DecNef for AVH in Schizophrenia

The overall objective of the current study is to assess the target engagement and efficacy of active decoded neurofeedback (DecNef) as measured by how closely a participant's brain activity aligns with the desired non-AVH-related activation pattern and improvements in AVH measured via the Auditory Hallucination Rating Scale (AHRS). Dose-response curves of target engagement over sessions will be generated.

Inclusion criteria

• Individuals aged 18 to 55, inclusive at screen
• Capable of understanding the study procedures and willing and able to provide informed consent
• Diagnosed with schizophrenia or schizoaffective disorder
• Taking an antipsychotic medication at a stable dose for at least 4 weeks. All oral and depot antipsychotics are allowable.
• Mean Auditory Hallucination Rating Scale (AHRS) score >2 (moderate) and AHRS Frequency ≥ 4 (hourly AVH: Frequent at least 3 to 6 per hour).
• Meeting the decoder performance criterion, operationalized as ≥ 55% decoding accuracy. Baseline MRI may be repeated once for subthreshold decoder-accuracy at the discretion of the PIs.
• Normal hearing, operationalized as normal conversational hearing.
• Willing to use qualified methods of contraception (listed in section 5.3) for the study duration (for persons of childbearing potential only, unless post-menopausal or surgically sterile).

Exclusion criteria

• Diagnosis of moderate or severe substance use disorder (excluding nicotine) within the previous 90 days
• Positive toxicology screen for any substances of abuse
• Participation in study of investigational medication/device within the past 4 weeks
• Pregnant persons. Persons of child-bearing potential must have a negative urine β-hCG pregnancy test at Visit 1 and Visit 1a (if applicable)
• Any clinically significant or unstable medical illness, condition, or disorder that is anticipated to potentially compromise participant safety during study, including history of seizure, epilepsy in self or first degree relatives, stroke, brain surgery, head injury with loss of consciousness > 1 hour or clear cognitive sequelae, intracranial metal implants, known structural brain lesions.
• Contraindication to MRI scanning, including metal implants or clinically meaningful claustrophobia
• Participants with suicidal ideation with intent or plan (indicated by affirmative answers to items 4 or 5 of the Suicidal Ideation section of the baseline C-SSRS) in the 3 months prior to screening or participants who represent a significant risk of suicide or violence in the opinion of the investigator.
• History of significant violent behavior in the past 3 months, posing a risk of homicide or having symptoms that would be exacerbated by study participation or travel to the site in the opinion of the investigator.