Transforming treatments for schizophrenia: Virtual reality, brain stimulation and social cognition.

Transcranial Alternating Current Stimulation (tACS) is a gentle non-invasive brain stimulation technique that can be used to change the activity of the brain. It uses a small amount of electric current that is passed between two electrodes placed on your scalp (head).Virtual reality is a technology that can be used to teach people new skills in a computerised virtual environment that feels like real-life. Participants will attend three research sessions at the Epworth Centre for Innovation in Mental Health (ECIMH) of approximately 2-3 hours. Session 1: Participants will be consented into the study and will participate in cognitive and social cognitive tasks as well as a clinical interview regarding current symptoms. Assessments completed during this session are outlined below. All assessments will be carried out by the PhD Candidate who has undergone training in the administration of all clinical, cognitive and social cognitive tasks. Clinical Assessments - Relevant demographic and health-related information. - Mini International Neuropsychiatric Interview 7.0.2 (MINI): The MINI is a brief diagnostic screening interview - Positive and Negative Syndrome Scale (PANSS) – Schizophrenia participants only Cognitive Assessments - MATRICS subtests (i.e. Trail-Making Task A, Brief Assessment of Cognition in Schizophrenia: Symbol Coding [BACS SC], Brief Visuospatial Memory Test-Revised [BVMT-R], Category Fluency: Animal Naming, Hopkins Verbal Learning Test-Revised [HVLT-R]) - Digit Span subtest from the Wechsler Adult Intelligence Scale (WAIS-IV) Working Memory Index. Social Cognitive Assessments - ToM: Abbreviated Faux Pas Task extracted from MINI-SEA - Attributional Bias: Internal, Personal and Situational Attributions Questionnaire (IPSAQ) - Social Knowledge: Situational Feature Recognition Test (SFRT) - Virtual Reality emotion recognition task and ToM task (a version of Penn Emotion Recognition task, Reading the Mind in the Eyes task, Hinting task) Disability and Functioning Questionnaires - Sheehan disability scale (SDS): self-report - Interpersonal Reactivity Index (IRI): self-report - Empathy Quotient (EQ): self-report Sessions 2 and 3: Participants will participate in two lab sessions separated by at least 72 hours. Both lab sessions will be the same except that for one session, participants will receive active 5Hz theta tACS while in the other, they will receive sham. Which condition participants receive and at what time is randomised and double blinded. Each participant will receive the active condition once and the sham condition once. Participants will also have recordings taken of their brainwaves at rest and while completing a social cognition computer task that is separate to the VR task. Virtual Reality: Participants will complete a theory of mind (ToM) VR task to allow activation of the right temporal parietal junction (rTPJ). Participants will wear a head mounted display (HMD) VR (i.e., Oculus Quest 2) to allow for increased possibility of immersion in the virtual environment. Within the tasks, participants will navigate social interactions with virtual avatars and will be required to evaluate the thought processes and intentions of these avatars to interact with them (e.g. a waiter brings out the wrong food to the participant at the restaurant. The program asks "you tell the waiter that they brought you the wrong meal. How should they respond?". Participants select the option they think is most true/correct from a multiple choice selection of possible responses such as "they offer to take it back and bring you the correct meal" or "they tell you to eat it anyway"). Feedback will be provided through the VR task about the participant interpretation of the avatars’ social interactions or cues. While participants are in the virtual environment completing this task, they will receive simultaneous theta-tACS to further modulate rTPJ activity; or sham-tACS to allow a comparison for the active condition. tACS: Theta tACS will be administered at a frequency of 5Hz, with a 1.75mA stimulation intensity. Stimulation duration will be limited to 16 minutes per session (including 30 seconds of “ramping up” at commencement, and 30 seconds “ramping down” at 15 minutes 30 seconds). These stimulation parameters are well within the currently recommended safe limits. Sham tACS will comprise 30 seconds of “ramping up” to peak intensity followed immediately by 30 seconds of “ramping down” to zero intensity stimulation at the beginning of the session to improve blinding by causing the characteristic scalp sensations, while not eliciting significant biological effects in proximity to experimental task completion. he tACS montage uses circular PiStim electrodes with water soluble gel (contact area 3.14cm2) at the 10-20 system locations of C4, C6, P2 and P4. The participants will begin the VR task immediately after the 30 seconds of ramp up stimulation.