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

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Wang, Linbo, Zhou, Cheng, Cheng, Wei, Rolls, Edmund T., Huang, Peiyu, Ma, Ningning, Liu, Yuchen, Zhang, Yajuan, Guan, Xiaojun, Guo, Tao et al.
(2022) Dopamine depletion and subcortical dysfunction disrupt cortical synchronization and metastability affecting cognitive function in Parkinson's disease. Human Brain Mapping, 43 (5). pp. 1598-1610. doi:10.1002/hbm.25745

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Official URL: https://doi.org/10.1002/hbm.25745

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Abstract

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 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.

Item Type: Journal Article
Subjects: B Philosophy. Psychology. Religion > BF Psychology
R Medicine > RC Internal medicine
Divisions: Faculty of Science, Engineering and Medicine > Science > Computer Science
SWORD Depositor: Library Publications Router
Library of Congress Subject Headings (LCSH): Cognition, Cognition -- Data processing, Dopa , Magnetic resonance imaging , Parkinson's disease -- Magnetic resonance imaging , Parkinson's disease
Journal or Publication Title: Human Brain Mapping
Publisher: John Wiley and Sons
ISSN: 1065-9471
Official Date: 1 April 2022
Dates:
DateEvent
1 April 2022Published
14 December 2021Available
29 November 2021Accepted
Volume: 43
Number: 5
Page Range: pp. 1598-1610
DOI: 10.1002/hbm.25745
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Open Access
RIOXX Funder/Project Grant:
Project/Grant IDRIOXX Funder NameFunder ID
2019M662082China Postdoctoral Science Foundationhttp://dx.doi.org/10.13039/501100002858
2021T140599China Postdoctoral Science Foundationhttp://dx.doi.org/10.13039/501100002858
81771216[NSFC] National Natural Science Foundation of Chinahttp://dx.doi.org/10.13039/501100001809
81971577[NSFC] National Natural Science Foundation of Chinahttp://dx.doi.org/10.13039/501100001809
82001767[NSFC] National Natural Science Foundation of Chinahttp://dx.doi.org/10.13039/501100001809
82071997[NSFC] National Natural Science Foundation of Chinahttp://dx.doi.org/10.13039/501100001809
82171888[NSFC] National Natural Science Foundation of Chinahttp://dx.doi.org/10.13039/501100001809
91630314[NSFC] National Natural Science Foundation of Chinahttp://dx.doi.org/10.13039/501100001809
LQ20H180012Natural Science Foundation of Zhejiang Provincehttp://dx.doi.org/10.13039/501100004731
LQ21H180008Natural Science Foundation of Zhejiang Provincehttp://dx.doi.org/10.13039/501100004731
2016YFC1306600National Science and Technology Infrastructure Programhttp://dx.doi.org/10.13039/501100012167
2018SHZDZX01Science and Technology Commission of Shanghai Municipalityhttp://dx.doi.org/10.13039/501100003399
2018SHZDZX01Zheijiang Labhttps://www.zhejianglab.com/en/about/overview/
2018SHZDZX01Science and Technology Commission of Shanghai Municipalityhttp://dx.doi.org/10.13039/501100003399
2020C03020Science and Technology Department of Zhejiang Provincehttp://dx.doi.org/10.13039/501100008990

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