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Functional Reorganization of Motor Subcircuits in Parkinson's disease
Constantina Theofanopoulou1,2,3,4, Neha Bajaj4, Alberto Muñoz Sánchez1,5
1The Rockefeller University, New York, NY, 10065, USA.
None:
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 (n = 58) and neurotypical older adults (n = 24), focusing on regions implicated in internally generated (IG) and externally generated (EG) movement pathways. For our analysis, we leveraged the reproducible NeuroMark independent component template and motor effectorspecific mapping of primary motor cortex (M1). Our results reveal both increased and decreased connectivity patterns in Parkinson's disease: M1 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. Our motor effector-specific analysis of disease severity scores (MDS-UPDRS) 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 M1 connectivity differences may be influenced by these behavioral 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.
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