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

Abstract

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.

A Guide to Literature Informed Decisions in the Design of Real Time fMRI Neurofeedback Studies: A Systematic Review

“…Subjects have also been able to use neurofeedback to regulate activity in the primary and secondary auditory cortex both up (Yoo et al, 2007) and down (Emmert et al, 2017;Sherwood et al, 2018). Neurofeedback aided down-regulation of the auditory cortex has been associated with reduction in auditory hallucinations (Orlov et al, 2018) and tinnitus (Haller et al, 2010).…”

Did I imagine that? The functional role of paracingulate cortex in reality monitoring

“…Together, the above findings suggest that neurofeedback training might have value as a treatment for hallucinations in schizophrenia by improving reality monitoring ability through alteration of the underlying functional networks. Recent fMRI neurofeedback proof of concept studies in schizophrenia add support to this proposal (30,38). We suggest further work to focus on replication of these Studies in a larger sample and their extension to include a schizophrenia patient population comprising individuals both with and without the experience of hallucinations.…”

“…Thereafter, in Study 2, and based on our findings from Study 1, we used fMRI neurofeedback to establish causal evidence for the involvement of paracingulate cortex in recollection of the source of imagined information in healthy individuals. Our choice of fMRI neurofeedback as a technique follows its successful recent deployment in a range of studies where individuals have been trained to self-regulate neural activity in brain regions and networks thought to underlie certain behaviours (26), cognitive functions (27,28) and psychiatric symptoms (29,30). As fMRI neurofeedback allows individuals to monitor and self-regulate their own brain activity in real time (31), training individuals to regulate neural activity in particular brain regions or networks enables causal inferences to be made about that region's involvement in a certain behaviour or function.…”

Voluntary Control of Auditory Hallucinations: Phenomenology to Therapeutic Implications

“…If this is the case, these different subgroups may also vary in their control abilities in a way that reflects their underlying deficits. Lastly, it should be noted that recent advances in neurofeedback training for treatment of auditory hallucinations appear to offer a theory-agnostic demonstration of direct control development 150,151 . In fact, the strategies participants use during neurofeedback sessions appear to be mostly implicit and perceptuallybased (see 151 , Supplement), implying that a perceptual component independent of higher-order cognitive strategy may be isolated from psychosocial factors that influence direct control development.…”