A Randomized Controlled Trial Exploring the Efficacy of Temporal Interference Stimulation for Negative Symptoms and Cognitive Impairment 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.
• All of the following criteria must be satisfied for enrolment:
‣ 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);
⁃ Age between 18 and 65 years, regardless of sex, with completion of at least junior secondary education and the capacity to undergo neurocognitive testing;
⁃ 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;
⁃ 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;
⁃ 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;
⁃ 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.