Bagarinao Epifanio, Kawabata Kazuya, Watanabe Hirohisa, Hara Kazuhiro, Ohdake Reiko, Ogura Aya, Masuda Michihito, Kato Toshiyasu, Maesawa Satoshi, Katsuno Masahisa, Sobue Gen
Department of Integrated Health Sciences, Nagoya University Graduate School of Medicine, Nagoya, Aichi, 461-8673Japan.
Brain & Mind Research Center, Nagoya University, Nagoya, Aichi, 466-8550Japan.
Brain Commun. 2022 Aug 20;4(5):fcac214. doi: 10.1093/braincomms/fcac214. eCollection 2022.
Cognitive and movement processes involved integration of several large-scale brain networks. Central to these integrative processes are connector hubs, brain regions characterized by strong connections with multiple networks. Growing evidence suggests that many neurodegenerative and psychiatric disorders are associated with connector hub dysfunctions. Using a network metric called functional connectivity overlap ratio, we investigated connector hub alterations in Parkinson's disease. Resting-state functional MRI data from 99 patients (male/female = 44/55) and 99 age- and sex-matched healthy controls (male/female = 39/60) participating in our cross-sectional study were used in the analysis. We have identified two sets of connector hubs, mainly located in the sensorimotor cortex and cerebellum, with significant connectivity alterations with multiple resting-state networks. Sensorimotor connector hubs have impaired connections primarily with primary processing (sensorimotor, visual), visuospatial, and basal ganglia networks, whereas cerebellar connector hubs have impaired connections with basal ganglia and executive control networks. These connectivity alterations correlated with patients' motor symptoms. Specifically, values of the functional connectivity overlap ratio of the cerebellar connector hubs were associated with tremor score, whereas that of the sensorimotor connector hubs with postural instability and gait disturbance score, suggesting potential association of each set of connector hubs with the disorder's two predominant forms, the akinesia/rigidity and resting tremor subtypes. In addition, values of the functional connectivity overlap ratio of the sensorimotor connector hubs were highly predictive in classifying patients from controls with an accuracy of 75.76%. These findings suggest that, together with the basal ganglia, cerebellar and sensorimotor connector hubs are significantly involved in Parkinson's disease with their connectivity dysfunction potentially driving the clinical manifestations typically observed in this disorder.
认知和运动过程涉及多个大规模脑网络的整合。这些整合过程的核心是连接枢纽，即与多个网络有强连接的脑区。越来越多的证据表明，许多神经退行性疾病和精神疾病都与连接枢纽功能障碍有关。我们使用一种名为功能连接重叠率的网络指标，研究了帕金森病中连接枢纽的改变。分析中使用了参与我们横断面研究的99例患者（男/女 = 44/55）和99例年龄及性别匹配的健康对照（男/女 = 39/60）的静息态功能磁共振成像数据。我们确定了两组连接枢纽，主要位于感觉运动皮层和小脑，它们与多个静息态网络的连接存在显著改变。感觉运动连接枢纽主要与初级加工（感觉运动、视觉）、视觉空间和基底神经节网络的连接受损，而小脑连接枢纽与基底神经节和执行控制网络的连接受损。这些连接改变与患者的运动症状相关。具体而言，小脑连接枢纽的功能连接重叠率值与震颤评分相关，而感觉运动连接枢纽的功能连接重叠率值与姿势不稳和步态障碍评分相关，这表明每组连接枢纽与该疾病的两种主要形式，即运动不能/强直和静止性震颤亚型之间可能存在关联。此外，感觉运动连接枢纽的功能连接重叠率值在区分患者和对照方面具有高度预测性，准确率为75.76%。这些发现表明，与基底神经节一起，小脑和感觉运动连接枢纽在帕金森病中显著受累，其连接功能障碍可能驱动了该疾病中通常观察到的临床表现。
