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Transcranial Magnetic Stimulation 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 The Harvard community has made this article openly available. Please share how this access benefits you. Your story matters. Citation Oberman, Lindsay M., Peter G. Enticott, Manuel F. Casanova, Alexander Rotenberg, Alvaro Pascual-Leone, and James T. McCracken. 2015. “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.” Frontiers in Human Neuroscience 8 (1): 1034. doi:10.3389/fnhum.2014.01034. http://dx.doi.org/10.3389/fnhum.2014.01034. Published Version doi:10.3389/fnhum.2014.01034 Accessed February 17, 2015 11:31:18 AM EST Citable Link http://nrs.harvard.edu/urn-3:HUL.InstRepos:13890712 Terms of Use This article was downloaded from Harvard University's DASH repository, and is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms- of-use#LAA (Article begins on next page) OPINION ARTICLE published: 06 January 2015 HUMAN NEUROSCIENCE doi: 10.3389/fnhum.2014.01034 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 Lindsay M. Oberman 1*, Peter G. Enticott 2, Manuel F. Casanova 3, Alexander Rotenberg 4,5, Alvaro Pascual-Leone 5 and James T. McCracken 6 1 Neuroplasticity and Autism Spectrum Disorder Program, Department of Psychiatry and Human Behavior, E.P.Bradley Hospital and Warren Alpert Medical School, Brown University, Providence, RI, USA 2 Cognitive Neuroscience Unit, School of Psychology, Deakin University, Burwood, VIC, Australia 3 Department of Psychiatry and Behavioral Science, University of Louisville, Louisville, KY, USA 4 Neuromodulation Program, Department of Neurology, Boston Children’s Hospital and Harvard Medical School, Boston, MA, USA 5 Berenson-Allen Center for Noninvasive Brain Stimulation, Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA 6 Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA, USA *Correspondence: [email protected] Edited by: Rachael D. Seidler, University of Michigan, USA Reviewed by: Jorge Leon Morales-Quezada, Laboratory of Neuromodulation, USA Keywords: Autism Spectrum Disorder, transcranial magnetic stimulation, pathophysiology, therapy, consensus The Centers for Disease Control and where small intracranial electrical cur- stimulation and knowledge of underlying Prevention currently estimate the preva- rents are generated by a rapidly fluctuating symptom pathophysiology. TMS is consid- lence of Autism Spectrum Disorder (ASD) extracranial magnetic field. In an effort to ered quite safe if applied within current in the U.S. at 1:68 children (Baio, 2014). share recent progress in the use of TMS in safety guidelines; however, it does pose Despite decades of research across mul- ASD, promote collaboration across labora- some risk for adverse side-effects (Rossi tiple levels of analysis, we currently lack tories, and establish consensus on param- et al., 2009). Though relatively few patients a reliable biomarker that may facilitate eters that may be useful for the study of with ASD have participated in TMS pro- diagnosis, illuminate pathophysiology, pathophysiology and the potential treat- tocols, the frequency and quality of side- or guide treatment. The development ment of ASD, leading experts in the effects shown thus far approximates that of novel treatment strategies for ASD field gathered in Atlanta, GA on May seen in the general population (Oberman will require efforts for better clinical 13th and 14th 2014 for the “Transcranial et al., 2013). As with any other condition, characterization, identification of more Magnetic Stimulation (TMS) Therapy factors including medications and medical homogeneous subgroups for studies, for Autism Consensus Conference” orga- history need to be assessed when deter- and improved understanding of under- nized and supported by the Clearly mining risk for an individual. There are lying pathophysiology. There is growing Present Foundation with additional sup- currently no identified ASD-specific risk support for early intensive interven- port from Neuronetics, Inc. and Autism factors for TMS-induced adverse effects. tions in this population (Reichow, 2012). Speaks. Even though ASD can be associated with Pharmacological treatments have been Alvaro Pascual-Leone began the confer- an increased risk for seizures, in TMS showntobeeffectiveintreatingsome ence by discussing the basic mechanisms studiestodate,thereisnoevidenceof of the common secondary and comorbid and safety of TMS in clinical populations. increased epileptogenic risk in ASD when features of ASD (Hampson et al., 2012), TMScanbeappliedinsinglepulsesto safety guidelines and recommendations but there is currently no pharmacotherapy investigate corticospinal excitability, pairs are followed. conclusively shown to improve the core of pulses to study intracortical inhibi- Manuel Casanova then provided a tar- symptoms (Oberman, 2012). tion and facilitation, and repeated trains geted review of the literature on the patho- Recently a number of investigators have of TMS (rTMS) to both to study and physiology of ASD. Postmortem studies begun to explore the use of transcra- therapeutically modulate excitability and have shown evidence of abnormalities of nial magnetic stimulation (TMS) as a plasticity in a number of neurologi- neuronal migration in the brains of indi- tool to characterize ASD pathophysiol- cal and psychiatric conditions (Kobayashi viduals with ASD (Bailey et al., 1998), ogy, and to test its therapeutic potential. and Pascual-Leone, 2003). The effects of which include displaced neurons manifest- TMS is a safe and well-tolerated method rTMS can be expected to differ consid- ing as focal cortical dysplasias in a major- for non-invasive focal cortical stimulation erably by virtue of varying parameters of ity of individuals with ASD (Casanova Frontiers in Human Neuroscience www.frontiersin.org January 2015 | Volume 8 | Article 1034 | 1 Oberman et al. Transcranial magnetic stimulation therapy for autism et al., 2013). Morphometric analysis of Low-frequency stimulation to left pars AUTHOR CONTRIBUTIONS cells within the malformed cortex has sug- triangularis resulted in improved object Lindsay M. Oberman, Peter G. gested a reduced number of interneurons naming in a single session study (Fecteau Enticott, Manuel F. Casanova, Alvaro (Casanova et al., 2013). This is consistent et al., 2011). High-frequency stimula- Pascual-Leone, and James T. McCracken with previous reports of abnormalities in tion, designed to enhance excitability, has contributed to the organization of the ASD within the peripheral cortical mini- suggested improvements in self-reported conference, were invited speakers to the column neuropil space, the compartment social relating and social anxiety follow- conference, and lead the discussion dur- where most inhibitory cells are located ing medial prefrontal cortex stimulation ing the conference. Alexander Rotenberg (Casanova et al., 2002). Both EEG and (Enticott et al., 2014) and significant contributed to the organization of the vibrotactile studies corroborate a deficit improvements in eye-hand coordina- conference, and the discussion during the of cortical lateral inhibition (Keita et al., tion following premotor stimulation conference. All authors contributed to the 2011; Puts et al., 2014). He proposed that (Panerai et al., 2013). Although an emerg- writing of the manuscript. this deficit could account for the seizures ing literature, these studies collectively and sensory abnormalities often reported provide support for the potential effi- ACKNOWLEDGMENT in ASD. cacy of rTMS in ASD (Oberman et al., The content is solely the responsibility Lindsay Oberman discussed the use 2013). However, the small study samples, of the authors and does not necessar- of TMS as an investigative device to lack of blind assessments, and limited ily represent the official views of Clearly study cortical excitability and plasticity in use of control or comparison conditions Present Foundation, Autism Speaks, or ASD. These studies show that a num- limit the interpretation of these early Neuronetics, Inc. ber of basic mechanisms and circuits are investigations. atypical while other measures appear to James McCracken concluded the con- be normal (see Oberman et al., 2013). ference by discussing key factors to con- REFERENCES Bailey, A., Luthert, P., Dean, A., Harding, B., Janota, I., Specifically, motor thresholds and base- sider when designing clinical trials for Montgomery, M., et al. (1998). A clinicopathologi- line motor-cortical excitability measures ASD. These factors included identification cal study of autism. Brain 121 (Pt 5), 889–905. doi: appear to be normal. There is hetero- of valid and reliable endpoints, incorpora- 10.1093/brain/121.5.889 geneity in the response to paired-pulse tion of blind assessments, need for cred- Baio, J. (2014). Prevalence of autism spectrum dis- paradigms with impaired inhibition in ible control conditions, establishment of order among children
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