Efficacy Associated with Repetitive Transcranial Magnetic Stimulation Targeting the Medial Superior Frontal Gyrus in Schizophrenia: A Pilot Randomized Controlled Study

Repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising adjunctive therapy for schizophrenia (SCZ). The medial superior frontal gyrus (mSFG) is a key network hub and a novel therapeutic target. Therefore, this study investigated the clinical and neuroimaging changes associated with left mSFG-targeted rTMS augmentation in SCZ. Patients were prospectively enrolled and randomly assigned to either the Conventional Therapy (CT, n=15) group or the CT combined with a 4-week course of 10Hz rTMS to the left mSFG (rTMS group, n=14). The changes in Positive and Negative Syndrome Scale (PANSS) scores, Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) scores, and bilateral mSFG volume/fractional amplitude of low-frequency fluctuations (fALFF) from pre- to post-treatment were compared within and between groups. Both groups showed significant within-group improvements in PANSS total score and several RBANS domains. The reduction in PANSS total score was significantly greater in the rTMS group compared to the CT group (p=0.049). However, no significant between-group differences were found for PANSS positive/negative subscales or RBANS Total Score change. Within-group analyses revealed volumetric increases in the mSFG bilaterally in the rTMS group and in the right hemisphere in the CT group. However, direct between-group comparisons of the magnitude of volume change (Δ volume) revealed no statistically significant differences for either the left or right mSFG. These structural observations should therefore be considered strictly exploratory. No significant changes in fALFF were detected in either group. In this pilot study, augmentation with left mSFG-targeted rTMS was associated with a greater reduction in overall symptom burden compared to conventional therapy alone and with a bilateral pattern of structural change in the target region. These preliminary findings warrant confirmation in larger, sham-controlled trials.