Visual P300 as a neurophysiological correlate of symptomatic improvement by a virtual reality-based computer AT system in patients with auditory verbal hallucinations: A Pilot study

Previous comparative trials showed that virtual reality (VR) therapies achieved larger effects than gold-standard cognitive-behavioral therapy (CBT) on overall auditory verbal hallucinations (AVHs). However, no trial has examined the corresponding underlying electrophysiological mechanisms. We performed a pilot randomized comparative trial evaluating the efficacy of a virtual reality-based computer AT system (CATS) over CBT for schizophrenia (SCZ) patients with treatment-resistant AVHs and explored these potential electrophysiological changes via the visual P300 component. Patients (CATS, n = 32; CBT, n = 33) completed the clinical assessments pre- and post-interventions and at 12-week follow-up. The visual P300 were measured before and after both therapies. The analysis of changes in psychiatric symptoms used linear mixed-effects models, and the P300 response in temporal and time-frequency domains was analyzed with repeated-measures analysis of variance. There was no interaction effect between change in clinical symptoms and treatment group. However, several statistically significant within-group improvements were found for CATS and CBT over time. AVH improved significantly after both treatments, as measured with the Psychotic Symptom Rating Scales-Auditory Hallucinations (PSYRATS-AH) sub-scores. Especially for the CATS group, omnipotence beliefs, anxiety symptoms, self-esteem, and quality of life also remained improved at the 12-week follow-up. Moreover, P300 amplitude had a significant interaction effect and correlation with AVH response. Overall, our analysis did not demonstrate general clinical superiority of CATS over CBT, but CATS improved refractory AVH in SCZ patients, likely by increasing P300 amplitude. These findings support the continued development of CATS for persistent AVH and suggest further trials to clarify the neurological effects of CATS.