Because this research is a modification of a previous study that was not obtained, and the intervention method has changed significantly, we are considering withdrawing this study and reapplying.

Impaired insight is a key factor in the conversion of high-risk individuals to schizophrenia, but there is a lack of targeted interventions. We found that an electroencephalogram (EEG) signal reflecting the function of self monitoring was a potential objective marker of impaired insight. And further functional magnetic resonance imaging (fMRI) analysis showed that the functional connectivity between anterior cingulate gyrus (ACC) and medial temporal gyrus (MTG) was related to insight. Studies have shown that ACC theta oscillation is the key to self monitoring, and theta-alpha phase synchronization between frontotemporal is closely related to cognition. Therefore, this project hypothesized that targeted regulation of ACC theta oscillations could promote theta-alpha phase synchronization and functional connectivity between ACC and MTG, thereby improving patients' insight. The first-episode and high-risk subjects were recruited to detect the theta oscillation of ACC, theta-Alpha phase synchronization and functional connectivity between ACC and MTG using EEG-fMRI. Deep transcranial magnetic stimulation was introduced to regulate ACC theta oscillations. The high-risk subjects were followed up for two years. It was estimated that the theta-alpha phase synchronization of ACC-MTG and insight in the active-dTMS group were significantly improved. And the outcome of the high-risk subjects is better. The project develops neuroregulatory techniques for impaired insight of schizophrenia and is expected to provide a solution for this clinical pain point.

The study will conduct randomized and controlled experimental design, including deep transcranial magnetic stimulation (dTMS) and sham stimulation (SH-dTMS). Each included participant will be given informed consent and then randomly assigned to different montage of stimulation. Participants are blind to the dTMS montage. Researchers in this study will include clinical evaluators, laboratory inspectors, dTMS operators, and statistical analysts. Before unblinding, each group of researchers will have no access to the information collected by the other groups. For example, except the dTMS operators, no one knows which stimulus montage any of the participants receive. The sessions of dTMS will be conducted twice daily for 5 consecutive days, and twice sessions of a day will be separated by 3 hours at least. Clinical assessments and laboratory tests will be administered at baseline and at the end of the last session. After the post-intervention tests, first stage unblinding will be conducted. At this moment, dTMS operators will provide the groups of A and B, but no corresponding montage, to the statistical analysts. After analyzing the differences between the two groups, second stage unblinding will be performed and the results of the clinical trial will be further analyzed by revealing the corresponding stimulus montage of each group. This study will be implemented at a single center, the Shanghai Mental Health Center (SMHC).

Inclusion Criteria:

• 14~35 years old;
• Meet the criteria of clinical high risk for psychosis or meet the DSM-V diagnostic criteria for schizophrenia;
• Meeting the following definition of impaired insight;
• Having completed at least six years of primary education;
• Being able to give informed consent, oral or written. Patients under 18 years old give oral consent and their next of kin or legal guardians give written consent.

Exclusion Criteria:

• Participating in any other clinical intervention research;
• Meeting the diagnostic criteria of psychotic disorders (including affective disorders);
• Threshold symptoms are induced by other mental disorders or psychoactive substances;
• Undergoing anti-psychotic medication for more than 2 weeks;
• Being diagnosed as organic brain diseases, or severe somatic diseases;
• Had Experienced traumatic brain injury, and got scores of 7;
• Dementia, or mental retardation (IQ<70);
• Being a condition of scalp infection;
• A pacemaker or other metal implants in the body, pregnancy, or claustrophobia.

Participants are blind to the dTMS montage. Researchers in this study will include clinical evaluators, laboratory inspectors, dTMS operators, and statistical analysis. Before unblinding, each group of researchers will have no access to the information collected by the other groups.