Effects and mechanisms of theta burst stimulation targeting individualized pre-supplementary motor area for post-stroke aphasia: study protocol for a randomized controlled trial

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.