A lack of efficacy of continuous theta burst stimulation over the left dorsolateral prefrontal cortex in autism: A double blind randomized sham‐controlled trial

Abstract

Although previous open-label trials suggest the therapeutic potential of inhibitory repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex (DLPFC) in autism spectrum disorder (ASD), methodological caveats exist. We conducted an 8-week randomized, double-blind shamcontrolled trial to investigate the efficacy of inhibitory continuous theta burst stimulation (cTBS, a variant of rTMS) over the left DLPFC in individuals with ASD. Sixty children, adolescents and young adults (aged 8-30 years) with ASD without co-occurring intellectual disabilities were randomized to a 16-session 8-week cTBS versus sham stimulation course, with a follow-up 4 weeks after the trial. The Active group was not superior to the Sham group in any clinical or neuropsychological metrics at Week 8 or Week 12. Time effects of 8-week cTBS on symptoms and executive function were remarkable in both Active and Sham groups, with comparable response rates and effect sizes of changes in symptoms/cognition between groups. Our results from a sufficiently powered sample do not endorse the superior efficacy of cTBS over the left DLPFC to the shamed stimulation for children, adolescents and adults with ASD. These findings suggest that earlier positive open-label trial findings may be generalized by generalized/placebo effects. This highlights the urgent need for more rTMS/TBS studies with rigorous trial designs in ASD.

Design and methodology for a proof of mechanism study of individualized neuronavigated continuous Theta burst stimulation for auditory processing in adolescents with autism spectrum disorder

“…Of note, Ni and colleagues recently applied intermittent theta burst stimulation (iTBS) to bilateral posterior superior temporal sulci (pSTS) in adults with ASD and showed improvements in parent-reported ASD symptoms and compulsive behaviors (as measured by AQ and Y-BOCS scales) ( 76 , 77 ), but no change in white matter macro/micro structure ( 78 ). However, when the same group applied cTBS to the dorsolateral prefrontal cortex (DLPFC), they did not find any significant improvement (as compared to sham stimulation) in executive functioning symptoms in a recently published study of children, adolescents, and adults with ASD ( 79 ). Taken together with the literature on aberrant functioning of the pSTC region and its relationship to ASD symptoms described above, Ni and colleagues findings suggest that the pSTC may be a better putative target than the DLPFC for future rTMS studies in ASD.…”