Cerebellar Network Organization in Parkinson's Disease: Functional Connectivity across Motor and Cognitive Circuits

Background The cerebellum is increasingly recognized as a key contributor to cognitive reserve and network organization in Parkinson's disease (PD). However, the relationship of cerebello‐cortical and cerebello‐basal ganglia connectivity with cognitive status and nigrostriatal integrity remains incompletely understood. Methods Resting‐state functional magnetic resonance imaging (fMRI) data from 172 participants with PD in the Parkinson's Precision Medicine Initiative were analyzed. Cerebello‐basal ganglia and cerebello‐cortical connectivity were investigated using region of interest (ROI)‐to‐ROI and seed‐to‐voxel approaches. Cerebellar connectivity was examined in relation to cognitive status, age, disease duration, motor severity, dopaminergic medication exposure, and contralateral putaminal striatal binding ratio (SBR). Results PD participants demonstrated robust positive cerebello‐basal ganglia connectivity, particularly between lobule VI/vermis VI and the pallidum. Greater age was associated with widespread reductions in cerebello‐basal ganglia coupling. Longer disease duration was associated with stronger connectivity within cerebellar and basal ganglia circuits, and among cognitively unimpaired participants, stronger lobule V connectivity with temporal regions. After adjustment for contralateral putaminal SBR, cognitively unimpaired participants generally demonstrated greater connectivity between left cerebellar regions and frontal networks, whereas cognitively impaired participants showed greater connectivity from posterior cerebellar and vermal regions, including regions implicated in cognitive processing, to temporal, parahippocampal, occipital, parietal, and somatosensory regions. Conclusions Cerebellar functional connectivity in PD shows region‐specific differences across cognitive status rather than uniform network loss with cognitive impairment. These findings support further investigation of cerebellar functional connectivity as a candidate biomarker of cognitive resilience and network adaptation in PD.