title: Abnormal Cortical Plasticity in Youth with Autism Spectrum Disorder: A Transcranial Magnetic Stimulation Case-Control Pilot Study.
abstract: 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.
authors.affiliation: 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.
authors.forename: Ernest V
authors.initials: EV
authors.lastname: Pedapati
authors.affiliation: 2 Division of Child and Adolescent Psychiatry, Cincinnati Children's Hospital Medical Center , Cincinnati, Ohio.
authors.forename: Donald L
authors.initials: DL
authors.lastname: Gilbert
authors.affiliation: 1 Division of Neurology, Cincinnati Children's Hospital Medical Center , Cincinnati, Ohio.
authors.forename: Craig A
authors.initials: CA
authors.lastname: Erickson
authors.affiliation: 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.
authors.forename: Paul S
authors.initials: PS
authors.lastname: Horn
authors.affiliation: 4 Division of Developmental and Behavioral Pediatrics, Cincinnati Children's Hospital Medical Center , Cincinnati, Ohio.
authors.forename: Rebecca C
authors.initials: RC
authors.lastname: Shaffer
authors.affiliation: 1 Division of Neurology, Cincinnati Children's Hospital Medical Center , Cincinnati, Ohio.
authors.forename: Logan K
authors.initials: LK
authors.lastname: Wink
authors.affiliation: 1 Division of Neurology, Cincinnati Children's Hospital Medical Center , Cincinnati, Ohio.
authors.forename: Cameron S
authors.initials: CS
authors.lastname: Laue
authors.affiliation: 2 Division of Child and Adolescent Psychiatry, Cincinnati Children's Hospital Medical Center , Cincinnati, Ohio.
authors.forename: Steve W
authors.initials: SW
authors.lastname: Wu
mesh_terms: D000293:Adolescent; D000067877:Autism Spectrum Disorder / Q000503:physiopathology*; D016022:Case-Control Studies; D002648:Child; D004576:Electromyography; D019054:Evoked Potentials, Motor / Q000502:physiology; D005260:Female; D006801:Humans; D016014:Linear Models; D008297:Male; D009044:Motor Cortex; D009473:Neuronal Plasticity; D010865:Pilot Projects; D013997:Time Factors; D050781:Transcranial Magnetic Stimulation / Q000379:methods*