Effects of non-invasive brain stimulation over the supplementary motor area on motor function in Parkinson's disease: A systematic review and meta-analysis

Background: Motor dysfunction profoundly affects individuals with Parkinson's disease (PD). Non-invasive brain stimulation (NIBS) targeting the supplementary motor area (SMA), a critical region for movement-related processing, offers a promising approach to enhance motor function for PD. Objective: This systematic review and meta-analysis aims to evaluate the efficacy of NIBS over the SMA (SMA-NIBS) in alleviating motor symptoms in PD. Methods: We conducted literature searches in MEDLINE, EMBASE, Physiotherapy Evidence Database, Web of Science, the Chinese National Knowledge Infrastructure, and Scopus. The meta-analysis utilized an inverse variance method and a random-effects model. Subgroup analyses were performed based on stimulation types (e.g., TMS and tDCS), stimulation protocols (e.g., facilitatory and inhibitory stimulation), and medication status during stimulation. Results: Twenty randomized control trials involving 442 individuals with PD were included. Compared to sham stimulation, SMA-NIBS significantly improved motor function as measured by the motor section of Unified Parkinson's Disease Rating Scale (UPDRS-III) (mean differences [MD]: −3.45, 95 % confidence interval [CI]: −5.65 to −1.26). Subgroup analysis revealed that only TMS (MD: −3.62, 95%CI: −6.15 to −1.08), not tDCS (MD: −2.47, 95 % CI: −5.03 to 0.08), has significant effect on motor function. Both facilitatory (MD: −2.59, 95 % CI: −3.37 to −1.82) and inhibitory stimulation (MD: −4.98, 95 % CI: −9.29 to −0.66) significantly improved the UPDRS-III score. Effectiveness was observed only during ON medication. Statistically significant effects of SMA-NIBS were reported on Freezing of Gait Questionnaire, not timed up and go test and walking speed. Conclusion: SMA-NIBS is a promising approach to enhance motor function in PD.