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Zhu L, Zhang W, Chen L, Ren Y, Cao Y, Sun T, Sun B, Liu J, Wang J, Zheng C. Brain Gray Matter Alterations in Hepatic Encephalopathy: A Voxel-Based Meta-Analysis of Whole-Brain Studies. Front Hum Neurosci 2022; 16:838666. [PMID: 35517986 PMCID: PMC9062230 DOI: 10.3389/fnhum.2022.838666] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2021] [Accepted: 02/28/2022] [Indexed: 12/03/2022] Open
Abstract
Background Previous studies on voxel-based morphometry (VBM) have found that there were gray matter alterations in patients with hepatic encephalopathy (HE). However, the reported results were inconsistent and lack a quantitative review. Therefore, this study aims for a quantitative meta-analysis of VBM analysis on patients with HE. Methods The studies in our meta-analysis were collected from Pubmed, Web of Science, and Embase, which were published from January 1947 to October 2021. The seed-based d mapping (SDM) method was applied to quantitatively estimate the regional gray matter abnormalities in patients with HE. A meta-regression analysis was applied to evaluate the relationship between plasma ammonia and gray matter alteration. Results There were nine studies, with sixteen datasets consisting of 333 participants with HE and 429 healthy controls. The pooled and subgroup meta-analyses showed an increase in gray matter volume (GMV) in the bilateral thalamus and the calcarine fissure but a decrease in the GMV in the bilateral insula, the basal ganglia, the anterior cingulate gyrus, and the cerebellum. The meta-regression showed that plasma ammonia was positively associated with the GMV in the left thalamus but was negatively associated with the GMV in the cerebellum and the bilateral striatum. Conclusion Gray matter volume in patients with HE largely varied and could be affected by plasma ammonia. The findings of this study could help us to better understand the pathophysiology of cognitive dysfunction in patients with HE.
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Affiliation(s)
- Licheng Zhu
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Weihua Zhang
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Lei Chen
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yanqiao Ren
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yanyan Cao
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Tao Sun
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Bo Sun
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jia Liu
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
| | - Jing Wang
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
| | - Chuansheng Zheng
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
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Attenuated link between the medial prefrontal cortex and the amygdala in children with autism spectrum disorder: Evidence from effective connectivity within the "social brain". Prog Neuropsychopharmacol Biol Psychiatry 2021; 111:110147. [PMID: 33096157 DOI: 10.1016/j.pnpbp.2020.110147] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2020] [Revised: 09/21/2020] [Accepted: 10/16/2020] [Indexed: 01/27/2023]
Abstract
Although accumulating neuroimaging studies have reported that social behavior deficits in children with autism spectrum disorders (ASD) are commonly attributed to the dysfunction of social brain regions underlying social cognition, the dynamic interaction within the social brain network and its association with social deficits remain unclear. Here, resting-state functional magnetic resonance imaging data obtained from Autism Brain Imaging Data Exchange (I and II) were analyzed in 105 children with ASD and 102 demographically matched typically developing controls (TDCs) (age range: 7-12 years old). Term-based meta-analysis combined the prior reference and anatomical labeling were used to define the regions of interests of the social brain network, and multivariate Granger causality analysis with blind deconvolution was employed to assess the effective connectivity within the social brain network in the ASD and TDC groups. Between-group comparison revealed significantly attenuated effective connectivity from the medial prefrontal cortex (mPFC) to the bilateral amygdala in children with the ASD group compared with TDC group. In addition, raw values of the effective connectivity from the mPFC to the bilateral amygdala were used to predict social deficits in ASD. Our findings indicate the impaired mPFC-amygdala pathway and its association with social deficits in children with ASD and provide a new perspective into the neuropathology of the developing autistic brain.
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Fede SJ, Abrahao KP, Cortes CR, Grodin EN, Schwandt ML, George DT, Diazgranados N, Ramchandani VA, Lovinger DM, Momenan R. Alcohol effects on globus pallidus connectivity: Role of impulsivity and binge drinking. PLoS One 2020; 15:e0224906. [PMID: 32214339 PMCID: PMC7098584 DOI: 10.1371/journal.pone.0224906] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2019] [Accepted: 03/03/2020] [Indexed: 12/19/2022] Open
Abstract
Despite the harm caused by binge drinking, the neural mechanisms leading to risky and disinhibited intoxication-related behaviors are not well understood. Evidence suggests that the globus pallidus externus (GPe), a substructure within the basal ganglia, participates in inhibitory control processes, as examined in stop-signaling tasks. In fact, studies in rodents have revealed that alcohol can change GPe activity by decreasing neuronal firing rates, suggesting that the GPe may have a central role in explaining impulsive behaviors and failures of inhibition that occur during binge drinking. In this study, twenty-five healthy volunteers underwent intravenous alcohol infusion to achieve a blood alcohol level of 0.08 g/dl, which is equivalent to a binge drinking episode. A resting state functional magnetic resonance imaging scan was collected prior to the infusion and at binge-level exposure. Functional connectivity analysis was used to investigate the association between alcohol-induced changes in GPe connectivity, drinking behaviors, and impulsivity traits. We found that individuals with greater number of drinks or heavy drinking days in the recent past had greater alcohol-induced deficits in GPe connectivity, particularly to the striatum. Our data also indicated an association between impulsivity and alcohol-induced deficits in GPe-frontal/precentral connectivity. Moreover, alcohol induced changes in GPe-amygdala circuitry suggested greater vulnerabilities to stress-related drinking in some individuals. Taken together, these findings suggest that alcohol may interact with impulsive personality traits and drinking patterns to drive alterations in GPe circuitry associated with behavioral inhibition, possibly indicating a neural mechanism by which binge drinking could lead to impulsive behaviors.
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Affiliation(s)
- Samantha J. Fede
- Clinical NeuroImaging Research Core, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, United States of America
| | - Karina P. Abrahao
- Laboratory for Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, Maryland, United States of America
- Departamento de Psicobiologia, Universidade Federal de Sao Paulo, Sao Paulo, São Paulo, Brazil
| | - Carlos R. Cortes
- Clinical NeuroImaging Research Core, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, United States of America
| | - Erica N. Grodin
- Clinical NeuroImaging Research Core, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, United States of America
| | - Melanie L. Schwandt
- Office of the Clinical Director, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, United States of America
| | - David T. George
- Office of the Clinical Director, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, United States of America
| | - Nancy Diazgranados
- Office of the Clinical Director, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, United States of America
| | - Vijay A. Ramchandani
- Section on Human Psychopharmacology, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, United States of America
| | - David M. Lovinger
- Laboratory for Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, Maryland, United States of America
| | - Reza Momenan
- Clinical NeuroImaging Research Core, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, United States of America
- * E-mail:
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Lin W, Chen X, Gao YQ, Yang ZT, Yang W, Chen HJ. Hippocampal atrophy and functional connectivity disruption in cirrhotic patients with minimal hepatic encephalopathy. Metab Brain Dis 2019; 34:1519-1529. [PMID: 31363985 DOI: 10.1007/s11011-019-00457-6] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2019] [Accepted: 07/03/2019] [Indexed: 12/21/2022]
Abstract
The hippocampus is a crucial pathological node for minimal hepatic encephalopathy (MHE) and it is associated with various cognitive impairments. Investigations on alterations involving hippocampal morphology and functional connectivity (FC) in MHE are limited. This study aimed to simultaneously evaluate hippocampal volume and FC alterations and their association with cognitive decline in MHE. Twenty-two cirrhotic patients with MHE, 31 cirrhotic patients without MHE (NHE), and 43 healthy controls underwent high-resolution T1-weighted imaging, resting-state functional magnetic resonance imaging, and cognition assessment based on Psychometric Hepatic Encephalopathy Score (PHES). The structural images were preprocessed using a voxel-based morphometry method, during which hippocampal volume was measured. The hippocampal connectivity network was identified using seed-based correlation analysis. Hippocampal volume and FC strength were compared across the three groups and correlated against the PHES results of the cirrhotic patients. Compared to the controls, MHE patients exhibited a significantly lower bilateral hippocampal volume. A slight decrease in hippocampal volume was obtained from NHE to MHE, but it did not reach statistically significance. In addition, the average FC strength of the bilateral hippocampal connectivity network was significantly lower in the MHE patients. In particular, the MHE patients showed a decrease in FC involving the left hippocampus to bilateral posterior cingulate gyrus and left angular gyrus. The MHE patients also showed FC reduction between the right hippocampus and bilateral medial frontal cortex. A progressive reduction in hippocampal FC from NHE to MHE was also observed. The bilateral hippocampal FC strength (but not hippocampal volume) was positively correlated with the PHES results of the cirrhotic patients. Our assessment of MHE patients revealed decreased hippocampal volume, which suggests regional atrophy, and reduced hippocampal connectivity with regions that are primarily involved in the default-mode network, thereby suggesting a functional disconnection syndrome. These alterations reveal the mechanisms underlying cognitive deterioration with disease progression.
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Affiliation(s)
- Weiwen Lin
- Department of Radiology, Fujian Medical University Union Hospital, Fuzhou, 350001, China
| | - Xuhui Chen
- Department of Radiology, Fujian Medical University Union Hospital, Fuzhou, 350001, China
| | | | - Zhe-Ting Yang
- Department of Radiology, Fujian Medical University Union Hospital, Fuzhou, 350001, China
| | - Weizhu Yang
- Department of Interventional Radiology, Fujian Medical University Union Hospital, Fuzhou, 350001, China.
| | - Hua-Jun Chen
- Department of Radiology, Fujian Medical University Union Hospital, Fuzhou, 350001, China.
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Disrupted metabolic and functional connectivity patterns of the posterior cingulate cortex in cirrhotic patients. Neuroreport 2018; 29:993-1000. [DOI: 10.1097/wnr.0000000000001063] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
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Corgiolu S, Barberini L, Suri JS, Mandas A, Costaggiu D, Piano P, Zaccagna F, Lucatelli P, Balestrieri A, Saba L. Resting-state functional connectivity MRI analysis in Human Immunodeficiency Virus and Hepatitis C Virus co-infected subjects. A pilot study. Eur J Radiol 2018; 102:220-227. [PMID: 29685540 DOI: 10.1016/j.ejrad.2018.03.022] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2017] [Revised: 03/13/2018] [Accepted: 03/15/2018] [Indexed: 01/27/2023]
Abstract
BACKGROUND AND PURPOSE Hepatitis C virus (HCV) co-infection's role on cognitive impairment of human immunodeficiency virus (HIV) positive patients is still debated and functional neuroimaging evaluation on this matter is lacking. To provide further insight about HCV's neuro-effects on HIV associated neurocognitive disorder (HAND), we performed a pilot resting state (RS) functional connectivity magnetic resonance imaging (fcMRI) study to find eventual functional connectivity alteration that could reflect HCV related cognitive performance degradation. METHODS Eighteen patients (8 HIV, 10 HIV + HCV), either impaired or not impaired, were assessed with RS fcMRI. A statistic model including cognitive testing results was elaborated during data processing to evaluate brain networks alteration related to actual cognitive status in patients. RESULTS Statistically significant different patterns of connectivity were found: HCV co-infection modified 17 ROIs' connectivity with 45 supra-threshold connections (p-FDR min 0.0022, max 0.0497). ROIs most involved were right pallidum, brainstem, vermian lobules 1-2 and right cerebellar lobule 10. Graph theory analysis did not demonstrate significant difference between networks, but HCV related modifications at ROI's local level were found, with particular involvement of ROIs of frontal lobe, basal ganglia and cerebellum. Increased fronto-striatal dysfunctions have been already reported as consequences of HCV infection and could reflect an additive effect. Cerebellar alterations are associated with HIV and HAND, but not with HCV infection, suggesting a synergic effect of HCV. CONCLUSION Our study demonstrates RS fcMRI can help to understand the interactions between HIV and HCV co-infection, and our preliminary results suggest synergic effects of HCV in HIV-related brain functional modification.
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Affiliation(s)
- Simone Corgiolu
- Department of Radiolgy, AOU of Cagliari, University of Cagliari, Italy.
| | - Luigi Barberini
- Department of Medical Imaging, Section of Medical Physics, AOU of Cagliari, University of Cagliari, Italy
| | - Jasjit S Suri
- AtheroPoint(TM) LLC, Roseville, CA, USA & Global Biomedical Technologies, Inc., Roseville, CA, USA
| | - Antonella Mandas
- Department of Internal Medicine, Section of Geriatrics, AOU of Cagliari, University of Cagliari, Italy
| | - Diego Costaggiu
- Department of Internal Medicine, Section of Geriatrics, AOU of Cagliari, University of Cagliari, Italy
| | - Paola Piano
- Department of Internal Medicine, Section of Geriatrics, AOU of Cagliari, University of Cagliari, Italy
| | - Fulvio Zaccagna
- Department of Radiology, University of Cambridge School of Clinical Medicine, Cambridge, CB2 0QQ, UK
| | - Pierleone Lucatelli
- Department of Radiological, Oncological and Anatomo-Pathological Sciences, Sapienza University of Rome, Rome, Italy
| | | | - Luca Saba
- Department of Radiolgy, AOU of Cagliari, University of Cagliari, Italy
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Altered amygdala and hippocampus effective connectivity in mild cognitive impairment patients with depression: a resting-state functional MR imaging study with granger causality analysis. Oncotarget 2018; 8:25021-25031. [PMID: 28212570 PMCID: PMC5421906 DOI: 10.18632/oncotarget.15335] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2016] [Accepted: 01/09/2017] [Indexed: 12/14/2022] Open
Abstract
Neuroimaging studies have demonstrated that the major depression disorder would increase the risk of dementia in the older with amnestic cognitive impairment. We used granger causality analysis algorithm to explore the amygdala- and hippocampus-based directional connectivity patterns in 12 patients with major depression disorder and amnestic cognitive impairment (mean age: 69.5 ± 10.3 years), 13 amnestic cognitive impairment patients (mean age: 72.7 ± 8.5 years) and 14 healthy controls (mean age: 64.7 ± 7.0 years). Compared with amnestic cognitive impairment patients and control groups respectively, the patients with both major depression disorder and amnestic cognitive impairment displayed increased effective connectivity from the right amygdala to the right lingual and calcarine gyrus, as well as to the bilateral supplementary motor areas. Meanwhile, the patients with both major depression disorder and amnestic cognitive impairment had enhanced effective connectivity from the left superior parietal gyrus, superior and middle occipital gyrus to the left hippocampus, the z values of which was also correlated with the scores of mini-mental state examination and auditory verbal learning test-immediate recall. Our findings indicated that the directional effective connectivity of right amygdala - occipital-parietal lobe – left hippocampus might be the pathway by which major depression disorder inhibited the brain activity in patients with amnestic cognitive impairment.
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Zhong WJ, Zhou ZM, Zhao JN, Wu W, Guo DJ. Abnormal spontaneous brain activity in minimal hepatic encephalopathy: resting-state fMRI study. Diagn Interv Radiol 2017; 22:196-200. [PMID: 26742646 DOI: 10.5152/dir.2015.15208] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
PURPOSE We aimed to assess the abnormality of baseline spontaneous brain activity in minimal hepatic encephalopathy (MHE) by amplitude of low frequency fluctuation (ALFF) and fraction ALFF (fALFF). METHODS A total of 14 MHE patients and 14 healthy controls were included in our study. Both ALFF and fALFF of functional magnetic resonance imaging were calculated for statistical analysis. RESULTS Compared with healthy controls, patients with MHE had significantly decreased ALFF in the bilateral medial prefrontal cortex (MPFC), left superior frontal gyrus, right precentral gyrus, left opercular part of inferior frontal gyrus, left gyrus rectus, bilateral precuneus, and the posterior lobe of right cerebellum; and they had significantly decreased fALFF in the bilateral MPFC, right middle frontal gyrus, right superior temporal gyrus, and the posterior lobe of left cerebellum. CONCLUSION ALFF and fALFF changes in many brain regions demonstrate abnormality of the spontaneous neuronal activity in MHE. Especially the impairment of right precuneus and left MPFC may play a critical role in manifestation of MHE. Changes of ALFF and fALFF in the precuneus and the MPFC can be used as a potential marker for MHE.
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Affiliation(s)
- Wei-Jia Zhong
- Department of Radiology, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
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Chen YC, Xia W, Chen H, Feng Y, Xu JJ, Gu JP, Salvi R, Yin X. Tinnitus distress is linked to enhanced resting-state functional connectivity from the limbic system to the auditory cortex. Hum Brain Mapp 2017; 38:2384-2397. [PMID: 28112466 DOI: 10.1002/hbm.23525] [Citation(s) in RCA: 84] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2016] [Revised: 12/15/2016] [Accepted: 12/15/2016] [Indexed: 02/04/2023] Open
Abstract
The phantom sound of tinnitus is believed to be triggered by aberrant neural activity in the central auditory pathway, but since this debilitating condition is often associated with emotional distress and anxiety, these comorbidities likely arise from maladaptive functional connections to limbic structures such as the amygdala and hippocampus. To test this hypothesis, resting-state functional magnetic resonance imaging (fMRI) was used to identify aberrant effective connectivity of the amygdala and hippocampus in tinnitus patients and to determine the relationship with tinnitus characteristics. Chronic tinnitus patients (n = 26) and age-, sex-, and education-matched healthy controls (n = 23) were included. Both groups were comparable for hearing level. Granger causality analysis utilizing the amygdala and hippocampus as seed regions were used to investigate the directional connectivity and the relationship with tinnitus duration or distress. Relative to healthy controls, tinnitus patients demonstrated abnormal directional connectivity of the amygdala and hippocampus, including primary and association auditory cortex, and other non-auditory areas. Importantly, scores on the Tinnitus Handicap Questionnaires were positively correlated with increased connectivity from the left amygdala to left superior temporal gyrus (r = 0.570, P = 0.005), and from the right amygdala to right superior temporal gyrus (r = 0.487, P = 0.018). Moreover, enhanced effective connectivity from the right hippocampus to left transverse temporal gyrus was correlated with tinnitus duration (r = 0.452, P = 0.030). The results showed that tinnitus distress strongly correlates with enhanced effective connectivity that is directed from the amygdala to the auditory cortex. The longer the phantom sensation, the more likely acute tinnitus becomes permanently encoded by memory traces in the hippocampus. Hum Brain Mapp 38:2384-2397, 2017. © 2017 Wiley Periodicals, Inc.
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Affiliation(s)
- Yu-Chen Chen
- Department of Radiology, Nanjing First Hospital, Nanjing Medical University, 210006, Nanjing, China
| | - Wenqing Xia
- Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, 210006, Nanjing, China
| | - Huiyou Chen
- Department of Radiology, Nanjing First Hospital, Nanjing Medical University, 210006, Nanjing, China
| | - Yuan Feng
- Department of Radiology, Nanjing First Hospital, Nanjing Medical University, 210006, Nanjing, China
| | - Jin-Jing Xu
- Department of Otolaryngology, Nanjing First Hospital, Nanjing Medical University, 210006, Nanjing, China
| | - Jian-Ping Gu
- Department of Vascular and Interventional Radiology, Nanjing First Hospital, Nanjing Medical University, 210006, Nanjing, China
| | - Richard Salvi
- Center for Hearing and Deafness, University at Buffalo, State University of New York, Buffalo, 14214, New York
| | - Xindao Yin
- Department of Radiology, Nanjing First Hospital, Nanjing Medical University, 210006, Nanjing, China
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Zhao Z, Wang X, Fan M, Yin D, Sun L, Jia J, Tang C, Zheng X, Jiang Y, Wu J, Gong J. Altered Effective Connectivity of the Primary Motor Cortex in Stroke: A Resting-State fMRI Study with Granger Causality Analysis. PLoS One 2016; 11:e0166210. [PMID: 27846290 PMCID: PMC5112988 DOI: 10.1371/journal.pone.0166210] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2016] [Accepted: 10/25/2016] [Indexed: 12/16/2022] Open
Abstract
The primary motor cortex (M1) is often abnormally recruited in stroke patients with motor disabilities. However, little is known about the alterations in the causal connectivity of M1 following stroke. The purpose of the present study was to investigate whether the effective connectivity of the ipsilesional M1 is disturbed in stroke patients who show different outcomes in hand motor function. 23 patients with left-hemisphere subcortical stroke were selected and divided into two subgroups: partially paralyzed hands (PPH) and completely paralyzed hands (CPH). Further, 24 matched healthy controls (HCs) were recruited. A voxel-wise Granger causality analysis (GCA) on the resting-state fMRI data between the ipsilesional M1 and the whole brain was performed to explore differences between the three groups. Our results showed that the influence from the frontoparietal cortices to ipsilesional M1 was diminished in both stroke subgroups and the influence from ipsilesional M1 to the sensorimotor cortices decreased greater in the CPH group than in the PPH group. Moreover, compared with the PPH group, the decreased influence from ipsilesional M1 to the contralesional cerebellum and from the contralesional superior parietal lobe to ipsilesional M1 were observed in the CPH group, and their GCA values were positively correlated with the FMA scores; Conversely, the increased influence from ipsilesional M1 to the ipsilesional middle frontal gyrus and middle temporal gyrus were observed, whose GCA values were negatively correlated with the FMA scores. This study suggests that the abnormalities of casual flow in the ipsilesional M1 are related to the severity of stroke-hand dysfunction, providing valuable information to understand the deficits in resting-state effective connectivity of motor execution and the frontoparietal motor control network during brain plasticity following stroke.
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Affiliation(s)
- Zhiyong Zhao
- Shanghai Key Laboratory of Magnetic Resonance, East China Normal University, Shanghai, 200062, China
| | - Xiangmin Wang
- Shanghai Key Laboratory of Magnetic Resonance, East China Normal University, Shanghai, 200062, China
| | - Mingxia Fan
- Shanghai Key Laboratory of Magnetic Resonance, East China Normal University, Shanghai, 200062, China
- * E-mail: (MF); (JJ)
| | - Dazhi Yin
- Institute of Neuroscience, State Key Laboratory of Neuroscience, Key Laboratory of Primate Neurobiology, CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China
| | - Limin Sun
- Department of Rehabilitation, Huashan Hospital, Fudan University, Shanghai, 200040, China
| | - Jie Jia
- Department of Rehabilitation, Huashan Hospital, Fudan University, Shanghai, 200040, China
- * E-mail: (MF); (JJ)
| | - Chaozheng Tang
- Department of Rehabilitation, Huashan Hospital, Fudan University, Shanghai, 200040, China
| | - Xiaohui Zheng
- Shanghai Key Laboratory of Magnetic Resonance, East China Normal University, Shanghai, 200062, China
| | - Yuwei Jiang
- Shanghai Key Laboratory of Magnetic Resonance, East China Normal University, Shanghai, 200062, China
| | - Jie Wu
- Shanghai Key Laboratory of Magnetic Resonance, East China Normal University, Shanghai, 200062, China
| | - Jiayu Gong
- Shanghai Key Laboratory of Magnetic Resonance, East China Normal University, Shanghai, 200062, China
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Chen YC, Feng Y, Xu JJ, Mao CN, Xia W, Ren J, Yin X. Disrupted Brain Functional Network Architecture in Chronic Tinnitus Patients. Front Aging Neurosci 2016; 8:174. [PMID: 27458377 PMCID: PMC4937025 DOI: 10.3389/fnagi.2016.00174] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2016] [Accepted: 06/28/2016] [Indexed: 12/16/2022] Open
Abstract
Purpose: Resting-state functional magnetic resonance imaging (fMRI) studies have demonstrated the disruptions of multiple brain networks in tinnitus patients. Nonetheless, several studies found no differences in network processing between tinnitus patients and healthy controls (HCs). Its neural bases are poorly understood. To identify aberrant brain network architecture involved in chronic tinnitus, we compared the resting-state fMRI (rs-fMRI) patterns of tinnitus patients and HCs. Materials and Methods: Chronic tinnitus patients (n = 24) with normal hearing thresholds and age-, sex-, education- and hearing threshold-matched HCs (n = 22) participated in the current study and underwent the rs-fMRI scanning. We used degree centrality (DC) to investigate functional connectivity (FC) strength of the whole-brain network and Granger causality to analyze effective connectivity in order to explore directional aspects involved in tinnitus. Results: Compared to HCs, we found significantly increased network centrality in bilateral superior frontal gyrus (SFG). Unidirectionally, the left SFG revealed increased effective connectivity to the left middle orbitofrontal cortex (OFC), left posterior lobe of cerebellum (PLC), left postcentral gyrus, and right middle occipital gyrus (MOG) while the right SFG exhibited enhanced effective connectivity to the right supplementary motor area (SMA). In addition, the effective connectivity from the bilateral SFG to the OFC and SMA showed positive correlations with tinnitus distress. Conclusions: Rs-fMRI provides a new and novel method for identifying aberrant brain network architecture. Chronic tinnitus patients have disrupted FC strength and causal connectivity mostly in non-auditory regions, especially the prefrontal cortex (PFC). The current findings will provide a new perspective for understanding the neuropathophysiological mechanisms in chronic tinnitus.
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Affiliation(s)
- Yu-Chen Chen
- Department of Radiology, Nanjing First Hospital, Nanjing Medical University Nanjing, China
| | - Yuan Feng
- Department of Radiology, Nanjing First Hospital, Nanjing Medical University Nanjing, China
| | - Jin-Jing Xu
- Department of Otolaryngology, Nanjing First Hospital, Nanjing Medical University Nanjing, China
| | - Cun-Nan Mao
- Department of Radiology, Nanjing First Hospital, Nanjing Medical University Nanjing, China
| | - Wenqing Xia
- Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University Nanjing, China
| | - Jun Ren
- Department of Radiology, Nanjing First Hospital, Nanjing Medical University Nanjing, China
| | - Xindao Yin
- Department of Radiology, Nanjing First Hospital, Nanjing Medical University Nanjing, China
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Neuropsychological functioning and health-related quality of life: pediatric acute liver failure study group results. J Pediatr Gastroenterol Nutr 2015; 60:75-83. [PMID: 25250681 PMCID: PMC4276462 DOI: 10.1097/mpg.0000000000000575] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVES Pediatric acute liver failure (PALF) is a rare but serious event, with poorly understood functional outcomes. The goal was to determine the prevalence of reduced neuropsychological functioning and health-related quality of life (HRQOL) following PALF. METHODS This multicenter study examined neuropsychological functioning and HRQOL 1 to 6 (median 3.8) years after PALF. Participants ages 6 to 16 (median 9.9) years were recruited from the PALF registry and administered measures of intelligence, visual spatial/visual motor coordination, attention, executive function, depression, and adaptive skills. HRQOL and fatigue were assessed using the Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL 4.0) and PedsQL Multidimensional Fatigue Scale. RESULTS A total of 36 patients participated; 50% were boys and 67% were white. Median age at PALF was 5.6 years. A history of grade 3 or 4 hepatic encephalopathy was reported in 5/36 (14%) participants and 23/36 (64%) received a liver transplant. Visual spatial ability was significantly better than norms (P = 0.009), but motor coordination was worse (P = 0.04). Teachers (P = 0.04 to P < 0.0001) and parents (P = 0.005) reported more executive deficits versus norms, and participants had worse attention (P = 0.02). Participants did not differ significantly from norms on IQ, depression, or adaptive functioning. All of the child self-report PedsQL Generic Core and fatigue scales were significantly lower than a matched healthy sample (P = 0.001 to P < 0.0001) and parent proxy report was lower on the fatigue scales (P = 0.001 to P < 0.0001). CONCLUSIONS Long-term PALF survivors demonstrate average IQ and visual spatial ability, but greater than expected impairments in motor skills, attention, executive function, HRQOL, and fatigue.
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Zhang LJ, Wu S, Ren J, Lu GM. Resting-state functional magnetic resonance imaging in hepatic encephalopathy: current status and perspectives. Metab Brain Dis 2014; 29:569-82. [PMID: 24562590 DOI: 10.1007/s11011-014-9504-9] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2013] [Accepted: 02/06/2014] [Indexed: 02/06/2023]
Abstract
Hepatic encephalopathy (HE) is a neuropsychiatric syndrome which develops in patients with severe liver diseases and/or portal-systemic shunting. Minimal HE, the earliest manifestation of HE, has drawn increasing attention in the last decade. Minimal HE is associated with a series of brain functional changes, such as attention, working memory, and so on. Blood oxygen level dependent (BOLD) functional MRI (fMRI), especially resting-state fMRI has been used to explore the brain functional changes of HE, yielding important insights for understanding pathophysiological mechanisms and functional reorganization of HE. This paper briefly reviews the principles of BOLD fMRI, potential applications of resting-state fMRI with advanced post-processing algorithms such as regional homogeneity, amplitude of low frequency fluctuation, functional connectivity and future research perspective in this field.
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Affiliation(s)
- Long Jiang Zhang
- Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, 305 Zhongshan East Road, Xuanwu District, Nangjing, Jiangsu Province, China, 210002,
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Zhang XD, Zhang LJ, Wu SY, Lu GM. Multimodality magnetic resonance imaging in hepatic encephalopathy: An update. World J Gastroenterol 2014; 20:11262-11272. [PMID: 25170210 PMCID: PMC4145764 DOI: 10.3748/wjg.v20.i32.11262] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2013] [Revised: 01/29/2014] [Accepted: 05/29/2014] [Indexed: 02/06/2023] Open
Abstract
Hepatic encephalopathy (HE) is a neuropsychiatric complication of cirrhosis or acute liver failure. Currently, HE is regarded as a continuous cognitive impairment ranging from the mildest stage, minimal HE to overt HE. Hyperammonaemia and neuroinflammation are two main underlying factors which contribute to the neurological alterations in HE. Both structural and functional impairments are found in the white mater and grey mater involved in HE. Although the investigations into HE pathophysiological mechanism are enormous, the exact pathophysiological causes underlying HE remain controversial. Multimodality magnetic resonance imaging (MRI) plays an important role in helping to understand the pathological process of HE. This paper reviews the up-to-date multimodality MRI methods and predominant findings in HE patients with a highlight of the increasingly important role of blood oxygen level dependent functional MRI.
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A tutorial to identify nonlinear associations in gene expression time series data. Methods Mol Biol 2014; 1164:87-95. [PMID: 24927837 DOI: 10.1007/978-1-4939-0805-9_8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/21/2023]
Abstract
The study of gene regulatory networks is the basis to understand the biological complexity of several diseases and/or cell states. It has become the core of research in the field of systems biology. Several mathematical methods have been developed in the last decade, especially in the analysis of time series gene expression data derived from microarrays and sequencing-based methods. Most of the models available in the literature assumes linear associations among genes and do not infer directionality in these connections or uses a priori biological knowledge to set the directionality. However, in several cases, a priori biological information is not available. In this context, we describe a statistical method, namely nonlinear vector autoregressive model to estimate nonlinear relationships and also to infer directionality at the edges of the network by using the temporal information of the time series gene expression data without a priori biological information.
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Altered modular organization of functional connectivity networks in cirrhotic patients without overt hepatic encephalopathy. BIOMED RESEARCH INTERNATIONAL 2014; 2014:727452. [PMID: 25165713 PMCID: PMC4066720 DOI: 10.1155/2014/727452] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/06/2013] [Revised: 04/06/2014] [Accepted: 04/10/2014] [Indexed: 01/16/2023]
Abstract
Minimal hepatic encephalopathy (MHE) is associated with changes in functional connectivity. To investigate the patterns of modular changes of the functional connectivity in the progression of MHE, resting-state functional magnetic resonance imaging was acquired in 24 MHE patients, 31 cirrhotic patients without minimal hepatic encephalopathy (non-HE), and 38 healthy controls. Newman's metric, the modularity Q value, was maximized and compared in three groups. Topological roles with the progression of MHE were illustrated by intra- and intermodular connectivity changes. Results showed that the Q value of MHE patients was significantly lower than that of controls (P < 0.01) rather than that of non-HE patients (P > 0.05), which was correlated with neuropsychological test scores rather than the ammonia level and Child-Pugh score. Less intrasubcortical connections and more isolated subcortical modules were found with the progression of MHE. The non-HE patients had the same numbers of connect nodes as controls and had more hubs compared with MHE patients and healthy controls. Our findings supported that both intra- and intermodular connectivity, especially those related to subcortical regions, were continuously impaired in cirrhotic patients. The adjustments of hubs and connector nodes in non-HE patients could be a compensation for the decreased modularity in their functional connectivity networks.
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Kullmann S, Giel KE, Teufel M, Thiel A, Zipfel S, Preissl H. Aberrant network integrity of the inferior frontal cortex in women with anorexia nervosa. NEUROIMAGE-CLINICAL 2014; 4:615-22. [PMID: 24936412 PMCID: PMC4053633 DOI: 10.1016/j.nicl.2014.04.002] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/27/2014] [Revised: 04/02/2014] [Accepted: 04/05/2014] [Indexed: 12/30/2022]
Abstract
Neuroimaging studies investigating the neural profile of anorexia nervosa (AN) have revealed a predominant imbalance between the reward and inhibition systems of the brain, which are also hallmark characteristics of the disorder. However, little is known whether these changes can also be determined independent of task condition, using resting-state functional magnetic resonance imaging, in currently ill AN patients. Therefore the aim of our study was to investigate resting-state connectivity in AN patients (n = 12) compared to healthy athlete (n = 12) and non-athlete (n = 14) controls. For this purpose, we used degree centrality to investigate functional connectivity of the whole-brain network and then Granger causality to analyze effective connectivity (EC), to understand directional aspects of potential alterations. We were able to show that the bilateral inferior frontal gyrus (IFG) is a region of special functional importance within the whole-brain network, in AN patients, revealing reduced functional connectivity compared to both healthy control groups. Furthermore, we found decreased EC from the right IFG to the midcingulum and increased EC from the bilateral orbitofrontal gyrus to the right IFG. For the left IFG, we only observed increased EC from the bilateral insula to the left IFG. These results suggest that AN patients have reduced connectivity within the cognitive control system of the brain and increased connectivity within regions important for salience processing. Due to its fundamental role in inhibitory behavior, including motor response, altered integrity of the inferior frontal cortex could contribute to hyperactivity in AN.
We evaluate resting-state functional (FC) and effective (EC) connectivity. We compare anorexia nervosa (AN) patients with healthy controls. AN patients show reduced FC in the inferior frontal gyrus (IFG). AN patients show reduced EC from the IFG and increased EC to the IFG. Altered FC patterns correlate with physical activity.
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Affiliation(s)
- Stephanie Kullmann
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany ; German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany ; Institute of Medical Psychology and Behavioral Neurobiology, Eberhard Karls University, Tübingen, Germany ; fMEG Center, University of Tübingen, Tübingen, Germany
| | - Katrin E Giel
- Institute of Medical Psychology and Behavioral Neurobiology, Eberhard Karls University, Tübingen, Germany
| | - Martin Teufel
- Department of Psychosomatic Medicine and Psychotherapy, Medical University Hospital, Tübingen, Germany
| | - Ansgar Thiel
- Department of Psychosomatic Medicine and Psychotherapy, Medical University Hospital, Tübingen, Germany
| | - Stephan Zipfel
- Institute of Sport Science, University Tübingen, Tübingen, Germany
| | - Hubert Preissl
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany ; German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany ; Institute of Medical Psychology and Behavioral Neurobiology, Eberhard Karls University, Tübingen, Germany ; fMEG Center, University of Tübingen, Tübingen, Germany
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