Biomarkers Obtained by Transcranial Magnetic Stimulation in Neurodevelopmental Disorders.

SUMMARY: Transcranial magnetic stimulation (TMS) is a method for focal brain stimulation that is based on the principle of electromagnetic induction where small intracranial electric currents are generated by a powerful fluctuating magnetic field. Over the past three decades, TMS has shown promise in the diagnosis, monitoring, and treatment of neurological and psychiatric disorders in adults. However, the use of TMS in children has been more limited. We provide a brief introduction to the TMS technique; common TMS protocols including single-pulse TMS, paired-pulse TMS, paired associative stimulation, and repetitive TMS; and relevant TMS-derived neurophysiological measurements including resting and active motor threshold, cortical silent period, paired-pulse TMS measures of intracortical inhibition and facilitation, and plasticity metrics after repetitive TMS. We then discuss the biomarker applications of TMS in a few representative neurodevelopmental disorders including autism spectrum disorder, fragile X syndrome, attention-deficit hyperactivity disorder, Tourette syndrome, and developmental stuttering.

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.

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

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 (P FDR'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.