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However, the impact of these pathological changes on large\u2010scale 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\u2010state blood\u2010oxygen\u2010level\u2010dependent signals in 159 PD patients and 152 normal control (NC) individuals were estimated. The relationships between subcortical atrophy, subcortical\u2013cortical 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 synchronization between the PD and NC groups. In addition, thalamic volume also reflected cognitive performance, and cortical synchronization\/metastability mediated the relationship between thalamic volume and cognitive performance in PD patients. Together, these results highlight that subcortical dysfunction and reduced dopamine levels are responsible for decreased cortical synchronization and metastability, further affecting cognitive performance in PD. This might lead to biomarkers being identified that can predict if a patient is at risk of developing dementia.<\/jats:p>","DOI":"10.1002\/hbm.25745","type":"journal-article","created":{"date-parts":[[2021,12,14]],"date-time":"2021-12-14T10:00:15Z","timestamp":1639476015000},"page":"1598-1610","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Dopamine depletion and subcortical dysfunction disrupt cortical synchronization and metastability affecting cognitive function in Parkinson's disease"],"prefix":"10.1002","volume":"43","author":[{"given":"Linbo","family":"Wang","sequence":"first","affiliation":[{"name":"Institute of Science and Technology for Brain\u2010Inspired Intelligence Fudan University  Shanghai China"},{"name":"Key Laboratory of Computational Neuroscience and Brain\u2010Inspired Intelligence (Fudan University) Ministry of Education  China"},{"name":"MOE Frontiers Center for Brain Science Fudan University 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