N EUROMETHODS. Series Editor Wolfgang Walz University of Saskatchewan Saskatoon, SK, Canada. For further volumes:

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1 N EUROMETHODS Series Editor Wolfgang Walz University of Saskatchewan Saskatoon, SK, Canada For further volumes:

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3 Transcranial Magnetic Stimulation Edited by Alexander Rotenberg Neuromodulation Program, Department of Neurology, Boston Children s Hospital, Harvard Medical School, Boston, MA, USA Jared Cooney Horvath Psychological Sciences, University of Melbourne, Melbourne, VIC, Australia Alvaro Pascual-Leone Berenson Allen Center for Noninvasive Brain Stimulation, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA

4 Editors Alexander Rotenberg Neuromodulation Program Department of Neurology Boston Children s Hospital Harvard Medical School Boston, MA, USA Jared Cooney Horvath Psychological Sciences University of Melbourne Melbourne, VIC, Australia Alvaro Pascual-Leone Berenson Allen Center for Noninvasive Brain Stimulation Department of Neurology Beth Israel Deaconess Medical Center Harvard Medical School Boston, MA, USA ISSN ISSN (electronic) ISBN ISBN (ebook) DOI / Springer New York Heidelberg Dordrecht London Library of Congress Control Number: Springer Science+Business Media New York 2014 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. Exempted from this legal reservation are brief excerpts in connection with reviews or scholarly analysis or material supplied specifically for the purpose of being entered and executed on a computer system, for exclusive use by the purchaser of the work. Duplication of this publication or parts thereof is permitted only under the provisions of the Copyright Law of the Publisher s location, in its current version, and permission for use must always be obtained from Springer. Permissions for use may be obtained through RightsLink at the Copyright Clearance Center. Violations are liable to prosecution under the respective Copyright Law. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. While the advice and information in this book are believed to be true and accurate at the date of publication, neither the authors nor the editors nor the publisher can accept any legal responsibility for any errors or omissions that may be made. The publisher makes no warranty, express or implied, with respect to the material contained herein. Printed on acid-free paper Humana Press is a brand of Springer Springer is part of Springer Science+Business Media (

5 Series Preface Experimental life sciences have two basic foundations: concepts and tools. The Neuromethods series focuses on the tools and techniques unique to the investigation of the nervous system and excitable cells. It will not, however, shortchange the concept side of things as care has been taken to integrate these tools within the context of the concepts and questions under investigation. In this way, the series is unique in that it not only collects protocols but also includes theoretical background information and critiques which led to the methods and their development. Thus it gives the reader a better understanding of the origin of the techniques and their potential future development. The Neuromethods publishing program strikes a balance between recent and exciting developments like those concerning new animal models of disease, imaging, in vivo methods, and more established techniques, including, for example, immunocytochemistry and electrophysiological technologies. New trainees in neurosciences still need a sound footing in these older methods in order to apply a critical approach to their results. Under the guidance of its founders, Alan Boulton and Glen Baker, the Neuromethods series has been a success since its first volume published through Humana Press in The series continues to flourish through many changes over the years. It is now published under the umbrella of Springer Protocols. While methods involving brain research have changed a lot since the series started, the publishing environment and technology have changed even more radically. Neuromethods has the distinct layout and style of the Springer Protocols program, designed specifically for readability and ease of reference in a laboratory setting. The careful application of methods is potentially the most important step in the process of scientific inquiry. In the past, new methodologies led the way in developing new disciplines in the biological and medical sciences. For example, physiology emerged out of anatomy in the nineteenth century by harnessing new methods based on the newly discovered phenomenon of electricity. Nowadays, the relationships between disciplines and methods are more complex. Methods are now widely shared between disciplines and research areas. New developments in electronic publishing make it possible for scientists that encounter new methods to quickly find sources of information electronically. The design of individual volumes and chapters in this series takes this new access technology into account. Springer Protocols makes it possible to download single protocols separately. In addition, Springer makes its print-on-demand technology available globally. A print copy can therefore be acquired quickly and for a competitive price anywhere in the world. Wolfgang Walz Saskatoon, SK, Canada v

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7 Pref ace Transcranial magnetic stimulation (TMS) is no longer a novel experimental method. TMS is an established therapeutic and diagnostic technique in clinical practice. Hundreds of clinical patients a year undergo TMS to treat their medication-resistant depression or to establish detailed cortical motor and language maps prior to surgical or other therapeutic interventions. In addition, TMS is a valuable neuroscientific tool, and many patients and healthy volunteers enroll each year into research studies that utilize TMS to characterize cortical reactivity and plasticity, evaluate corticospinal and cortico-cortical connectivity, explore causal relations between brain activity and behavior, assess the impact of pharmacologic and other interventions, etc. According to PubMed, more TMS studies have been published in the last 5 years than in the previous 20 years, and 2013, at the writing of this preface, was on track to break the 1,000 papers in a year mark. Clinical trials are currently underway around the globe exploring the effects of TMS in diverse disease states including autism, epilepsy, migraine, tinnitus, stroke recovery, schizophrenia, Parkinson s, and Alzheimer s disease. As with any tool, the rapidly growing use of TMS is a mixed blessing. On the one hand, an expanded TMS practitioner base allows for more, better, and deeper exploration of the technological, scientific, diagnostic, and therapeutic possibilities. On the other hand, as the number of TMS users grows, it becomes more and more difficult to maintain a keen grasp of foundational and emerging methodologies. Without care, the TMS research field can easily divide into a number of camps with each utilizing and purporting the benefits of their own devices, stimulation protocols, and methodologies. Fractionation based on informed practice and therapeutic evolution is not necessarily a bad thing; however, fractionation due to non-standardized or incoherent education and communication is potentially dangerous for the future of TMS. This book aims to enable new and existing practitioners to learn and follow established TMS protocols. We describe many tried and true techniques: from single to multiple pulse TMS paradigms; from clinical to academic pursuits; from electromyographic to neuroimaging measurements. We hope that this work will serve not only as a good methodological introduction to those new to the TMS field, but also as a source of continual reference for experienced practitioners. Boston, MA, USA Melbourne, VIC, Australia Boston, MA, USA Alexander Rotenberg Jared Cooney Horvath Alvaro Pascual- Leone vii

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9 Contents Series Preface Preface Contributors v vii xi PART I TRANSCRANIAL MAGNETIC STIMULATION FUNDAMENTALS 1 The Transcranial Magnetic Stimulation (TMS) Device and Foundational Techniques Alexander Rotenberg, Jared Cooney Horvath, and Alvaro Pascual-Leone 2 Transcranial Magnetic Stimulation (TMS) Safety Considerations and Recommendations Umer Najib and Jared Cooney Horvath 3 Neuronavigation for Transcranial Magnetic Stimulation Roch Comeau 4 Reaching Deep Brain Structures: The H-Coils Yiftach Roth and Abraham Zangen PART II TRANSCRANIAL MAGNETIC STIMULATION METHODS 5 Single-Pulse Transcranial Magnetic Stimulation (TMS) Protocols and Outcome Measures Faranak Farzan 6 Paired-Pulse Transcranial Magnetic Stimulation (TMS) Protocols Andrew Vahabzadeh-Hagh 7 Repetitive Transcranial Magnetic Stimulation (rtms) Protocols Lindsay Oberman PART III EXPERIMENTAL DESIGN 8 Offline and Online Virtual Lesion Protocols Shirley Fecteau and Mark Eldaief 9 State-Dependent Transcranial Magnetic Stimulation (TMS) Protocols Juha Silvanto and Zaira Cattaneo PART IV MULTIMODAL CONSIDERATIONS 10 Combination of Transcranial Magnetic Stimulation (TMS) with Functional Magnetic Resonance Imaging Joan A. Camprodon and Mark A. Halko 11 Electroencephalography During Transcranial Magnetic Stimulation: Current Modus Operandi Marine Vernet and Gregor Thut ix

10 x Contents PART V CLINICAL CONSIDERATIONS 12 Transcranial Magnetic Stimulation (TMS) Clinical Applications: Therapeutics Jared Cooney Horvath, Umer Najib, and Daniel Press 13 Transcranial Magnetic Stimulation (TMS) Clinical Applications: Diagnostics Josep Valls-Sole 14 A Review of Current Clinical Practice in the Treatment of Major Depression Mark A. Demitrack and David G. Brock 15 Protocol for Depression Treatment Utilizing H-Coil Deep Brain Stimulation Yiftach Roth and Abraham Zangen 16 Navigated Transcranial Magnetic Stimulation: Principles and Protocol for Mapping the Motor Cortex Jari Karhu, Henri Hannula, Jarmo Laine, and Jarmo Ruohonen 17 Speech Mapping with Transcranial Magnetic Stimulation Phiroz E. Tarapore Index

11 Contributors DAVID G. BROCK Neuronetics Inc, Malvern, PA, USA JOAN A. CAMPRODON Massachusetts General Hospital, Boston, MA, USA ZAIRA CATTANEO University of Pavia, Pavia, Italy ROCH COMEAU Rogue Research Inc., Montreal, QC, Canada MARK A. DEMITRACK Neuronetics Inc., Malvern, PA, USA MARK ELDAIEF Berenson-Allen Center for Noninvasive Brain Stimulation, Beth Israel Deaconess Medical Center, Boston, MA, USA FARANAK FARZAN Centre for Addiction and Mental Health, Toronto, ON, Canada SHIRLEY FECTEAU Laval University, Quebec City, QC, Canada MARK A. HALKO Berenson-Allen Center for Noninvasive Brain Stimulation, Beth Israel Deaconess Medical Center, Boston, MA, USA HENRI HANNULA Nexstim Ltd., Helsinki, Finland JARED COONEY HORVATH Psychological Sciences, University of Melbourne, Melbourne, VIC, Australia JARI KARHU Nexstim Ltd., Helsinki, Finland JARMO LAINE Nexstim Ltd., Helsinki, Finland UMER NAJIB Ruby Memorial Hospital, Morgantown, WV, USA LINDSAY OBERMAN E.P. Bradley Hospital, East Providence, RI, USA ALVARO PASCUAL-LEONE Berenson Allen Center for Noninvasive Brain Stimulation, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA DANIEL PRESS Berenson-Allen Center for Noninvasive Brain Stimulation, Beth Israel Deaconess Medical Center, Boston, MA, USA ALEXANDER ROTENBERG Neuromodulation Program, Department of Neurology, Boston Children s Hospital, Harvard Medical School, Boston, MA, USA YIFTACH ROTH Ben-Gurion University of the Negev, Be er Sheva, Israel JARMO RUOHONEN Nexstim Ltd., Helsinki, Finland JUHA SILVANTO O.V. Lounasmaa Laboratory, Aalto University, Aalto, Finland PHIROZ E. TARAPORE University of California San Francisco, San Francisco, CA, USA GREGOR THUT University of Glasgow, Glasgow, UK ANDREW VAHABZADEH-HAGH David Geffen School of Medicine, UCLA, Los Angeles, CA, USA JOSEP VALLS-SOLE Hospital Clinic, Barcelona, Spain MARINE VERNET University Pierre et Marie Curie, Paris, France ABRAHAM ZANGEN Ben-Gurion University of the Negev, Be er Sheva, Israel xi