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J Child Adolesc Psychopharmacol. 2016 Sep;26(7):625-31. doi: 10.1089/cap.2015.0183. Epub 2016 Mar 23.

Abnormal Cortical Plasticity in Youth with Autism Spectrum Disorder: A Transcranial Magnetic Stimulation Case-Control Pilot Study.

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1 Division of Neurology, Cincinnati Children's Hospital Medical Center , Cincinnati, Ohio.
2 Division of Child and Adolescent Psychiatry, Cincinnati Children's Hospital Medical Center , Cincinnati, Ohio.
3 Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center , Cincinnati, Ohio.
4 Division of Developmental and Behavioral Pediatrics, Cincinnati Children's Hospital Medical Center , Cincinnati, Ohio.



This case-control study investigated the use of a low-intensity repetitive transcranial magnetic stimulation (rTMS) protocol to measure motor cortex (M1) plasticity in youth with autism spectrum disorder (ASD) compared with typically developing children (TDC). We hypothesized that impairments in long-term potentiation-like properties represent a neurophysiological biomarker of abnormal cortical function in ASD.


We studied youth with ASD aged 11-18 years and matched controls (TDC). Intermittent theta burst stimulation (iTBS) was delivered to the dominant M1 at an intensity of 70% of resting motor threshold. Suprathreshold single-pulse TMS was performed to compare amplitudes of motor-evoked potentials (MEP) measured from surface electromyography electrodes on a target muscle before (20 pulses) and after (10 pulses/time point) iTBS at predefined timepoints (up to 30 minutes) to measure any potentiation effects. A linear mixed model was used to examine group differences in MEP amplitudes over time following iTBS.


Nine youth with ASD (mean age 15.6; 7 males; 6 right-hand dominant) and 9 TDC (mean age 14.5; 5 males; 9 right-hand dominant) participated. All subjects tolerated the procedure well. Both groups had a mean increase in excitability after iTBS for 30 minutes; however, the time course of excitability changes differed (F9,144 = 2.05; p = 0.038). Post-hoc testing identified a significant decrease in amplitude of the ASD group at 20 minutes following iTBS compared with the TDC after correcting for multiple comparisons.


In this study, we demonstrate early evidence for a potential physiological biomarker of cortical plasticity in youth with ASD using a rapid low-intensity rTMS protocol with a discriminate measure at 20 minutes following stimulation. The procedure was well tolerated by all 18 participants. Future work will include modification of the protocol to improve the ability to distinguish subtypes of ASD based on behavioral and cognitive testing.

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Conflict of interest statement

All contributing authors have read and approved the submission of this manuscript to the journal. Additionally, all authors report no direct conflicts with the content of this report. Dr. Pedapati receives research support from the Cincinnati Children's Hospital Research Foundation and the American Academy Child and Adolescent Psychiatry. Dr. Gilbert has received honoraria from the Tourette Syndrome Association/Centers for Disease Control and Prevention and the American Academy of Pediatrics, serves on the medical advisory board for the Tourette Syndrome Association, has received book royalties from Elsevier. Dr. Gilbert has received research support (for Tourette Syndrome, ADHD) from the NIH (NIMH R01 MH092520, NIMH R01 MH081854, NIMH R01 104651, NINDS R01 NS085023), from Ecopipam Pharmaceuticals (clinical trial, Tourette Syndrome). Dr. Erickson is a consultant to and holds equity in Confluence Pharmaceuticals and is a consultant to Alcobra Pharmaceuticals. Dr. Erickson is a past consultant to the Roche Group and Novartis. Dr. Erickson holds nonrelated IP held by CCHMC and Indiana University. Dr. Erickson receives research grant support from the John Merck Fund, CCHMC, Autism Speaks, the National Fragile X Foundation, The Roche Group, Neuren Pharmaceuticals, Synapdx, and Riovant Sciences Ltd. Dr. Horn receives research support from the NIH/NINDS and the John Merck Fund. Dr. Shaffer has no disclosures to report. Dr. Wink's current research is supported by the Simons Research Foundation, the John Merck Fund, United Stated Department of Defense, Autism Speaks, SynapDx, and Riovant Sciences Ltd. Dr. Wink has served as a past consultant for Otsuka. Cameron Laue has no disclosures to report. Dr. Wu receives research support from NIH (R01MH078160) and from Ecopipam Pharmaceuticals (clinical trial, Tourette Syndrome).

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