Dopamine depletion and subcortical dysfunction disrupt cortical synchronization and metastability affecting cognitive function in Parkinson's disease

作者：Linbo Wang, Cheng Zhou, Wei Cheng, Edmund T. Rolls, Peiyu Huang, Ningning Ma, Yuchen Liu, Yajuan Zhang, Xiaojun Guan, Tao Guo, Jingjing Wu, Ting Gao, Min Xuan, Quanquan Gu, Xiaojun Xu, Baorong Zhang, Weikang Gong, Jingnan Du, Wei Zhang, Jianfeng Feng, Minming Zhang · 发表于：Human Brain Mapping · 年份：2021 · DOI：10.1002/hbm.25745 · 被引用次数：25 · 研究领域：Functional Brain Connectivity Studies、Neural dynamics and brain function、Neurological disorders and treatments

Parkinson's disease (PD) is primarily characterized by the loss of dopaminergic cells and atrophy in subcortical regions. However, the impact of these pathological changes on large-scale dynamic integration and segregation of the cortex are not well understood. In this study, we investigated the effect of subcortical dysfunction on cortical dynamics and cognition in PD. Spatiotemporal dynamics of the phase interactions of resting-state blood-oxygen-level-dependent signals in 159 PD patients and 152 normal control (NC) individuals were estimated. The relationships between subcortical atrophy, subcortical-cortical fiber connectivity impairment, cortical synchronization/metastability, and cognitive performance were then assessed. We found that cortical synchronization and metastability in PD patients were significantly decreased. To examine whether this is an effect of dopamine depletion, we investigated 45 PD patients both ON and OFF dopamine replacement therapy, and found that cortical synchronization and metastability are significantly increased in the ON state. The extent of cortical synchronization and metastability in the OFF state reflected cognitive performance and mediates the difference in cognitive performance between the PD and NC groups. Furthermore, both the thalamic volume and thalamocortical fiber connectivity had positive relationships with cortical synchronization and metastability in the dopaminergic OFF state, and mediate the difference in cortical synchroniz...