4.: Exploring the neural circuitry of rapid eye movement sleep behaviour disorder in Parkinson’s disease using functional MRI

Abstract

Rapid eye movement (REM) sleep behaviour disorder (RBD) is observed in over half of all Parkinson’s disease (PD) patients. The development of this symptom has also been associated with cognitive dysfunction, freezing of gait and visual hallucinations. These associations raise the possibility of common neural underpinnings. This study aims to explore impairments in neural circuitry of RBD, identified electrophysiologically within a cohort of patients with PD. Patients with and without RBD will be compared utilizing resting state functional MRI. Thirty one patients with PD underwent neurological, sleep assessment and resting state functional MRI. The REM atonia index was derived for all participants as an objective measure of REM sleep without atonia and patients with a REM atonia index less than 0.9 were deemed positive for RBD. RBD positive and negative patients were compared between regions of interests (ROI), using correlations between the blood-oxygen-level dependent time course in 50 Brodmann areas, along with 4 mm bilateral ROI centered on the putamen, the caudate and the ventral striatum. Patients identified to be RBD positive showed a significant decrease in the connectivity between the left putamen and the dorsolateral prefrontal cortex bilaterally. Connectivity between the left putamen and the right frontal eye fields was reduced. Similarly there was reduced connectivity between the right caudate and the right frontal eye fields. Patients with RBD and PD in this study displayed impaired connectivity within frontostriatal networks subserving cognition and cognitive control. The cortical regions that were “disconnected” in the RBD positive patients have also been implicated in the pathophysiology of freezing of gait and visual hallucinations, suggesting that commonalities between these disorders may reflect the breakdown of effective communication within neural networks underlying cognitive control. Identifying a similar pattern of connectivity using resting state MRI could be used to predict PD in at risk populations and if identified in PD cohorts, could predict attributes associated with significant comorbidity and burden to the community.