Reduced regional activity and functional connectivity within sensorimotor network in Parkinson’s patients with restless legs syndrome

Abstract

Background: Restless legs syndrome is an important sleep disturbance in Parkinson’s disease. Restless legs syndrome causes an urge to move the legs accompanying sensations which can be difficult to describe but include aching, burning, tingling, or crawling. However, the underlying pathophysiology of restless legs syndrome in Parkinson’s disease remains unknown and no imaging investigation has been conducted to explore its mechanism to date. Objective: This study is to investigate the brain functional changes in Parkinson’s disease with restless legs syndrome (PD-RLS+) patients using functional magnetic resonance imaging. Methods: Data of functional magnetic resonance imaging were collected from 14 PD-RLS+ patients, 20 Parkinson’s disease without restless legs syndrome (PD-RLS−) patients, as well as 19 normal controls during restless legs syndrome-free periods. Intraregional brain activity was evaluated by regional homogeneity method and compared between each pair of the three groups. Area with significantly altered regional homogeneity between two patient groups was further selected as seed in subsequent functional connectivity analysis. Correlations between clinical variables and the altered regional homogeneity and functional connectivity were then assessed in patient groups. Results: Compared with PD-RLS−, PD-RLS+ had much reduced brain activity in the right precentral gyrus, which was negatively associated with restless legs scores in Parkinson’s disease patients. Comparison between PD-RLS+ and normal controls revealed that brain activities were increased in the left brainstem and reduced in the left lingual, fusiform and inferior occipital gyri, middle cingulate and paracingulate gyri, and supplement motor area. Further functional connectivity analysis between right precentral gyrus and left postcentral/precentral gyri decreased dramatically within PD-RLS+ patients, which were also negatively correlated with restless legs symptoms in patient groups. Conclusion: PD-RLS+ patients showed diminished regional homogeneity and functional connectivity within the precentral and postcentral gyri, which implies that the functional abnormalities in sensorimotor network may disrupt the lateral pain pathway, contributing to restless legs syndrome symptoms in Parkinson’s disease patients. This may provide imaging evidence to explore the pathophysiology of Parkinson’s disease-related restless legs syndrome.