VOL. 29 • NO. 3 • June 2014

THE OFFICIAL NEWSLETTER OF THE WORLD FEDERATION OF

Experiments Into Readiness for Action INSIDE features 50th Anniversary of the IAPRD and PSN Join Hands: First Course and Botox Workshop The specialty of neurology shows remarkable growth in last decade By Lüder Deecke potential and a selection of the in Pakistan. special session inaugurated and main research results of our page 2 chaired by Mark Hallett, Bethesda, experiments into readiness for Maryland, at the International action. A Neurology Cooperation Around Congress of Clinical the World (ICCN2014) in March 2014 in Berlin The History of the Since I wrote my last column, many celebrated the 50th anniversary of the Bereitschaftspotential events have occurred. Bereitschaftspotential. The session in- In 1964, my mentor Hans Helmut page 3 cluded lectures by Lüder Deecke, Vienna: Kornhuber (1928-2009) and I discovered “Experiments Into Readiness for Action — the readiness potential (Kornhuber and Bereitschaftspotential;” Hiroshi Shibasaki, Deecke, 1964). We submitted the full voluntary movement and named it the in Literary Works Around Akio Ikeda, Kyoto, Japan: “Generator paper in the same year. It was published Bereitschaftspotential (BP) or readiness the World Mechanisms of BP and Its Clinical Applica- in the first 1965 issue of “Pflügers Archiv” potential. (See Figure 1B.) There are few other neurological tion;” Gert Pfurtscheller, Graz, Austria: (Kornhuber and Deecke, 1965). The BP is the electrophysiological sign disorders with such a constant presence “Movement-Related Desynchronization We described a novel method, reverse of planning, preparation and initiation in literary works as apoplexy. and Resting State Sensorimotor Net- averaging, for recording brain electrical of volitional acts. How did the idea come page 4 works;” and Ross Cunnington, Brisbane, activity prior to voluntary movement up to record brain potentials preceding Australia: “Concurrent fMRI-EEG and the in humans by noninvasive means and human voluntary movements in the EEG? Editor’s Update and Selected Bereitschafts-BOLD-Effect.” The session presented the first fundamental results It began on a Saturday in May 1964 when Articles From JNS was well accepted. obtained with this method. We found Kornhuber invited his doctoral student Check out the latest articles from the In this paper, I would like to give an that a negative electrical cortical po- L.D. for lunch into the ‘Gasthof zum Journal of Neurological Sciences. outline of the history of the Bereitschafts- tential consistently preceded human see BEREITSCHAFTSPOTENTIAL, page 6 page 11 The World of Neurology Comes Together at the AAN Annual Meeting he 2014 Annual Meeting of the the Presidential Lecture on “Challenges tion of a unique basic and translational re- American Academy of Neurology to Ethics and Professionalism Facing the molecular and func- search, and innovative technical T (AAN) attracted more than 13,000 Contemporary Neurologist.” The George tional microglia sig- developments were shared and neurology professionals to Philadelphia, C. Cotzias Lecture featured Stefan M. nature in health and discussed at the Contemporary a city rich in its own neurology-related Pulst, MD, FAAN, speaking on “Degen- disease; emerging Clinical Issues Plenary Session. history. More than 2,500 presentations erative Ataxias: From Genes to Thera- concepts in chronic This year’s topics were acute of cutting-edge research were available pies.” The Sidney Carter Award in Child traumatic encepha- ischemic stroke, Friedreich’s to attendees from across the world. Neurology went to Darryl C. De Vivo, lopathy; functional ataxia, insomnia, epilepsy, func- The number of non-U.S. attendees was MD, FAAN, who expounded on “Rare connectivity and tional (psychogenic) disorders nearly 4,000. Diseases and Neurological Phenotypes.” functional imag- and the Parkinson’s disease Science and continuing medical educa- Finally, David M. Holtzman, MD, FAAN, ing in movement Progression Marker Initiative. tion are the main draws to the Annual shared “Alzheimer’s Disease in 2014: disorders; and the At the Frontiers in Trans- Meeting, and this year was no exception. Mapping a Road Forward,” as the Robert global epidemic in lational Plenary One of the highlights was the Presiden- Wartenberg lecturer. stroke. Session, attendees heard about tial Plenary Session, the AAN’s premier The Hot Topics Plenary Session Abstracts related the clinical aspects of tissue lecture awards for clinically relevant re- presented recent research findings and to new therapeutic environments for brain repair; search. James L. Bernat, MD, FAAN, gave clinical implications regarding identifica- developments, clinical applications of see Annual Meeting, page 5 2 www.wfneurology.org • JUNE 2014

From the Editor-in-Chief International Colloquium that included topics such as “Dealing With Common Disorders With Limited Resources,” WORLD FEDERATION OF NEUROLOGY Editor in Chief The section elected Farrah Mateen “Successful Examples of International Donald H. Silberberg AAN Meeting from in the Department of Neurology Collaboration,” and Information on Assistant Editor at Massachusetts General fellowships in the U.S. An Keith Newton in Review Hospital as its new presi- Integrated Neuroscience Ses- WFN OFFICERS dent. If you are interested sion featured oral presenta- President Raad Shakir (United Kingdom) By Donald Silberberg in seeing the activities of tions on the “Global Impact First Vice President William Carroll (Australia) Secretary-Treasurer General Wolfgang Grisold s an addendum to the report the Global Health Section, of Non-Communicable (Austria) from the American Academy contact Franziska Schwarz at Neurological Diseases,” with of Neurology in this issue, I Franziska [email protected]. poster sessions before and ELECTED TRUSTEES A Gallo Diop (Senegal) wish to add that in 2012 the AAN International activities after. Finally, an Ethics Collo- Gustavo Roman (USA) established a Global Health Section. during the Philadelphia quium included a presentation REGIONAL DIRECTORS At the section meeting during the meeting included: on “Clinical Trials Involving Mohamed S. El-Tamawy (Pan Arab) Timothy Pedley (North America) 2014 AAN meeting in Philadelphia, a conference titled Donald H. International Subjects.” Richard Hughes (Europe) Jerome Chin, the outgoing presi- “Controversies in Global Silberberg In these ways, the AAN Riadh Gouider (Pan Africa) Marco Tulio Medina (Latin America) dent of the section, announced that Health: Corticosteroids for is now playing an important Man Mohan Mehndiratta (Asia-Oceania) the section now has more than 300 Meningitis,” a seminar on role in global neurology

EXECUTIVE DIRECTOR members, including many from “Global Health Challenges: together with the World Keith Newton outside the U.S. Neurology in Developing Countries,” an Federation of Neurology. • 1 Lyric Square Hammersmith, London W6 0NB, UK Tel: +44 (0) 203 542 7857/8 Fax: +44 (0) 203 008 6161 [email protected] IAPRD and PSN Join Hands: EDITOR OF THE JOURNAL and treatment while neurodegeneration OF THE NEUROLOGICAL SCIENCES John England (USA) in children: diagnostic issues in developing First Movement Disorder countries was presented by Tipu Sultan from Children Hospital Lahore. A unique and thought-provoking session of this was Course and Botox Workshop in the Neurology Training and Advo- WORLD NEUROLOGY, an official publication of the World Federation of Neurology, provides reports cacy session. This session highlighted the from the leadership of the WFN, its member By Abdul Malik, MBBS, DCN, MD conference, the Sardar Alam, outgoing glimpses on post-graduate neurology in societies, neurologists around the globe and news from the cutting-edge of clinical neurology. Con- he specialty of neurology shows Pakistan Society of Neurology (PSN) Pakistan by Sarwar Siddiqi, psychiatric care tent for World Neurology is provided by the World remarkable growth in last decade in president, welcomed the delegates and and interface with neurology by Prof. Iqbal Federation of Neurology and Ascend Integrated Pakistan. The 21st meeting of the presented the report of the last two years Afridi, neurosurgery care and interface Media. T Disclaimer: The ideas and opinions expressed in Pakistan Society of Neurology (PSN) was of the society’s works. Prof. M. Wasay, with neurology by Prof. Junaid Ashraf and World Neurology do not necessarily reflect those of organized in collaboration with the Inter- chairman of the organizing committee, advocacy for neurological care in Pakistan the World Federation of Neurology or the publisher. The World Federation of Neurology and Ascend national Association of Parkinson’s and stated the statistics of neurology care and Prof. Rasheed Jooma. Integrated Media will not assume responsibility for Related Disorders (IAPRD) March 28-30 in neurologist in Pakistan. He said that for There were 15 original oral presenta- damages, loss or claims of any kind arising from or related to the information contained in this Karachi, Pakistan. every one million people only one neurolo- tions and 20 poster presentations from publication, including any claims related to the There were eight scientific sessions and a gist is available. all major institutes of the country. This products, drugs or services mentioned herein. half-day Botox Hands-On Workshop in this Editorial Correspondence: Send editorial correspon- conference. The speakers from Netherlands, dence to World Neurology, Dr. Donald H. Silberberg at [email protected]. the United States, Saudi Arabia and Pakistan World Neurology, ISSN: 0899-9465, is published shared their experiences pertaining to bimonthly by Ascend Integrated Media, 7015 College Blvd., Suite 600, neurology. The core of the discussion was Overland Park, KS, 66211. the advances in movement disorders and the Phone +1-913-344-1300 Fax: +1-913-344-1497. newer therapies now emerging. The guest ©2014 World Federation of Neurology faculty from the IAPRD had given a detailed overview on the topic. An ample demonstration on patients was given with the title of “Botulinum Toxin Hands-On Use in Dystonia” by Prof. Daniel Publishing Partner Truong from The Parkinson and Movement Ascend Integrated Media Disorder Institute (U.S.). He also delivered a President and CEO lecture on Clinical Approach and Manage- Cameron Bishop ment of Dystonias. Prof. Ronald Pfeiffer, Vice President of Content vice chair of the Department of Neurol- Rhonda Wickham ogy at the University of Tennessee Health Vice President of eMedia Science Center (U.S.) gave us an updated Scott Harold overview on Autonomic Dysfunction in PSN conference organizers and faculty with Erik Wolters, Daniel Truong and R. Pfeiffer. Vice President of Sales Parkinson’s Disease and Drug-Induced Donna Sanford Movement Disorders. The keynote speaker In the scientific sessions, Asif Moin, year, PSN officially had given best oral Project Manager was Prof. Erik Wolters, IAPRD president, from Saudi Arabia, delivered the talk on presentation and poster presentation Amanda Marriott who is working in the Universities of Maas- utilization of SPECT and PET in epilepsy; awards. There was also an inaugural din- Art Directors tricht and Zurich. He delivered his lectures Qasim Bashir discussed initial experience in ner in which the primary guest was Prof. Lorel Brown Lindsey Haynes on the topics of Behavioral Dysfunction in establishing an interventional neurology/ Asghar Butt, vice president of CPSP. Parkinson’s Disease and Parkinson’s Disease neuroendovascular surgery program in Prof. Masood Hameed Khan, vice chair Editorial Offices 7015 College Blvd., Suite 600 — Revisited. Lahore: procedural types and outcomes; of DUHS was honored during the social Overland Park, KS 66211 More than 200 exceedingly participa- Qurat Khan from AKU deliberated on portion of the evening. +1-913-469-1110 tive audiences from all parts of the coun- introduction to behavioral neurology; The conference was a great success in try attended all of the scientific sessions. Bushra Afroze talked on biotinidase defi- terms of participation, and the quality of In the inaugural session of the three-day ciency — clinical presentation, diagnosis training and education was superb. • www.wfneurology.org • JUNE 2014 3

PRESIDENt’S COLUmn Neurology Cooperation Around the World

ince I wrote my last column, many Teaching courses with events have occurred. The neurologi- live and videotaped Scal world is moving so fast. The WFN cases attract a huge remains at the forefront of developments interest and create lively of international activities and is leading in discussions. cooperation and promotion of neurology. The WFN grants In January, the Sudanese Neurological round is now open, and Society held its ninth annual meeting in we hope to receive as Khartoum. I had the privilege to be invited many applications as as well as the president of the Pan African possible. The Grants Association of Neurological Sciences, Prof. Committee will start Riadh Gouider, and the president of the work after the closing Pan Arab Union of Neurological Societies date, and decisions Prof. Mohammad Tamawy. The atten- will be conveyed to the dance and interest was large and intense. applicants immediately. There was an impressive eagerness to learn The plan is that the among young neurology trainees in all WFN will partner with topics, and the hands-on workshops with other organizations to bedside patients were fully subscribed. It increase the amounts of is heartening to see that relatively small the grants. societies in Africa can provide so much The Vienna World high-quality teaching and care. Congratu- Congress was not only Figure 1. (From left to right) Jonas Yeung, president of the Hong Kong Neurological Society; Man Mohan Mehndi- lations to Prof. Ammar El Tahir and Prof. a scientific success but ratta, president of AOAN; Wai-Sin Chan, deputy director, Health Bureau, Macau Special Administrative Region; Chin Ion Lei, director, Health Bureau, Macau Special Administrative Region; Patrick Li, president of the Hong Kong Osheik Seidi for their efforts. also a great financial College of Physicians; Ping Wing NG, co-chair of AOCN 2014; Leonard Li, co-chair of AOCN 2014; Lawrence Wong, The 15th Cairo Neurology Congress success for the WFN. I, secretary of AOAN and chair, Scientific Committee, AOCN 2014. was held in February and again the topics on behalf of the WFN, and attendance were impressive. Prof. am most indebted to Wolfgang Grisold, WFN Secretary-Treasur- the Austrian Society for its hard work; and launched during the joint EFNS/ENS mode, which has fully dominated its activi- er General attended the meeting. Tamawy to the EFNS which suspended its annual meeting in Istanbul. The book is essential ties, to the area of disease management and Prof. Osama Abdul Ghani are to be congress for 2013 to allow just one major reading for all. and appreciation of the huge burden of congratulated for an excellent effort. I am neurology congress to take place in Europe. The WFN and other peer organizations neurological diseases in the world. This, sure that across the world many national The financial returns to all indeed exceeded have created the World Brain Alliance. See when it evolves further, is a seismic shift societies have expectations, which bodes well for the finan- http://www.wfneurology.org. This was in thinking, and the WFN should be ready had their annual cial survival and strength of the WFN. started during the previous presidency, and when it happens. The close collaboration congresses and As this issue is being published, the I had the honor of being present during its and financing of many projects through this only enrich- amalgamation of the EFNS/ENS in the inception in 2010. The presidents of peer the WHO is crucial for neurology, and es the field. The joint meeting in Istanbul will have taken societies last met in Vienna and will meet the WFN should be at the top table in the WFN will be place. This will create a most solid associa- again to formulate a structure and proceed decision-making process. delighted to be tion. The WFN looks forward to the birth as the force speaking for all those involved Many tasks lie ahead for the WFN involved in any of the European Academy of Neurology in brain health. trustees. For examples, finding and hiring way and to help (EAN) and the elections of its officers so that Other activities to report are the a PCO when the contract with the current promote and our relations and close collaboration will collaboration with the WHO. This has PCO Kenes expires with the last contracted advertise these continue as before with its two predecessors. matured and is progressing well. The De- congress in WCN 2015 in Santiago; and raad congresses. The WFN’s strength and ability to reach partment of Mental Health and Substance finding a publisher for JNS when the shakir From its goals can only be achieved with the help Abuse is where neurology lies in the WHO contract with Elsevier expires at the end of national to of strong regional associations willing to structure. Shekhar Saxena and Tarun Dua 2014. These are important decisions, and regional congresses. The Asian Oceanian collaborate to further the cause of advancing are major contributors to the success of the the trustees will have to look at all of the Congress of Neurology (AOCN) 2014 was neurology globally. If one reads the EAN’s collaboration. Moreover, Oleg Chestnov, options and come up with the most suit- organized by the Hong Kong Neurological Purpose and Values, these goals are well laid WHO’s assistant director general, has able ones for the WFN. Society and held in Macau. The congress out in Article 4 of its bylaws. agreed to talk to the attendees of the World As delegates were informed, the Nomi- was attended by members from all over Asia. The WFN was born on the July 22, Congress of Neurology in 2015 in Santiago, nating Committee is soliciting nominations The Hong Kong Society in collaboration 1957, and during the Vienna World Con- Chile. The WFN is a major funder to our for the post of elected trustee. Prof. Gustavo with the Chinese Neurological Society was gress, the Council of Delegates voted to WHO activities and will continue to be so. Roman will finish his second term and is not instrumental in producing an excellent pro- commemorate that day every year as the The ICD11 process is being finalized, and eligible for re-election. His contributions gram. Prof. William Carroll, WFN first vice World Brain Day. The task was given to the process is on target. The WFN and the to the WFN as a trustee and as chair of the president, attended the congress, and Man Prof. Mohammad Wasay, chair of the WHO are again collaborating in the pro- Latin America Initiative are immense. I, on Mohan Mehedirata, AOAN president, was Public Awareness and Advocacy Commit- duction of the successful Neurology Atlas, behalf of all trustees, committees and mem- also present; the organization was excellent. tee. The details are in the April issue of second edition, as the first edition is now 10 ber societies, would like to thank him for a Profs. Wing-Ping Ng and Laurence Wong World Neurology. By the time this is pub- years old. This process involves gathering wonderful job, which was done with grace, are again to be congratulated. (See Figure 1.) lished, all delegates should have received information from Ministries of Health and elegance and professionalism. It seems that wherever in the world further correspondence. all WFN member societies so that the data The next Council of Delegates meet- neurologists meet, there is always a sense The WFN history is rich and diverse. are verified and are useful tools for all. ing will be held in September in Boston, of camaraderie and togetherness. It is Prof. Johan Aarli, WFN past president, is The involvement of the WFN with Massachusetts. This will be during the also clear that topics vary in their scientific the author of The WFN History: The First the Non Communicable Diseases (NCDs) joint meeting of the American and Euro- slant and their emphasis on training; but 50 years, published by Oxford University declaration is vital for the future of neurol- pean MS societies, and we look forward the eagerness to learn among neurologists Press. By the time this issue of World ogy. There is now a clear perception that to seeing as many society representatives in training is the same across the world. Neurology is distributed, the book will be the WHO is moving from the preventative there as possible. • 4 www.wfneurology.org • JUNE 2014 Stroke in Literary Works Around the World

By Axel Karenberg Apprenticeship (VII,6; 1795/96): “Altogether ters and supplemented by technical diagnosis here are few other neurological disor- unexpectedly my father had a shock of palsy; and therapeutic options. To exemplify this ders with such a constant presence in it lamed his right side, and deprived him of shift, there are George Simenon with his Non- T literary works as apoplexy. As early as the proper use of speech. We had to guess Maigret book The Bells of Bicetre (1962) and 1600, the notions “apoplexy” and “apople- at everything that he required; for he never Kathrin Schmidt’s novel You Won’t Die (2009). jía” appear in dra- could pronounce the word that he intended … In literary works, apoplexy serves different mas written by His impatience mounted to the highest pitch: goals. The sudden outbreak of the disease Shakespeare and his situation touched me to the inmost heart.” can set the plot going, let take it the defin- Lope de Vega. The diverse causes of the disease taken up ing turn or end a story line. Above all, in More detailed in the “belles lettres” reflect its multifactorial recent prose texts, the symptoms bring the descriptions origin conceived in premodern medicine. fictional patients to get to the bottom of their of the disease Melancholic “gloominess” or “thick blood” former life. But the illness also can assume a enrich popular was grounded on the ancient idea of an ab- metaphoric function. The recurrent cerebral novels of the 19th normal blending of the bodily humors. In this insults of the protagonist Oblomow in Iwan century. Authors A. Gontscharows’ such as Balzac, homonymous epic Dumas, Flaubert Axel Karenberg (1859) were meant to and Zola must be illustrate the agoniz- Johann Wolfgang von Goethe (1749-1832), author of “Wilhelm Meister’s Apprenticeship.” mentioned here as well as the epical sagas of ing czaristic feudal Dostojewski and Tolstoi 1,2. The American system. In a similar the understanding of a patient’s fate and help author John Steinbeck used a “stroke” in his way, the American to support present-day stroke medicine. • work East of Eden as did Philip Roth in his author John Gries- morbid narratives. In the German-speaking emer in his New References world, stroke is dealt with in more than 100 York novel Heart 1. Perkin JD. The neurology of literature. In: Bo- fictional works. Attack (2009) fixed gousslavsky J et al. (eds.): Neurological Disorders Naturally, literary productions treating the acute symptoms in Famous Artists, Part 3. Basel: Karger 2010, pp. this subject resort to contemporary medical Effi Briest by Theodor Fontane. Original cover of the first edition (1896). of his protagonist on 227-37. knowledge 3. Until the middle of the 20th 9-11 in order to link 2. van den Doel EM. Balzac’s serous apoplexies. century, literature focused mainly on two perspective, the disease could be provoked by individual and collective fate, facts and fiction Arch Neurol 1987; 44:1303-5. aspects of apoplexy: its typical symptoms and the “cold and moist evening air” or by “taking to a meaningful picture. 3. von Engelhardt D. Neurologische Erkrankungen explanations of its origin. The presentation a bath at 9° C.” (e.g. in E.T.A. Hoffmann, Fictional texts are never bare clinical case im Medium der Literatur. In: Kömpf D (ed.). of symptoms abide by a strict code: sudden 1825 and in Theodor Fontane’s Effi Briest, histories, they never render exclusively neuro- 100 Jahre Deutsche Gesellschaft für Neurologie. onset, motor deficiency and unfavorable 1894/95). Only approaching present times, logical textbook knowledge. It is the compo- Berlin: DGN 2007, pp. 346-53. outcome. The majority of authors was deeply the thematic focus and the narrative perspec- nents that lie beyond the medical horizon that impressed by the loss of the ability to produce tive shifted slowly but constantly. Along with arouse the interest of physicians and a broader Karenberg is from the Institute for the History of speech — above all after Goethe’s early depic- a more detailed description of the symptoms, public. The anthropological dimension, the Medicine and Medical Ethics, at the University of tion of motor aphasia in Wilhelm Meister’s the story is now set in hospitals and rehab cen- look at human despair and hope can further Cologne, Germany.

Mark Your Calendars book review each slice of each image. The second section of the book fo- Neuroanatomy of Language cuses on cytoarchitecture. Large format 2014 images are provided that illustrate the layers of the cortex from each of the Movement Disorder Society Regions of the critical areas of the brain. Brodmann Annual Congress 2014 labeling is used for most illustrations, June 8-12 Academic Press, 2014; 186 pages The book is divided into three major although Economo and Koskinas labels Stockholm sections. The first section of the book are used for some critical areas. The http://www.movementdisorders.org/congress/ he human brain contains billions of focuses on gross anatomy of the human location of most samples is illustrated past_and_future.php neurons, and these neurons interact brain. There is a comprehensive discus- with images of gross location on a brain T in a variety of ways that are only sion of the gross morphological features illustrating Brodmann’s areas, and some Congress of the European Committee for beginning to be understood. One of the of the brain. This is accompanied by corresponding anatomic loci in the ma- Treatment and Research great challenges that humans confront images that can be obtained with MRI. caque monkey brain are also provided. in Multiple Sclerosis 2014 is determining the way in which the hu- Petrides illustrates gross anatomy in The third section of the book Sept. 10-13 man brain can support complex behav- axial, sagittal and coronal orienta- describes the named, long white matter Boston, United States iors such as reading and understanding tions with a T1 sequence obtained at projections of the human brain. Cor- http://www.ectrims.eu/conferences-and-meetings this text. We can begin to confront this 3 tesla with 1 mm isotropic voxels, but responding projections in the macaque challenge by improving our understand- few additional details of the imaging monkey brain are illustrated as well. Ninth World Stroke Congress ing of human neuroanatomy. sequence are provided. These illustra- White matter connectivity is illustrated Oct. 22-25 Michael Petrides is an internationally tions are useful since most volumetric primarily within the left hemisphere, and Istanbul renowned neuroanatomist. His new, large imaging is obtained at 3 tesla with 1 hemispheric differences are not detailed. http://www.world-stroke.org/meetings/world-stroke-congress format book is titled, “Neuroanatomy mm3 voxels, although a 7 tesla scanner In addition to the averaged results of of Language Regions of the Human may have illustrated the anatomy with white matter projections, in situ tractog- 10th International Congress on Non- Brain.” The book is generously illustrated additional detail. Slices are provided at raphy in individual subjects is provided Motor Dysfunctions in Parkinson’s in color, including unique illustrations approximately every 4 mm. Each slice is to demonstrate each of the major white Disease and Related Disorders from his own work. The illustrations are associated with an orienting location in matter fasciculi. The text provides an im- Dec. 4-7 clearly labeled. The accompanying text is the space of the Montreal Neurological portant discussion of the distinction be- Nice, France authoritative and describes the relevant Institute ICBM152 generation VI aver- tween the superior longitudinal fasciculus http://www.kenes.com/nmdpd anatomical features in clear language. age brain, and most sulci are labeled on and the arcuate fasciculus, and considers www.wfneurology.org • JUNE 2014 5

Annual meeting tries, and relax before the next session. major national and international news preventive strategies for the neurologic continued from page 1 A significant portion of the meeting outlets and neurology trade publications. diseases that can be so devastating to was devoted to helping U.S. neurologists AAN President Timothy A. Pedley, our patients.” opportunities and challenges of robot- understand the many changes initiated by MD, FAAN, remarked on the strong media Plans are already under way for the assisted and facilitated neurorecovery; Congress and federal regulatory agencies interest in the meeting. 2015 Annual Meeting, to be held April network-based neurodegeneration; as part of health care reform. Neurolo- “The frequently tragic and debilitating 18-25 in Washington, DC. Until then, the using fixed circuits to generate flexible gists, like other physicians, are under nature of so many brain diseases provides AAN will continue to connect neurolo- behaviors; advances in the Human Con- tremendous pressure to reduce treatment a focus for our attention when we come gists with the best in science and educa- nectome Project; and the nightlife of costs without compromising the quality together at the Annual Meeting to share tion through several gatherings, including astrocytes. of care. our experiences and chart our progress,” The Sports Concussion Conference in The Controversies in Neuroscience The AAN works hard to guide mem- said Pedley. “The scale of media cover- July; the AAN Fall Conference in October; Plenary Session featured pairs of experts bers through these issues using a variety age and public interest reminds us of the and Breakthroughs in Neurology 2014: debating three of the most current and of resources and tools, while advocat- tremendous responsibility we have to Translating Today’s Discoveries into To- controversial issues in neurology: “Does ing on their behalf with members of work even harder to discover more effec- morrow’s Clinic, to be held in December. preventing relapses protect against Congress and administration officials tive treatments and, eventually, cures or As always, the world is invited. • progressive MS?,” “Is intervention for in Washington, DC. U.S. Senator Bob asymptomatic AVM useful?” and “Should Casey (D-PA) spoke with neurologists neurologists prescribe marijuana for concerned about cuts to federal health neurological disorders?” programs for the elderly and the eco- The Clinical Trials Plenary Session nomically disadvantaged. What Have You Learned at the AAN Annual Meeting addressed important topics that affect Another Pennsylvania legislator, Con- That You Will Take Back to Your Practice? patient care identified from submit- gressman Chaka Fattah of the U.S. House ted abstracts that had recently been of Representatives, spoke at the Brain “I attended the Global Health “The clinical sessions, especially presented at other society meetings, Health Fair about his initiative to support Challenges: Neurology in Developing those on the new agents for multiple including stroke, MS, migraine, intracra- brain research. This fair is a free public Countries. It was eye-opening to learn sclerosis, are very good. MS treat- nial hypertension and glioblastoma. The event presented by the American Brain about the global burden of disease and ment has been closed, very routine week concluded with the Neurology Foundation. The fair typically draws specifically the difficulties in treating and patients are getting tired of the Year in Review Plenary Session, which 1,000 to 2,000 people from the region epilepsy in developing countries. same injections. examined advances in MS, headache/ who are living with brain disease or car- It won’t affect my current practice but It’s good to see that clinical pain, neuromuscular diseases, move- ing for a family member or friend. They reminds me of the need to think outside research is progressing in this area. ment disorders, neurocritical care and hear about new research and treatments of the small world in which I practice. It Hopefully in a few years — not 10 Alzheimer’s disease. from neurologists, health organizations also reignited an interest in participating years — there will be new drugs avail- More science was available at numer- and the medical industry. in short-term medical mission work like I able for MS patients. Patients are being ous platform sessions, seven poster Media from across the globe gathered was able to do in medical school.” included earlier in studies and being sessions and a new, fast-paced series of to provide powerful coverage of neurol- treated better and earlier.” Poster Blitz presentations. ogy’s largest meeting. Reporters and David B. Watson, MD Morgantown, West Virginia Douglas Sato, MD Another new feature at this year’s photographers shared the latest news in Sendai-Miyagi, Japan meeting was an International Lounge, brain research with their readers and lis- which provided an opportunity for foreign teners back home. The AAN pressroom “I live in Zambia and there are only guests to mingle, network with leading was lively with representatives from two neurologists in Zambia for 13 “I really appreciate the speakers neurologists from the U.S. and other coun- million people. It’s a very small com- who gave a high level interpretation of munity! Coming here, I get to meet the the clinical trials. We all know the data. people face-to-face that I’ve emailed, It’s the interpretation that really helps spoken to and trained with over the us start a discussion and collaborate in detail the dual-route hypothesis the years. We are talking about collabora- nationally.” postulates dorsal and ventral projections tion and building our global health Ishida Koto, MD between anterior language regions in programs. This AAN meeting — it’s New York the frontal lobe and posterior temporal neurology on steroids!” language regions. Omar Siddiqi, MD Petrides provides an interesting his- Lusaka, Zambia “The ICU monitoring session was torical discussion of the development of very helpful. I work at the V.A. We are our understanding of the neuroanatomy short-staffed, and we are short on staff of language, beginning with Pierre Paul “I like that the issue of ethics was qualified to perform multiple tasks such Broca’s revolutionary presentation of addressed in the Presidential Plenary as ICU monitoring. The ideas I learned Leborgne and Lelong. He also provides Session and its impact to medicine. We about ICU monitoring is directly appli- interesting illustrations of MRIs of the are all living with ethics in our daily cable to my facility.” brains of these two patients. Major lives.” Gabriel Bucurescu, MD figures such as Wernicke, Marie and De- Philadelphia Barbara A. Dworetzky, MD jerine are mentioned as well, although Boston other seminal early investigators such essentially all cerebral as Lichtheim are not acknowledged. Pe- regions and provides key illustrations from “For me, it’s learning the research ideas trides also reviews the seminal electrical macaque monkey. “I attended a very educational for the future. I’m a junior resident so I’m stimulation studies of Penfield. Indeed, A truly positive feature of this book is series of debates on the controversies enjoying all the sessions, especially the interesting historical perspectives are the multiple perspectives that are adopted pertaining to ICU EEG monitoring genetic talks.” provided throughout the book. in a single, comprehensive volume. An of critically ill patients. It was great to Janice Wong, MD It is appropriate that a volume about additional perspective might have been hear from experts in the field argu- Boston, MA neuroanatomy focuses on language provided by the anatomically based ing their viewpoints on an important since this topic is the historical origin of neurotransmitter work from Zilles and unanswered question in neurocritical our study of human cerebral anatomy. Amunts. • care. This has inspired me to review “What I’m hearing is confirma- Petrides notes at the beginning of the book the literature myself and come to my tory: In stroke, there often is no clear that most areas of the brain are arguably This book was reviewed by Murray Grossman, pro- own conclusion. Clearly, there is more decision. So, it’s confirmation to what’s related to language. The focus of the book fessor of neurology, director of the Fronto-Temporal research that needs to be done.” been discussed here.”

Dementia Center at the University of Pennsylvania is tilted toward the language regions of the Krishnan Vaishnav Markus Naumann, MD brain, but Petrides generously describes School of Medicine. Boston, MA Augsburg, Germany 6 www.wfneurology.org • JUNE 2014 bereitschaftspotential Obviously, we interpret evolution as a external simuli. We dislike the term at the time. He visited Richard Jung, continued from page 1 process making organisms freer and freer; “self-paced,” suggesting regular pace, and Kornhuber and I showed Walter our one also can say making them more and while it is so important to make the first results. It was Walter who in a later Schwanen’ at the foot of the Schlossberg more autonomous. Similarly, we consider movements at irregular intervals, which publication coined the term “opistho- hill in Freiburg, Germany (near the Black an adept, e.g. Shaolin monk, who works make them more volitional, and regular chronic averaging” for our methodology. Forest). hard on his own personality, to become pace makes them more automatic. At Our first movements under study were We sat in the beautiful garden and more and more free. Kornhuber was of that time (1964), this was a remarkable simple movements (rapid flexions of the discussed our frustration with the fact that the opinion and demonstrated that one instruction for subjects, to which I think forefinger). the brain was investigated — at that time can make freedom a topic of scientific we owe our success. And, thus, a brain Another methodological prerequisite — only as a responsive apparatus, i.e. as a investigation. Not to deal with freedom potential evolved completely differ- is to investigate monophasic movements, mere reacting system. Neurophysiologists only philosophically but also to explore it ent from W. Grey Walter’s (1924-1971) i.e. that the flexed finger remains in were engaged worldwide only in what using scientific means (Kornhuber, 1978; expectance wave or CNV (both having the flexed position until the end of the was called “the responsive brain” (later 1984; 1987; 1988; 1992; 1993). been first published in 1964). By the analysis epoch. Using wrist extension culminating in a book with this title by Immanuel Kant, the great German way, Walter came from Bristol in 1964 and flexion in one flick of the hand is not McCallum & Knott, 1976). We felt that it philosopher of the enlightenment (who to make summer vacation in the Black good, since this employs two movements would be far more exciting to investigate coincidentally was born in the same town, Forest, which was fashionable for British instead of one. what is going on in our brain before we Königsberg, as Kornhuber) was the first make a voluntary movement. No sooner to distinguish between two fundamental said than done. aspects of freedom, namely freedom We went back to the lab and started from and freedom to. Freedom to is the immediately planning the experiment. much more important aspect here, and However, we soon ran into an important this distinction was taken up and further problem: Brain potentials in the EEG are developed by Kornhuber. The scientific the result of averaging. For us to get the breeding ground for the experiments results we needed, the averaging process toward the Bereitschaftspotential was thus must be triggered by the movement or already prepared well in advance. Rather action itself. But how can you trigger than being a serendipitous discovery, the on an event that comes as unpredictably Bereitschaftspotential was therefore the re- and spontaneously as a human voluntary sult of a new branch of research planned movement? by Kornhuber and myself. It was Hans Kornhuber, who found the solution: We would store the EEG on The Laboratory: Original magnetic tape along with the electromyo- Experimental Setup gram (EMG) of the movements and then in Freiburg/Germany play the tape backward in the time-re- During the experiments, the subject sat in versed direction from the present back to a Faraday cage for electrical shielding. The the past, i.e. using reverse averaging with EEG was recorded using a Schwarzer-EEG the start of the movement as the trigger. Type E 502 with tube amplifiers and the At that time, magnetic tape recorders only EMG by a Tönnies-EMG and Stimulation had a high-speed rewind, and programma- Unit. Data were stored using a Telefunken ble computers were not yet available, so four-channel magnetic tape recorder M we were literally removing the tape reels 24-4, frequency-modulated. The tape reels from the recorder, turning them around, were turned around for reversed averag- and placing them back on the recorder. By ing. The center-piece of the experimental these means, we found a brain potential, setup is shown in Figure 1A: Mnemotron which was electrically negative and started CAT Computer 400 B with Mosely Auto- already 1½ to 1¼ seconds prior to the graf. (See Figure 1: How Kornhuber and I movement or action. Negativity in the came to the opportunity to use this then- brain means activity. ultra-modern device for our experiments.) This method of recording of the Figure 1B gives one of our first results, readiness potential — Bereitschaftspoten- a slowly increasing ramp-up of negativity tial by reverse averaging was the basis of was recorded, which was stronger over my doctoral thesis, which I completed in the contralateral hemisphere. Negativ- 1965 at the with ity culminated at movement onset (and Korn-huber as my doctoral supervisor. after the action returning to positivity), The experiments that led to the discovery which we called the Bereitschaftspotential. Figure 1: Original experimental setup (A) and first results (B) in Freiburg, Germany, at the University Hospital of Neurology with , Hansastr. 9a, Freiburg, of the Bereitschaftspotential were inspired In the lower set of graphs in Figure 1B, known popularly as “Neurophys.” by a positive concept of will, i.e. individual this negativity was demonstrated by a humans have, indeed, their own will and bipolar recording to show phase reversal A: The centerpiece of the laboratory — the Mnemotron CAT Computer (Computer of Average own decision-making power, so that we around the precentral electrode. We called Transients) 400 B and Mosely Autograf (XY-Plotter). Prof Richard Jung, head of the hospital, are capable of designing our lives largely the pre-movement negativity the “Bere- had been offered a post at the Max Planck Institute in Munich. For rejecting this, his home by ourselves and use goal-oriented action itschaftspotential” and in our English sum- University of Freiburg gave him the CAT Averager as a present for staying. The two inserted photos show on the left (age 36 in 1964) and Lüder Deecke on the to create our own future. mary of Kornhuber and Deecke (1965) right (age 26 in 1964). Kornhuber lectured on human offered the English translation “readiness freedom in a seminar for students of all potential.” Somehow the tongue-twister B: Above: Changes in brain potentials with voluntary movements of the left hand based on unipo- faculties. He conducted a survey among Bereitschaftspotential was preferred and lar recordings of the precentral region versus the nose (Subject G.F., average of 512 movements). his listeners as to who is freer: humans is now a German word in the English Onset of movement at the arrow (0 sec) – left of the arrow brain activity prior to movement onset or chimpanzees, chimpanzees or rhesus language. — right of the arrow brain activity after the onset of movement. Note the negative potential at readiness and the positive potential after the action. The graph shows higher amplitudes over the monkeys, rhesus monkeys or cats, cats or We instructed our subjects to make contralateral (right) hemisphere. Negative polarity is up. salamanders, salamanders or spiders, and their movements: so on until down to the earthworm. The • at irregular intervals Below: The bipolar serial recording with sagittal electrodes with voluntary movements of the right seminar participants answered the ques- • out of hand (average from 400 movements. Subject B.C.). The graph shows phase reversal around the tion of freedom unambiguously, namely • of their own accord precentral electrode: The premotor negativity and the postmotor positivity are strongest over the central region. In the fronto-precentral recording negativity of the precentral electrode is down, according to the position of the animal in The movements we analyzed were in the pre-centro-occipital recording negativity of the precentral electrode is up. the evolution. therefore entirely self-initiated without www.wfneurology.org • JUNE 2014 7

By comparing active movements with the surface of the skull. This has been basal ganglia are an important component In May 1979, Kornhuber and I analogous passive ones, we aimed to solved by Kornhuber and his associate of the cortico-basal ganglia-thalamo- organized the MOSS V congress (one show that the BP occurs prior to active who used the onset of the movement cortical loop. This loop was known by of the series of the EPIC congresses) in movements only. To initiate passive move- to trigger a reverse computation of the neurosurgeons long ago and created the Reisensburg Castle, near Ulm, Germany. ments, the experimenter pulled a string potentials up to 2 seconds before the onset prerequisites for the thalamotomies in Afterward, we edited a book of the con- that was fixed to the subject’s finger and of the movement. The subject initiates classical stereotaxic surgery. The cortico- ference proceedings: Progress in Brain ran over a pulley, so that pulling would these movements “at will” at irregular basal ganglia-thalamocortical loop was lat- Research Vol 54 (Kornhuber & Deecke cause the subject’s finger to flex. Indeed, intervals of er confirmed and [Eds] 1980). The next conference on the we did not detect any BP prior to such many seconds. called motor loop Bereitschaftspotential was an internation- passive movements, but recorded evoked In this way, it by Alexander et al symposium in April 1988 in Vienna. potentials after movement onset elicited was possible Working with patients al (1986), and by which I organized in honor of Korn- by the passive movement. Post-movement to average Mahlon DeLong huber’s 60th birthday. The proceedings onset potentials also occurred in the active 250 records of (1990). Nowadays, also were published as a book (Deecke, state. We referred to these as “reafferent the potentials means investigating we have to “think Eccles, Mountcastle [Eds] 1990). potentials” because the term “evoked po- evoked at vari- in loops,” and tentials” should, by definition, be reserved ous sites over lesion experiments made the motor loop The Dispute With Libet for potentials that are elicited by external the surface is the key to the In October 1988, Sir John Eccles invited stimuli. of the skull, by nature, and if understanding scientists working on the motor system to as shown by of Parkinson’s contribute to a study week in the Vatican, Citation Classics the numbers disease. In our Ci- titled “The Principles of Design and Our first full paper (Kornhuber and in Figure 4-3 carefully studied, their tation Classic No. Operation of the Brain” and a resulting Deecke, 1965) became a Citation Classic and the cor- 4 (Deecke & Ko- book (Eccles & Creutzfeldt [Eds] 1990). I on Jan. 22, 1990. Eugene Garfield of the responding pathological state can rnhuber 1978), we met at earlier conferences, journal database Current Contents (CC) traces. (Figure found differences and he also attended the Vatican Study “awarded” this label to papers that were 4-3 is taken tell us a lot about the in the BP between Week. We liked each other and became frequently cited. For a paper written in from Deecke, Parkinson’s dis- friends, although not being of the same German, this does not occur too often. Scheid. Korn- ease patients and opinion regarding the freedom of human Garfield gave a translation of the Ger- huber [1969] normal function. normals. One of will. He worked with Wundt’s event clock man title: “Changes in Brain Potentials and shows the best examples and asked his subjects to remember the With Willful and Passive Movements in the compari- of how the BP position of a red dot on the clock at the in- Humans: the Readiness Potential and son between in Parkinsonian stant when the “conscious urge to move” Reafferent Potentials.” As part of receiving finger and arm movements.) These experi- patients looks like came from an elderly occurred to him or her. Libet made a big Citation Classic status, we were asked to ments at least provide a partial answer to woman among our subjects — she was claim in his Vatican lecture (Libet 1990) by write up how we arrived at our discovery the question: What is happening in my a duchess — suffering from Parkinson´s saying that freedom is firmly linked with (Citation Classic Commentary), and we brain at the time I am deciding on some disease who was trying hard in our BP , the state of full aware- gave our commentary the title: “Readiness motor act?” experiment to meet our performance ness. He brings it to the point in his own for Movement – The Bereitschaftspoten- Citation Classic No. 3, Deecke, Gröz- criteria. The main feature was that we words: “The unconscious initiation of a tial Story” (Kornhuber HH & Deecke L inger, Kornhuber (1976), resulted from my found a high amplitude BP over the vertex freely voluntary act.” Libet is correct in (1990). habilitation thesis, a requirement to be- but not very much of a BP in the contra- this statement, but his interpretation is not The Citation Classic Commentary was come a professor at a German university. lateral and ipsilateral precentral leads due correct. He takes it for granted that in our published both in CC Life Sciences and in This paper in Biological Cybernetics, “Vol- to her PD. Experiments were carried out unconscious or preconscious inner world CC Clinical Medicine. Three more of our untary Finger Movement in Man: Cerebral in patients with bilateral Parkinsonism there is no freedom, and thus concluded papers became Citation Classics: No. 2 Potentials and Theory,” comprises a lot of selected for pronounced akinesia but mini- that we have free will in the control of was Deecke, Scheid, Kornhuber (1969). experiments performed in Ulm with many mal tremor, and in age-matched healthy the movement but not in its initiation. Here we continued our investigation into figures and a comprehensive analysis of control subjects. The vertex maximum of This is because the “W” in his paradigm the cerebral activity preceding willful the BP and its components. Three differ- the Bereitschaftspotential had previously (conscious wish) comes later than the start movement, and also compared finger ent brain potentials preceding voluntary been explained by volume conduction. of the readiness potential. movements with arm movements. The rapid finger flexion were distinguished: It was argued that a vertex electrode col- Kornhuber and I, joined by the 1963 Nobel Laureate for medicine, Sir 1. Early negative activity of the Bere- lects activity from both motor cortices. In philosopher Daniel C. Dennett, are of John Eccles was interested in our work. In itschaftspotential — widespread bilateral Parkinsonism, however, we see a the opinion that there are conscious his 1977 book, “The Self and Its Brain,” 2. Pre-motion positivity, PMP – wide- bilateral reduction of the Bereitschaftspo- and unconscious agendas in the brain, which he co-auhored with Karl R. Popper, spread tential in the precentral area, whereas over and both are important. The conscious he wrote about our research: “There is a 3. Motor potential (MP) – unilateral, other cortical areas (in particular vertex and unconscious agendas of the brain delightful parallel between these impres- restricted to the contralateral motor and mid-parietal), it was not significantly were the subject of a workshop at the sively simple experiments and the experi- cortex. reduced. This publication therefore estab- European Neurological Society (ENS) ments of Galileo Galilei who investigated Two years later, Citation Classic lished the SMA participation in the gen- Congress 2010 in Berlin, where Dennett the laws of motion of the universe with No. 4 (Deecke & Kornhuber, 1978) was eration of the BP, and our findings were and Adrian Owen were the speakers. metal balls on an inclined plane.” published. This paper in Brain Research, confirmed by CD Marsden (1938-1998) I also expressed our view in a paper in In his previous book, “The Under- “An electrical sign of participation of the (Marsden et al 1996). Barrett, Shibasaki Brain Sciences (Deecke L, 2012). Libet’s standing of the Brain” (Eccles JC 1973), he mesial ‘supplementary’ in & Neshige (1986) reported that the BP is paradigm is a mixture of cerebral and wrote (page 108): “In an initial investi- human voluntary movements” first sug- normal in PD. But Dick et al (1989) found subjective events, and the problem lies in gation by Grey Walter, the subject was gests that the early component of the BP, that the BP is abnormal in PD. Our group the subjective event (W). trained to perform a movement after a BP1 or BPearly is generated by the SMA repeated the experiments and confirmed It is hard to trace back split seconds, double stimulus sequence: a condition- and — as we found later — also by the the findings of Dick et al 1989. Harasko, and 200 msec is very, very short. I tried ing, then a later indicative stimulus. An cingulate motor area (CMA). Both being van der Meer et al 1996 cited in Lang and the Libet paradigm myself with students, expectancy wave was observed as a nega- clinicians, Kornhuber and I also investi- Deecke 1998 ibidem Figure 5 on page 235. and we were not able to accurately per- tivity over the cerebral cortex before the gated patients and were early on able to Results: In the PD patients (N=8), the BP form in his paradigm with Wundt’s event indicative stimulus. Essentially, this wave is link Parkinson’s disease (PD) with the Be- starts later and is initially lower in ampli- clock position that has to be recalled produced by the conditioned expectancy reitschaftspotential. Working with patients tude as compared to the normal controls retrospectively. Wundt’s event clock has of the indicative stimulus and not by a means investigating lesion experiments (N=8). After the onset of movement, the been designed for sensory psychophysical voluntary movement. The problem is to made by nature, and if carefully studied, amplitudes are equal and even sometimes experiments. have a movement executed by the subject their pathological state can tell us a lot larger in the PD patients as compared to In a voluntary movement paradigm entirely on his own volition, and yet to about the normal function. the controls. Thus, Parkinsonian patients (BP-paradigm), it is like a “foreign body,” have accurate timing in order to average Kornhuber had worked on the basal start later with their BP, but then keep up because it is an external stimulus and the very small potentials recorded from ganglia and cerebellum and found that the with the normal controls. thus disturbs the “volitionality,” so to say, 8 www.wfneurology.org • JUNE 2014 the willfullness of the movement or ac- in sensory systems. In the motor system, — their activities cancel each other. We to movement onset. In the time range of tion. In conclusion, Kornhuber and I feel processes that are initially conscious can were using two strategies to overcome BF 1, dipole source analysis localized the that the importance of consciousness has become unconscious through autom- the problem of cancellation. The first, source in the SMA only, whereas dipole been underestimated by the behavior- atiza-tion (also cf. Wu et al 2004). The published by Lang et al (1991), involved source analysis containing also the time ists. It is not an epiphenomenon. If after switching on of consciousness shortly investigating a patient with a stroke in range of BF 2 resulted in dipole models, brain injury, consciousness is regained, before the movement is a great expen- one of his SMAs (the right in this case). including dipoles in the primary motor the lesion can (partially) be compensated, diture for the brain and shows that even The patient had only one SMA left, and area. In summary, with a whole-head however never without consciousness. such “unimportant” repeated movements we were able to record early starting MEG system, it was possible for the first Conscious awareness is a shining light needed for the averaging procedure are magnetic fields of his left SMA — he time to detect SMA activity in healthy of freedom, although it should not be controlled, if they are voluntary. performed right-sided movements. The subjects with MEG.” overestimated either. Consciousness is known to be paper’s abstract summarizes this: “Previ- For most of the vital functions, restricted and its time is valuable, only ous studies by fMRI – functional Magnetic consciousness is not necessary, and it important events get access to it. As mea- (MEG) failed to consistently localize the Resonance Imaging is not the only sign of freedom. The surements of the “channel capacities” of activity of the supplementary motor In 2003, Marjan Jahanshahi and our chair- experiment of Libet et al (1983), which the senses in psychophysical experiments area (SMA) prior to voluntary move- man of the session, Mark Hallett, edited a showed that the BP is not, right from the have shown, there is a selection/filtering ments in healthy human subjects. Based book titled, “The Bereitschaftspotential — beginning, accompanied by a conscious- of the important matters between the on the assumption that the SMA of ei- Movement-Related Cortical Potentials” ness about the intention of movement information flow in our senses and that ther hemisphere is active prior to volun- (Jahanshahi M & Hallett M 2003). The is taken at present as the main argument in our consciousness. This sophisticated tary movements, the negative findings closing chapter is written by Deecke for advocating a total determinism, a selection also is unconsciously organized of previous studies could be explained and Kornhuber (Deecke & Kornhuber, complete unfreedom of humans. This and represents an enormous compression by the hypothesis that magnetic fields of 2003). The book and chapter for the first position is not tenable. What would be of information of at least 104; informa- current dipole sources in the two SMAs time compile all of the evidence that the essential to study is the original planning tion flow through the receptors and affer- may cancel each other. The present BP or better “BP-like movement-related and decision. This, however, has been ent nerves is at least 105 bit/sec (by order MEG study was performed in a patient activity” can be recorded from the basal completed already before the beginning of magnitude), whereas only 10 bit/sec with a complete vascular lesion of the ganglia. This cannot be done by EEG or of the experiment, when subjects gave show up in consciousness. The will, how- right SMA. In this case, it was possible MEG, but requires the fMRI. And not their informed consent to the experi- ever, always takes part, albeit sometimes to consistently localize a current dipole just the routine fMRI but an fMRI im- menter’s instructions. Repetitions of merely to the degree that it delegates as source in the intact left SMA starting proved in such a way that the temporal stereotyped simple movements are not much as possible to unconscious routines about 1,200 msec prior to the initiation resolution is high enough to justify the suitable for such an investigation. and expert systems of the brain. The of voluntary movements of the right term “event-related fMRI” and in our Thoughts of planning and motivation unconscious processes therefore do not thumb.” special case “movement-related fMRI.” are as we all know performed in the light lessen freedom; on the contrary, they Our second strategy was to use a mul- This was achieved by Cunnington et al of consciousness. The conscious aware- form its primary basis. tichannel whole scalp MEG instrument on (1999) who showed that it was feasible ness to want to make a movement does healthy subjects. In Vienna, we had a CTF to record a BP equivalent in the haemo- occur, in investigations of the BP, about Magnetoencephalography (MEG) system with 143 channels and used a so- dynamic response of the fMRI. Using 200 ms prior to the muscle contraction — In 1981, Hal Weinberg invited me phisticated analysis (two-dipole and three- single-event fMRI in combination with Libet’s W. This is roughly the same time as a distinguished visiting professor to dipole model in the same subject) to study fuzzy clustering analysis, it is possible to span needed for a motor reaction upon the Simon Fraser University in Greater the Bereitschaftsfield (BF) prior to tapping analyze the “Bereitschafts BOLD effect” an expected auditory stimulus. Although Vancouver, Canada, and we were the movements (Erdler et al 2000). The pa- in the form of the haemodynamic re- the decision to act already has been made first to record the MEG equivalent of the per’s abstract states: “Despite the fact that sponse time course. This haemodynamic earlier, consciousness is switched on in BP, the “Bereitschaftsfeld, BF” (Deecke, the knowledge about the structure and response resembles the BP or BF but is order to be able the function of the delayed in time (Cunnington et al 2002). to make changes supplementary mo- The movement-related fMRI ex- to the movement tor area (SMA) is periments of Cunnington et al (2002) if necessary — The movement-related fMRI experiments of steadily increasing, had great localizatory power and were changes that can the role of the SMA particularly valuable for mapping the go as far as not Cunnington et al (2002) had great localizatory in the human brain, mesial surfaces of the hemispheres, where executing the ac- e.g., the contribu- SMA and CMA are located. In this paper, tion at all (Libet’s power and were particularly valuable for tion of the SMA to self-initiated movements were compared veto), and to be the Bereitschafts- with externally triggered movements. In able to learn from potential, still both conditions, the following structures the success of the mapping the mesial surfaces of the remains unclear were active: pre-SMA, SMA proper and movement. In both and controversial. CMA (cingulate motor area, i.e. part of cases, the follow- hemispheres, where SMA and CMA are located. The goal of this the anterior cingulate gyrus. The border ing brain areas are study was to con- between pre-SMA and SMA proper is the activated: the SMA, tribute further to VAC line (vertical anterior commissure the pre-SMA, the this discussion by line). Although both pre-SMA and SMA anterior portion taking advantage proper are active in self-initiated move- of the cingulate cortex (CMA) and a part Weinberg Brickett 1982). We investigated of the increased spatial information of a ments and also in externally triggered of the motor cortex (Cunnington et al the Bereitschaftsfeld accompanying foot whole-scalp MEG system enabling us to ones, there are slight differences: The 2000), for which the basal ganglia do the movements as did Riita Hari and her record the magnetic equivalent of the Be- activity with self-initiated movements is groundwork (Kornhuber and Deecke group (Hari et al 1983). We also investi- reitschaftspotential 1, the Bereitschaftsfeld slightly more anterior. It is true that the 2012). However, with the self-initiated gated slow magnetic fields of the brain 1 (BF 1) or readiness field 1. Five subjects pre-SMA has somewhat greater involve- movement — but not with externally preceding speech in Vancouver (Wein- performed a complex, and one subject a ment in self-initiated movements, but it is triggered movements — additionally the berg et al 1983). simple, finger-tapping task. It was possible clear that it is not the pre-SMA alone that basal ganglia are activated before the Using our own MEG in Vienna, we to record the BF 1 for all subjects. The first is active (Shibasaki & Hallett 2006) but movement (Cunnington et al, 2002). This later investigated the problem of why appearance of the BF 1 was in the range that both pre-SMA and SMA proper are preparatory process for the spontaneous the SMA (and CMA) activity was not so of -1.9 to -1.7 s prior to movement onset, always activated in voluntary movement. movement, through which the readiness visible in the MEG (the onset time of except for the subject performing the Using the fMRI, it also was possible to for movement in the SMA builds up, the BF was not earlier than 600 msec). simple task (-1 s). Analysis of the develop- show that the SMA/CMA is active, when remains unconscious for the first 400 ms, The answer is that the two SMAs on the ment of the magnetic field distribution a movement is not executed but only as Libet has demonstrated. mesial surface of the brain are opposing and the channel waveforms showed the imagined. Kasess et al (2008) compared It is not unusual for something to hap- each other, and if they are both active beginning of the Bereitschaftsfeld 2 (BF movements that are actually executed pen unconsciously in the brain as well as — which is the case most of the time 2) or readiness field 2 at about -0.5 s prior with those that are only imagined. They www.wfneurology.org • JUNE 2014 9

have reported on this which may be recommended as further area since the 1990s, reading (Kornhuber & Deecke 2012). but the researcher I am ending with the photo taken at who worked most the session with Mark Hallett’s cam- intensively on its func- era, and with the abstracts of the other tion is Jun Tanji (Tanji speakers. They are published in Clin. 1994). The cingulate Neurophysiol. and can be found at www. motor areas, located ICCN2014. in the banks of the cingulate sulcus, S4 Generator Mechanism of BP constitute a portion of and Its Clinical Application the cingulate cortex of Hiroshi Shibasaki, Akio Ikeda (Kyoto/JP) primates. The rostral Since discovery of the slow negative cingulate motor area electroencephalographic (EEG) activ- (CMAr) is crucial for ity preceding self-initiated movement by reward-based planning Kornhuber and Deecke in 1964, various of motor selection, source localization techniques in normal whereas the caudal subjects and epicortical recording in epi- (CMAc) is not (Shima lepsy patients have disclosed the generator et al 1991). Cunning- mechanisms of each identifiable compo- ton recently expanded nent of the movement-related cortical on this, and inves- potentials (MRCPs). Regarding simple tigated concurrent movements, the initial slow segment of fMRI-EEG and the BP (early BP) begins about 2 sec before Bereitschafts-BOLD- the movement onset in the pre-supple- effect (cf. his abstract mentary motor area (pre-SMA) with no at the end). movement site-specificity and in the SMA To conclude, let proper with some somatotopic organiza- Figure 2: Chairman and speakers in the session “Bereitschaftspotential – 50 Years After Its Discovery” at the Interna- tional Congress of Clinical Neurophysiology 2014 (ICCN2014) on March 20, 2014, in Berlin. From left to right: Gert me shortly report tion, and shortly thereafter in the lateral Pfurtscheller, Graz, Austria; Ross Cunnington, Brisbane, Australia; Lüder Deecke, Vienna; Hiroshi Shibasaki, Kyoto, on the visual hand- premotor cortex bilaterally with relatively Japan; and Mark Hallett, Bethesda, Maryland (Chairman). tracking experiments clear somatotopy. About 400 ms before of brothers Wilfried the movement onset, the steeper negative obtained the interesting result that that the generation of an image in our and Michael Lang slope (late BP) occurs in the contralateral SMA/CMA were active in both imagina- “mind´s eye” may need considerable ef- (Lang et al 1983; Deecke et al 1984). In primary motor cortex (M1) and lateral tion and execution, however the mo- fort, and when we increase the effort we these tracking experiments, designed by premotor cortex with precise somatotopy. tor cortex, M1, was active in executed achieve a sharper image. them, the temporal course of the moving Both early and late BPs are influenced by movements only. In this context, we may Another important finding of the fMRI stimulus was known to the subject while complexity of the movements while late report on earlier work using DC-EEG studies was that movement-related activity the direction of the moving stimulus BP is influenced by discreteness of finger (Uhl et al 1990) and Single Photon Emis- also was recorded from the basal ganglia (which changes suddenly at a certain movements. Volitional motor inhibition sion Computed Tomography (SPECT) (Cunnington et al 2002). This finding is time) was unpredictable: The SMA or muscle relaxation is preceded by BP, (Goldenberg et al (1989) in mental important and makes perfect sense in view showed antici-patory behavior in that the which is quite similar to that preceding imagery. We were able to show that the of the cortico-basal ganglia-thalamocorti- BP declined ½ sec before the expected voluntary muscle contraction. Regarding frontal cortex (of which the SMA/CMA cal loop (cf. Kornhuber, 1974a; Alexander change, whereas the directed attention movements used for daily living such as form a part) is necessary to bring about et al (1986); DeLong, 1990). The activity potential (which had its maximum over grasping and reaching, BP starts from the the mental imagery (Lang et al 1988; Uhl traveling through this loop comes from the parietal area) continued to remain parietal cortex, more predominantly of et al 1990). the SMA/CMA and goes to the M1. On its high until 200 msec after the direction the dominant hemisphere. BP has been Mental imagery is the term in the way, it not only informs the basal ganglia change of the stimulus, when the sensory applied for investigating pathophysiology psychological literature meaning our that a movement is about to be initiated processing was completed. Thus, the of various movement disorders. ability to see something in our mind’s but also draws upon the expertise of the frontal lobe, after deciding what to do, Early BP is smaller in patients with eye. In Uhl et al 1990, we investigated basal ganglia as large stores of (over) delegated further action to posterior corti- Parkinson disease, probably reflecting the slow cerebral potentials (DC poten- learned movements and skills. The basal cal areas, which are competent to use the deficient thalamic input to SMA. BP tials) accompanying mental imagery. ganglia do the groundwork for the motor visual stimuli and to decide in detail how is smaller or even absent in patients with The interesting result was that — with cortex M1. In this context, the “chunk- to perform the tracking task. lesions in the dentato-thalamic path- the willful attempt to see something in ing hypothesis” of the Hallett group is From these and similar experiments way. Because BP does not occur before your mind’s eye (mental imagery) — the attractive (Gerloff et al, 1997). These and from previous results on lesions involuntary movements, BP is used for frontal cortex was activated first and only findings are exactly in line with our SMA (Kleist, 1934; Shallice, 1991), Kornhuber detecting the participation of the “vol- thereafter the posterior (sensory) areas hypothesis, where we envisage the SMA as developed a theory on the components untary motor system” in the generation of the brain were activated. The strong a job distributor and supervisor. The SMA of volition and their functional local- of apparently involuntary movements initial DC negativity of the frontal cortex organizes sequential tasks in such a way ization in the frontal lobes (Kornhuber, in patients with psychogenic movement demonstrated that these frontal areas that it breaks down the sequences into 1984; Lang et al, 1983, 84; Deecke et al, disorders. fulfill an important role in mental imag- handy pieces and reserves the appropriate 1985). One of the stages of volition is ery: They show that mental imagery is time slots for their launch. This is what planning, and for planning, a working an act of volition, and these frontal areas we understand by spatial and temporal is required. The brain is a coop- S5 Movement-Related Desynchro- are needed for the act of bringing about coordination. The interesting finding of erative system, but one with strategic nization and Resting State Senso- the imagery. In the SPECT study (using Cunnington et al (2002, Figure 21) was, organization. There is little doubt that rimotor Networks the same subjects), analogous results however, that activity in the lentiform in humans the prefrontal-orbital cortex Gert Pfurtscheller (Graz/AT) were obtained. These experiments have nucleus (at the junction between the controls the highest level of planning Preparation for a voluntary movement shown that our “motivational brain” is putamen and the external pallidum) was and decision-making. The frontal lobe is is not only accompanied by the “Bere- not only involved when it “exerts itself ” found for self-initiated movements only. For the most humane part of humans. It is itschaftspotential” (BP) and the pre-move- in the form of movement or action, but externally triggered movements, there was due to our frontal lobe that we have the ment desynchronization (ERD) of central also when it comes to “endogenous acts” no evidence of increased activation within personality we have, equipped with what alpha and beta band rhythms but also by (pure mental acts) such as mental imag- the basal ganglia. we call reasoned free will. a concomitant heart rate (HR) decelera- ery, learning with mental rehearsal and A last word about the CMA, the This is all laid out in a book that was tion. The intimate connection between thinking. We all know from introspection cingulate motor area: Kornhuber and I recently published in English in the U.S., brain and heart was enunciated by Claude 10 www.wfneurology.org • JUNE 2014

Bernard more than 150 years ago (Darwin Rome Vatican (1990) Jahanshahi M Hallett M (Eds) The Bere- 1999, pp. 71-72, originally published 1872) Barrett G, Shibasaki H, Neshige R (1986) itschaftspotential, movement-related corti- and is based on central commands pro- Cortical potential shifts preceding volun- Deecke L, Heise B, Kornhuber HH, Lang cal potentials. Kluwer Academic / Plenum jecting to cardiovascular neurons in the tary movement are normal in Parkinson- M, Lang W (1984) Brain potentials as- Publishers New York, viii 334 pp (2003) brain stem and modulating the HR. ism. Electroenceph Clin Neurophysiol sociated with voluntary manual tracking: ISBN 0-306-47407-7 One interesting question is, why do BP, 63:340-348 Bereitschaftspotential, conditioned pre- ERD and HR changes start already some motion positivity, directed attention poten- Kant, I. 1785. “Grundlegung zur seconds prior to movement onset? It has Cunnington R, Windischberger C, Deecke tial and relaxation potential. Anticipatory Metaphysik der Sitten.” Riga: Hartknoch. been documented that the resting state L, Moser E (1999) The use of single event activity of the limbic and frontal cortex In: sensorimotor network can oscillate at fMRI and fuzzy clustering analysis to Karrer R, Cohen J, Tueting P, eds., Ann NY Kant, I. 1795. “Zumewigen Frieden.” ~ 0.1 Hz observed in EEG, NIRS-HbO2/ examine haemodynamic response time Acad Sci Vol 425: 450-464 Königsberg: Nicolovius. Hb and fMRI-BOLD signals (Vanhatalo courses in supplementary motor and et al PNAS 2004, Sasai et al Neuroimage primary motor cortical areas. Biomed Deecke L, Kornhuber HH, Lang W, Lang Kasess CH. Windischberger C, Cunnington 2011). This suggests that the ongoing brain Technik 44 (Suppl 2): 116-119 M, Schreiber H (1985) Timing functions of R, Lanzenberger R, Pezawas L, Moser E activity can display slow/ultraslow excit- the frontal cortex in sequential motor- and (2008) The suppressive influence of SMA ability fluctuations in the range of ~10 Cunnington R, Windischberger C, Deecke learning tasks. Hum Neurobiol 4: 143-154. on M1 in motor imagery revealed by fMRI sec, and voluntary movements are most L, Moser E (2002) The preparation and and dynamic causal modeling. NeuroImage likely initiated if the excitability in resting execution of self-initiated and externally Deecke L, Kornhuber HH (2003) Human 40(2) 828-837 state sensorimotor networks reaches a spe- triggered movement: A study of event- freedom, reasoned will and the brain: The cific threshold. Remarkable is that a close related fMRI. NeuroImage 15: 373-385 Bereitschaftspotential story. In: M Jahan- Kleist K (1934) Gehirnpathologie. Barth, coupling can exist between cerebral and shahi, M Hallett (Eds) The Bereitschafts- Leipzig Kornhuber HH, Deecke L (1964) cardiovascular ~0.1 Hz oscillations. Cunnington R, Windischberger C, Deecke potential, movement-related cortical Hirnpotentialänderungen beim Menschen L, Moser E (2003) The preparation and potentials. Kluwer Academic / Plenum vor und nach Willkürbewegungen, darg- S97 Concurrent fMRI-EEG readiness for voluntary movement: a Publishers New York, pp 283-320 ISBN estellt mit Magnetbandspeicherung und and the Bereitschafts-BOLD-Effect high-field event-related fMRI study of the 0-306-47407-7 Rückwärtsanalyse. Pflügers Arch.281: 52. *Ross Cunnington Bereitschafts-BOLD response. NeuroIm- Kornhuber HH, Deecke L (1965) Hirnpoten- 1University of Queensland, School of age 20: 404-412 Deecke L (2012) There are conscious and tialänderungen bei Willkürbewegungen und Psychology & Queensland Brain Institute, unconscious agendas in the brain and both passiven Bewegungen des Menschen: Bere- Brisbane, Australia Deecke, L., Scheid, P., Kornhuber, HH are important our will can be conscious as itschaftspotential und reafferente Potentiale. The cortical correlates of voluntary 1969. “Distribution of readiness potential, well as unconscious. Brain Sci 2, 405-420 Pflügers Arch 284: 1-17 ‘Citation Classic’ actions precede movement by up to pre-motion positivity and motion potential 1-2 sec, as evident in the Bereitschafts- of the human cerebral cortex preceding DeLong MR (1990) Primate models of Kornhuber, HH 1974. “Cerebral cor- potential. This sustained activity prior voluntary finger movements.” Exp. Brain movement disorders of basal ganglia ori- tex, cerebellum and basal gangalia: an to movement is strongly influenced Res. 7, 158-168, criteria met for Citation gin. Trends Neurosci 13: 281-285 introduction to their motor functions.” In: by attention and by arousal levels, Classic. Schmitt, F.U., Worden, F.G. eds.: The Neu- showing less activity when actions are Dick JPR, Rothwell JC, Day BL, Cantello R, rosciences. Third Study Program. Cambridge relatively unattended and when arousal Deecke, L., Grözinger, B., Kornhuber, Buruma O, Gioux M, Benecke R, Berardelli Mass.: MIT Press. 267-280. level is low. While fMRI has revealed HH 1976. “Voluntary finger movement in A, Thompson PD, Marsden CD (1989) key regions that contribute to pre- man: Cerebral potentials and theory.” Biol The Bereitschaftspotential is abnormal in Kornhuber HH: (1974) The vestibular movement activity, the relationship Cybern 23, 99-119, criteria met for Cita- Parkinson‘s disease. Brain 112:233-244 and the general motor system. In: HH between activity in these regions and tion Classic. Kornhuber (Ed.) Handbook of Sensory the Bereitschaftspotential is not well Eccles, J. C. (1973) The understanding of the Physiology VI/2 Vestibular System Part 2 understood. By using concurrent EEG Deecke, L., Kornhuber, HH 1978. “An brain. New York. McGraw-Hill. xv 238 pp Springer Berlin pp 581-620 and fMRI measurement and single-trial electrical sign of participation of the correlation analysis, we find that the mesial ”supplementary” motor cortex in Eccles JC, Creutzfeldt O (Eds) (1990) The Kornhuber HH, Deecke L (Eds): Motiva- cingulate motor area in the mid cingu- human voluntary finger movement.” Brain principles of design and operation of the tion, motor and sensory processes of the late cortex plays a key role in driving Res. 159, 473-476, criteria met for Citation brain. Pontificiae Academiae Scientiarum brain: Electrical potentials, behavior and sustained activity in the higher motor Classic. Scripta Varia 78. Rome. Vatican clinical use. Amsterdam, Elsevier, Prog areas prior to voluntary action. Specifi- Brain Res Vol 54, 811 pp (1980) cally, we find that trials in which early Deecke, L; Weinberg, H.; Brickett, P. Erdler M, Beisteiner R, Mayer D, Kaindl T, Bereitschaftspotential activity is large (1982). Magnetic fields of the human brain Edward V, Windischberger C, Lindinger G, Kornhuber HH, Deecke L, Lang W, Lang are associated with greater activity in accompanying voluntary movement. Deecke L (2000) Supplementary motor area M (1989) Will, volitional action, attention the mid cingulate cortex, and a greater Bereitschaftsmagnetfeld. Exp. Brain Res. activation preceding voluntary movement and cerebral potentials in man: Bere- influence of the mid cingulate cortex on 48: 144–148. is detectable with a whole scalp magneto- itschaftspotential, performance-related sustained activity in the supplementary encephalography system. NeuroImage 11: potentials, directed attention potential, motor area. This key role of the cingu- Deecke L, Boschert J, Weinberg H, Brick- 697-707 EEG spectrum changes. pp 107-168 in late motor area in driving sustained ac- ett P (1983) Magnetic fields of the human Hershberger WA, ed., Volitional action. tivity of the supplementary motor prior brain (Bereitschaftsmagnetfeld) preceding Gerloff C, Corwell B, Chen R, Hallett M, Conation and control. Elsevier Science/ to movement can explain how factors voluntary foot and toe movements. Exp Cohen LG (1997) Stimulation over the hu- North Holland. such as attention and arousal level also Brain Res 52: 81-86 man supplementary motor area interferes have such a strong influence on early with the organization of future elements Kornhuber HH, Deecke L (1990) Readi- neural activity of the Bereitschaftspo- Deecke L, Eccles JC, Mountcastle (Eds) in complex motor sequences. Brain 120: ness for movement — The Bereitschafts- tential. (1990) From Neuron to Action. An 1587-1602 potential story. Citation Classic Commen- Thanks go to Dr. Volker Deecke, Appraisal of Fundamental and Clini- tary. Current Contents Life Sciences 33 (4): 14. senior lecturer, Centre for Wildlife cal Research. Springer Publisher. Berlin Goldenberg G, Podreka I, Uhl F, Steiner M, Conservation, University of Cumbria, Heidelberg New York. xii 677 pp ISBN Willmes K, Deecke L (1989) Cerebral cor- Kornhuber HH, Deecke L (1990) Readi- UK, for his comments and help with 3-540-52072-4 relates of imagining colors, faces and a map ness for movement – The Bereitschaftspo- the English. – I. SPECT of regional cerebral blood flow. tential story. Citation Classic Commentary. Deecke L, Lang W (1990) Movement- Neuropsychologia 27:1315-1328 Current Contents Clinical Medicine 18 (4): 14 References: related potentials and complex actions: Coordinating role of the supplementary Hari R, Antervo A, Katila T, Poutanen T, Kornhuber, HH (1978) “Motorische Sys- Alexander GE, DeLong MR, Strick PL motor area. In: Eccles JC, Creutzfeldt O Seppänen M, Tuomisto T and Varpula T teme und Sensomotorische Integration.” (1986) Parallel organization of functionally (Eds): The principles of design and opera- (1983) Cerebral magnetic fields associated In: Stamm, R.A., Zeier, H. eds.: Die Psy- aggregated circuits linking basal ganglia tion of the brain. Pontificiae Academiae with voluntary limb movements in man. chologie des 20. Jahrhunderts. Bd. VI. Zürich: and cortex. Ann Rev Neurosci 9: 357-381. Scientiarum Scripta Varia 78, pp 303-336, Nuovo Cimento 1983, 2D: 484–494. Kindler. 750-762. www.wfneurology.org • JUNE 2014 11

Kornhuber, HH 1984 “Attention, readi- Lang W, Lang M, Kornhuber A, Deecke Libet B (1990) Cerebral processes that Shima K, Aya K, Mushiake H, Tanji J ness for action, and the stages of volun- L, Kornhuber HH (1983) Human cerebral distinguish conscious experience from (1991) Two movement-related foci in tary decision.” Exp. Brain Res. Suppl. 9, potentials and visuo-motor learning. unconscious mental functions. In: Eccles the primate cingulate cortex observed in 420-429. Pflügers Arch Eur J Physiol 399: 342-344. JC, Creutzfeldt O (Eds): The principles of signal-triggered and self-paced forelimb design and operation of the brain. Pontifi- movements. J Neurophysiol 65:188-202 Kornhuber, HH 1987. “Handlung- Lang W, Lang M, Heise B, Deecke L, ciae Academiae Scientiarum Scripta Varia Tanji J (1994) The supplementary motor sentschluß, Aufmerksamkeit und Kornhuber HH (1984) Brain potentials 78, pp 186-202, Rome Vatican area in the cerebral cortex. Neurosci Res Lernmotivation im Spiegel menschlicher related to voluntary hand tracking, mo- 19: 251-268 Hirnpotentiale, mit Bemerkungen zu tivation and attention. Hum Neurobiol 3: Wille und Freiheit.” In: Heckhausen, 235 – 240. Marsden CD, Deecke L, Freund H-J, Hal- Uhl F, Goldenberg G, Lang W, Lindinger H., Gollwitzer, P.M., Weinert, F.E. eds.: lett M, Passingham RE, Shibasaki H, Tanji G, Steiner M, Deecke L (1990) Cerebral Jenseits des Rubikon: Der Wille in den Lang W, Lang M, Podreka I, Steiner M, J, Wiesendanger M (1996) The functions correlates of imagining colours, faces Humanwissenschaften. Berlin, Heidelberg: Uhl F, Suess E, Müller C, Deecke L (1988) of the supplementary motor area: Sum- and a map - II. Negative cortical DC- Springer. 376-401. DC-potential shifts and regional cerebral mary of a workshop. Advances in Neurol- potentials. Neuropsychologia 28:81-93 blood flow reveal frontal cortex involve- ogy, Vol. 70: Supplementary Sensorimotor Kornhuber, HH 1988. “The human ment in human visuomotor learning. Exp Area, HO Lüders (Ed) pp 477-487 Walter WG, Cooper R, Aldridge VJ, brain: from dream and cognition to Brain Res 71: 353-364 McCallum WC, Winter AL (1964) Con- fantasy, will, conscience and freedom.” McCallum, WC, Knott JR (1976) The re- tingent negative vari-ation: An electric In: Markowitsch, H.J. ed.: Information Lang W, Cheyne D, Kristeva R, Beisteiner sponsive brain. John Wright & Sons Ltd. sign of sensori-motor association and processing by the brain. Toronto, Bern, R, Lindinger G, Deecke L (1991) Three- Bristol 272 pp. expectancy in the human brain. Nature Stuttgart: Hans Huber Publ. 241-258. dimensional localization of SMA activity 203: 380-384. preceding voluntary movement. A study Popper KR, Eccles JC (1977) The self Kornhuber, HH 1992. “Gehirn, Wille, of electric and magnetic fields in a patient and its brain. An argument for interac- Weinberg H, Brickett P, Deecke L, Freiheit.” Rev. Metaphys. et Morale. 2. with infarction of the right supplementary tionism. Springer International. Berlin, Boschert J (1983) Slow magnetic fields 203-223. motor area. Exp Brain Res 87: 688-695 Heidelberg, London New York 597 pp. of the brain preceding movements and speech. Proceedings of the IV Int Work- Kornhuber, HH 1993. “Prefrontal cortex Lang W, Deecke L (1998) Psychophysiolo- Shallice, T., Burgess, P. 1991. “Higher- shop on Biomagnetism, Rome Sept, and homosapiens: on creativity and gie der Motorik. Chapter 5 in: F Rösler order cognitive impairments and frontal 1982 Il Nuovo Cimento 2: 495-504 reasoned will.” Neu-rol. Psychiat. Brain (Ed) Volume 5 Ergebnisse und Anwendun- lobe lesions in man.” In: Levin, H.S., Wu T, Kansaku K, Hallett M (2004) How Res 2, 1-6. gen der Psychophysiologie. Enzyklopädie Eisenberg, H.M., Benton, A.L. eds.: self-initiated memorized movements be- der Psychologie, Serie I Biologische Psy- Frontal lobe function and dysfunction. New come automatic: a functional MRI study. Kornhuber HH, Deecke L (2012) The chologie. Hogrefe Göttingen, pp 225-283 York, Oxford: Oxford University Press, J Neurophysiol 91:1690-1698. will and its brain — an appraisal of 125-138. reasoned free will. University Press of Libet B, Gleason CA, Wright EW, Pearl Kornhuber HH & Deecke L, The America, Lanham, MD, USA, xvi 116 pp DK (1983) Time of conscious intention to Shibasaki H, Hallett M (2006) What is Will and its Brain, University Press of ISBN978-0-7618-5862-1 act in relation to onset of cerebral activity the Bereitschaftspotential? Clin Neuro- America publisher, 2012. (readiness-potential). Brain 106: 623-642 physiol 117:2341-2356

Editor’s Update and Selected Articles From JNS

By John D. England, MD be able to recognize the efforts and ed to the initial trial and were treated 2) Marinos Dalakas provides a importance of our reviewers in a more with maintenance IVIg (0.4 g/kg thoughtful editorial on the above- n behalf of the Editorial Board, I tangible manner. every three to six weeks) for an aver- noted article and places its results would like to thank all of the indi- Most readers are becoming aware age of 5.9 years (range 1 to 17 years). into the perspective of current O viduals who review articles for the of the fact that Elsevier, the publisher Twenty-three patients achieved treatment options for myasthenia Journal of the Neurological Sciences (JNS). of JNS, now provides free access to se- mild improvement, and 14 patients gravis (MG). He emphasizes the The integrity of a scientific journal lected articles from JNS for members achieved moderate improvement as point that IVIg appears to exert such as JNS depends heavily upon the of the World Federation of Neurol- measured by the Myasthenia Gravis only a short-term and transient im- quality of independent peer-review. ogy. In consultation with members of Foundation of America (MGFA) clini- munomodulation in MG and does I continue to be impressed with the the Editorial Board, I select two “free- cal classification scheme. A beneficial not provide immunosuppression high quality and thoroughness of the access” articles, which are profiled in response was associated with bulbar of the disease. At this time, the reviewers’ each issue of World Neurology. onset, seropositivity and high titer of evidence supports restricting the critiques of In this issue, we feature two paired acetylcholine receptor antibody, and use of IVIg in MG to short-term manuscripts. articles: older age of disease onset. Prob- treatment of unstable patients until I am especial- ably the most important observation immunosuppressive treatments ly impressed 1) Hellmann, et al. reviewed the re- in this study was that none of the become effective. However, only a and thankful sponse to maintenance intravenous patients achieved full remission with prospective trial of IVIg therapy for that such immununoglobulin (IVIg) in a co- maintenance IVIg. Although IVIg im- MG will provide definitive conclu- busy and hort of 52 patients with myasthenia proved symptoms of MG and allowed sions regarding its long-term effec- committed gravis (MG) who had not responded reduction of other medications, it did tiveness in managing this disease. individu- adequately to pyridostigmine, pred- not provide a sustained effect or true (Dalakas M. IVIg in the chronic als still take nisone, azathioprine, or combina- remission of the disease. (Hell- management of myasthenia gra- the time to John D. England, MD tions of these medications. Fifteen mann MA, Mosberg-Galili R, Lotan vis: Is it enough for your money? review articles. of the patients did not respond to I, Steiner I. Maintenance IVIg J Neurol Sci 2014;338:1-2) • One of my goals for this year is to an initial trial of IVIg, and were not therapy in myasthenia gravis does seek advice from the Editorial Board treated with additional doses of not affect disease activity. J Neurol England is editor-in-chief of the Journal of the and Elsevier about how we might IVIg. Thirty-seven patients respond- Sci 2014;338:39-42) Neurological Sciences. 12 www.wfneurology.org • JUNE 2014

in memoriam

Theodore L. Munsat, MD I met Munsat at the WFN World tion, intelligence, humor, kindness with Congress of Neurology 1997 in Argentina a great ability to make easier the hardest with his wife Carla. We invited him to an things, a natural leader, a gentleman, an International Symposium as part of the honorable man. He had a warm and sincere A Tribute from the Sociedad scientific activities after the Neurologica Argentina congress, in Tucumán, Calchaquies ever too late for a tribute, especially He was honored with the A.B. Baker Valleys, in for a man like Theodore Leon Mun- Award for Education from the AAN, the the North N sat (1930-2013). He was an extraordi- Sheila Essey Award for ALS Research of Argen- nary man and a natural educator who gave and the Lifetime Achievement Award tina, where the opportunity to improve neurology from the WFN Research Group on Neu- several con- worldwide. romuscular Diseases. ferences of Among other educational activities, He developed a number of success- ALS took Munsat helped launch the American ful educational programs. More than place, with Ted Munsat worked with the WFN to improve education in developing countries Academy of Neurology’s (AAN´s) con- 42 countries all over the world were Alan Mac like Argentina in 199. tinuing education publication, Continuum, benefited with a continuing medical Comas, Roberto Sica and other international personality. he loved helping others every was chairman of the World Federation education (CME), using the journal Con- leaders in neuromuscular diseases. chance he could. of Neurology (WFN) Amyotrophic Lat- tinuum, generously donated by the AAN In that opportunity began the idea to de- I admired and respected him as a man, as eral Sclerosis (ALS), chairman of WFN with an extraordinary local impact. velop an educational program for Argentina. a professional and as a teacher. He has left a Research and Education Committees, He worked within the WFN to The educational program began in profound mark on the world of neurology. served as president of the AAN (1989-91), improve neurology and education in 2003 and benefitted over a decade of The Sociedad Neurológica Argentina wishes and was emeritus professor of neurology many developing countries, including continuity to hundreds of neurologists to give this tribute and extend our gratitude. at Tufts University Scholl of Medicine, educational programs in Honduras and in our country with a significant educa- Dear Ted, thank you very much for all between other relevant activities. Indeed, Argentina. He directed his energies to tional imprint. you have done; we shall remember your exceptional merits for only one man. teaching neurology internationally. I want to highlight his passion for educa- legacy always. •

various cultural and religious traditions Maynard M. Cohen (1920-2014) (XVth WCN Vancouver 1993), engaging the leading experts in the field from the U.S. and other countries of the globe. reat scientist, one of the pio- President Richard Masland and the treasurer of the new research group, During his service (until 1995), neers of the American modern then-Chairman of the WFN Research participating in the new activities in the he supported activities of the group. G neurology, lover of philosophy Council John Walton proposed to form Federation. As co-editor of the book, When we needed new, experienced and culture, philanthropist. Maynard a new he cared that contributions from less colleagues for the organization, he pro- M. Cohen, MD, PhD, professor and Research developed countries find a place in it. posed new active members for the RG chairman emeritus in the Department Group on He concluded his own chapter with Committee: Donna Bergen and Don of Neurological Sciences at the Rush- Organiza- visionary words: “This symposium, the Silberberg, who have stayed active in Presbyterian-St. Luke’s Medical Center tion and support of the World Federation of the WFN. His wife, Doris Vidaver, par- in Chicago, and past AAN president, Delivery Neurology, and the formation of the ticipated kindly with her experience in died on Feb. 18, 2014, in Miami in his of Neu- Research Group on Organization and humanities and in medicine, especially 94th year. rological Delivery of Neurological Services are in neurology. As the world-renowned neurologist, Services but the initial steps. The larger task still The World Federation of Neurology he was the U.S. delegate to the World (WFN RG lies ahead.” (Neurology in Developing will memorialize his activities, for which Federation of Neurology (1985-1989). ODNS) Countries, B.I. Churchill Livingstone, he received in 1993 the WFN Certificate At the delegates’ preparatory meet- in order 1991, p.75). of Appreciation. They are now being ing (1987) in New Delhi for the XIVth to search Despite his years, he showed re- continued also as an integrative part of WCN, he strongly supported the orga- for best Maynard M. Cohen, MD, PhD markable enthusiasm and energy as co- the WFN mission and programs. Many nization of the symposium, proposed solutions organizer of our meetings (New Delhi, neurologists active in those years still by Yugoslav and Indian neurologists: in delivery of neurological services Vienna, Marrakesh, Vancouver and remember our early initiatives and the “Neurology in Developing Countries” around the world (both in industrial others), as well as initiatives in many humane care of Maynard M. Cohen for during the New Delhi WCN in 1989. and developing countries), respecting parts of the world. He organized an im- people around the world. • After the successful symposium, in local and regional, social and economic portant symposium, “Ethical Problems which our respected friend gave a conditions. in Neurology,” concerning problems in Bosko Barac, MD, DMS, is the founding chair- beautiful contribution, the then-WFN Cohen accepted to serve as secretary managing neurological ailments due to man of the WFN RG ODNS (ret.).