tDCS Combined With rTMS for Negative Symptoms of Schizophrenia

Despite major advances in the field of psychopharmacology in recent years, the majority of treated schizophrenia patients retain disabling symptoms, most commonly a variety of negative symptoms. Currently, clinical treatment of schizophrenia remains dominated by pharmacological control. The current use of antipsychotic medications is effective in controlling the positive symptoms of schizophrenia, but has little effect on the negative symptoms. Neuroimaging and neurophysiological studies have shown that negative symptoms are associated with abnormal brain activity in the combined right and left dorsolateral prefrontal and temporoparietal joint regions, and that physical therapy techniques can modulate cortical activity. Therefore, this study aims to investigate the efficacy of transcranial direct current stimulation(tDCS) combined with repetitive transcranial magnetic stimulation(rTMS) on negative symptoms in patients with schizophrenia and to explore possible mechanisms.The double-blind randomized placebo-controlled study comparing active tDCS stimulation combined with active rTMS stimulation, active rTMS stimulation combined with sham tDCS stimulation, and active tDCS stimulation combined with sham rTMS stimulation to sham tDCS stimulation combined with sham rTMS stimulation at 4 weeks of treatment and 2 weeks of follow-up in patients with predominantly negative symptoms with schizophrenia was studied for efficacy. In addition to the primary observation of changes in the Negative Symptom Assessment Scale (SANS), secondary outcomes include changes in Positive and Negative symptom scale (PANSS) total and negative total scores, changes in the MATRICS Consensus Cognitive Battery (MCCB), changes in local brain activity (functional magnetic resonance imaging, fMRI), white matter integrity (diffusion tensor imaging, DTI), changes in laboratory examination indices changes and changes in psycho-behavioral and EEG index.This is the first clinical trial combining tDCS with rTMS for the treatment of schizophrenia patients with predominantly negative symptoms. This study will provide solid evidence for the combination of tDCS with rTMS for the treatment of negative symptoms in schizophrenia. This study will also help to further explore the mechanisms of tDCS combined with rTMS for the treatment of negative symptoms in schizophrenia in terms of imaging and behavior.

Inclusion Criteria:Meets Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) diagnostic classification criteria for schizophrenia.Age 18-60 years old, gender is not limited.Predominantly negative symptoms (PANSS-negative symptom score≥20; or PANSS negative scores are higher than positive scores).Stable psychiatric symptoms (negative symptoms, positive symptoms) for more than 4 weeks or more.No adjustment in the type or dose of antipsychotics taken in the past 1 months and in the next 1 monthsPatients and Guardians agree to participate in this study and sign an informed consent form.Exclusion Criteria:Patients with severe physical illness, infectious diseases and immune system diseases, severe neurological diseases, mental retardation or organic brain diseases.Pregnant or lactating women.Other brain stimulation treatment (ECT, MECT, etc) within past 3 months.History of previous seizures.Those evaluated as unsuitable for tDCS and rTMS and those who do not cooperate with treatment.Additional exclusion criteria for patients participating in the MRI scanning Participants have to fill out a detailed questionnaire covering safety aspects in relation to research in a 3 Tesla magnetic field and MRI environment. These criteria are:MRI incompatible implants in the body (such as cochlear implant, insulin pump, pace maker or other metal implants).Any risk of having metal particles in the eye, due to manual work without proper eye protections.Tattoos containing red pigments.Claustrophobia.The refusal to be informed of structural brain abnormalities that could be detected during the experiment.-