Real-Time Functional Magnetic Resonance Imaging Neurofeedback for the Relief of Distressing Auditory-Verbal Hallucinations: Methodological and Empirical Advances.

Auditory-verbal hallucinations (AVH) are often associated with high levels of distress and disability in individuals with schizophrenia-spectrum disorders. In around 30% of individuals with distressing AVH and diagnosed with schizophrenia, traditional antipsychotic drugs have little or no effect. Thus, it is important to develop mechanistic models of AVH to inform new treatments. Recently a small number of studies have begun to explore the use of real-time functional magnetic resonance imaging neurofeedback (rtfMRI-NF) for the treatment of AVH in individuals with schizophrenia. rtfMRI-NF protocols have been developed to provide feedback about brain activation in real time to enable participants to progressively achieve voluntary control over their brain activity. We offer a conceptual review of the background and general features of neurofeedback procedures before summarizing and evaluating existing mechanistic models of AVH to identify feasible neural targets for the application of rtfMRI-NF as a potential treatment. We consider methodological issues, including the choice of localizers and practicalities in logistics when setting up neurofeedback procedures in a clinical setting. We discuss clinical considerations relating to the use of rtfMRI-NF for AVH in individuals distressed by their experiences and put forward a number of questions and recommendations about best practice. Lastly, we conclude by offering suggestions for new avenues for neurofeedback methodology and mechanistic targets in relation to the research and treatment of AVH.

Real-time fMRI neurofeedback to down-regulate superior temporal gyrus activity in patients with schizophrenia and auditory hallucinations: a proof-of-concept study.

Neurocognitive models and previous neuroimaging work posit that auditory verbal hallucinations (AVH) arise due to increased activity in speech-sensitive regions of the left posterior superior temporal gyrus (STG). Here, we examined if patients with schizophrenia (SCZ) and AVH could be trained to down-regulate STG activity using real-time functional magnetic resonance imaging neurofeedback (rtfMRI-NF). We also examined the effects of rtfMRI-NF training on functional connectivity between the STG and other speech and language regions. Twelve patients with SCZ and treatment-refractory AVH were recruited to participate in the study and were trained to down-regulate STG activity using rtfMRI-NF, over four MRI scanner visits during a 2-week training period. STG activity and functional connectivity were compared pre- and post-training. Patients successfully learnt to down-regulate activity in their left STG over the rtfMRI-NF training. Post- training, patients showed increased functional connectivity between the left STG, the left inferior prefrontal gyrus (IFG) and the inferior parietal gyrus. The post-training increase in functional connectivity between the left STG and IFG was associated with a reduction in AVH symptoms over the training period. The speech-sensitive region of the left STG is a suitable target region for rtfMRI-NF in patients with SCZ and treatment-refractory AVH. Successful down-regulation of left STG activity can increase functional connectivity between speech motor and perception regions. These findings suggest that patients with AVH have the ability to alter activity and connectivity in speech and language regions, and raise the possibility that rtfMRI-NF training could present a novel therapeutic intervention in SCZ.