Real-time fMRI neurofeedback modulates auditory cortex activity and connectivity in schizophrenia patients with auditory hallucinations: A controlled study.

Background and Hypothesis: We have reported previously a reduction in superior temporal gyrus (STG) activation and in auditory verbal hallucinations (AHs) after real-time fMRI neurofeedback (NFB) in schizophrenia patients with AHs. Study Design: With this randomized, participant-blinded, sham-controlled trial, we expanded our previous results. Specifically, we examined neurofeedback effects from the STG, an area associated with auditory hallucinations. The effects were compared to Sham-NFB from the motor cortex, a region unrelated to hallucinations. Twenty-three adults with schizophrenia or schizoaffective disorder and frequent medication-resistant hallucinations performed mindfulness meditation to ignore pre-recorded stranger's voices while receiving neurofeedback either from the STG (n=10, Real-NFB) or motor cortex (n=13 Sham-NFB). Individuals randomized to Sham-NFB received Real-NFB in a subsequent visit, providing a within-subject 'Real-after-Sham-NFB' comparison. Study Results: Both groups showed reduced AHs after NFB, with no group differences. Compared to the Sham-NFB group, the Real-NFB group showed more reduced activation in secondary auditory cortex (AC) and more reduced connectivity between AC and cognitive control regions including dorsolateral prefrontal cortex (DLPFC) and anterior cingulate. The connectivity reduction was also observed in the Real-after-Sham-NFB condition. Secondary AC-DLPFC connectivity reduction correlated with hallucination reduction in the Real-NFB group. Replicating prior results, both groups showed reduced primary auditory cortex activation, suggesting mindfulness meditation may regulate bottom-up processes involved in hallucinations. Conclusions: Our findings emphasize delivering NFB from brain regions involved in medication-resistant AHs. They provide insights into auditory cortex and cognitive control network interactions, highlighting complex processing dynamics and top-down modulation of sensory information.