Repetitive Transcranial Magnetic Stimulation for Treatment of Autism Spectrum Disorder: A Systematic Review and Meta-Analysis

Abstract

Background: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder manifesting as lifelong deficits in social communication and interaction, as well as restricted repetitive behaviors, interests and activities. While there are no specific pharmacological or other physical treatments for autism, in recent years repetitive Transcranial Magnetic Stimulation (rTMS), a technique for non-invasive neuromodulation, has attracted interest due to potential therapeutic value. Here we report the results of a systematic literature review and meta-analysis on the use of rTMS to treat ASD.Methods: We performed a systematic literature search on PubMed, Web of Science, Science Direct, Bielefeld Academic Search, and Educational Resources Information Clearinghouse. Search terms reflected diagnoses and treatment modalities of interest. Studies reporting use of rTMS to treat core ASD or cognitive symptoms in ASD were eligible. Two researchers performed article selection and data extraction independently, according to PRISMA guidelines. Changes in ASD clinical scores or in cognitive performance were the main outcomes. Random effects meta-analysis models were performed.Results: We found 23 eligible reports, comprising 4 case-reports, 7 non-controlled clinical trials, and 12 controlled clinical trials, comparing the effects of real TMS with waiting-list controls (n = 6) or sham-treatment (n = 6). Meta-analyses showed a significant, but moderate, effect on repetitive and stereotyped behaviors, social behavior, and number of errors in executive function tasks, but not other outcomes. Most studies had a moderate to high risk of bias, mostly due to lack of subject- and evaluator-blinding to treatment allocation. Only 5 studies reported stability of these gains for periods of up 6 months, with descriptions that improvements were sustained over time.Conclusions: Existing evidence supports that TMS could be useful to treat some dimensions of ASD. However, such evidence must be regarded with care, as most studies did not adequately control for placebo effects. Moreover, little is known regarding the most effective stimulation parameters, targets, and schedules. There is an urgent need for further randomized, double-blind, sham-controlled trials, with adequate follow-up periods, to test the efficacy of transcranial magnetic stimulation to treat these disorders. Available evidence must be regarded as preliminary and insufficient, at present, to support offering TMS to treat ASD.

Social Cognition in Schizophrenia and Autism Spectrum Disorders: A Systematic Review and Meta-Analysis of Direct Comparisons

“…Schizophrenia and autism spectrum disorders (ASD) are two conditions characterized by significant impairments in social cognition ( 1 , 3 ). Impaired social cognition is a major driver of poor psychosocial functioning in both disorders and has been increasingly considered as one of the key treatment targets in psychosocial and biological therapeutic interventions ( 4 – 6 ).…”

Treatment of Adults with Autism and Major Depressive Disorder Using Transcranial Magnetic Stimulation: An Open Label Pilot Study

“…Repetitive transcranial magnetic stimulation (rTMS) uses patterned focal magnetic stimulation to potentiate (strengthen), and depotentiate (weaken) the targeted neural circuit [Pascual-Leone et al, 1998]. Given the view that core symptoms of ASD may be the result of disrupted neural connectivity, several preliminary investigations have examined the potential utility of rTMS to treat these symptoms [Barahona-Correa, Velosa, Chainho, Lopes, & Oliveira-Maia, 2018;Enticott et al, 2014;Oberman, Rotenberg, & Pascual-Leone, 2015]. Trials applying depotentiating rTMS to the DLPFC have resulted in reduced irritability and repetitive behaviors, while enhancing autonomic balance [Casanova et al, 2014;Wang et al, 2016].…”

“…Trials applying depotentiating rTMS to the DLPFC have resulted in reduced irritability and repetitive behaviors, while enhancing autonomic balance [Casanova et al, ; Wang et al, ]. Other studies (summarized in a meta‐analysis) mostly looking at depotentiating rTMS applied to DLPFC have concluded treatment may reduce repetitive behaviors, but has inconsistent effects on social interactions [Barahona‐Correa et al, ]. Given that there appears to be both hypoconnectivity and hyperconnectivity relating to core symptoms of ASD, there has also been interest in the application of potentiating rTMS to the DLPFC, with one study finding that treatment with potentiating rTMS significantly improved the social relatedness subscale of the Ritvo Autism Asperger Diagnostic Scale, but not on other ASD scales or mentalization measures [Enticott et al, ].…”

Effects of repetitive transcranial magnetic stimulation on children with low‐function autism

“…Low‐frequency rTMS (≤1 Hz) can increase the inhibition of stimulated cortical regions, and high‐frequency rTMS (≥5 Hz) can increase the excitability of stimulated cortical regions . rTMS is very safe if within safety guideline . Many studies have also shown the effectiveness of rTMS intervention in autistic patients.…”

“…16,17 rTMS is very safe if within safety guideline. 18,19 Many studies have also shown the effectiveness of rTMS intervention in autistic patients. Researchers believe this is due to a bias in the excitation and inhibition ratio of the cerebral cortex.…”