High-frequency rTMS over supplementary motor or primary motor cortex on reach-to-grasp in Parkinson's disease: A randomised controlled trial.

OBJECTIVES: This study investigated the effects of a single-session of high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) on reach-to-grasp (RTG) performance in Parkinson's disease (PD), comparing stimulation over the supplementary motor area (SMA), primary motor cortex (M1), combined SMA + M1, and sham stimulation. METHODS: Thirty-six individuals with mild-to-moderate PD were randomised into four groups (n = 9/group),each receiving a single 20-minute session of 10-Hz HF-rTMS. RTG performance under both barrier and non-barrier conditions, alongside cortical excitability and inhibition, was evaluated before and after stimulation. RESULTS: Under the non-barrier condition, RTG coordination demonstrated a significant group × time interaction, with improved association time lag only after SMA stimulation (P < 0.05). For RTG planning, the SMA group showed superior gains compared with sham across all conditions. Although no significant between-group differences were found for RTG execution, both the SMA and M1 groups exhibited significant within-group improvements in movement and deceleration times. Combined stimulation produced no additive or synergistic benefits, yielding outcomes comparable to single-site stimulation. All real stimulation groups demonstrated prolonged cortical inhibition. CONCLUSION: The SMA appears to be a superior target for enhancing RTG coordination and planning in PD, potentially acting as a neural bypass for dysfunctional basal ganglia-thalamocortical circuits. The absence of synergy in the combined protocol suggests homeostatic metaplasticity may limit multisite gains, highlighting the SMA as a "temporal orchestrator" and supporting target-specific rTMS tailored to kinematic deficits. SIGNIFICANCE: These findings establish the SMA as a promising target and support HF-rTMS as a viable adjunct therapy for motor rehabilitation in PD.