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 (ΔMEPMax) 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 (PFDR’s < 0.03). ΔMEPMax was negatively correlated with age in the ASD group (r = −0.67, P = 0.025), but not in the TD group (r = −0.12, P = 0.65). Cumulative cTBS aftereffects were not significantly different between the two BDNF subgroups (P-values > 0.18).Conclusions: The results support the utility of cTBS measures of cortical plasticity as a biomarker for children and adolescents with HF-ASD and an aberrant developmental trajectory of LTD-like plasticity in ASD.
Highlights
Autism spectrum disorder (ASD) is characterized by social communication deficits and restricted, repetitive, and stereotyped behaviors and interests (American Psychiatric Association, 2013)
We extend the scope of previous continuous theta-burst stimulation (cTBS) studies in 10–16 years old children with high-functioning ASD addressing two questions: (1) are cTBS aftereffects different between ASD and typically developing (TD) groups?; and (2) does the developmental trajectory of cortical plasticity, as measured by cTBS aftereffects, differ between the two groups?
The difference in cumulative AUC measures of cTBS aftereffects between the two groups was significant over all the intervals (PFDR’s < 0.03), indicating greater facilitatory response to cTBS in the ASD group relative to the TD group
Summary
Autism spectrum disorder (ASD) is characterized by social communication deficits and restricted, repetitive, and stereotyped behaviors and interests (American Psychiatric Association, 2013). Due to the large variability in the clinical phenotype of ASD and manifestation of symptoms over a range of ages in childhood, a clinical diagnosis of ASD can be challenging and is often not made until 3–5 years of age. For this reason, a neurophysiologic ASD biomarker is highly desirable, for improving diagnostic specificity and for enabling metrics of therapeutic target-engagement and outcomes. Aberrant synaptic plasticity in patients with ASD can be measured in vivo at the circuit level by transcranial magnetic stimulation (TMS; Huang et al, 2005; Hallett, 2007; PascualLeone et al, 2011). TMS, when combined with electromyography (EMG), electroencephalography (EEG), or neuroimaging such as functional magnetic resonance imaging (fMRI) can quantify the extent of modulation of cortical reactivity induced by an intervention, providing an index of brain plasticity (PascualLeone et al, 2011)
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