Functional reorganization of motor subcircuits in Parkinson's disease.

Abstract

Parkinson's disease disrupts motor control across multiple body parts, yet the neural mechanisms underlying these impairments remain incompletely defined. We compared resting-state functional connectivity in people with mild-to-moderate Parkinson's disease scanned in the OFF-medication state (n = 58) and neurotypical older adults (n = 24), focusing on regions implicated in internally generated and externally generated movement pathways. For our analysis, we leveraged the reproducible NeuroMark independent component template and motor effector-specific mapping of primary motor cortex. Our results reveal both increased and decreased connectivity patterns in Parkinson's disease: primary motor cortex subregions associated with control of the leg, hand, and larynx showed robust increases in connectivity exclusively with cerebellar territories, particularly Crus II and Lobules VIIIa/VIIIb. The postcentral gyrus (primary somatosensory cortex) showed primarily increased connectivity with cerebellar regions and the insula. In contrast, the caudate nucleus displayed a mixed profile, with increased connectivity to the superior temporal gyrus and decreased connectivity to the superior medial frontal gyrus and cerebellar Crus II. A post hoc brain-behaviour analysis further suggested that reduced connectivity between the caudate and superior medial frontal gyrus may be associated with greater overall disease severity. Our motor effector-specific analysis of disease severity scores in people with Parkinson's disease revealed mild impairments across all categories (leg, hand, larynx) but disproportionately greater hand-related deficits, suggesting that some of the observed primary motor cortex connectivity differences may be influenced by these behavioural asymmetries. These anatomically precise, effector-specific alterations suggest compensatory recruitment of cerebellar circuits in Parkinson's disease and provide a framework for targeting motor subcircuits in rehabilitation, including dance-based interventions.