The efficacy of low frequency repetitive transcial magnetic stimulation in treating auditory verbal hallucinations in schizophrenia: insights from functional gradient analyses

Background Auditory Verbal Hallucinations (AVH) constitute a prominent feature of schizophrenia. Although low-frequency repetitive transcranial magnetic stimulation (rTMS) has demonstrated therapeutic benefits in ameliorating AVH, the foundation mechanisms of its efficacy necessitate further elucidation. Objective This study investigate the cortical gradient characteristics and their associations with clinical responses in schizophrenia patients with AVH, mediated through 1 Hz rTMS targeting the left temporoparietal junction. Method Functional gradient metrics were employed to examine the hierarchy patterns of cortical organization, capturing whole-brain functional connectivity profiles in patients and controls. Results The 1 Hz rTMS treatment effectively ameliorated the positive symptoms in patients, specifically targeting AVH. Intimal evaluations revealed expanded global gradient distribution patterns and specific principal gradient variations in certain brain regions compared to a control cohort. Following treatment, these divergent global and local patterns showed signs of normalizing. Furthermore, there was observed a closer alignment in between-network dispersion among various networks after treatment, including the somatomotor, attention, and limbic networks, indicating a potential harmonization of brain functionality. Conclusion Low-frequency rTMS induces alternations in principal functional gradient patterns, may serve as imaging markers to elucidate the mechanisms underpinning the therapeutic efficacy of rTMS on AVH in schizophrenia.