Transcranial direct current stimulation improves social functioning in autism spectrum disorder

A double-blind, sham-controlled study by researchers from the Hong Kong Polytechnic University shows that cathodal transcranial direct current stimulation (tDCS) of the left dorsolateral prefrontal cortex (dlPFC) paired with cognitive remediation is a feasible and effective treatment for improving social functioning and information processing in adolescents and young adults with autism spectrum disorder (ASD) who have average to borderline IQ.

Animal and human studies suggest that the ratio of excitatory to inhibitory (E/I) synaptic inputs in local brain circuits of ASD patients is higher than in that of healthy controls. [Neuron 2019;101:648-661; Sci Rep 2020;10:9191; Mol Autism 2022;13:20] In particular, a recent neuroimaging meta-analysis showed that left dlPFC is hyperactivated in ASD patients during tasks requiring attention control, response inhibition and cognitive flexibility. [Sci Rep 2022;12:20603] tDCS is a noninvasive technique that modulates the E/I balance by inducing subthreshold changes in resting membrane potentials of the targeted neuronal population. [Front Hum Neurosci 2013;7:602; Sci Rep 2020;10:20111]

“Given that left dlPFC impairment has been consistently implicated in cognitive dysfunction in ASD, and that altered E/I balance has been reported in this region, tDCS targeting of the left dlPFC should yield promising results,” proposed the researchers.

A total of 60 individuals with ASD (age, 14–21 years; IQ ≥60) were randomly assigned 1:1 to receive either active or sham tDCS (10 sessions in total; 20 min/session) combined with 20 minutes of online cognitive remediation in the form of 10 games targeting multiple executive functions, including interference control, multitasking, set shifting, visual information processing, and working memory. Social functioning, information processing efficiency (IPE) during cognitive tasks, and theta- and gamma-band E/I balance were measured 1 day before and after the treatment. [Brain Stimul 2023;16:1604-1616]

The active tDCS group showed significant improvements in social functioning, according to Social Responsiveness Scale – Second Edition (SRS-2), after prefrontal tDCS treatment (p=0.012). The mean within-group difference (before vs after treatment) was -12.87 (p<0.001), which was significantly greater than the score reduction in the sham group of 4.93 (p=0.026). Notably, the significant difference in total score reduction between the two groups was driven by a significant difference in the restricted, repetitive behaviour subscore reduction (p=0.002).

Significant improvement in IPE was also observed after prefrontal tDCS treatment (p=0.002). “Importantly, the observed stimulation-induced improvements in social functioning and IPE during cognitive tasks was highly significant among unmedicated as well as medicated patients, suggesting that the observed effects are likely due to tDCS rather than any potential interaction between antipsychotic or other medications and tDCS,” remarked the researchers.

Electroencephalography data showed that cathodal tDCS protocol was effective in reducing the theta-band E/I ratio of cortical midline structures, and that this reduction significantly predicted IPE enhancement (p=0.041). “Future work should examine cathodal tDCS effects on both the theta- and gamma-band E/I ratio in a more diverse sample of ASD participants, as well as how anodal and cathodal tDCS differentially modulate the theta- and gamma-band E/I ratios to help clinicians select the best prefrontal tDCS protocol for individual ASD patients,” suggested the researchers.