Objective: To elucidate the role of impaired interactions between the basal ganglia and the cerebellum in the PI development in PD patients.

Background: Postural instability (PI) is a significant risk factor for falls in Parkinson’s disease (PD) and has limited response to dopaminergic therapy. Maintaining balance involves a dynamic interaction between higher-order cognition and the specialized circuits of the cerebellar-basal ganglia network, which are critical for postural stability.

Method: 37 PD patients categorized into PI-positive (Group 1) and PI-negative (Group 2), and 20 age-matched controls underwent comprehensive evaluation. Assessment included the TUG test, a 5-point postural stability scale (0–4), and cognitive screening via MoCA and MMSE. Neuroimaging analysis was performed using rs-fMRI (SPM12/CONN toolbox).

Results: Patients with PI had a longer PD duration, poorer TUG performance and more pronounced cognitive decline (Table). Compared to controls, both PD groups demonstrated increased functional connectivity (FC) within cerebellar and cerebello-thalamic circuits (p≤0,001). While cerebellar-basal ganglia FC was extensively reduced in both PD groups. The cerebellar vermis (regions VI-X), showed altered connectivity with the putamen and caudate, reflecting motor and gait impairments. The decrease in FC was most marked in the 1^st group and correlated with the PI severity and TUG score. Vermis-somatomotor FC was severely impaired in the 1st group, reaching a complete loss of connectivity between several ROIs, whereas the 2^nd group showed upregulated connectivity in these circuits. PD patients with PI exhibited weaker vermis – dorsolateral prefrontal cortex FC compared to 2^nd group, and this reduced connectivity significantly correlated with lower MoCA score.

Conclusion: The upregulated FC within the cerebellum and vermis–somatomotor network, occurring alongside diminished cerebello-basal ganglia FC, likely serves as a homeostatic response to basal ganglia dysfunction. This may represent a critical compensatory strategy for maintaining postural stability during the earlier PD stages.  Deterioration of the connections between the vermis and somatomotor and dorsolateral prefrontal cortex reflects a failure of compensation during the PD progression. This disruption not only reflects cognitive impairment but also appears to be a key factor in the PI development.

Table. Comparative assessment of patient groups

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MDS Abstracts - https://www.mdsabstracts.org/abstract/cerebellar-basal-ganglia-circuitry-in-the-pathogenesis-of-parkinsonian-postural-instability/