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Cerebellar Network Compensation in Parkinsons Disease: Functional Connectivity Across Motor and Cognitive Circuits

Lin, C.-Y. R.; Magalhaes, T.; Yonce, S. S.; Rampalli, I.; Mahabir, R.; Bernard, J. A.

2026-05-22 neurology
10.64898/2026.05.19.26352927 medRxiv
Show abstract

Introduction. The cerebellum is increasingly recognized as a key contributor to cognitive reserve and network adaptation in Parkinsons disease (PD). However, how cerebellocortical and cerebellobasal ganglia connectivity reorganizes across disease duration and cognitive status remains incompletely understood. Methods. Resting state fMRI data from the Parkinsons Progression Markers Initiative were analyzed in 172 individuals with PD. We investigated cerebellobasal ganglia and cerebellocortical 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. Results. Across all participants, cerebellar lobule VI and vermis VI showed robust positive connectivity with the pallidum, along with high intracerebellar coupling. When controlling for dopaminergic medication, lobule V connectivity with the primary motor cortex was reduced. Age was associated with lower cerebellobasal 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 and temporal cortex connectivity as well as higher Crus I and precentral gyrus connectivity than PD with cognitive dysfunction. Motor symptom severity was not related to connectivity. Conclusions. Cerebellar connectivity patterns in PD are linked to disease duration and cognitive preservation. Enhanced cerebellocortical coupling in cognitively normal PD may reflect compensatory network recruitment that diminishes with cognitive decline.

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