tACS for Working Memory in Schizophrenia

Official title

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

Overview

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.

Detailed description

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.

Interventions

• Device transcranial alternating current stimulation
  For montage 1, active electrode at P3 (10-10 system), return electrodes at P1, P5, PO3, CP3. For montage 2, active electrode at P4, return electrodes at P2, P6, PO4, CP4. Conductive paste ensures impedance \<10 kΩ. Individual alpha frequency is used, calculated before each session from mean EEG at P3/P4 during SIRP task. Stimulation intensity is 2 mA (peak-to-zero) via electric field modeling. Stimulation is delivered during SIRP task, 30 min total per session (including 15s ramp-up/down), with
• Device sham stimulation
  Sham stimulation provides only a 15-second ramp-up and ramp-down current at the beginning and end of each session to mimic the initial tingling or itching sensation on the scalp produced by real stimulation, but delivers no effective stimulation current during the main phase of the task period.

Primary outcome measures

• Working Memory Accuracy [Time frame: Day 1 (baseline, prior to first intervention); within 15 minutes after Session 1; Day 9 (prior to second intervention, after 7-day washout); within 15 minutes after Session 2.]
• Working Memory Reaction Time [Time frame: Day 1 (baseline, prior to first intervention); within 15 minutes after Session 1; Day 9 (prior to second intervention, after 7-day washout); within 15 minutes after Session 2.]

Secondary outcome measures (10)

• Changes in MCCB Performance [Time frame: Baseline, on the day after each of the two interventions]
• Changes in Positive and Negative Symptom Scale (PANSS) Scores [Time frame: Before and one week after each of the two interventions.]
• Changes in Scale for the Assessment of Negative Symptoms (SANS) Scores [Time frame: Before and one week after each of the two interventions.]
• Changes in Calgary Depression Scale for Schizophrenia (CDSS) Scores [Time frame: Before and one week after each of the two interventions.]
• Changes in Brain Function [Time frame: Baseline, on the day after each of the two interventions.]
• Changes in Neuroelectrophysiological Signals [Time frame: Baseline, 30 minutes after each of the two interventions.]
• Changes in 40Hz Auditory Steady-State Response (40Hz-ASSR) [Time frame: Baseline, 30 minutes after each of the two interventions.]
• Changes in Mismatch Negativity (MMN) [Time frame: Baseline, 30 minutes after each of the two interventions.]
• Changes in P300 Event-Related Potential [Time frame: Baseline, 30 minutes after each of the two interventions.]
• Hallucination and Delusion Visual Analog Scale (HD-VAS) Score [Time frame: Within 15 minutes after completion of Session 1; within 15 minutes after completion of Session 2.]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

China · 1 center

• The Second Xiangya Hospital of Central South University — Changsha

Identifiers

NCT: NCT07701343 · LYG20260081

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗