Cerebellar Network Compensation in Parkinson's Disease: Functional Connectivity Across Motor and Cognitive Circuits

The cerebellum is increasingly recognized as a key contributor to cognitive reserve and network adaptation in Parkinson's disease (PD). However, how cerebello-cortical and cerebello-basal ganglia connectivity reorganizes across disease duration and cognitive status remains incompletely understood.

Resting-state fMRI data from the Parkinson's Progression Markers Initiative were analyzed in 172 individuals with PD. We investigated cerebello-basal ganglia and cerebello-cortical connectivity using ROI-to-ROI and seed-to-voxel pipelines respectively, providing novel insights into both subcortical and cortical effects. Effects of age, disease duration, cognitive status, motor symptom severity, and dopaminergic medication were assessed.

Across all participants, cerebellar lobule VI and vermis VI showed robust positive connectivity with the pallidum, along with high intra-cerebellar coupling. When controlling for dopaminergic medication, lobule V connectivity with the primary motor cortex was reduced. Age was associated with lower cerebello-basal ganglia connectivity widespread across nodes, evident across medication states. Disease duration showed region-specific effects: in cognitively normal PD, longer duration corresponded to stronger lobule V-temporal cortex connectivity and higher Crus I-precentral gyrus connectivity than PD with cognitive dysfunction. Motor symptom severity was not related to connectivity.

Cerebellar connectivity patterns in PD are linked to disease duration and cognitive preservation. Enhanced cerebello-cortical coupling in cognitively normal PD may reflect compensatory network recruitment that diminishes with cognitive decline. These findings position cerebellar networks as candidate markers of compensatory capacity and disease trajectory in PD.