Electric and Physiological Markers, Underlying Mechanisms and Modulation of Cognitive Functioning and Therapeutic Improvement in Response to tACS/CBTp (Transcranial Alternating Current Stimulation Applied at the Beginning of the Cognitive Behavioral Therapy for Psychosis Session) in Combination With the Usual Pharmacological Treatment in Schizophrenia

Rationale. 1% Canadians suffer from Schizophrenia (SZ), a neurodegenerative condition with a high rate of relapse, and important personal, familial and social burden, involving a high cost for care. The suicide rate for people with schizophrenia is over 20 times higher than the general population. While there is no cure, programs and treatments are available to help manage symptoms; however, these have limitations. 60% of patients with SZ do not respond adequately to treatment with medication alone (currently the primary, and often only approach). When CBT for Psychosis (CBTp) is used alongside medication, some improvements have been observed but the debilitating negative symptoms remain (such as reduction of emotional expression, lack of social involvement, inability to initiate goal-directed activities, etc.), which are key factors in long-term disability. A new treatment, transcranial alternating current stimulation (tACS) has therapeutic results in Alzheimer's.

The investigators propose combining these two therapies (CBTp and tACS), in a novel way to increase the overall improvement of negative symptoms in people living with schizophrenia.

Rationale: schizophrenia is characterized by abnormalities in neural circuitries resulting dysfunctional cognition and behavior. Recent randomized double blind clinical trials of tACS in Alzheimer's disease showed a significant improvement in memory performance, along with restoration of intracortical connectivity, as compared to sham tACS. The investigators propose similar cognitive enhancements in people living with schizophrenia. This technique has never been applied before in our studied population and has never used in combination with CBT.

Methodology. Description of intervention: CBTp: 16 individual-basis, 50 minutes length, weekly sessions (CBTp intervention) and 2 booster CBTp sessions at follow up visits (at one month and three months after intervention). tASC/CBTp: two different groups, one with gamma band electric stimulation for 20 minutes at the beginning of the CBTp session (after the first 20 minutes of brain stimulation the tACS device automatically stops and the device remains in place, while the CBTp session continues to run for 30 more minutes) and another group with sham tACS/CBTp (tACS is sham, but CBTp is intervention). For each group the investigators will follow the same protocol.

Number of visit (V): V. 1 (screening, week 0=W. 0); V.2 (enrollment/baseline, W.2, followed by starting intervention); V. 3 (Intervention Session 8/mid-term, W.9); V.4 (End of Intervention W. 17); V.5 (follow-up 1, W.21); V.6 (follow-up 2, W.29). Measures: Primary outcome measures/dependent variables: PANSS, Negative Symptom Assessment, Cognitive Flexibility Scale. Secondary physiological measures: EEG data and HRV: baseline, and end of intervention visit. Secondary psychological measures (WHO Disability Assessment Scale, Brief Betrayal Trauma Survey, BEM Sex Role Inventory Perceived Stress Scale, Working Alliance Inventory, Quality of Life and Enjoyment Scale, STROOP Color and Word test and Personal Evaluation in Transition of Treatment Scale). Eligibility screening measures: EEG; Columbia Suicide Severity Rating Scale; MOCA (over age 65): at screening. The chart review, performed at screening will help with selecting eligible participants. Statistical analysis plan: on SPSS, version 29, main tests will include repeated measures, mixed design analysis of variance and t-tests for two-group comparisons.