From the Departments of Neurology (S.A.N., M.C.C., M.K., A.B., A.Z.S., S.E.P., J.S.P.), Radiology (S.A.N., M.C.C., A.Z.S., S.E.P., J.S.P.), Otolaryngology (R.C.P.), Neuroscience (S.E.P., J.S.P.), Psychology (S.E.P.), Physical Therapy (J.S.P.), and Occupational Therapy (J.S.P.), Washington University School of Medicine, St. Louis, MO; University of Rochester Medical Scientist Training Program and Neurosciences Graduate Program (A.E.M.); and Departments of Neurology, Neuroscience, and Pediatrics (J.W.M.), University of Rochester, NY.
Neurology. 2020 Oct 20;95(16):e2246-e2258. doi: 10.1212/WNL.0000000000010791. Epub 2020 Sep 10.
To test the hypothesis that there is shared regional or global functional connectivity dysfunction in a large cohort of patients with isolated focal dystonia affecting different body regions compared to control participants. In this case-control study, we obtained resting-state MRI scans (three or four 7.3-minute runs) with eyes closed in participants with focal dystonia (cranial [17], cervical [13], laryngeal [18], or limb [10]) and age- and sex-matched controls.
Rigorous preprocessing for all analyses was performed to minimize effect of head motion during scan acquisition (dystonia n = 58, control n = 47 analyzed). We assessed regional functional connectivity by computing a seed-correlation map between putamen, pallidum, and sensorimotor cortex and all brain voxels. We assessed significant group differences on a cluster-wise basis. In a separate analysis, we applied 300 seed regions across the cortex, cerebellum, basal ganglia, and thalamus to comprehensively sample the whole brain. We obtained participant whole-brain correlation matrices by computing the correlation between seed average time courses for each seed pair. Weighted object-oriented data analysis assessed group-level whole-brain differences.
Participants with focal dystonia had decreased functional connectivity at the regional level, within the striatum and between lateral primary sensorimotor cortex and ventral intraparietal area, whereas whole-brain correlation matrices did not differ between focal dystonia and control groups. Rigorous quality control measures eliminated spurious large-scale functional connectivity differences between groups.
Regional functional connectivity differences, not global network level dysfunction, contributes to common pathophysiologic mechanisms in isolated focal dystonia. Rigorous quality control eliminated spurious large-scale network differences between patients with focal dystonia and control participants.
检验以下假说，即与对照组相比，患有不同部位局灶性肌张力障碍的大样本患者存在共享的局部或全局功能连接障碍。在这项病例对照研究中，我们获得了闭眼状态下的静息态 MRI 扫描（3 或 4 次 7.3 分钟运行），参与者包括局灶性肌张力障碍患者（颅神经[17]、颈部[13]、喉部[18]或肢体[10]）和年龄及性别匹配的对照组。
对所有分析进行严格的预处理，以最大限度地减少扫描采集过程中的头部运动影响（分析时，肌张力障碍组 58 例，对照组 47 例）。我们通过计算壳核、苍白球和感觉运动皮层与所有脑体素之间的种子相关图来评估区域功能连接。我们基于聚类的基础来评估显著的组间差异。在另一个分析中，我们在皮层、小脑、基底节和丘脑上应用了 300 个种子区域，以全面采样整个大脑。我们通过计算每个种子对的种子平均时间序列之间的相关性来获得参与者的全脑相关矩阵。加权面向对象数据分析评估了全脑水平的组间差异。
与对照组相比，局灶性肌张力障碍患者的纹状体内部和外侧初级感觉运动皮层与腹侧顶内区之间的功能连接降低，而局灶性肌张力障碍组和对照组的全脑相关矩阵无差异。严格的质量控制措施消除了组间虚假的全脑功能连接差异。
局部功能连接差异，而不是全局网络水平的功能障碍，是孤立性局灶性肌张力障碍共同的病理生理机制。严格的质量控制消除了局灶性肌张力障碍患者和对照组之间虚假的全脑网络差异。
