The clinical, social and financial burden of Autism Spectrum Disorders (ASD) is staggering. They are the most prevalent of the developmental disorders and their incidence is rising. However, the ASD phenotype variability is large, and ASD symptoms can manifest over a range of ages and to different degrees. In part for these reasons, the ASD clinical diagnosis is challenging and often is not made until 3-5 years of age. Thus, there remains an unmet need for a valid and reliable endophenotype which 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. The overarching goal of this proposal is to explore te utility of transcranial magnetic stimulation (TMS) measures of brain plasticity as a novel neurophysiologic endophenotype in high- and low-functioning adults and children with ASD. Our work to date demonstrates the potential utility of these measures in higher-functioning adults with ASD, and pilot data support the feasibility and safety of applying the same measures to children and lower functioning individuals in whom the value of such an endophenotype would be particularly high. We thus propose to apply single-pulse TMS to evaluate the modulation in corticospinal reactivity induced by a specific repetitive TMS protocol known as theta burst stimulation (TBS). The comparison of the motor responses induced by single-pulse TMS before and following TBS is a unique noninvasive measure of brain plasticity in humans, and we have found that it shows a reliable abnormality in high-functioning adult individuals with ASD. Our hypothesis is that the alteration of TBS-induced modulation of TMS responses is a common neuropathophysiologic trait that is reliably linked to the ASD phenotype, and that will not be limited to high functioning adults but be also valid in children and low-functioning individuals. W thus anticipate that data from the proposed studies will address an important need for a rapid, noninvasive, reliable and safe endophenotype available to patients with ASD across ages and level of function.

Public Health Relevance

The diagnosis of ASD can be difficult, is based on the manifestation of certain behaviors that show remarkable variability across affected individuals, and is frequently made relatively late in childhood. We aim to establish a neurophysiologic biomarker that will aid in ASD diagnosis, inform the development of effective therapies, and predict treatment response in future clinical trials. We propose to test the hypothesis that measures of brain plasticity obtained with transcranial magnetic stimulation will serve this purpose and be reliable and valid across the lifespan and across various functioning levels.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
Project #
Application #
Study Section
Child Psychopathology and Developmental Disabilities Study Section (CPDD)
Program Officer
Gilotty, Lisa
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Beth Israel Deaconess Medical Center
United States
Zip Code
Jannati, Ali; Block, Gabrielle; Oberman, Lindsay M et al. (2017) Interindividual variability in response to continuous theta-burst stimulation in healthy adults. Clin Neurophysiol 128:2268-2278
Fried, Peter J; Jannati, Ali; Davila-PĂ©rez, Paula et al. (2017) Reproducibility of Single-Pulse, Paired-Pulse, and Intermittent Theta-Burst TMS Measures in Healthy Aging, Type-2 Diabetes, and Alzheimer's Disease. Front Aging Neurosci 9:263
Gonzalez-Heydrich, Joseph; Enlow, Michelle Bosquet; D'Angelo, Eugene et al. (2016) N100 Repetition Suppression Indexes Neuroplastic Defects in Clinical High Risk and Psychotic Youth. Neural Plast 2016:4209831
Sharer, Elizabeth A; Mostofsky, Stewart H; Pascual-Leone, Alvaro et al. (2016) Isolating Visual and Proprioceptive Components of Motor Sequence Learning in ASD. Autism Res 9:563-9
Oberman, Lindsay M; Enticott, Peter G; Casanova, Manuel F et al. (2016) Transcranial magnetic stimulation in autism spectrum disorder: Challenges, promise, and roadmap for future research. Autism Res 9:184-203
Gonzalez-Heydrich, Joseph; Bosquet Enlow, Michelle; D'Angelo, Eugene et al. (2015) Early auditory processing evoked potentials (N100) show a continuum of blunting from clinical high risk to psychosis in a pediatric sample. Schizophr Res 169:340-345
Oberman, Lindsay M; Rotenberg, Alexander; Pascual-Leone, Alvaro (2015) Use of transcranial magnetic stimulation in autism spectrum disorders. J Autism Dev Disord 45:524-36
Oberman, Lindsay M; Pascual-Leone, Alvaro (2014) Hyperplasticity in Autism Spectrum Disorder confers protection from Alzheimer's disease. Med Hypotheses 83:337-42
Oberman, Lindsay M; Enticott, Peter G; Casanova, Manuel F et al. (2014) Transcranial magnetic stimulation (TMS) therapy for autism: an international consensus conference held in conjunction with the international meeting for autism research on May 13th and 14th, 2014. Front Hum Neurosci 8:1034
Oberman, Lindsay M; Pascual-Leone, Alvaro; Rotenberg, Alexander (2014) Modulation of corticospinal excitability by transcranial magnetic stimulation in children and adolescents with autism spectrum disorder. Front Hum Neurosci 8:627