Abnormal intrinsic brain functional network dynamics in Parkinson’s disease

Abstract

Parkinson's disease is a neurodegenerative disorder characterized by nigrostriatal dopamine depletion. Previous studies measuring spontaneous brain activity using resting state functional magnetic resonance imaging have reported abnormal changes in broadly distributed whole-brain networks. Although resting state functional connectivity, estimating temporal correlations between brain regions, is measured with the assumption that intrinsic fluctuations throughout the scan are stable, dynamic changes of functional connectivity have recently been suggested to reflect aspects of functional capacity of neural systems, and thus may serve as biomarkers of disease. The present work is the first study to investigate the dynamic functional connectivity in patients with Parkinson's disease, with a focus on the temporal properties of functional connectivity states as well as the variability of network topological organization using resting state functional magnetic resonance imaging. Thirty-one Parkinson's disease patients and 23 healthy controls were studied using group spatial independent component analysis, a sliding windows approach, and graph-theory methods. The dynamic functional connectivity analyses suggested two discrete connectivity configurations: a more frequent, sparsely connected within-network state (State I) and a less frequent, more strongly interconnected between-network state (State II). In patients with Parkinson's disease, the occurrence of the sparsely connected State I dropped by 12.62%, while the expression of the more strongly interconnected State II increased by the same amount. This was consistent with the altered temporal properties of the dynamic functional connectivity characterized by a shortening of the dwell time of State I and by a proportional increase of the dwell time pattern in State II. These changes are suggestive of a reduction in functional segregation among networks and are correlated with the clinical severity of Parkinson's disease symptoms. Additionally, there was a higher variability in the network global efficiency, suggesting an abnormal global integration of the brain networks. The altered functional segregation and abnormal global integration in brain networks confirmed the vulnerability of functional connectivity networks in Parkinson's disease.

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