Translating Neurocognitive Models of Auditory-Verbal Hallucinations into Therapy: Using Real-time fMRI-Neurofeedback to Treat Voices.

Auditory-verbal hallucinations (AVHs) are frequent and disabling symptoms, which can be refractory to conventional psychopharmacological treatment in more than 25% of the cases. Recent advances in brain imaging allow for a better understanding of the neural underpinnings of AVHs. These findings strengthened transdiagnostic neurocognitive models that characterize these frequent and disabling experiences. At the same time, technical improvements in real-time functional magnetic resonance imaging (fMRI) enabled the development of innovative and non-invasive methods with the potential to relieve psychiatric symptoms, such as fMRI-based neurofeedback (fMRI-NF). During fMRI-NF, brain activity is measured and fed back in real time to the participant in order to help subjects to progressively achieve voluntary control over their own neural activity. Precisely defining the target brain area/network(s) appears critical in fMRI-NF protocols. After reviewing the available neurocognitive models for AVHs, we elaborate on how recent findings in the field may help to develop strong a priori strategies for fMRI-NF target localization. The first approach relies on imaging-based "trait markers" (i.e., persistent traits or vulnerability markers that can also be detected in the presymptomatic and remitted phases of AVHs). The goal of such strategies is to target areas that show aberrant activations during AVHs or are known to be involved in compensatory activation (or resilience processes). Brain regions, from which the NF signal is derived, can be based on structural MRI and neurocognitive knowledge, or functional MRI information collected during specific cognitive tasks. Because hallucinations are acute and intrusive symptoms, a second strategy focuses more on "state markers." In this case, the signal of interest relies on fMRI capture of the neural networks exhibiting increased activity during AVHs occurrences, by means of multivariate pattern recognition methods. The fine-grained activity patterns concomitant to hallucinations can then be fed back to the patients for therapeutic purpose. Considering the potential cost necessary to implement fMRI-NF, proof-of-concept studies are urgently required to define the optimal strategy for application in patients with AVHs. This technique has the potential to establish a new brain imaging-guided psychotherapy for patients that do not respond to conventional treatments and take functional neuroimaging to therapeutic applications.