tACS for Working Memory in Schizophrenia

Efficacy and Mechanisms of Transcranial Alternating Current Stimulation in Improving Working Memory in Patients With Schizophrenia

This study is a randomized, single-blind, sham-controlled crossover trial enrolling 30 schizophrenia patients, each receiving one active and one sham tACS session (7-day washout), targeting P3/P4 at individual alpha frequency (2mA, 30min) during a working memory task, with accuracy and reaction time as primary outcomes, alongside EEG and neurophysiological measures, to test the efficacy and mechanisms of individualized alpha-tACS on working memory.

This study is a randomized, single-blind, sham-controlled, crossover exploratory trial that plans to enroll 30 inpatients with schizophrenia, randomized 1:1 into two groups, with all participants receiving one active and one sham tACS session in a crossover manner separated by a 7-day washout. Stimulation targets the parietal P3/P4 sites at individual alpha frequency, with an intensity of 2 mA and a duration of 30 minutes per session, delivered concurrently with a working memory task (SIRP). Primary outcomes are SIRP accuracy and reaction time, with concurrent task-state EEG recording, along with assessments of clinical symptoms, cognitive function, and neurophysiological markers including ASSR, MMN, and P300. The study aims to explore the efficacy and underlying neural mechanisms of individualized alpha-tACS in improving working memory in schizophrenia.

Inclusion Criteria:

• Aged 18-50 years, meeting the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnostic criteria for schizophrenia, confirmed by the Structured Clinical Interview for DSM-5 (SCID-5).
• Spatial span T-score <40 on the MATRICS Consensus Cognitive Battery (MCCB).
• Taking 1-2 antipsychotic medications, with stable dosage for at least 1 week prior to enrollment. No use of mood stabilizers, antidepressants, or excessive benzodiazepines (lorazepam equivalent >2 mg/day). The type and dosage of antipsychotic medications remain unchanged during the treatment period.
• Impaired functioning in daily activities.
• Willing to participate in this study and provide written informed consent.

Exclusion Criteria:

• Previously diagnosed with or comorbid any other DSM-5 mental disorder besides schizophrenia.
• Presence of significant mood symptoms or substance use disorder (other than caffeine and/or tobacco).
• Presence of any contraindication to transcranial alternating current stimulation (tACS).
• Received other forms of electrical or magnetic stimulation therapy within 1 month prior to enrollment.
• History or current presence of any major physical illness, neurological disorder, or traumatic brain injury that may affect brain structure or function.
• Pregnant or breastfeeding women, or women planning to become pregnant during the study period.