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.

Study Overview

• Status: Recruiting
• Conditions: Schizophrenia; Working Memory
• Intervention / Treatment: Device: sham stimulation; Device: transcranial alternating current stimulation

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.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Renrong Wu; Phone Number: 15874179855; Email: wurenrong@csu.edu.cn

Study Locations

• China
  • Hunan
    • Changsha, Hunan, China, 410011
      • Recruiting
      • The second Xiangya Hospital of Central South University
      • Contact: Jimin Zhang; Phone Number: 18738858423; Email: zhangjimin@csu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Sham Comparator: sham group; sham stimulation	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.
Experimental: active group; transcranial alternating current stimulation	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 continuous sine wave output.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Working Memory Accuracy	Assessment of task accuracy on the Sternberg Item Recognition Paradigm (SIRP). Participants are required to judge whether a probe stimulus belongs to a previously memorized set, with memory set sizes of 1 and 5. The outcome is measured as the percentage of correct responses (0-100%) across all trials, with higher scores indicating better working memory performance.	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	Assessment of response speed on the Sternberg Item Recognition Paradigm (SIRP). Participants are required to judge whether a probe stimulus belongs to a previously memorized set, with memory set sizes of 1 and 5. The outcome is measured as the mean response latency for correct responses only, calculated from stimulus onset to the participant's button press, with shorter times indicating faster processing speed.	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

Outcome Measure	Measure Description	Time Frame
Changes in MCCB Performance	Assessment of cognitive function using the MATRICS Consensus Cognitive Battery (MCCB), a standardized cognitive assessment tool designed for schizophrenia and other neuropsychiatric conditions. The MCCB evaluates 9 cognitive domains: attention, information processing speed, verbal learning and memory, visual learning and memory, spatial working memory, reasoning and problem solving, social cognition, executive function, and fine motor skills. The overall cognitive composite score ranges from 20 to 100 (T-score), with higher scores indicating better cognitive performance.	Baseline, on the day after each of the two interventions
Changes in Positive and Negative Symptom Scale (PANSS) Scores	Scores range from 30 to 210, with higher scores indicating more severe positive and negative symptoms.	Before and one week after each of the two interventions.
Changes in Scale for the Assessment of Negative Symptoms (SANS) Scores	Scores range from 0 to 120; higher scores indicate more severe negative symptoms.	Before and one week after each of the two interventions.
Changes in Calgary Depression Scale for Schizophrenia (CDSS) Scores	Scores range from 0 to 27; higher scores indicate more severe affective symptoms.	Before and one week after each of the two interventions.
Changes in Brain Function	Functional magnetic resonance imaging (fMRI), based on blood oxygen level-dependent (BOLD) contrast, can detect changes in blood oxygenation and analyze changes in brain function after intervention.	Baseline, on the day after each of the two interventions.
Changes in Neuroelectrophysiological Signals	Changes in neuroelectrophysiological signals are collected through task-based electroencephalography (EEG).	Baseline, 30 minutes after each of the two interventions.
Changes in 40Hz Auditory Steady-State Response (40Hz-ASSR)	The 40Hz auditory steady-state response recorded by EEG, including evoked power and inter-trial phase coherence, will be measured. The unit of measurement for evoked power is μV², and for coherence is unitless.	Baseline, 30 minutes after each of the two interventions.
Changes in Mismatch Negativity (MMN)	Mismatch negativity amplitude recorded by EEG using an oddball paradigm will be measured. The unit of measurement is microvolts (μV).	Baseline, 30 minutes after each of the two interventions.
Changes in P300 Event-Related Potential	P300 amplitude recorded by EEG using an oddball paradigm will be measured. The unit of measurement is microvolts (μV).	Baseline, 30 minutes after each of the two interventions.
Hallucination and Delusion Visual Analog Scale (HD-VAS) Score	Assessment of acute post-intervention changes in hallucination and delusion severity using a patient-rated visual analog scale (VAS). The scale consists of a 0-100 mm horizontal line, on which participants mark their current symptom severity. The distance (in millimeters) from the left anchor ("no symptoms") to the participant's mark is measured with a ruler. This scale serves as a supplementary measure to the PANSS to capture immediate symptom changes following each intervention. Scores range from 0 to 100 mm, with higher scores indicating more severe hallucinations and delusions.	Within 15 minutes after completion of Session 1; within 15 minutes after completion of Session 2.

Collaborators and Investigators

• Sponsor: Central South University

Study record dates

Study Major Dates

• Study Start (Estimated): July 6, 2026
• Primary Completion (Estimated): October 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: July 2, 2026
• First Submitted That Met QC Criteria: July 8, 2026
• First Posted (Actual): July 14, 2026

Study Record Updates

• Last Update Posted (Actual): July 14, 2026
• Last Update Submitted That Met QC Criteria: July 8, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Schizophrenia; Working Memory; Transcranial Alternating Current Stimulation
• Additional Relevant MeSH Terms: Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Schizophrenia; Therapeutics; Behavioral Disciplines and Activities; Electric Stimulation Therapy; Convulsive Therapy; Psychiatric Somatic Therapies; Electroshock; Psychological Techniques; Transcranial Direct Current Stimulation
• Other Study ID Numbers: LYG20260081

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No