Efficacy and Safety of Temporal Interference Stimulation in Treatment-Resistant Schizophrenia: An Exploratory Study.

Inclusion Criteria: 1. Right-handed male or female participants aged 18 to 65 years, inclusive. 2. Diagnosis of schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), established by a psychiatrist at the attending-physician level or above and confirmed by the Mini International Neuropsychiatric Interview, version 7.0.2 (MINI 7.0.2). 3. Inadequate response to sequential treatment with at least two antipsychotic medications of different chemical classes, each administered at an adequate dose (≥600 mg/day chlorpromazine equivalents) for an adequate duration (≥6 consecutive weeks at a therapeutic dose). 4. Stable dose of antipsychotic medication for at least 4 weeks before enrollment. 5. A score of 4 (moderate) or higher on at least two of the following Positive and Negative Syndrome Scale (PANSS) items: delusions, hallucinatory behavior, suspiciousness/persecution, or unusual thought content. 6. Ability to understand the study procedures, willingness to participate voluntarily and comply with the study procedures, and provision of written informed consent. Exclusion Criteria: 1. Current diagnosis of another major psychiatric disorder other than schizophrenia that, in the investigator's judgment, may confound the diagnosis of schizophrenia or interfere with the assessment of treatment efficacy or safety. 2. Receipt of other neuromodulation treatments, including modified electroconvulsive therapy (MECT), repetitive transcranial magnetic stimulation (rTMS), or transcranial direct current stimulation (tDCS), within the previous 3 months, or previous participation in an interventional clinical trial involving vagus nerve stimulation (VNS) or deep brain stimulation (DBS). 3. A score ≥3 on Item 3 (suicide) of the 17-item Hamilton Depression Rating Scale (HAMD-17), or a score \>3 on any of the following PANSS items: P4 Excitement, G14 Poor Impulse Control, P7 Hostility, or G8 Uncooperativeness. 4. Contraindications to magnetic resonance imaging (MRI), including intracranial metallic implants, implanted cardiac pacemakers, or cochlear implants. 5. Skull defects or fissures, or inability to tolerate stimulation-related adverse effects. 6. Treatment-resistant epilepsy or other serious medical conditions that, in the investigator's judgment, may potentially affect treatment or participation in the study. 7. Pregnancy. 8. Any other condition that, in the investigator's judgment, makes the participant unsuitable for participation in the study.