Using Transcranial Alternating Current Stimulation to Improve Executive Function in 22q11.2 Deletion Syndrome

Prevalence of adverse events following tACS (safety and tolerability)

Safety and tolerability of using at-home stimulation in a group of youths with neurodevelopmental disorders (i.e., 22q11DS) with the help of caregivers. It will be measured using a homemade questionnaire assessing the presence and intensity of side effects of tACS (e.g., headache, tingling, skin redness, neck pain). Each side effect will be rated on a intensity scale from 1 (absent) to 4 (severe). In addition, we will assess whether the side effect is associated with tACS, from 1 (no association) to 5 (certain association). This questionnaire is present in the Clinical Report Form (CRF) and will be filled after each stimulation session (both tACS and sham stimulation).

Change in verbal working memory performance using Digit Span subtest (Weschler's child/adult intelligence scale (2004, 2011).

We will investigate whether there is a direct positive effect of tACS on verbal working memory using parallel versions of Digit Span (forward, reverse, and sequencing conditions) inspired Weschler's child/adult intelligence scale (Weschler, 2004, 2011). This will be assessed at three visits: baseline (i.e., pre-stimulation), post-stimulation, 1-month follow-up.

Change in visuospatial working memory performance using Leiter-3 scales (Roid, Mille, Pomplun, & Koch, 2013), Testing of Attentional Performance (Zimmermann & Fimm, 2002), and CANTAB software (Cambridge Cognition, 2019)

We will investigate whether there is a direct positive effect of tACS on visual working memory using parallel versions of Forward memory and Reverse memory subtests, inspired from Leiter-3 (Roid, Mille, Pomplun, \& Koch, 2013) and visual n-back task from Testing of Attentional Performance (Zimmermann \& Fimm, 2002), and Spatial Working Memory from CANTAB (Cambridge Cognition, 2019). This will be assessed at three visits: baseline (i.e., pre-stimulation), post-stimulation, 1-month follow-up.

Change in the oscillatory response of the brain related to working memory with EEG using time-frequency + cross-frequency coupling analyses

Using a visual working memory EEG task, we will explore the oscillatory response of the brain related to working memory. For the EEG analyses, we will use a pipeline that has already been applied to previous data and described in detail (Mancini, Rochas, Seeber, Grent-'t-Jong, et al., 2022a; Mancini, Rochas, Seeber, Roehri, et al., 2022b). All participants will do one EEG at each visit (baseline, post-stimulation, 1-month follow-up).

Change in psychotic experiences using Ecological Momentary Assessment (EMA)

Participants will complete a EMA protocol for approximately 3 months (one notification per day). The protocol will be implemented on the RealLife Exp app, developed for clinical research purposes. The data is encrypted at rest and its transmission is secured using several different methods. The data will be transferred on the server of the University of Geneva. Participants will complete the EMA questionnaire once they hear a notification. A follow-up call will be scheduled with the participant to ensure compliance. At each beep, psychotic experiences will be assessed using a series of items (e.g. " Seeing or hearing things others don't perceive ") rated on a 7-point Likert scale (1 = " not at all " to 7 = " extremely "). Feller et al. (2021) showed an association between psychotic experiences (measured by EMA) and severity of psychotic symptoms (measured by a gold standard assessment) in 22q11DS. Their study shows feasibility and validity of assessing psychotic experiences with EMA.