Treatment of Executive Function Deficits in autism spectrum disorder with repetitive transcranial magnetic stimulation: A double-blind, sham-controlled, pilot trial

Abstract

Background: In youth and young adults with autism spectrum disorder (ASD), executive function (EF) deficits may be a promising treatment target with potential impact on everyday functioning.

Objective: To conduct a pilot randomized, double-blind, parallel, controlled trial evaluating repetitive transcranial magnetic stimulation (rTMS) for EF deficits in ASD.

Method: In Toronto, Ontario (November 2014 to June 2017), a 20-session, 4-week course of 20 Hz rTMS targeting dorsolateral prefrontal cortex (DLPFC) (90%RMT) was compared to sham stimulation in 16-35 year-olds with ASD (28 male/12 female), without intellectual disability, who had impaired everyday EF performance (n = 20 active/n = 20 sham). Outcome measures evaluated protocol feasibility and clinical effects of active vs. sham rTMS on EF performance. The moderating effect of baseline functioning was explored.

Results: Of eligible participants, 95% were enrolled and 95% of randomized participants completed the protocol. Adverse events across treatment arms were mild-to-moderate. There was no significant difference between active vs. sham rTMS on EF performance. Baseline adaptive functioning moderated the effect of rTMS, such that participants with lower baseline functioning experienced significant EF improvement in the active vs. sham group.

Conclusions: Our pilot RCT demonstrated the feasibility and acceptability of using high frequency rTMS targeting DLPFC in youth and young adults with autism. No evidence for efficacy of active versus sham rTMS on EF performance was found. However, we found promising preliminary evidence of EF performance improvement following active versus sham rTMS in participants with ASD with more severe adaptive functioning deficits. Future work could focus on examining efficacy of rTMS in this higher-need population.

Clinical trial registration: Repetitive Transcranial Magnetic Stimulation (rTMS) for Executive Function Deficits in Autism Spectrum Disorder and Effects on Brain Structure: A Pilot Study; https://ichgcp.net/clinical-trials-registry/NCT02311751?term = ameis&rank = 1; NCT02311751. The trial was funded by: an American Academy of Child and Adolescent Psychiatry (AACAP) Pilot Research Award, the Innovation Fund from the Alternate Funding Plan of the Academic Health Sciences Centres of Ontario, and an Ontario Mental Health Foundation (OMHF) Project A Grant and New Investigator Fellowship.

Keywords: Autism; Clinical trial; Executive functioning; Intervention; Repetitive transcranial magnetic stimulation; Youth.

Crown Copyright © 2020. Published by Elsevier Inc. All rights reserved.

Figures

Fig. 1.

CONSORT flow diagram.

Fig. 2.

Change in spatial working memory performance in active and sham rTMS groups. across baseline (Pre: n = 20 active, n = 20 sham), post rTMS (Post: n = 18 active, n = 20 sham) and one-month follow-up (F-Up: n = 17 active, n = 17 sham) time-points. Spatial working memory = total number of errors on the spatial working memory test from the Cambridge Neuropsychological Test Automated Battery (CANTAB).

Fig. 3.

Change in BRIEF Metacognition Index in active and sham rTMS groupsacross baseline (Pre: n = 20 active, n = 20 sham), post rTMS (Post: n = 18 active, n = 20 sham) and one-month follow-up (F-Up: n = 17 active, n = 17 sham) time-points. Metacognition Index = Behavioral Rating Inventory for Executive Function Metacognition Index (higher scores denote more real-world executive function impairment).

Fig. 4.

Moderating effect of baseline adaptive functioning on change in spatial working memory performance following rTMS across baseline (Pre: n = 20 active, n = 20 sham), post rTMS (Post: n = 18 active, n = 20 sham) and one-month follow-up (F-Up: n = 17 active, n = 17 sham) time-points. The significant group-by-time-by-VABS-II (Vineland Adaptive Behavior Scale-II) adaptive composite score is presented in participants following a median split to depict differences in response in participants with low versus high baseline adaptive functioning. Error bars indicate the 95%CI for mean spatial working memory score (in the original scale of the outcome) at a given time point.

Fig. 5.

Moderating effect of gender on change in spatial working memory performance following rTMS across baseline (Pre: n = 20 active, n = 20 sham), post rTMS (Post: n = 18 active, n = 20 sham) and one-month follow-up (F-Up: n = 17 active, n = 17 sham) time-points. Spatial working memory = total number of errors on the spatial working memory test from the Cambridge Neuropsychological Test Automated Battery (CANTAB). Error bars indicate the 95%CI for mean spatial working memory score (in the original scale of the outcome) at a given time point.