Concurrent virtual reality and transcranial alternating current stimulation for social cognition and neural activity in schizophrenia: A proof-of-concept study

Abstract Social cognition, including theory of mind (ToM), is impaired in people with schizophrenia which can significantly impact daily functioning. Current interventions for social cognitive impairment are often time consuming and have limited ecological validity. Combining emerging technologies such as virtual reality (VR) and transcranial alternating current stimulation (tACS) may help address these limitations. The current study applied theta tACS to the right temporoparietal junction (rTPJ) during VR social cognition training in 15 participants with schizophrenia. Neurophysiological (event-related potentials and spectral power) and behavioural outcome measures (ToM task performance) were assessed. Participants underwent two experimental sessions. One session involved VR with concurrent active theta tACS (5Hz frequency) and the other consisted of VR with concurrent sham theta tACS. Resting state electroencephalography (EEG) and ToM tasks with concurrent EEG were measured pre- and post- VR-tACS. Order of stimulation condition was randomised, and stimulation and assessments were all double-blinded. We found ToM task response time improved after VR, regardless of tACS condition. While only VR and active tACS, but not sham, resulted in a widespread increase in resting state theta power. This is the first study to combine VR and tACS in a psychiatric population to address social cognition and provides initial evidence to support the feasibility and efficacy of a combined VR-tACS protocol in schizophrenia. Implications for future research are discussed. Competing Interest Statement KEH was a past founder of Resonance Therapeutics. PBF has received reimbursement for educational activities from Otsuka Australia Pharmaceutical Pty Ltd and equipment for research from Brainsway Ltd. Clinical Trial ACTRN12621001649808 Funding Statement KG was supported by a Monash University Departmental Scholarship, an Australian Government Research Training Program (RTP) Scholarship and an Epworth HealthCare Capacity Building Grant. KEH was supported by a National Health and Medical Research Council (NHMRC) fellowship (1135558). PBF is supported by an MHMRC Leadership Award. ATH was supported by and Alfred Deakin Postdoctoral Research Fellowship. Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Monash Health Human Research Ethics Committee gave ethical approval for this work. Monash University Human Research Ethics Committee, Alfred Health and Epworth HealthCare provided governance approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data Availability All data produced in the present study are available upon reasonable request to the authors