5.4 TRANSCRANIAL MAGNETIC STIMULATION MEASURES AS EMERGING BIOMARKERS OF ADHD IN AUTISM SPECTRUM DISORDER

The neural correlates distinguishing youth with autism spectrum disorder (ASD) without ADHD (ASD-ADHD) and ASD with co-occurring ADHD (ASD+ADHD) are poorly understood despite significant phenotypic and prognostic differences. Paired-pulse transcranial magnetic stimulation (TMS) measures, including intracortical facilitation (ICF), short interval cortical inhibition (SICI), and cortical silent period (CSP), were measured in an age-matched cohort of youth with ASD-ADHD (n = 20), ASD+ADHD (n = 29), and typically developing comparison (TDC) controls (n = 24). ASD-ADHD and ASD+ADHD groups did not differ by IQ or social functioning; however, ASD+ADHD had significantly higher inattention and hyperactivity ratings. ICF (higher ratio indicates greater facilitation) in ASD+ADHD (mean = 1.0, SD = 0.19) was less than ASD-ADHD (mean = 1.3, SD = 0.36) or TDC (mean = 1.2, SD = 0.24) (F2,68 = 6.5, p = 0.003; post hoc tests, ASD+ADHD vs either TDC or ASD-ADHD, p ≤ 0.05). Across all ASD youth (ASD-ADHD and ASD+ADHD), ICF was inversely correlated with worse inattention (Conners 3-Inattention (r = –0.41; p < 0.01). ICF remains intact in ASD-ADHD but is impaired in ASD+ADHD. Lack of ICF is associated with inattention and executive function across ASD. ADHD may have a distinct electrophysiological “signature” in ASD youth. ICF may constitute an emerging biomarker to study the physiology of ADHD in ASD, which may align with disease prognosis or treatment response. The nature of ICD further suggests that subcortical alterations may be involved in ADHD co-occurrence in ASD. Despite some reservations regarding variability, TMS biomarkers may have utility in probing endophenotypes of disease.