Abstract
BACKGROUND: Recent functional magnetic resonance imaging (fMRI) evidence suggests that pre-supplementary motor area (pre-SMA) activity supports language recovery in post-stroke aphasia (PSA). As a key hub within domain-general cognitive networks, the pre-SMA represents a promising target for individualized neuromodulation. While intermittent theta burst stimulation (iTBS) can enhance language recovery, its efficacy may be limited by generalized targeting strategies. OBJECTIVE: This study aims to investigate the efficacy of fMRI-guided, neuronavigated iTBS targeting the individualized pre-SMA for promoting language recovery in subacute PSA and to elucidate its underlying neural mechanisms via functional connectivity (FC) analysis. METHODS: In this single-center, randomized, double-blind, sham-controlled trial, 40 participants with early subacute PSA (1-3 months post-stroke) are allocated to receive either active or sham iTBS targeting the left or right pre-SMA, localized via individualized MRI mapping. Participants will undergo a 2-week intervention, with language and neuroimaging assessments conducted at baseline, immediately post-intervention, and at a 1-month follow-up. Primary outcome measures are the Western Aphasia Battery (WAB). Second outcomes measures will be including the Boston Naming Test (BNT), the Boston Diagnostic Aphasia Examination (BDAE), non-language cognitive assessment (NLCA), alongside functional connectivity analysis from resting-state fMRI. EXPECTED OUTCOMES: We anticipate that this trial demonstrates the efficacy of individualized pre-SMA iTBS in improving language recovery in PSA. Furthermore, we expect to identify treatment-induced neuroplastic changes in functional and structural brain connectivity. The findings could establish a novel precision neuromodulation approach for aphasia rehabilitation by identifying patient-specific biomarkers of treatment response. CLINICAL TRIAL REGISTRATION: https://www.chictr.org.cn/, ChiCTR2500108996.