Objective: To explore the pathogenesis of dyskinesia, the present study was conducted to investigate that how large-scale functional network interactions change dynamically in the temporal domain of Parkinson’s disease (PD) patients with and without levodopa-induced dyskinesia (LID).

Background: LID is one disabling motor complication of chronic levodopa therapy in patients with PD. The precise pathophysiological mechanisms underlying this motor disorder remain largely unclear. Traditional resting state functional connectivity on levodopa-induced dyskinesia is measured with the assumption that intrinsic fluctuations during the MRI scan are stationary. Dynamic resting state functional network connectivity have recently been proposed to capture temporal variations of functional network connectivity throughout MRI scan.

Method: We evaluated 41 PD patients with LID (LID group) and 34 clinically matched PD patients without LID (No-LID group) using dynamic functional network connectivity approach, on and off their levodopa medication. Group spatial independent component analysis, sliding-window approach followed by k-means clusters were used to study the time-varying resting state functional MRI.

Results: The dynamic analysis identified seven networks configured into five discrete dynamic brain states: four less frequent and strongly inter-network connected, State 1-4, and a more frequent, relatively sparsely and weakly intra-network connected, State 5. At OFF phase, no significant differences of fractional windows and dwell time were found in PD patients with and without LID. At ON phase, State 1 occurred more frequently and dwelled longer in LID group compared than No-LID group. When switching from OFF to ON phase, LID group occurred more frequently and dwelled longer in State 2 and occurred less frequently and dwelled shorter in State 3, while No-LID group occurred more often and dwelled longer in State 5. Additionally, correlation analysis demonstrates that more severe dyskinesia correlates with more time spent in State 2 during ON phase.

Conclusion: The present study indicates that more severe dyskinesia was associated with prolonged time spent in in a state dominated by strong interconnections between cognitive executive network and sensorimotor network, visual network, centred on inferior frontal cortex in cognitive executive network.

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