dACC-Targeted Temporal Interference for Negative and Cognitive Symptoms in Schizophrenia

This randomized, double-blind, sham-controlled trial aims to evaluate the efficacy and safety of dorsal anterior cingulate cortex-targeted temporal interference stimulation in individuals with schizophrenia. Participants will be randomly assigned to receive either active or sham stimulation for 10 sessions over two consecutive weeks. The primary outcome is the change in negative symptoms, assessed using the Negative Symptom Subscale of the Positive and Negative Syndrome Scale. Cognitive performance, detailed dimensions of negative symptoms, psychosocial functioning, quality of life, and treatment-related adverse events will also be evaluated. Neuroimaging assessments will be conducted before and after the intervention to explore potential neural mechanisms underlying the clinical effects of temporal interference stimulation.

Inclusion Criteria: * All of the following criteria must be satisfied for enrolment: 1. A confirmed diagnosis of schizophrenia established according to the criteria set forth in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5); 2. Age between 18 and 65 years, regardless of sex, with completion of at least junior secondary education and the capacity to undergo neurocognitive testing; 3. Clinically meaningful negative symptoms, operationalized as a PANSS negative symptom subscale (PANSS-NS) total score ≥ 20 with a rating of ≥ 3 on a minimum of one individual PANSS-NS item ; the PANSS positive symptom subscale score must additionally not exceed 19; 4. Objective cognitive impairment evidenced by an age- and sex-adjusted composite z-score of ≤ -1.0 on the Chinese version of the Brief Assessment of Cognition in Schizophrenia (BACS), reflecting performance at least one standard deviation below normative values derived from Mandarin-speaking populations; 5. Maintenance on an unchanged antipsychotic regimen - with no modification to medication type or dose - for at least 30 days prior to informed consent and continuing throughout the trial; 6. Voluntary agreement to participate, documented by written informed consent following thorough explanation of study objectives and procedures; where applicable, a legally authorized representative may provide or co-sign consent. Exclusion Criteria: * Individuals will be ineligible if any of the following conditions apply: 1. A concurrent psychiatric diagnosis requiring active clinical management, including but not limited to major depressive episode or bipolar disorder, or the presence of a comorbid neurological disorder or serious physical illness; 2. Current or past substance use disorder, encompassing problematic consumption of alcohol or illicit substances; 3. A documented seizure disorder or marked electroencephalographic abnormalities, particularly epileptiform activity; 4. Evidence of structural brain pathology, including organic lesions, prior traumatic brain injury, or previous neurosurgical intervention; 5. Presence of ferromagnetic implants or any other contraindication to MRI or tTIS exposure, including intracranial metallic clips, implanted cardiac devices, or cochlear implants; 6. Current use of glucocorticoids or other pharmacological agents known to meaningfully alter cortical excitability; 7. Prior exposure to any neuromodulatory intervention - including modified electroconvulsive therapy (MECT), repetitive transcranial magnetic stimulation (TMS), or transcranial direct current stimulation (tDCS) - within the 30 days preceding enrolment.