Abstract

Alterations in brain function in Parkinson’s disease (PD) patients with diphasic dyskinesia have not been investigated. We aimed to explore the alterations in regional brain function. Each of 53 levodopa (LD)-treated PD patients had two resting-state functional magnetic resonance imaging (rs-fMRI) scans in the same morning, before and after taking LD. The regional homogeneity (ReHo) approach was used to reveal local synchronization changes. Two-way factorial repeated measures analysis of covariance, with group as a between-subject factor and LD effect as a within-subject factor, was performed to explore the two main effects and interaction. Interactive analysis was used to show outcomes that combined disease status and LD effect. Spearman’s correlations were used to detect associations between interactive brain regions and severity of dyskinetic symptoms, assessed by the Unified Dyskinesia Rating Scale (UDyRS) scores, along with moderation analyses. There was no significant difference in the main group effect analysis. Significantly different clusters obtained from main LD effect analysis were in left caudate nucleus and putamen. ReHo values decreased in the caudate nucleus and increased in the putamen during the ON state after taking LD. Interaction between group and LD effect was found in left medial superior frontal gyrus (mSFG), where there were the lowest ReHo values, and was negatively correlated with UDyRS scores in the diphasic dyskinetic group during the ON state. The relationship was independent of LD dose. Abnormal local synchronization in the mSFG is closely associated with the development of diphasic dyskinesia in PD patients.

Highlights

  • In levodopa-induced dyskinesia (LID), which is a common motor complication in Parkinson’s disease (PD), levodopa (LD) has been confirmed to be the major contributor to abnormal involuntary movements[1]

  • There was no significant difference in disease duration, UPDRS-III score, Hoehn and Yahr staging scale (H&Y) stage, LD equivalent daily dose (LEDD) or Mini Mental State Examination (MMSE) between PD patients with diphasic dyskinesia and those without dyskinesia

  • This means that after taking antiparkinsonian drugs, there was the same trend towards change of regional homogeneity (ReHo) values in the left caudate nucleus in patients with diphasic dyskinesia (p = 0.061, corrected) as in patients without dyskinesia

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Summary

Introduction

In levodopa-induced dyskinesia (LID), which is a common motor complication in Parkinson’s disease (PD), levodopa (LD) has been confirmed to be the major contributor to abnormal involuntary movements[1]. LID can be subdivided into peak-dose dyskinesia, diphasic dyskinesia, and off-period dystonia[1,2]. Peak-dose dyskinesia is the most common motor complication, followed by diphasic dyskinesia[1]. Diphasic dyskinesia tends to be associated with aberrant function in more brain regions, and is reported to be more troublesome than peak-dose dyskinesia[1]. Several studies have explored the functional changes in relevant brain regions in peak-dose dyskinetic patients[3,4,5,6,7], but to the best of our knowledge, alterations in brain function in patients with diphasic dyskinesia have not been investigated. We used regional homogeneity (ReHo) to explore regional brain pathology in PD patients with diphasic dyskinesia. ReHo is a data-driven method, which can reveal changes in temporal neural activities in different brain regions[8]

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