Using Transcranial Alternating Current Stimulation to enhance working memory in youths at genetic risk for psychosis

Abstract Atypical cognitive development is associated to the risk to develop a psychotic disorder in the general population, as not only it precedes the emergence of the first psychotic symptoms, but it also predicts their later severity and further cognitive decline. Thus, early modulatory intervention targeting cognition might potentially attenuate the burden of the illness. 22q11.2 deletion syndrome (22q11DS) is the neurogenetic disorder with the highest genetic risk for schizophrenia. Individuals with 22q11DS are characterized by impaired visuo-spatial memory. For this reason, we designed a non-invasive brain stimulation protocol to enhance visual working memory (WM). 26 youths with a confirmed diagnosis of 22q11DS were included in this study. We employed individual parameters for the stimulation to model anatomical variability. T1 and T2-weighted MRIs and EEG recordings during a WM task were acquired on the first day. Time-frequency analysis and theta-gamma phase-amplitude coupling between temporal and prefrontal seeds were conducted to determine the individual theta-band (4-8Hz) peak for the stimulation. Current flow modeling using individual MRI was performed with the software SimNIBS. The resulting parameters were used for the in-phase theta stimulation, with 3 electrodes placed on the left prefrontal cortex and 3 on the left temporal cortex. Participants were randomized to the order of sham and real stimulation for the following 2 days and underwent an EEG task during the WM task and during a control task before and after each stimulation session. This is the first brain stimulation study in individuals with 22q11DS and we showed that the use tACS is safe in this population, as no major side effects were reported. Behavioural results highlighted an increase in the number of correct answers to the WM task by 10% but not to the control task. These preliminary findings encourage the application of repeated sessions of tACS in this clinical population. Research Category and Technology and Methods Clinical Research: 8. Transcranial Alternating Current Stimulation (tACS) Keywords: psychosis, working memory, brain oscillations, tACS