Modulation of motor cortical excitability by continuous theta-burst stimulation in adults with autism spectrum disorder

Objective: To test whether change in motor evoked potential (ΔMEP) induced by continuous theta-burst stimulation (cTBS) of motor cortex (M1) distinguishes adults with autism spectrum disorder (ASD) from neurotypicals, and to explore the contribution of two common polymorphisms related to neuroplasticity. Methods: 44 adult neurotypical (NT) participants (age 21–65, 34 males) and 19 adults with ASD (age 21–58, 17 males) prospectively underwent M1 cTBS. Their data were combined with previously obtained results from 35 NT and 35 ASD adults. Results: ΔMEP at 15 minutes post-cTBS (T15) was a significant predictor of diagnosis (p = 0.04) in the present sample (n=63). T15 remained a significant predictor in a larger sample (n=91) and when partially imputed based on T10–T20 from a yet-greater sample (N=133). T15 also remained a significant predictor of diagnosis among brain-derived neurotrophic factor (BDNF) Met+ and apolipoprotein E (APOE) ε4− subjects (p's < 0.05), but not among Met− or ε4+ subjects (p's > 0.19). Conclusions: ΔMEP at T15 post-cTBS is a significant biomarker for adults with ASD, and its utility is modulated by BDNF and APOE polymorphisms. Significance: M1 cTBS response is a physiologic biomarker for adults with ASD in large samples, and controlling for BDNF and APOE polymorphisms can improve its diagnostic utility.