In a randomised, sham-controlled clinical trial, multisession transcranial direct current stimulation (tDCS) paired with concurrent cognitive remediation training has been shown to promote social functioning in individuals with autism spectrum disorder (ASD). These findings, derived from a total of 41 ASD patients aged 14–21 years, are published in the journal Brain Stimulation.
“To the best of our knowledge, this was the first double-blind RCT [randomised controlled trial] to investigate the clinical, neuropsychological and neurophysiological effects of tDCS with left dlPFC [dorsolateral prefrontal cortex] cathode placement and right supraorbital region anode placement, delivered with concurrent, computerised cognitive remediation training, in adolescents and young adults with ASD,” co-first author Yvonne Han (The Hong Kong Polytechnic University, Hong Kong) and colleagues write in their report.
“By matching individuals on age, IQ, sex, and handedness, in the active and sham tDCS groups—which were also matched for baseline ASD symptom severity and current social functioning—we demonstrated that our protocol was a safe and efficacious treatment.”
To assess the clinical effects and neurophysiological mechanisms of prefrontal tDCS alongside cognitive remediation training, the researchers randomly assigned study participants to either active or sham tDCS groups. Patients received 1.5mA (milliampere) of prefrontal tDCS with the Starstim device (Neuroelectrics) for 20 minutes over two consecutive weeks. TDCS was delivered concurrently with a computerised cognitive remediation training programme. The authors detail that individuals undergoing sham tDCS received the same cognitive remediation training and underwent the same tDCS protocol as those in the active group—except for the 20-minute stimulation.
To measure the change in overall social functioning and inflexible behaviours before and after treatment, the Social Responsiveness Scale—2nd Edition (SRS-2) was used as the primary outcome measure. The underlying cognitive processes of social functioning, as well as prefrontal resting-state functional connectivity (rsFC), were also measured.
A total of 46 patients were randomised at the start of the trial, with 20 active group patients (mean age=17 years; 18 males) and 21 sham group patients (mean age=17 years; 20 males) ultimately being available for analysis. Han and colleagues report that results from these 41 participants indicated that multisession, prefrontal tDCS “significantly enhanced the social functioning of ASD individuals”, demonstrated by highly significant reductions in the total SRS-2 score in the active group versus nonsignificant reductions in the sham group.
“This improvement was associated with enhanced emotion recognition and cognitive flexibility,” they write. “Specifically, this tDCS protocol optimised information processing efficiency and the optimisation showed a trend to be associated with enhanced rsFC in the right medial prefrontal cortex.”
A significant group-by-time interaction was also found between the active and sham tDCS groups regarding SRS-2 restricted, repetitive behaviour (RRB) subscores, with post-hoc paired sample t-tests revealing highly significant RRB score reductions in participants in the active group and nonsignificant reductions in participants in the sham group. And, although the group-by-time interaction effect for SRS-2 social communication index (SCI) subscores was nonsignificant, post-hoc paired sample t-tests revealed highly significant SCI score reductions in the active group versus nonsignificant reductions in the sham group.
Han and colleagues detail that—while significantly more participants in the active tDCS group experienced short-term itchiness over the stimulation site compared to participants in the sham tDCS group—this was resolved within 10 minutes after each treatment session. No other significant differences in side-effects were observed between the two groups.
The authors note that their results are consistent with previous preliminary studies in that multisession tDCS, delivered concurrently with cognitive remediation training, yielded “large and significant effects” on social communication and RRBs in individuals with ASD. They add that their finding of prefrontal tDCS enhancing the rsFC of the brain’s right medial prefrontal regions (a major hub that enables socially relevant information to be processed in response to different social situations more efficiently) is consistent with a prior meta-analysis of neuroimaging studies as well.
However, Han and colleagues note that, “despite contributing significantly to understanding the effects of tDCS on ASD”, several factors could limit the generalisability of their study—including a relatively narrow range of ages and IQ scores in its patient population, the inclusion of female participants, and a small sample size. As such, they conclude that their data should be regarded as preliminary until they have been verified by larger-scale studies and future RCTs.