PURPOSE In multiple sclerosis (MS), how brain functional changes relate to clinical conditions is still a matter of debate. The aim of this study was to investigate how functional connectivity (FC) reorganization at three different scales, ranging from local to whole brain, is related to tissue damage and disability. METHODS One-hundred-nineteen patients with MS were clinically evaluated with the Expanded Disability Status Scale and the Multiple Sclerosis Functional Composite. Patients and 42 healthy controls underwent a multimodal 3 T MRI, including resting-state functional MRI. RESULTS We identified 16 resting-state networks via independent component analysis and measured within-network, between-network, and whole-brain (global efficiency and degree centrality) FC. Within-network FC was higher in patients than in controls in default mode, frontoparietal, and executive-control networks, and corresponded to low clinical impairment (default mode network versus Expanded Disability Status Scale r = - 0.31, p < 0.01; right frontoparietal network versus Paced Auditory Serial Addition Test r = 0.33, p < 0.01). All measures of between-network and whole-brain FC, except default mode network global efficiency, were lower in patients than in controls, and corresponded to high disability (i.e., basal ganglia global efficiency versus Timed 25-Foot Walk r = - 0.25, p < 0.03; default mode global efficiency versus Expanded Disability Status Scale r = - 0.44, p < 0.001). Altered measures of within-network, between-network, and whole-brain FC were combined in functional indices that were linearly related to disease duration, Paced Auditory Serial Addition Test and lesion load and non-linearly related to Expanded Disability Status Scale. CONCLUSION We suggest that the combined evaluation of functional alterations occurring at different levels, from local to whole brain, could exhaustively describe neuroplastic changes in MS, while increased within-network FC likely represents adaptive compensatory processes, decreased between-network and whole-brain FC likely represent loss of functional network integration consequent to structural disruption.

中文翻译：

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应对多发性硬化症损害的多尺度静息状态功能重组。

目的在多发性硬化症（MS）中，脑功能变化与临床状况的关系仍是一个有争议的问题。这项研究的目的是研究从局部到整个大脑的三种不同规模的功能连接（FC）重组与组织损伤和残疾的关系。方法使用扩展残疾状况量表和多发性硬化功能复合材料对119例MS患者进行临床评估。患者和42名健康对照者接受了包括静息状态功能性MRI在内的多模式3 T MRI。结果我们通过独立的成分分析确定了16个静止状态网络，并测量了网络内，网络间和全脑（全局效率和中心度）FC。在默认模式下，患者的网络内FC高于对照组，额叶前额和执行控制网络，与低临床损害相对应（默认模式网络与扩展残疾状态量表r =-0.31，p <0.01；右侧额叶前额网络与有节奏的听觉串行加法检验r = 0.33，p <0.01）。除默认模式网络全局效率外，所有网络间和全脑FC指标在患者中均低于对照组，并且对应于高度残疾（即，基底神经节全局效率与25步步行定时r =-0.25， p <0.03；默认模式全局效率与扩展残疾状态量表r =-0.44，p <0.001）。网络内，网络间和全脑FC的变化度量结合了与疾病持续时间呈线性关系的功能指标，进行听觉序列加性试验和病灶负荷，与扩展的残疾状态量表非线性相关。结论我们建议，从局部到整个大脑的不同水平发生的功能改变的综合评估可以详尽地描述MS的神经增生性变化，而网络内FC的增加可能代表适应性代偿过程，网络与全脑FC的减少可能表示由于结构中断而导致的功能网络集成丢失。