Effects of prefrontal transcranial direct current stimulation on social functioning in autism spectrum disorder: A randomized clinical trial

This triple-arm, double-blind, randomized clinical trial investigated the effect of multisession prefrontal transcranial direct current stimulation (tDCS) on social functioning in individuals with autism spectrum disorder (ASD). A total of 105 individuals (age 14-21 years) diagnosed with ASD were randomized into the active-tDCS, sham-tDCS, and waitlist control groups. The experimental group received 20 min of 1.5 mA tDCS stimulation (cathode: F3; anode: Fp2) for 10 days with concurrent computerized cognitive remediation training. Changes in overall social functioning, social communication, and restricted, repetitive behaviors (RRB) were measured by the Social Responsiveness Scale-2nd edition (SRS-2). Two-level hierarchical linear mixed-model analysis showed significant group*time interactions for SRS-2 total [F(2, 107.09) = 7.82; p = 0.001] and RRB [F(2, 90.26) = 5.62; p = 0.005] T-scores. When compared with the waitlist control group, the changes in scores were only significant in active-tDCS (SRS-2 total T-score p < 0.001, d = 0.61; SRS-2 RRB T-score p = 0.002, d = 0.88), but not sham-tDCS (SRS-2 total T-score p < 0.12, d = 0.30; SRS-2 RRB T-score p = 0.54, d = 0.17) group. Multiple sessions of prefrontal tDCS coupled with cognitive training is a safe and effective treatment for improving social functioning in people with ASD. Trial Registration: ClinicalTrials.gov (ID: NCT03814083; URL: ).Lay abstractCurrently available pharmacological and behavioral interventions for adolescents and young adults with autism spectrum disorder (ASD) yield only modest effect in alleviating their core behavioral and cognitive symptoms, and some of these treatment options are associated with undesirable side effects. Hence, developing effective treatment protocols is urgently needed. Given emerging evidence shows that the abnormal connections of the frontal brain regions contribute to the manifestations of ASD behavioral and cognitive impairments, noninvasive treatment modalities that are capable in modulating brain connections, such as transcranial direct current stimulation (tDCS), have been postulated to be potentially promising for alleviating core symptoms in ASD. However, whether tDCS can reduce behavioral symptoms and enhance cognitive performance in ASD remains unclear. This randomized controlled trial involving 105 adolescents and young adults with ASD showed that multiple sessions of a tDCS protocol, which was paired up with computerized cognitive training, was effective in improving social functioning in adolescents and young adults with ASD. No prolonged and serious side effects were observed. With more future studies conducted in different clinical settings that recruit participants from a wider age range, this tDCS protocol may be potentially beneficial to a broad spectrum of individuals with autism.