Continuous Theta-Burst Stimulation in Children With High-Functioning Autism Spectrum Disorder and Typically Developing Children

Abstract

Objectives: A neurophysiologic biomarker for autism spectrum disorder (ASD) is highly desirable and can improve diagnosis, monitoring, and assessment of therapeutic response among children with ASD. We investigated the utility of continuous theta-burst stimulation (cTBS) applied to the motor cortex (M1) as a biomarker for children and adolescents with high-functioning (HF) ASD compared to their age-and gender-matched typically developing (TD) controls. We also compared the developmental trajectory of long-term depression-(LTD-) like plasticity in the two groups. Finally, we explored the influence of a common brain-derived neurotrophic factor (BDNF) polymorphism on cTBS aftereffects in a subset of the ASD group.Methods: Twenty-nine children and adolescents (age range 10-16) in ASD (n = 11) and TD (n = 18) groups underwent M1 cTBS. Changes in MEP amplitude at 5-60 min post-cTBS and their cumulative measures in each group were calculated. We also assessed the relationship between age and maximum cTBS-induced MEP suppression (∆MEP Max ) in each group. Finally, we compared cTBS aftereffects in BDNF Val/Val (n = 4) and Val/Met (n = 4) ASD participants.Results: Cumulative cTBS aftereffects were significantly more facilitatory in the ASD group than in the TD group (P FDR 's < 0.03). ∆MEP Max was negatively correlated with age in the ASD group

Modulation of motor cortical excitability by continuous theta-burst stimulation in adults with autism spectrum disorder: The roles of BDNF and APOE polymorphisms

“…Moreover, consistent with the results of several previous studies (Théoret et al 2005;Minio-Paluello et al 2009;Enticott et al 2010Enticott et al , 2013bEnticott et al , 2013aOberman et al 2012Oberman et al , 2016 the present study (by T20) compared to those found previously, i.e., T40-T60 in the ASD group (Oberman et al 2012). This difference in pattern of cTBS aftereffects may be attributed to interindividual variability of cTBS responses, differences in proportions of BDNF, APOE, and other relevant SNPs, or differences in demographics, neuropsychological characteristics, or neuroactive medications in the ASD group across studies, as suggested recently (Jannati et al 2020).…”

“…The present results can also be considered in the context of studies on aberrant TBS responses in children and adolescents with HF-ASD (Oberman et al 2014;Jannati et al 2020).…”

“…Following previous studies investigating brain plasticity mechanisms with rTMS (Oberman et al 2010(Oberman et al , 2012(Oberman et al , 2014(Oberman et al , 2016Fried et al 2016Fried et al , 2017Jannati et al 2017Jannati et al , 2019Jannati et al , 2020, we focused on the primary motor cortex in the left hemisphere, as it is typically the dominant hemisphere regardless of handedness. It is unlikely, however, that the observed differences in cTBS metrics of cortical plasticity between the two groups result from an ASD-related pathophysiological process specific to motor cortex.…”

“…Recently, we found that children and adolescents with high-functioning (HF) ASD had abnormally greater facilitatory responses to cTBS relative to typically developing children (Jannati et al 2020).…”

“…Moreover, cTBS measures of plasticity showed a maturational trajectory in children and adolescents with high-functioning ASD (HF-ASD), in which the extent of, or the maximum, cTBSinduced suppression of MEPs increased linearly with age (Oberman et al 2014;Jannati et al 2020).…”