This preliminary, randomized, double-blind, placebo-controlled clinical trial will evaluate frontal gamma coherence neurofeedback in adults with schizophrenia. Thirty participants will be randomly assigned to receive either active neurofeedback or placebo neurofeedback using a study-provided mobile platform. Participants will complete baseline assessments in person at the University of California San Diego, receive training on home use of the neurofeedback platform, and complete twice-weekly 30-minute sessions at home for 12 weeks. Participants will return for midpoint and end-of-treatment assessments to evaluate feasibility, tolerability, cognitive outcomes, and neurophysiological target engagement.

In this preliminary placebo-controlled, double-blind randomized clinical trial (RCT), eligible participants will be randomized (block permutation) to either Active frontal coherence gamma neurofeedback (gcoh-NFB, n = 15) or Placebo neurofeedback (placebo-NFB, n = 15). All participants will present in person to Univ. of Ca. San Diego (UCSD) for Baseline assessments of primary and secondary outcome measures, and will receive training on self-administration of gcoh-NFB from home. All participants will be provided with mobile treatment platform, with instructions to practice gcoh-NFB from home twice weekly (30 minutes per session) for 12 weeks (24 sessions total). Study personnel will reach out to patient by phone and video at least weekly to facilitate gcoh-NFB self administration. Staff will be available by phone and video more frequently, as indicated by participant performance or preference. All participants will return to UCSD for midpoint (Week 6, or after 12 sessions) and end-of-treatment (Week 12, or after 24 session) in person assessments of primary and secondary outcome measures, and maintenance or return of mobile treatment platform. For participants randomized to Active gcoh-NFB, mobile treatment platform presents reinforcement signals coupled in real time to target neurobiological features. For participants randomized to Placebo-NFB, mobile treatment platform presents reinforcement signals recorded previously during active gcoh-NFB sessions from other participants.

Inclusion Criteria:

1. Voluntary informed consent to participate and capacity to consent as measured by the University of California, San Diego Brief Assessment of Capacity to Consent (UBACC1) instrument;
2. Age 18 to 55;
3. Meet DSM-5 criteria for a current diagnosis of schizophrenia or schizoaffective disorder based on a SCID-5 interview and available medical record review;
4. Clinically stable as operationalized by (a) not having been admitted to a psychiatric hospital within the three months prior to assessment, (b) having had no change in antipsychotic medication dosage within four weeks prior to the baseline assessment, and (c) ascertained to be clinically and medically stable by one of the study investigators

Exclusion Criteria:

1. Electroconvulsive therapy within six months of the baseline assessment;
2. Medical conditions that can impact cognition, including self-reported history of seizure disorder; multiple sclerosis; stroke or major vascular disease; HIV/AIDS; brain cancer; prior head injury involving loss of consciousness;
3. Current (but not past) major depression;
4. Substance use disorder other than nicotine or caffeine in the past year;
5. Inability to read or speak English (with corrected vision or hearing if needed);
6. Unable to adequately see or manually manipulate a smartphone, tablet or other mobile device;
7. Uncooperativeness with the laboratory assessment protocol leading to missing data;
8. Color blindness that interferes with assessment;
9. Testing in the past 6 months on the cognitive measures

Individual participant data will not be made publicly available. Because this SBIR-funded project involves translation of a proprietary EEG neurofeedback platform, the scientific data, device-use data, analytic outputs, and platform-related data are expected to include proprietary SBIR/STTR data. BioSignal Solutions LLC will preserve final research datasets and associated documentation internally to support NIH reporting, human-subjects oversight, regulatory development, intellectual-property protection, and scientific publications, as applicable. Aggregate findings may be disseminated through NIH reports, presentations, regulatory communications, and peer-reviewed publications. Any case-by-case sharing of data underlying a publication would be considered only if consistent with SBIR/STTR data rights, intellectual-property strategy, privacy protections, informed consent, IRB determinations, contractual obligations, applicable laws, and award terms.