title: Modulation of corticospinal excitability by transcranial magnetic stimulation in children and adolescents with autism spectrum disorder.
abstract: The developmental pathophysiology of autism spectrum disorders (ASD) is currently not fully understood. However, multiple lines of evidence suggest that the behavioral phenotype may result from dysfunctional inhibitory control over excitatory synaptic plasticity. Consistent with this claim, previous studies indicate that adults with Asperger's Syndrome show an abnormally extended modulation of corticospinal excitability following a train of repetitive transcranial magnetic stimulation (rTMS). As ASD is a developmental disorder, the current study aimed to explore the effect of development on the duration of modulation of corticospinal excitability in children and adolescents with ASD. Additionally, as the application of rTMS to the understanding and treatment of pediatric neurological and psychiatric disorders is an emerging field, this study further sought to provide evidence for the safety and tolerability of rTMS in children and adolescents with ASD. Corticospinal excitability was measured by applying single pulses of TMS to the primary motor cortex both before and following a 40 s train of continuous theta burst stimulation. 19 high-functioning males ages 9-18 with ASD participated in this study. Results from this study reveal a positive linear relationship between age and duration of modulation of rTMS after-effects. Specifically we found that the older participants had a longer lasting response. Furthermore, though the specific protocol employed typically suppresses corticospinal excitability in adults, more than one third of our sample had a paradoxical facilitatory response to the stimulation. Results support the safety and tolerability of rTMS in pediatric clinical populations. Data also support published theories implicating aberrant plasticity and GABAergic dysfunction in this population.
authors.affiliation: Department of Neurology, Berenson-Allen Center for Noninvasive Brain Stimulation, Beth Israel Deaconess Medical Center - Harvard Medical School Boston, MA, USA ; Neuromodulation Program and Division of Epilepsy and Clinical Neurophysiology, Department of Neurology, Boston Children's Hospital - Harvard Medical School Boston, MA, USA ; Neuroplasticity and Autism Spectrum Disorder Program, E. P. Bradley Hospital, East Providence, RI USA ; Department of Psychiatry and Human Behavior, Warren Alpert Medical School of Brown University, East Providence, RI USA.
authors.forename: Lindsay M
authors.initials: LM
authors.lastname: Oberman
authors.affiliation: Department of Neurology, Berenson-Allen Center for Noninvasive Brain Stimulation, Beth Israel Deaconess Medical Center - Harvard Medical School Boston, MA, USA.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Pascual-Leone
authors.affiliation: Department of Neurology, Berenson-Allen Center for Noninvasive Brain Stimulation, Beth Israel Deaconess Medical Center - Harvard Medical School Boston, MA, USA ; Neuromodulation Program and Division of Epilepsy and Clinical Neurophysiology, Department of Neurology, Boston Children's Hospital - Harvard Medical School Boston, MA, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Rotenberg
keywords: GABA; autism spectrum disorders; development; plasticity; theta burst stimulation; transcranial magnetic stimulation