The Cerebellum is Involved in Motor Improvements After Repetitive Transcranial Magnetic Stimulation in Parkinson's Disease Patients

Accumulating evidence indicates that repetitive transcranial magnetic stimulation (rTMS) ameliorates motor symptoms in patients with Parkinson's disease (PD); however, patients' responses to rTMS are different. Here, we aimed to explore neural activity changes in patients with PD exhibiting different responses to high-frequency rTMS treatments using functional magnetic resonance imaging (fMRI). We treated 24 patients with PD using 10-session rTMS (10 Hz) over the supplementary motor area (SMA) for 10 days. Resting-state functional magnetic resonance imaging (rs-fMRI), the Unified Parkinson's Disease Rating Scale Part III (UPDRS-III) and other neuropsychological scales were performed at the baseline and endpoint of rTMS treatment. The changes in the fractional amplitude of low-frequency fluctuation (fALFF) were calculated. Significant improvements were observed in motor symptoms, especially in the sub-symptoms of bradykinesia. All the participants were subsequently stratified into responders and non-responders according to the UPDRS-III reduction. We identified increased fALFF values in the left Crus II of the cerebellar hemisphere and bilateral thalamus as responsive signs to rTMS. Furthermore, the motor response to rTMS over the SMA, measured by the reduction in UPDRS-III and bradykinesia scores, was positively associated with increased fALFF values in the left Crus2 of cerebellar hemisphere, left lobule VIIB of cerebellar hemisphere, right lobule VI of the cerebellar hemisphere, and the right postcentral gyrus. These findings provide evidence for the involvement of cerebellar activity in the motor response to rTMS treatment.