Objective: To test the causal relation between cerebellar function and learning in PD.

Background: Neuroimaging studies reveal that people with Parkinson’s disease (PwPD) exhibit increased cerebellar (CB) activity during motor tasks, presumably to compensate for the injured basal ganglia (BG). However, the CB’s compensatory role in enabling motor learning remains uncertain. If compensatory, CB activity must drive BG-driven learning, and its disruption must impair learning. We tested motor learning in PwPD using a reinforcement task while measuring CB activity via transcranial magnetic stimulation (TMS).

Method: PwPD (n = 29|H-Y=1.5±0.5|UPDRS III=9±5) participated in 2 sessions (1-wk apart). In first session under sham stimulation, PwPD performed a reinforcement task [baseline & retention trials:20|perturbation:320 with visual perturbation (25⁰)] with their arm hidden. They received feedback only on trial outcome (changing the target color) enhancing BG contributions. Learning was defined as the difference in reach angles (RA) between the first- & last-10 retention & baseline trials. In second session, learners (n=18) received 1Hz rTMS at 90% of the resting motor threshold, disrupting the CB before the task to examine changes in learning. In contrast, non-learners (n=11) received extra cursor position feedback during the task to enhance CB contributions and facilitate learning.  We assessed CB inhibition (CBI) to the motor cortex (M1) via TMS at baseline, early, and end of perturbation trials. A Test Stimulus (TS) at the M1 dorsal interossei hotspot produced a 1mV motor-evoked potential (MEP). Conditioning Stimulus (CS) to the ipsilateral CB 5ms before TS yielded a CBI-ratio (CBI-ratio=MEP_amplitude (CS-TS) / (TS-only)).

Results: Only 18 PwPD learned the task in the sham condition with significant RA differences (-10⁰±5⁰) between retention and baseline trials. Learners showed higher CBI-ratio at early (0.87±.15) and end (0.77±.18) points versus baseline (0.74±.18), suggesting compensation. CB disruption impaired learning in learners (-1⁰±0.5⁰), whereas additional feedback enabled learning in non-learners (-5⁰±1.4⁰).

Conclusion: This study’s results establish a causal link between CB activity and learning in PwPD. However, the mechanism for compensation is different for learners and non-learners, specifically with the need for extra feedback, warranting further investigation.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/does-the-cerebellum-compensate-to-enable-motor-learning-in-parkinsons-disease/