Cerebellum and basal ganglia connectivity in isolated REM sleep behaviour disorder and Parkinson’s disease: an exploratory study

Abstract

REM sleep behaviour disorder (RBD) is a parasomnia characterised by dream-enacting behaviour with loss of muscle atonia during REM sleep and is a prodromal feature of α-synucleinopathies like Parkinson’s disease, dementia with Lewy bodies, and multiple system atrophy. Although cortical-to-subcortical connectivity is well-studied in RBD, cerebellar and subcortical nuclei reciprocal connectivity is less established. Nonetheless, it could be relevant since RBD pathology involves brainstem structures with an ascending gradient. In this study, we utilised resting-state functional MRI to investigate 13 people with isolated RBD (iRBD), 17 with Parkinson’s disease and 16 healthy controls. We investigated the connectivity between the basal ganglia, thalamus and regions of the cerebellum. The cerebellum was segmented using a functional atlas, defined by a resting-state network-based parcellation, rather than an anatomical one. Controlling for age, we found a significant group difference (F 4,82 = 5.47, p FDR = 0.017) in cerebellar-thalamic connectivity, with iRBD significantly lower compared to both control and Parkinson’s disease. Specifically, cerebellar areas involved in this connectivity reduction were related to the default mode, language and fronto-parietal resting-state networks. Our findings show functional connectivity abnormalities in subcortical structures that are specific to iRBD and may be relevant from a pathophysiological standpoint. Further studies are needed to investigate how connectivity changes progress over time and whether specific changes predict disease course or phenoconversion.

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