An efficient network such as the human brain features a combination of global integration of information, driven by long-range connections, and local processing involving short-range connections. Whether these connections are equally damaged in multiple sclerosis is unknown, as is their relevance for cognitive impairment and brain function. Therefore, we cross-sectionally investigated the association between damage to short- and long-range connections with structural network efficiency, the functional connectome and cognition. From the Amsterdam multiple sclerosis cohort, 133 patients (age = 54.2 ± 9.6) with long-standing multiple sclerosis and 48 healthy controls (age = 50.8 ± 7.0) with neuropsychological testing and MRI were included. Structural connectivity was estimated from diffusion tensor images using probabilistic tractography (MRtrix 3.0) between pairs of brain regions. Structural connections were divided into short- (length < quartile 1) and long-range (length > quartile 3) connections, based on the mean distribution of tract lengths in healthy controls. To determine the severity of damage within these connections, (i) fractional anisotropy as a measure for integrity; (ii) total number of fibres; and (iii) percentage of tract affected by lesions were computed for each connecting tract and averaged for short- and long-range connections separately. To investigate the impact of damage in these connections for structural network efficiency, global efficiency was computed. Additionally, resting-state functional connectivity was computed between each pair of brain regions, after artefact removal with FMRIB's ICA-based X-noiseifier. The functional connectivity similarity index was computed by correlating individual functional connectivity matrices with an average healthy control connectivity matrix. Our results showed that the structural network had a reduced efficiency and integrity in multiple sclerosis relative to healthy controls (both P < 0.05). The long-range connections showed the largest reduction in fractional anisotropy (z = -1.03, P < 0.001) and total number of fibres (z = -0.44, P < 0.01), whereas in the short-range connections only fractional anisotropy was affected (z = -0.34, P = 0.03). Long-range connections also demonstrated a higher percentage of tract affected by lesions than short-range connections, independent of tract length (P < 0.001). Damage to long-range connections was more strongly related to structural network efficiency and cognition (fractional anisotropy: r = 0.329 and r = 0.447. number of fibres r = 0.321 and r = 0.278. and percentage of lesions: r = -0.219; r = -0.426, respectively) than damage to short-range connections. Only damage to long-distance connections correlated with a more abnormal functional network (fractional anisotropy: r = 0.226). Our findings indicate that long-range connections are more severely affected by multiple sclerosis-specific damage than short-range connections. Moreover compared to short-range connections, damage to long-range connections better explains network efficiency and cognition.

中文翻译：

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长距离连接受到更严重的损害，并且与多发性硬化症的认知相关。


像人脑这样的高效网络具有由远程连接驱动的全局信息整合和涉及短程连接的本地处理的组合。这些连接在多发性硬化症中是否同样受到损害尚不清楚，它们与认知障碍和大脑功能的相关性也是未知的。因此，我们横断面研究了短程和长程连接损伤与结构网络效率、功能连接组和认知之间的关联。来自阿姆斯特丹多发性硬化症队列，纳入了 133 名长期患有多发性硬化症的患者（年龄 = 54.2 ± 9.6）和 48 名接受神经心理学测试和 MRI 的健康对照者（年龄 = 50.8 ± 7.0）。使用概率纤维束成像 (MRtrix 3.0) 从成对的大脑区域之间的扩散张量图像估计结构连接性。根据健康对照中束长度的平均分布，结构连接分为短程（长度 < 四分位数 1）和长程（长度 > 四分位数 3）连接。为了确定这些连接内损坏的严重程度，（i）分数各向异性作为完整性的衡量标准； (ii) 纤维总数； (iii)计算每个连接束受病变影响的束的百分比，并分别对短距离和长距离连接进行平均。为了研究这些连接的损坏对结构网络效率的影响，计算了全局效率。此外，在使用 FMRIB 的基于 ICA 的 X 噪声器去除伪影后，计算了每对大脑区域之间的静息态功能连接。 通过将个体功能连接矩阵与平均健康控制连接矩阵相关联来计算功能连接相似性指数。我们的结果表明，相对于健康对照，多发性硬化症中结构网络的效率和完整性均降低（均为 P < 0.05）。长程连接显示分数各向异性 (z = -1.03, P < 0.001) 和纤维总数 (z = -0.44, P < 0.01) 的最大减少，而在短程连接中仅分数各向异性受到影响（z = -0.34，P = 0.03）。长距离连接还表明，与短距离连接相比，受病变影响的束的比例更高，与束长度无关（P < 0.001）。远程连接的损伤与结构网络效率和认知密切相关（各向异性分数：r = 0.329 和 r = 0.447。纤维数量 r = 0.321 和 r = 0.278。损伤百分比：r = -0.219；r = -0.426，分别）比短距离连接的损坏。只有长距离连接的损坏与更异常的功能网络相关（分数各向异性：r = 0.226）。我们的研究结果表明，长距离连接比短距离连接更容易受到多发性硬化症特异性损伤的影响。此外，与短程连接相比，远程连接的损坏更好地解释了网络效率和认知。