Confirmatory Trial of Gamma Neurofeedback to Improve Working Memory in Schizophrenia

NCT07592169 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: R01MH139831
• Study Type: interventional
• Target: 104
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study is a confirmatory, double-blind, placebo-controlled randomized clinical trial (RCT) testing whether gamma EEG neurofeedback (EEG-NFB) improves working memory in adults with schizophrenia or schizoaffective disorder. Participants are randomly assigned to receive either active gamma EEG-NFB (real-time feedback of frontal gamma brain activity) or sham EEG-NFB (false pre-recorded feedback), twice weekly for 12 weeks. Working memory (N-back task), brain gamma coherence, and everyday community functioning are assessed at baseline, mid-treatment, end of treatment, and follow-up.

Conditions

Schizoaffecitve Disorder; SCHIZOPHRENIA 1 (Disorder)

Keywords

schizophrenia; neurofeedback; EEG; gamma oscillations; working memory; randomized controlled trial; n-back; community functioning

Outcome Measures

Primary Outcomes (3)

• N-back 2-back target accuracy (d-prime)

  Working memory performance on the N-back task (2-back condition), analyzed with mixed model repeated measures (MMRM).

  Baseline to Week 12

• Frontal gamma coherence during N-back task

  EEG-derived frontal gamma coherence (30-50 Hz, F3-F4) measured during 2-back task performance.

  Baseline to Week 12

• Independent Living Skills Survey (ILSS) total score

  Functional outcome assessing independent living skills relevant to community functioning.

  Baseline to Week 12

Study Arms (2)

Gamma EEG-NFB

EXPERIMENTAL

Participants receive real-time gamma EEG neurofeedback targeting frontal gamma coherence (F3 and F4 electrodes, 30-50 Hz) via a CGX wireless 32-electrode headset. Each session includes a 1-minute resting baseline followed by two 15-minute training blocks. Positive reinforcement (images and music) is contingent on meeting an individualized gamma coherence threshold. Sessions are twice weekly for 12 weeks (30 total sessions).

Behavioral: EEG Neurofeedback

Sham EEG-NFB

SHAM COMPARATOR

Participants undergo identical procedures to the active arm including EEG electrode placement and the same session structure, twice weekly for 12 weeks. However, the feedback displayed is pre-recorded from prior participants and has no relationship to the participant's own brain activity. Participants and outcome assessors are blinded to group assignment.

Behavioral: EEG Neurofeedback

Interventions

EEG Neurofeedback BEHAVIORAL

Gamma EEG neurofeedback delivered via CGX/Cognionics wireless headset (FDA cleared for research use). Active arm receives real-time gamma coherence feedback; sham arm receives pre-recorded feedback unrelated to own brain activity.

Also known as: EEG NFB

Gamma EEG-NFB; Sham EEG-NFB

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• \. DSM-5 diagnosis of schizophrenia or schizoaffective disorder, confirmed by the Structured Clinical Interview for DSM-5 (SCID-5) 2. Age 18-55 years 3. Clinically stable: no psychiatric hospitalization in the 3 months prior to enrollment 4. No change in antipsychotic medication type or dosage within 4 weeks prior to baseline assessment 5. Ascertained to be clinically and medically stable by a study investigator 6. Does not meet DSM-5 diagnostic criteria for bipolar disorder or current major depressive episode 7. No electroconvulsive therapy (ECT) within 6 months of baseline assessment 8. Able to read and speak English (corrected vision or hearing aids acceptable) 9. Able and willing to provide written informed consent

You may not qualify if:

• \. Self-reported history of seizure disorder 2. Diagnosed with multiple sclerosis 3. History of stroke or major vascular disease, including insulin-dependent diabetes mellitus 4. HIV/AIDS diagnosis 5. Current (not past) major depressive episode 6. Substance use disorder other than nicotine use disorder or caffeine use disorder in the past year 7. Brain cancer (primary or metastatic) 8. Prior head injury involving loss of consciousness 9. Inability to read or speak English 10. Color blindness that interferes with administration of study assessments 11. Neuropsychological or cognitive testing in the past 6 months using the same measures as this study 12. Score on Letter-Number Sequencing greater than 1 standard deviation above the age-normed mean

Sponsors & Collaborators

• University of California, San Diego: lead

MeSH Terms

Conditions

Schizophrenia

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Study Officials

• Fiza Singh, MD

  University of California, San Diego

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Autumn Harris Study Coordinator

CONTACT

858-267-2257; fnlab@health.ucsd.edu

Jason Holden Lab Manager, PhD

CONTACT

858-267-2257; fnlab@health.ucsd.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: May 11, 2026
• First Posted: May 18, 2026
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): November 30, 2029
• Study Completion (Estimated): May 31, 2030
• Last Updated: May 18, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Within 12 months of primary results publication (estimated 2031)
• Access Criteria: De-identified individual participant data and supporting documents will be available to qualified researchers who submit a data access request through the NIMH Data Archive (NDA) at https://nda.nih.gov. Requestors must complete a Data Use Certification (DUC) agreeing to conditions of use including protecting participant confidentiality, not attempting to re-identify participants, and not sharing data outside the approved research team. Access is reviewed and approved by the NDA Data Access Committee.