Rt-fMRI Neurofeedback and AH in Schizophrenia

Auditory hallucinations in schizophrenia are one of the major symptoms of this disease and a major source of psychological discomfort. They are often difficult or impossible to treat with existing methods. This study will test the use of real-time fMRI neurofeedback to mitigate auditory verbal hallucinations in patients whose hallucinations are resistant to medication. Half of the patients will receive real time fMRI neurofeedback from a brain region involved in auditory hallucinations and half will receive it from motor cortex.

Auditory verbal hallucinations (AH) have long been a hallmark of schizophrenia (SZ) and are one of its major diagnostic features. They are difficult to manage with existing treatment options. Here, neurofeedback will be used to regulate the superior temporal gyrus (STG) activation which will not only lead to activation changes in the STG, but also to changes in the default mode network (DMN). The investigators will study SZ patients with medication resistant AH in the rt-fMRI intervention arm and in the sham-rt-fMRI arm. In both arms, the task and the rt-fMRI session structure will be identical. The SZ-intervention group will receive feedback from the STG while SZ-sham group will receive feedback from the motor cortex. In addition, 2 functional fMRI tasks will examine the effect of rt-fMRI neurofeedback and of sham-rt-fMRI on brain response. The investigators will randomly assign 48 SZ patients to either SZ-intervention (n=24) or SZ-sham-rtfMRI (n=24). The STG targeted neurofeedback is predicted to bring changes in brain regions involved in AH (STG and DMN) in SZ-intervention group only. The R61 GO criterion will be BOLD signal reduction in the STG, and resting state connectivity reduction between MPFC-PCC, post rt-fMRI-feedback in SZ-intervention group.

In the R61 phase of the study,changes in a target brain region(s) will be demonstrated after the rt-fMRI based neurofeedback session.

Inclusion Criteria: a diagnosis of schizophrenia or schizoaffective disorder based on SCID interview (DSM-5) and the presence of auditory hallucinations (PANSS, item 3, score ≥4) with frequency of AH being at least once daily; age between 18-55 years; estimated IQ of above 80 as measured by WASI; English as the primary language; right-handed as determined by the Edinburgh Handedness Inventory (scoring + 60; Oldfield, 1971); an ability and desire to participate in the testing program as explained by an experimenter and confirmed with a written consent form. Exclusion Criteria: history of ECT for the last 5 years; history of neurological illness or a traumatic head injury, defined as loss of consciousness for more than 5 minutes and/or structural sequelae following head trauma; history of severe or moderate alcohol (AUD) or substance use disorder (SUD) in the past five years, or mild AUD or SUD within the last year, according to DSM-5; the use, in the preceding year of steroids or barbiturates, which can affect cognitive function; hearing, vision or upper body impairment alcohol use in the last 24 hours;