Transcranial Magnetic Stimulation Provides a Means to Investigate Cortical Excitability and Plasticity in Autism Spectrum Disorder

Background:   The etiology and neurobiology of Autism Spectrum Disorder (ASD) is complex and insufficiently understood. Recent studies across multiple research areas, including genetics, animal model research, and human studies have implicated mechanisms of cortical excitability and plasticity in the pathophysiology of ASD. Our group has pioneered the development of transcranial magnetic stimulation (TMS) and repetitive TMS (rTMS) metrics of cortical excitability and plasticity as putative endophenotypes in ASD. However, both the intraindividual and interindividual reliability of these measures has not been clearly established.  Additionally, how abnormalities at the local circuit level impact developmental and experience-based functional brain connectivity and how the functioning of these circuits impact behavior is still a mystery.

Objectives:  To use TMS to explore cortical excitability and plasticity in ASD.

Methods: Our published and ongoing studies employ TMS-based measures of cortical excitability and plasticity in children and adults with ASD including single-pulse, paired-pulse, and rTMS protocols.

Results: Across multiple studies, application of an rTMS protocol proposed to index non-­Hebbian plasticity and GABAergic inhibitory tone (theta burst stimulation (TBS)) results in a prolonged modulation of corticospinal excitability in adults with ASD. Specifically, while controls show a modulation of the TMS-induced motor evoked potentials (MEPs) for approximately 30-­40 minutes following TBS, the effect lasted for over 60 minutes in individuals with ASD. This finding is quite reliable at the group level, but has proved elusive to replicate at the individual level.  State-dependent factors relating to expectation and attention likely impact the reliability of this measure. Additionally, we find that a subgroup of individuals with ASD show paradoxical responses to paired pulse and rTMS protocols thought to be related to GABAergic tone. 

Conclusions:   We continue to explore the utility of TMS and rTMS indices of excitability and plasticity in an effort to develop a valid and reliable endophenotype that would facilitate ASD diagnosis early in life, enable efficient study of ASD risk factors, and eventually serve as a useful biomarker to inform the development of effective therapies and assess treatment response in future clinical trials, however, given the heterogeneity of this disorder (both at the behavioral and physiological level) individual and subgroup analyses, rather than group averages, need to be considered when determining the validity of these measures.