional connectivity within the brain, and altered, bi-directionally and asymmetrically, functional, and effective connectivity between the brain and heart. The protective effects of adrenergic blockers paralleled the suppression of brain and heart connectivity, especially in the right hemisphere associated with central regulation of sympathetic function. Collectively, our results demonstrate that blockade of brain-heart connection via alpha- and beta-adrenergic blockers significantly prolonged the detectable activities of both the heart and the brain in asphyxic rat. The beneficial effects of combined alpha and beta blockers may help extend the survival of cardiac arrest patients.