Functional Connectivity Alterations Reveal Complex Mechanisms Based on Clinical and Radiological Status in Mild Relapsing Remitting Multiple Sclerosis.
Functional Connectivity Alterations Reveal Complex Mechanisms Based on Clinical and Radiological Status in Mild Relapsing Remitting Multiple Sclerosis.
复制标题
DOI：
10.3389/fneur.2018.00690
复制
发表时间：
2018
影响因子：
3.4
通讯作者：
Mason DF
中科院分区：
文献类型：
--
作者：
Castellazzi G;Debernard L;Melzer TR;Dalrymple-Alford JC;D'Angelo E;Miller DH;Gandini Wheeler-Kingshott CAM;Mason DF
静息态功能磁共振成像（rs-fMRI）为研究多发性硬化（MS）患者在不同疾病阶段的功能重组提供了重要的信息。在这项横断面研究中，我们首先通过rs-fMRI评估了62例轻度残疾（MSSS < 3）的复发缓解型MS（RRMS）患者的总体T2病变负荷（T2 LL）和MS严重程度评分（MSSS）对静息状态网络（RSN）的影响。独立成分分析（伊卡），其次是双重回归分析证实了功能连接（FC）的改变，许多RRMS受试者相比，健康对照组。前默认模式网络（DMNa）和上级楔前叶网络（PNsup）表现出最大的FC减少区域，而感觉运动网络区M1（SMNm 1）和内侧视觉网络（MVN）表现出最大的FC增加区域。为了更好地理解这些改变的性质以及MS功能改变的机制，我们提出了一种基于线性回归的方法，该方法考虑了FC变化及其与T2 LL和MSSS的相关性。根据FC和T2 LL之间相关性的符号，以及与MSSS相关性的符号，我们提出了以下可能的潜在机制来解释改变的FC：（1）MS病变导致的FC减少，（2）“真实”功能性代偿机制，（3a）功能性代偿尝试，（3b）“虚假”功能性代偿，（4a）神经变性，（4 b）症状前状况（损害先于MS临床表现）。我们的数据显示了满足这6个条件中的4个的区域（即，1，2，3b，4 b），支持FC增加具有复杂性质的建议，可能超过试图限制MS进展引起的脑损伤的潜在代偿机制的简单假设。探索RRMS受试者与短病程（MSshort）和RRMS相似的残疾，但较长的病程（MSlong）之间的差异，我们发现，MSshort和MSlong的特点是明显不同的模式FC，主要涉及感觉和认知网络分别。总体而言，这些结果表明，在多个大规模网络中与放射学（T2 LL）和临床（MSSS，疾病持续时间）状态相关的FC改变分析可能为复发性MS演变的病理生理学提供新的见解。
Resting state functional MRI (rs-fMRI) has provided important insights into functional reorganization in subjects with Multiple Sclerosis (MS) at different stage of disease. In this cross-sectional study we first assessed, by means of rs-fMRI, the impact of overall T2 lesion load (T2LL) and MS severity score (MSSS) on resting state networks (RSNs) in 62 relapsing remitting MS (RRMS) patients with mild disability (MSSS < 3). Independent Component Analysis (ICA) followed by dual regression analysis confirmed functional connectivity (FC) alterations of many RSNs in RRMS subjects compared to healthy controls. The anterior default mode network (DMNa) and the superior precuneus network (PNsup) showed the largest areas of decreased FC, while the sensory motor networks area M1 (SMNm1) and the medial visual network (MVN) showed the largest areas of increased FC. In order to better understand the nature of these alterations as well as the mechanisms of functional alterations in MS we proposed a method, based on linear regression, that takes into account FC changes and their correlation with T2LL and MSSS. Depending on the sign of the correlation between FC and T2LL, and furthermore the sign of the correlation with MSSS, we suggested the following possible underlying mechanisms to interpret altered FC: (1) FC reduction driven by MS lesions, (2) “true” functional compensatory mechanism, (3a) functional compensation attempt, (3b) “false” functional compensation, (4a) neurodegeneration, (4b) pre-symptomatic condition (damage precedes MS clinical manifestation). Our data shows areas satisfying 4 of these 6 conditions (i.e., 1,2,3b,4b), supporting the suggestion that increased FC has a complex nature that may exceed the simplistic assumption of an underlying compensatory mechanism attempting to limit the brain damage caused by MS progression. Exploring differences between RRMS subjects with short disease duration (MSshort) and RRMS with similar disability but longer disease duration (MSlong), we found that MSshort and MSlong were characterized by clearly distinct pattern of FC, involving predominantly sensory and cognitive networks respectively. Overall, these results suggest that the analysis of FC alterations in multiple large-scale networks in relation to radiological (T2LL) and clinical (MSSS, disease duration) status may provide new insights into the pathophysiology of relapse onset MS evolution.
登录
查看更多内容
DOI：
10.1098/rstb.2005.1634
发表时间：
2005-05-29
影响因子：
6.3
作者：
Beckmann, CF;DeLuca, M;Smith, SM
通讯作者：
Smith, SM
影响因子：
5.8
作者：
Basile, B.;Castelli, M.;Bozzali, M.
通讯作者：
Bozzali, M.
影响因子：
4.4
作者：
Chard, Declan T.;Jackson, Jonathan S.;Wheeler-Kingshott, Claudia A. M.
通讯作者：
Wheeler-Kingshott, Claudia A. M.
DOI：
10.1073/pnas.0601417103
发表时间：
2006-09-12
影响因子：
11.1
作者：
Damoiseaux, J. S.;Rombouts, S. A. R. B.;Beckmann, C. F.
通讯作者：
Beckmann, C. F.
影响因子：
4.2
作者：
Binnewijzend, Maja A. A.;Schoonheim, Menno M.;Barkhof, Frederik
通讯作者：
Barkhof, Frederik