Dataset Information

Altered Functional Connectivity in White and Gray Matter in Patients With Multiple Sclerosis.

ABSTRACT: Background: Functional magnetic resonance imaging (fMRI) has been widely used to assess neural activity changes in gray matter (GM) in patients with multiple sclerosis (MS); however, brain function alterations in white matter (WM) relatively remain under-explored. Purpose: This work aims to identify the functional connectivity in both the WM and the GM of patients with MS using fMRI and the correlations between these functional changes and cumulative disability as well as the lesion ratio. Materials and Methods: For this retrospective study, 37 patients with clinically definite MS and 43 age-matched healthy controls were included between 2010 and 2014. Resting-state fMRI was performed. The WFU Pick and JHU Eve atlases were used to define 82 GM and 48 WM regions in common spaces, respectively. The time courses of blood oxygen level-dependent (BOLD) signals were averaged over each GM or WM region. The averaged time courses for each pair of GM and WM regions were correlated. All 82 × 48 correlations for each subject formed a functional correlation matrix. Results: Compared with the healthy controls, the MS patients had a decreased temporal correlation between the WM and the GM regions. Five WM bundles and four GM regions had significantly decreased mean correlation coefficients (CCs). More specifically, the WM functional alterations were negatively correlated with the lesion volume in the bilateral fornix, and the mean GM-averaged CCs of the WM bundles were inversely correlated with the lesion ratio (r = -0.36, P = 0.012). No significant correlation was found between WM functional alterations and the paced auditory serial addition test score, Expanded Disease Severity Scale score, and Multiple Sclerosis Severity Score (MSSS) in MS. Conclusions: These findings highlight current gaps in our knowledge of the WM functional alterations in patients with MS and may link WM function with pathological mechanisms.

SUBMITTER: Huang J

PROVIDER: S-EPMC7738428 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Altered Functional Connectivity in White and Gray Matter in Patients With Multiple Sclerosis.

Huang Jing J Li Muwei M Li Qiongge Q Yang Zhipeng Z Xin Bowen B Qi Zhigang Z Liu Zheng Z Dong Huiqing H Li Kuncheng K Ding Zhaohua Z Lu Jie J

Frontiers in human neuroscience 20201202

<b>Background</b>: Functional magnetic resonance imaging (fMRI) has been widely used to assess neural activity changes in gray matter (GM) in patients with multiple sclerosis (MS); however, brain function alterations in white matter (WM) relatively remain under-explored. <b>Purpose</b>: This work aims to identify the functional connectivity in both the WM and the GM of patients with MS using fMRI and the correlations between these functional changes and cumulative disability as well as the lesio ...[more]

PMID: 33343314

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Project description:T cells are considered pivotal in the pathology of multiple sclerosis (MS), but their function and antigen specificity are unknown. To unravel the role of T cells in MS pathology, we performed a comprehensive analysis on T cells recovered from paired blood, cerebrospinal fluid (CSF), normal-appearing white matter (NAWM) and white matter lesions (WML) from 27 MS patients with advanced disease shortly after death. The differentiation status of T cells in these compartments was determined by ex vivo flow cytometry and immunohistochemistry. T-cell reactivity in short-term T-cell lines (TCL), generated by non-specific stimulation of T cells recovered from the same compartments, was determined by intracellular cytokine flow cytometry. Central memory T cells predominated in CSF and effector memory T cells were enriched in NAWM and WML. WML-derived CD8+ T cells represent chronically activated T cells expressing a cytotoxic effector phenotype (CD95L and granzyme B) indicative for local antigenic stimulation (CD137). The same lesions also contained higher CD8+ T-cell frequencies expressing co-inhibitory (TIM3 and PD1) and co-stimulatory (ICOS) T-cell receptors, yet no evidence for T-cell senescence (CD57) was observed. The oligoclonal T-cell receptor (TCR) repertoire, particularly among CD8+ T cells, correlated between TCL generated from anatomically separated WML of the same MS patient, but not between paired NAWM and WML. Whereas no substantial T-cell reactivity was detected towards seven candidate human MS-associated autoantigens (cMSAg), brisk CD8+ T-cell reactivity was detected in multiple WML-derived TCL towards autologous Epstein-Barr virus (EBV) infected B cells (autoBLCL). In one MS patient, the T-cell response towards autoBLCL in paired intra-lesional TCL was dominated by TCRV?2+CD8+ T cells, which were localized in the parenchyma of the respective tissues expressing a polarized TCR and CD8 expression suggesting immunological synapse formation in situ. Collectively, the data suggest the involvement of effector memory cytotoxic T cells recognizing antigens expressed by autoBLCL, but not the assayed human cMSAg, in WML of MS patients.

Project description:BackgroundObesity is associated with decreased brain gray- (GM) and white-matter (WM) volumes in regions. Laparoscopic sleeve gastrectomy (LSG) is an effective bariatric surgery associated with neuroplastic changes in patients with obesity at 1 month postLSG.ObjectiveTo investigate whether LSG can induce sustained neuroplastic recovery of brain structural abnormalities, and whether structural changes are accompanied by functional alterations.SettingUniversity hospital, longitudinal study.MethodsStructural magnetic resonance imaging and voxel-based morphometry analysis were employed to assess GM/WM volumes in 30 obese participants at preLSG and 1 and 3 months postLSG. One-way analysis of variance modeled time effects on GM/WM volumes, and then alterations in resting-state functional connectivity (RSFC) were assessed.ResultsSignificant time effects on GM volumes were in caudate (F = 11.20), insula (INS; F = 10.11), posterior cingulate cortex (PCC; F = 13.32), and inferior frontal gyrus (F = 12.18), and on WM volumes in anterior cingulate cortex (F = 15.70), PCC (F = 15.56), and parahippocampus (F = 17.96, PFDR < .05). Post hoc tests showed significantly increased GM volumes in caudate (mean change ± SEM .018 ± .005 and P = .001, .031 ± .007 and P < .001), INS (.027 ± .008 and P = .003, .043 ± .009 and P < .001), and PCC (.008 ± .004 and P = .042, .026 ± .006 and P < .001), and increased WM volumes in anterior cingulate cortex (.029 ± .006 and P < .001, .041 ± .008 and P < .001), PCC (.017 ± .004 and P < .001, .032 ± .006 and P < .001), and parahippocampus (.031 ± .008 and P =.001, .075 ± .013 and P < .001) at 1 and 3 months postLSG compared with preLSG. Significant increases in GM volumes were in caudate (.013 ± .006 and P = .036), PCC (.019 ± .006 and P = .006), and inferior frontal gyrus (.019 ± .005 and P = .001), and in WM volumes in anterior cingulate cortex (.012 ± .005 and P = .028), PCC (.014 ± .006 and P = .017), and parahippocampus (.044 ± .014 and P = .003) at 3 relative to 1 month postLSG. GM volumes in INS and PCC showed a positive correlation at 1 (r = .57, P = .001) and 3 months postLSG (r = .55, P = .001). GM volume in INS and PCC were positively correlated with RSFC of INS-PCC (r = .40 and P = .03, r = .55 and P = .001) and PCC-INS (r = .37 and P = .046, r = .57 and P < .001) at 1 month postLSG. GM volume in INS was also positively correlated with RSFC of INS-PCC (r = .44, P = .014) and PCC-INS (r = .38, P = .037) at 3 months postLSG.ConclusionLSG induces sustained structural brain changes, which might mediate long-term benefits of bariatric surgery in weight reduction. Associations between regional GM volume and RSFC suggest that LSG-induced structural changes contribute to RSFC changes.

Dataset Information

Altered Functional Connectivity in White and Gray Matter in Patients With Multiple Sclerosis.

Publications

Altered Functional Connectivity in White and Gray Matter in Patients With Multiple Sclerosis.

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