Impact of low-frequency repetitive transcranial magnetic stimulation on functional network connectivity in schizophrenia patients with auditory verbal hallucinations

Auditory verbal hallucinations (AVH) are a key symptom of schizophrenia. Low-frequency repetitive transcranial magnetic stimulation (rTMS) has shown potential in the treatment of AVH. However, the underlying neural mechanismof rTMS in the treatment of AVH remains largely unknown. In this study, we used a static and dynamic functional network connectivity approach to investigate the connectivity changes among the brain functional networks in schizophrenia patients with AVH receiving 1 Hz rTMS treatment. The static functional network connectivity (sFNC) analysis revealed that patients at baseline had significantly decreased connectivity between the default mode network (DMN) and language network (LAN), and within the executive control network (ECN) as well as within the auditory network (AUD) compared to controls. However, the abnormal network connectivity patterns were normalized or restored after rTMS treatment in patients, instead of increased connectivity between the ECN and LAN, as well as within the AUD. Moreover, the dynamic functional network connectivity (dFNC) analysis showed that the patients at baseline spent more time in this state that was characterized by strongly negative connectivity between the ENC and AUD, as well as within the AUD relative to controls. While after rTMS treatment, the patients showed a higher occurrence rate in this state that was characterized by strongly positive connectivity among the LAN, DMN, and ENC, as well as within the ECN. In addition, the altered static and dynamic connectivity properties were associated with reduced severity of clinical symptoms. Both sFNC and dFNC analyses provided complementary information and suggested that low-frequency rTMS treatment could induce intrinsic functional network alternations and contribute to improvements in clinical symptoms in patients with AVH.