Cognitive impairment in multiple sclerosis is associated with functional connectivity abnormalities, but the pathological substrates of these abnormalities are not well understood. It has been proposed that resting-state network nodes that integrate information from disparate regions are susceptible to metabolic stress, which may impact functional connectivity. In multiple sclerosis, pathology could increase metabolic stress within axons, damaging the anatomical connections of network regions, and leading to functional connectivity changes. We tested this hypothesis by assessing whether resting state network regions that show functional connectivity abnormalities in people with cognitive impairment also show anatomical connectivity abnormalities. Multimodal MRI and neuropsychological assessments were performed in 102 relapsing remitting multiple sclerosis patients and 27 healthy controls. Patients were considered cognitively impaired if they obtained a z-score of ≤1.5 on ≥2 tests of the Brief Repeatable Battery of Neuropsychological Tests (n=55). Functional connectivity was assessed with Independent Component Analysis of resting state fMRI images, and anatomical connectivity with Anatomical Connectivity Mapping of diffusion-weighted MRI. Exploratory analyses of fractional anisotropy and cerebral blood flow changes were conducted to assess local tissue characteristics. We found significantly decreased functional connectivity in the anterior and posterior default mode networks and significant increases in the right and left frontoparietal networks in cognitively impaired relative to cognitively preserved patients. Networks showing functional abnormalities also showed reduced anatomical connectivity and white matter microstructure integrity as well as reduced local tissue cerebral blood flow. Our results identify key pathological correlates of functional connectivity abnormalities associated with impaired cognitive function in multiple sclerosis, consistent with metabolic dysfunction in functional network regions.

中文翻译：

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认知障碍多发性硬化症患者的同时解剖，生理和网络变化

多发性硬化症的认知障碍与功能连接异常有关，但这些异常的病理学基础尚不十分清楚。已经提出，整合来自不同区域的信息的静止状态网络节点容易受到代谢压力的影响，这可能会影响功能连接性。在多发性硬化症中，病理可能会增加轴突内的代谢压力，破坏网络区域的解剖学连接，并导致功能连接性改变。我们通过评估在认知障碍患者中表现出功能连接异常的静止状态网络区域是否也显示了解剖学连接异常来检验该假设。在102位复发缓解型多发性硬化症患者和27位健康对照者中进行了多模式MRI和神经心理学评估。如果患者在神经心理测验的简短可重复组中进行≥2次测验（n = 55）的z得分≤1.5，则认为患者的认知能力受损。使用静息状态fMRI图像的独立成分分析评估功能连通性，并使用扩散加权MRI的解剖学连通性映射评估解剖学连通性。探索性分析分数各向异性和脑血流量的变化，以评估局部组织特征。我们发现相对于认知保留的患者，认知功能受损的患者在前和后默认模式网络中的功能连通性显着降低，并且在右，左前额叶网络中的显着增加。显示功能异常的网络还显示出降低的解剖学连通性和白质微结构完整性，以及减少的局部组织脑血流量。我们的结果确定了与多发性硬化症认知功能受损相关的功能连接异常的关键病理相关性，与功能性网络区域的代谢功能障碍一致。