Using transcranial alternating current stimulation to enhance working memory skills in youths with 22q11.2 deletion syndrome: A randomized double-blind sham-controlled study.

Abnormal cognitive development, particularly working memory (WM) deficits, is among the first apparent manifestations of psychosis. Yet, cognitive impairment only shows limited response to current pharmacological treatment. Alternative interventions to target cognition are highly needed in individuals at high risk for psychosis, like carriers of 22q11.2 deletion syndrome (22q11.2DS). Here we applied theta-tuned transcranial alternating current stimulation (tACS) between frontal and temporal regions during a visual WM task in 34 deletion carriers. We conducted a double-blind sham-controlled study over three consecutive days. The stimulation parameters were derived from individual structural MRI scan and HD-EEG data acquired at baseline (Day 1) to model current intensity and individual preferential theta peak. Participants were randomized to either sham or tACS (Days 2 and 3) and then completed a visual WM task and a control task. Our findings reveal that tACS was safe and well-tolerated among participants. We found a significantly increased accuracy in the visual WM but not the control task following tACS. Moreover, this enhancement in WM accuracy was greater after tACS than during tACS, indicating stronger offline effects than online effects. Our study therefore supports the application of repeated sessions of brain stimulation in 22q11.2DS.

Visual processing deficits in 22q11.2 Deletion Syndrome.

Carriers of the rare 22q11.2 microdeletion present with a high percentage of positive and negative symptoms and a high genetic risk for schizophrenia. Visual processing impairments have been characterized in schizophrenia, but less so in 22q11.2 Deletion Syndrome (DS). Here, we focus on visual processing using high-density EEG and source imaging in 22q11.2DS participants (N = 25) and healthy controls (N = 26) with an illusory contour discrimination task. Significant differences between groups emerged at early and late stages of visual processing. In 22q11.2DS, we first observed reduced amplitudes over occipital channels and reduced source activations within dorsal and ventral visual stream areas during the P1 (100-125 ms) and within ventral visual cortex during the N1 (150-170 ms) visual evoked components. During a later window implicated in visual completion (240-285 ms), we observed an increase in global amplitudes in 22q11.2DS. The increased surface amplitudes for illusory contours at this window were inversely correlated with positive subscales of prodromal symptoms in 22q11.2DS. The reduced activity of ventral and dorsal visual areas during early stages points to an impairment in visual processing seen both in schizophrenia and 22q11.2DS. During intervals related to perceptual closure, the inverse correlation of high amplitudes with positive symptoms suggests that participants with 22q11.2DS who show an increased brain response to illusory contours during the relevant window for contour processing have less psychotic symptoms and might thus be at a reduced prodromal risk for schizophrenia.