PROTOCOL. 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 (tACS/CBTpSZ Study) (Preprint)

BACKGROUND The current guidelines give to the cognitive behavioral therapy for psychosis (CBTp), in association with medication, an important role in the treatment of schizophrenia (SZ). Although beneficial in addressing positive symptoms, CBTp has uncertain results on the negative ones. We are proposing a new, non-invasive therapeutic brain stimulation model using alternating current (tACS), targeting band gamma oscillation stimulation, to augment the CBTp efficacy, using EEG brain oscillation activity as an electric marker of improvement of cognitive deficits in SZ. OBJECTIVE Main objective: to elicit cognitive readiness, and therapeutic engagement by adding tACS to each CBTp session in individuals with SZ, expecting at the end-point an improvement of cognition (measured by Cognitive Flexibility Scale and Stroop improvement in electrical brain activity, measured by EEG (tendency to organize the neural oscillations in the gamma frequency range, mainly in frontal lobes), along with general clinical improvement measured by PANSS. We are also aiming to evaluate the possible improvement of level of functioning and to determine if the response to tACS/CBTp intervention is gender specific. The demographic data collected (chart review), will allow correlations with the possible therapeutic improvement. METHODS This is a pilot, prospective, randomized, repeated-measures, single-blind study design. We expect 28 patients to consent and participate from a pool of 150 potentially eligible patients from Providence Care Hospital - Mental Health Services. We will use SPSS, version 29; main tests will include repeated measures, mixed design analysis of variance. RESULTS Our expectation are: CBTp will improve the scores of psychological /psychosocial tests at the end of therapy for both groups, but it will be superior for the group with tACS intervention; Considering that cognitive and emotional status is gender dependent, we expect that the therapeutic response could be gender specific; CBTp will enhance EEG activity in clients with SZ at the end of therapy for both groups, but it will be superior for the group with tACS pre intervention; The baseline HRV will predict symptom improvement and will increase over the course of therapy. CONCLUSIONS This study proposes a new therapeutic protocol, using the non-invasive therapeutic brain stimulation model using alternating current (tACS), targeting band gamma oscillation stimulation, to augment the CBTp efficacy in people living with schizophrenia, under their regular antipsychotic medication. We hope our research will help improving especially the treatment resistant negative symptoms of people living with schizophrenia, improving their quality of life, decreasing the rate of relapse and the costs of care. CLINICALTRIAL ClinicalTrials.gov NCT06889025