Effect of repetitive transcranial magnetic stimulation modulating supplementary motor area in stroke rehabilitation: Systematic review of randomized controlled trials

Background: Repetitive transcranial magnetic stimulation (rTMS) is a promising adjunct in stroke rehabilitation, with increasing focus on the supplementary motor area (SMA) for its role in motor and language network reorganization. This systematic review evaluated randomized controlled trials (RCTs) assessing rTMS targeting the SMA or modulating its connectivity to improve motor and language outcomes in adults after ischemic or hemorrhagic stroke. Methods: A comprehensive literature search was performed across PubMed, Web of Science, and Google Scholar, focusing on peer-reviewed RCTs published in English. Studies were eligible if they involved adults with stroke at any recovery stage and assessed rTMS targeting or analyzing the SMA. Two independent reviewers screened records, extracted data, and assessed risk of bias using the Cochrane Risk of Bias 2.0 tool. The review adhered to PRISMA guidelines and was registered in PROSPERO (CRD420251051684). Results: Among 74 screened for full text, five RCTs were included. Across studies, rTMS interventions targeting the SMA or modulating SMA-related networks improved motor and language outcomes in stroke patients. Neuroimaging measures consistently demonstrated increased SMA activation and strengthened SMA-primary motor cortex (M1) connectivity after rTMS, which correlated with clinical improvements. Balance and postural control outcomes showed the most consistent benefits, while upper-limb motor and language improvements varied in magnitude and follow-up duration. Conclusion: Heterogeneity in studies, small sample sizes, and concerns about randomization and reporting limit our ability to draw definitive conclusions. SMA-targeted or network-level rTMS appears to facilitate functional recovery after stroke, supported by neuroimaging evidence of brain network reorganization. Further large, standardized RCTs are necessary to establish optimal protocols, confirm efficacy, and assess long-term outcomes.