PROGRESS IN BRAIN RESEARCH VOLUME 177 COMA SCIENCE: CLINICAL AND ETHICAL IMPLICATIONS EDITED BY STEVEN LAUREYS Coma Science Group, Cyclotron Research Center and Department of Neurology, `ge, Lie `ge, Belgium University of Lie NICHOLAS D SCHIFF Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, NY, USA ADRIAN M OWEN MRC Cognition and Brain Sciences Unit, Cambridge, UK This volume is an official title of Coma and Consciousness Consortium funded by the James S McDonnell Foundation and the European Cooperation in the field of Scientific and Technical Research (COST) Action BM0605: Consciousness: A Transdisciplinary, Integrated Approach AMSTERDAM – BOSTON – HEIDELBERG – LONDON – NEW YORK – OXFORD PARIS – SAN DIEGO – SAN FRANCISCO – SINGAPORE – SYDNEY – TOKYO Elsevier 360 Park Avenue South, New York, NY 10010-1710 Linacre House, Jordan Hill, Oxford OX2 8DP, UK Radarweg 29, PO Box 211, 1000 AE Amsterdam, The Netherlands First edition 2009 Copyright r 2009 Elsevier B.V All rights reserved No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form or by any means electronic, mechanical, photocopying, recording or otherwise without the prior written permission of the publisher Permissions may be sought directly from Elsevier’s Science & Technology Rights Department in Oxford, UK: phone (+44) (0) 1865 843830; fax (+44) (0) 1865 853333; email: permissions@elsevier.com Alternatively you can submit your request online by visiting the Elsevier web site at http://www.elsevier.com/locate/permissions, and selecting Obtaining permission to use Elsevier material Notice No responsibility is assumed by the publisher for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions or ideas contained in the material herein Because of rapid advances in the medical sciences, in particular, independent verification of diagnoses and drug dosages should be made British Library Cataloguing in Publication Data A catalogue record for this book is available from the British Library Library of Congress Cataloging-in-Publication Data A catalog record for this book is available from the Library of Congress ISBN: 978-0-444-53432-3 (this volume) ISSN: 0079-6123 (Series) For information on all Elsevier publications visit our website at elsevierdirect.com Printed and bound in Great Britain 09 10 11 12 13 10 List of Contributors A Arzi, Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel P Azouvi, AP-HP, Department of Physical Medicine and Rehabilitation, Raymond Poincare Hospital, Garches; University of Versailles-Saint Quentin, France; Er 6, UPMC, Paris, France T Bekinschtein, MRC Cognition and Brain Sciences Unit; Impaired Consciousness Research Group, Wolfson Brain Imaging Centre, University of Cambridge, UK A Belmont, AP-HP, Department of Physical Medicine and Rehabilitation, Raymond Poincare Hospital, Garches, France; Er 6, UPMC, Paris, France J.L Bernat, Neurology Department, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA H Blumenfeld, Department of Neurology; Departments of Neurobiology and Neurosurgery, Yale University School of Medicine, New Haven, CT, USA M Boly, Coma Science Group, Cyclotron Research Center and Neurology Department, University of ` ` Liege and CHU Sart Tilman Hospital, Liege, Belgium M.-A Bruno, Coma Science Group, Cyclotron Research Center and Neurology Department, University ` ` of Liege, Liege; Fund for Scientific Research – FNRS, Belgium C Buhmann, Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany A Casali, Department of Clinical Sciences, University of Milan, Milan, Italy C Chatelle, Coma Science Group, Cyclotron Research Center and Neurology Department, University of ` ` Liege, Liege, Belgium I Chervoneva, Department of Pharmacology and Experimental Therapeutics, Division of Biostatistics, Thomas Jefferson University, Philadelphia, PA, USA E Chew, Department of Physical Medicine and Rehabilitation, Harvard Medical School, Spaulding Rehabilitation Network, Boston, MA, USA N Childs, Texas NeuroRehab Center, Austin, TX, USA M.R Coleman, Impaired Consciousness Research Group, Wolfson Brain Imaging Centre; Academic Neurosurgery Unit, University of Cambridge, Cambridge, UK ` ` V Cologan, Coma Science Group, Cyclotron Research Centre, University of Liege, Liege, Belgium D Coughlan, Brain Injury Program, Braintree Rehabilitation Hospital, Braintree; Sargent College of Health and Rehabilitation Sciences, Boston University, Boston, MA, USA ` ` B Dahmen, Coma Science Group, Cyclotron Research Centre, University of Liege, Liege, Belgium A Demertzi, Coma Science Group, Cyclotron Research Center and Neurology Department, University ` ` of Liege, Liege, Belgium A Dennison, Charlotte Institute of Rehabilitation, Carolinas Medical Center, Charlotte, NC ` A.M de Noordhout, Neurology Department, University of Liege, Centre Hospitalier Regional de la ` Citadelle, Liege, Belgium M.C Di Pasquale, Moss Rehabilitation Research Institute/Albert Einstein Healthcare Network, Philadelphia, PA, USA B Eifert, Fachkrankenhaus Neresheim Hospital, Neresheim, Germany A.K Engel, Department of Neurophysiology and Pathophysiology, Center of Experimental Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany v vi D.J Englot, Department of Neurology, Yale University School of Medicine, New Haven, CT, USA J.J Fins, Division of Medical Ethics, Weill Medical College of Cornell University, New York, NY, USA ´ ˆ ` D Galanaud, Department of Neuroradiology, Pitie-Salpetriere Hospital, Paris, France J.T Giacino, JFK Johnson Rehabilitation Institute; New Jersey Neuroscience Institute, Edison, NJ, USA R Goebel, Department of Cognitive Neuroscience, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, The Netherlands; Maastricht Brain Imaging Centre (M-BIC), Maastricht, The Netherlands D Golombek, Chronobiology Lab, University of Quilmes/CONICET, Buenos Aires, Argentina ` ` O Gosseries, Coma Science Group, Cyclotron Research Centre, University of Liege, Liege, Belgium ă ă S Hacker, Institute of Medical Psychology and Behavioral Neurobiology, University of Tubingen, ă Tubingen, Germany W Hamel, Department of Neurosurgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany F Hammond, Charlotte Institute of Rehabilitation, Carolinas Medical Center, Charlotte, NC U Hidding, Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany J Hirsch, fMRI Research Center, Columbia University, New York, NY, USA K Kalmar, JFK Johnson Rehabilitation Institute; New Jersey Neuroscience Institute, Edison, NJ, USA D.I Katz, Brain Injury Program, Braintree Rehabilitation Hospital, Braintree, MA; Department of Neurology, Boston University School of Medicine, Boston, MA, USA ă A Kubler, Institute of Psychology I, Biological Psychology, Clinical Psychology and Psychotherapy, ¨ ¨ University of Wurzburg, Wurzburg, Germany; Institute of Medical Psychology and Behavioral ă ă Neurobiology, University of Tubingen, Tubingen, Germany N Lapitskaya, Neurorehabilitation Research Department, Hammel Neurorehabilitation and Research ` Centre, Hammel, Denmark; Coma Science Group, Cyclotron Research Centre, University of Liege, ` Liege, Belgium S Laureys, Coma Science Group, Cyclotron Research Center and Neurology Department, University and ` ` ` University Hospital of Liege; Fund for Scientific Research – FNRS; University of Liege, Liege, Belgium D Ledoux, Coma Science Group, Cyclotron Research Center and Intensive Care Department, University ` ` of Liege, Liege, Belgium N Levy, Oxford Centre for Neuroethics, Littlegate House, Oxford, UK D Long, Bryn Mawr Rehabilitation Hospital, Malvern, PA, USA ă D Lule, Institute of Medical Psychology and Behavioral Neurobiology, University of Tubingen, ` ` ă Tubingen, Germany; Coma Science Group, Cyclotron Research Centre, University of Liege, Liege, Belgium ´ I Lutte, Medico-legal Department, Faculty of Medicine, Universite Libre de Bruxelles and Coma Science ` ` Group, Cyclotron Research Centre, University of Liege, Liege, Belgium S Majerus, Center for Cognitive and Behavioral Neuroscience and Coma Science Group, University of ` ` Liege, Liege; Fund for Scientific Research – FNRS, Belgium R Malach, Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel M Massimini, Department of Clinical Sciences; Department of Neurophysiology, University of Milan, Milan, Italy A Maudoux, Coma Science Group, Cyclotron Research Centre, and ENT department, CHU Sart Tilman ` ` Hospital, University of Liege, Liege, Belgium P Maurer, Fachkrankenhaus Neresheim Hospital, Neresheim, Germany W Mercer, Texas NeuroRehab Center, Austin, TX, USA vii C.K.E Moll, Department of Neurophysiology and Pathophysiology, Center of Experimental Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany M.M Monti, MRC Cognition and Brain Sciences Unit; Impaired Consciousness Research Group, Wolfson Brain Imaging Centre, University of Cambridge, UK ` G Moonen, Department of Neurology, CHU University Hospital, Liege, Belgium ă D Muller, Department of Neurosurgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany ă A Munchau, Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany M Nichols, Brain Injury Program, Braintree Rehabilitation Hospital, Braintree, MA, USA J.F Nielsen, Neurorehabilitation Research Department, Hammel Neurorehabilitation and Research Centre, Hammel, Denmark Y Nir, Department of Psychiatry, University of Wisconsin, Madison, WI, USA ` ` Q Noirhomme, Coma Science Group, Cyclotron Research Centre, University of Liege, Liege, Belgium P Novak, Sunnyview Hospital and Rehabilitation Center, Schenectady, NY, USA S Ovadia, Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel M Overgaard, CNRU, Hammel Neurorehabilitation and Research Unit, Aarhus University Hospital, Hammel, Denmark A.M Owen, MRC Cognition and Brain Sciences Unit; Impaired Consciousness Research Group, Wolfson Brain Imaging Centre, University of Cambridge, UK M Papa, Medicina Pubblica Clinica e Preventiva, Second University of Naples, Naples, Italy ´ ´´ ˆ ˆ F Pellas, Medecine Reeducative, Hopital Caremeau, CHU Nımes, Cedex, France J.D Pickard, Impaired Consciousness Research Group, Wolfson Brain Imaging Centre; Academic Neurosurgery Unit, University of Cambridge, UK M Polyak, Brain Injury Program, Braintree Rehabilitation Hospital, Braintree, MA, USA ´ ˆ ` L Puybasset, Department of Anesthesiology-Reanimation, Pitie-Salpetriere Hospital, Paris, France J Reithler, Department of Cognitive Neuroscience, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, The Netherlands; Maastricht Brain Imaging Centre (M-BIC), Maastricht, The Netherlands A Roche, Brain Injury Program, Braintree Rehabilitation Hospital, Braintree, MA, USA D Rodriguez-Moreno, fMRI Research Center, Columbia University, New York, NY, USA M Rosanova, Department of Clinical Sciences, University of Milan, Milan, Italy J Savulescu, Oxford Centre for Neuroethics, Littlegate House, Oxford, UK N.D Schiff, Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, NY, USA C Schnakers, Coma Science Group, Cyclotron Research Center and Neuropsychology Department, ` ` University of Liege, Liege, Belgium A Sharott, Department of Neurophysiology and Pathophysiology, Center of Experimental Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany ` A Soddu, Coma Science Group, Cyclotron Research Centre, University of Liege, Belgium; Medicina Pubblica Clinica e Preventiva, Second University of Naples, Naples, Italy B Sorger, Department of Cognitive Neuroscience, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, The Netherlands; Maastricht Brain Imaging Centre (M-BIC), Maastricht, ` ` The Netherlands; Coma Science Group, Cyclotron Research Centre, University of Liege, Liege, Belgium M Stanziano, Medicina Pubblica Clinica e Preventiva, Second University of Naples, Naples, Italy T Taira, Department of Neurosurgery, Tokyo Women’s Medical University, Shinjuku, Tokyo, Japan viii G Tononi, Department of Psychiatry, University of Wisconsin, Madison, WI, USA L Tshibanda, Coma Science Group, Cyclotron Research Center and Neuroradiology Department, ` ` University and University Hospital of Liege, Liege, Belgium C Vallat-Azouvi, UGECAM-antenne UEROS, Raymond Poincare Hospital, Garches, France; Er 6, UPMC, Paris, France A Vanhaudenhuyse, Coma Science Group, Cyclotron Research Center and Neurology Department, ` ` University and University Hospital of Liege, Liege, Belgium M Westphal, Department of Neurosurgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany J Whyte, Moss Rehabilitation Research Institute/Albert Einstein Healthcare Network, Philadelphia, PA, USA R Zafonte, Department of Physical Medicine and Rehabilitation, Harvard Medical School, Spaulding Rehabilitation Network, Boston, MA, USA N.D Zasler, Concussion Care Centre of Virginia, Ltd.; Tree of Life Services, Inc., Richmond, VA; Department of Physical Medicine and Rehabilitation, Virginia Commonwealth University, Richmond, VA; Department of Physical Medicine and Rehabilitation, University of Virginia, Charlottesville, VA, USA A Zeman, Cognitive and Behavioural Neurology, Peninsula Medical School, Exeter, UK ă ă C Zickler, Medical Psychology and Behavioral Neurobiology, University of Tubingen, Tubingen, Germany S Zittel, Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany Foreword Consciousness is the appearance of a world In its absence there is no self, no environment, no pain, no joy; there is simply nothing at all Following Thomas Nagel, without consciousness there is ‘nothing like it is to be’ (Nagel, 1974) Understanding the boundaries of consciousness is therefore of the highest clinical and ethical importance The new enterprise of ‘coma science’ is at the very forefront of this mission, and the present volume — edited and in several chapters co-authored by the three pioneers of the field — represents an essential and timely contribution Coma science is perhaps the most dynamic yet empirically grounded sub-field within the rapidly maturing science of consciousness It seeks to understand not only coma itself, but also the many differentiated varieties of impaired conscious level following brain injury, including the vegetative state, the minimally conscious state and the locked-in state Its key objectives include: (i) reliable diagnosis of residual consciousness in patients unable to produce verbal or behavioural reports, (ii) establishing non­ verbal or even non-behavioural means of communication where residual consciousness persists and ultimately (iii) delivering improved prognosis and even treatment, for example via novel applications of deep-brain stimulation or pharmacological intervention More broadly, coma science provides an invaluable window into the mechanisms of consciousness in general, by revealing which structural and functional brain properties are either necessary or sufficient for the appearance of a world As has often been the case in the history of science, the proper understanding of a natural phenomenon may be best pursued by examining those situations in which it is perturbed While the general goals of consciousness science carry substantial implications for our understanding of our place in nature, the specific objectives of coma science impose clear and present clinical and ethical challenges Here are just of few of those discussed in the following pages: How is death to be defined (Bernat)? When should treatment be withheld, or applied more aggressively (e.g Katz et al., Fins)? What ´ is the quality of life like for patients (Azouvi et al., Lule et al., Zasler, Lutte)? What are reliable criteria for residual consciousness, or for the capacity to suffer (e.g Giacino et al., Coleman et al., Majerus et al., Boly et al., and others)? These challenges cannot be relegated to the armchair They arise on a daily basis at the patient’s bedside, in the intensive care, neurology, neurosurgery or neurorehabilitation units, often with family members in attendance and sometimes with limited time for deliberation Principled responses are urgently required, and this volume should be a primary port-of-call for their formulation Its contents, collated and often co-written by Steven Laureys, Nicholas Schiff and Adrian Owen, span a remarkable range of issues relevant to coma science, all the while maintaining an impressive focus on the clinical and ethical implications they generate A particularly worthwhile feature is the integration of novel theoretical approaches to consciousness For example, both Massimini et al and Boly et al discuss how theories based on ‘information integration’ (Tononi, 2008) may be applied to clinical cases, potentially providing a means to assay residual consciousness without relying on indirect behavioural measures (Seth et al., 2008) It is indeed by combining theory and practice, by integrating insights from philosophy to pharmacology to functional neuroimaging, and not least by conveying the excitement of real progress, that this volume belongs on the shelf not only of neurologists and ethicists, but also of every scientist interested in the neural basis of human consciousness ix x References Nagel, T (1974) What is it like to be a bat? Philosophical Review, 83, 435–450 Seth, A K., Dienes, Z., Cleeremans, A., Overgaard, M., & Pessoa, L (2008) Measuring consciousness: Relating behavioural and neurophysiological approaches Trends in Cognitive Sciences, 12(8), 314–321 Tononi, G (2008) Consciousness as integrated information: A provisional manifesto The Biological Bulletin, 215(3), 216–242 Anil Seth University of Sussex Foreword This is a strange and exciting time to be interested in how brains minds It is an exciting time, for not a week passes that yet another finding about how the brain works is published There is a discernable sense of progress here, unfortunately amplified in the continued and already stale interest that the press and other media manifest towards anything neuroscientific It is a strange time too, at least for someone who’s been around for quite a while When I first became interested in cognitive psychology, about 25 years ago, almost nobody worked on consciousness per se I was not either Instead, I was focused on the mechanisms of implicit learning — what is it that we can learn without awareness? The first half of each of my lectures here and there about the topic was dedicated to pre-emptive precautionary arguments: It is a complex domain, our measures are uncertain and imprecise, some authors strongly disagree, there is ongoing controversy Today, I hardly have to say anything at all about the existence of learning without awareness: It goes without saying that the phenomenon exists So that’s a first strange turn of events: In the space of 25 years, not only does everybody agree that the brain can process information without consciousness, but also many even believe that whatever the brain does is better done without consciousness than with consciousness The pendulum, however, always swings back, and it is not too difficult to imagine which way it will go next A second reason why these are strange times is that it feels like we are reinventing cognitive psychology all over again Most imaging studies are replications of earlier behavioural findings Likewise, most studies about consciousness are replications of earlier studies in which the infamous C word had been carefully blotted out in one way or another And yet, there is also tremendous innovation in our methods, and in the way in which traditional questions in cognitive psychology are approached anew It is a real joy to see an entire new generation of philosophers who know their empirical literature come up with new designs for testing out hypotheses that are informed by deep, substantive ideas about the mind Likewise, it is sobering to see neuroscientists lose some of their arrogance and realise that their experiments are not, perhaps, as incisive as they had initially thought It is only by striving to combine subjective and objective data that the field will make genuine progress This is the only field in which I have witnessed genuine interdisciplinary progress A third reason that these are strange times is because, in what feels like an instant, we have moved from living in the present to living in the future Nothing illustrates this better than this excellent volume, edited by Steven Laureys, Nicholas Schiff and Adrian Owen How astonishing and unexpected it is that we can now use brain imaging to obtain subjective reports! What an incredible hope brain–computer interfaces represent for people no longer able to control their environment! And how exciting is the possibility that deep-brain stimulation will perhaps offer a new potent form of therapy These developments, at the border between clinical and fundamental neuroscience, were almost unthinkable just a few years ago Crucially, such developments have both clinical and fundamental import ‘Coma science’ is only beginning, and this volume will no doubt be remembered as its starting point Axel Cleeremans ´ Universite Libre de Bruxelles (Coordinator of the European Cooperation in the field of Scientific and Technical Research Action on ‘Consciousness: A Transdisciplinary, Integrated Approach’) xi 410 of consciousness at the patient’s bedside In S Laureys, N D Schiff, & A M Owen (Eds.), Coma science: Clinical and ethical implications – Progress in Brain Research (this volume) Oxford: Elsevier ă Moll, C K E., Sharott, A., Hamel, W., Munchau, A., Buhmann, C., Hidding, U., et al (2009) Waking up the brain A case study of stimulation-induced wakeful unawareness during anesthesia In S Laureys, N D Schiff, & A M Owen (Eds.), Coma science: Clinical and ethical implications – Progress in Brain Research (this volume) Oxford: Elsevier Monti, M M., Coleman, M R., & Owen, A M (2009) From V1 to volition: Hierarchical assessment of visual cognition and attention with fMRI In S Laureys, N D Schiff, & A M Owen (Eds.), Coma science: Clinical and ethical implications – Progress in Brain Research (this volume) Oxford: Elsevier Overgaard, M (2009) How can we know if patients in coma, vegetative state or minimally conscious state are conscious? In S Laureys, N D Schiff, & A M Owen (Eds.), Coma science: Clinical and ethical implications – Progress in Brain Research (this volume) Oxford: Elsevier Owen, A M., & Coleman, M (2008) Functional imaging in the vegetative state Nature Reviews Neuroscience, 9, 235–243 Owen, A M., Coleman, M R., Davis, M H., Boly, M., Laureys, S., & Pickard, J D (2006) Detecting awareness in the vegetative state Science, 313, 1402 Owen, A M., Coleman, M R., Davis, M H., Boly, M., Laureys, S., & Pickard, J D (2007) Response to comments on ‘‘Detecting awareness in the vegetative state’’ Science, 315, 1221c Owen, A M., Coleman, M R., Menon, D K., Berry, E L., Johnsrude, I S., Rodd, J M., et al (2005a) Using a hierarchical approach to investigate residual auditory cognition in persistent vegetative state In S Laureys (Ed.), The boundaries of consciousness: Neurobiology and neuropathology Progress in Brain Research (Vol 150, pp 461–476) London: Elsevier Owen, A M., Coleman, M R., Menon, D K., Johnsrude, I S., Rodd, J M., Davis, M H., et al (2005b) Residual auditory function in persistent vegetative state: A combined PET and fMRI study Neuropsychological Rehabilitation, 15(3–4), 290–306 ´ Perlbarg, V., Puybasset, L., Tollard, E., Lehericy, S., Benali, H., & Galanaud, D (2009) Relation between brain lesion location and clinical outcome in patients with severe traumatic brain injury: A diffusion tensor imaging study using voxel-based approaches Human Brain Mapping, in press Available at http://www3.interscience.wiley.com/ journal/122440012/abstract?CRETRY=1&SRETRY=0 Perrin, F., Schnakers, C., Schabus, M., Degueldre, C., Goldman, S., Bredart, S., et al (2006) Brain response to one’s own name in vegetative state, minimally conscious state, and locked-in syndrome Archives of Neurology, 63, 562–569 Rodd, J M., Davis, M H., & Johnsrude, I S (2005) The neural mechanisms of speech comprehension: fMRI studies of semantic ambiguity Cerebral Cortex, 15, 1261 Schacter, D L (1994) Priming and multiple memory systems: Perceptual mechanisms of implicit memory In D L Schacter & E Tulving (Eds.), Memory systems (pp 233–268) Cambridge, MA: MIT Press Schiff, N D., Giacino, J T., Kalmar, K., Victor, J D., Baker, K., Gerber, M., et al (2007) Behavioural improvements with thalamic stimulation after severe traumatic brain injury Nature, 448, 600–603 Schnakers, C., Giacino, J., Kalmar, K., Piret, S., Lopez, E., Boly, M., et al (2006) Does the FOUR score correctly diagnose the vegetative and minimally conscious states? 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in functional magnetic resonance imaging (fMRI) and their potential relevance to deficits of consciousness In S Laureys, N D Schiff, & A M Owen (Eds.), Coma science: Clinical and ethical implications – Progress in Brain Research (this volume) Oxford: Elsevier Sorger, B., Dahmen, B., Reithler, J., Gosseries, O., Maudoux, A., Laureys, S., et al (2009) Another kind of ‘BOLD response’: Answering multiple choice questions by differential single-trial fMRI responses In S Laureys, N D Schiff, & A M Owen (Eds.), Coma science: Clinical and ethical implications – Progress in Brain Research (this volume) Oxford: Elsevier Staffen, W., Kronbichler, M., Aichhorn, M., Mair, A., & Ladurner, G (2006) Selective brain activity in response to one’s own name in the persistent vegetative state Journal of Neurology, Neurosurgery & Psychiatry, 77, 1383–1384 Taira, T (2009) Intrathecal administration of GABA agonists in the vegetative state In S Laureys, N D Schiff, & A M Owen (Eds.), Coma science: Clinical 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W., et al (2004) Principles of a braincomputer interface (BCI) based on real-time functional magnetic resonance imaging (fMRI) IEEE Transactions on Biomedical Engineering, 51, 966–970 Whyte, J., Gosseries, O., Chervoneva, I., DiPasquale, M C., Giacino, J., Kalmar, K., et al (2009) Predictors of shortterm outcome in brain injured patients with disorders of consciousness In S Laureys, N D Schiff, & A M Owen (Eds.), Coma science: Clinical and ethical implications – Progress in Brain Research (this volume) Oxford: Elsevier Yamamoto, T., & Katayama, Y (2005) Deep brain stimulation therapy for the vegetative state Neuropsychological Rehabilitation., 15(3/4), 406–413 Zafonte, R., Hammond, F., Dennison, A., & Chew, E (2009) Pharmacotherapy of arousal: Balancing the risks and benefits In S Laureys, N D Schiff, & A M Owen (Eds.), Coma science: Clinical and ethical implications – Progress in Brain Research (this volume) Oxford: Elsevier Zasler, N (2009) Life expectancy and disorders of consciousness after traumatic brain injury In S Laureys, N D Schiff, & A M Owen (Eds.), Coma science: Clinical and ethical implications – Progress in Brain Research (this volume) Oxford: Elsevier Zeman, A (2009) The problem of unreportable awareness In S Laureys, N D Schiff, & A M Owen (Eds.), Coma science: Clinical and ethical implications – Progress in Brain Research (this volume) Oxford: Elsevier Subject Index Accelerated forgetting rate associated with TBI, 91 Access consciousness, 361–364, 366–369, 385 Acetylcholine, 296–303 Alzheimer’s Disease Neuroimaging Initiative (ADNI), 284 Amantadine, 301, 303–304, 307–308 Ambulatory automatisms, 149 Amitriptyline, 305, 308 Amnesia diencephalic, 91 post-traumatic amnesia (PTA), 90 posttraumatic confusional state with, 74 retrograde, 92 Amphetamine, 295, 298, 301–303, 310 Amygdaloid complex, 162 Amyotrophic lateral sclerosis (ALS) patients, 276, 339–341 See also Locked-in syndrome (LIS) patients alternative communication devices, 346 depression rate, 344–345 psychological adaptation in, 343–344 quality of life assessments in, 341–344 social participation, 345–346 wish to die, 346–347 Anarthria, 36 Animal model network effects of temporal lobe seizures, 156–160 Anisotropy, 236, 404 See also Fractional anisotropy (FA) reduction of, 225, 226 water diffusion, 221 Anosognosia, 103 ANOVA design, 52 Anterograde episodic memory, 90–92 Antidepressants, to enhance arousal, 305, 308 Aphasia in altered states of consciousness, 51–52, 52–56 ERP in, 54 fMRI studies, 54 post-scan interviews in, 54 resting state metabolism, 53 structural information in, 52 Apomorphine, 305, 308 Arousal changes reflected eyeblink variability, 175 defined, 173, 293–294 evaluation of, 173 neuroanatomy, 294–299 basal forebrain, 297–299 cholinergic pontine tegmentum, 294–295 dorsal pathway, 296 hypothalamic arousal systems, 296–297 noradrenergic locus ceruleus, 295 reticular formation, 294 serotonergic raphe nuclei, 295 thalamo-cortical activating system, 296 ventral pathway, 296–299 neurotransmitter systems important in arousal, 298–299 nonpharmacologic technique, 306, 309–310 deep brain stimulation, 306 noninvasive brain stimulation, 306, 309–310 pharmacotherapy of, 302–309 systematic approach to, 174 Aspen workgroup, 74 Attention behavioral aspects, 96 clinically-oriented model of, 96 divided attention, 97–99 focused attention, 97 mental fatigue, 99 mental slowness, 96 phasic alertness, 96–97 413 414 sustained attention, 97 theoretical aspects, 96 Attention deficit hyperactivity disorder (ADHD), 303 Auditory fMRI paradigm, for DOC assessment, 239 Auditory language processing, 56 Aura, 151 Automatisms, 365–366 defined, 149 Autonomic activation, 133–135 Awareness, 362–364, 377–379, 384, 387, 400–402, 404–408 Baclofen, 317–324 Balint’s syndrome, 386 Basal forebrain, and arousal, 297–299 Basic-rest activity cycle (BRAC), 173 Behavioral assessment case report (AZ), 40–42 limitations of, 38–39 methods for, 36–37 Behavioral scales, 37–38 Behavioural arousal, 130–131 See also Arousal Behavioural assessment tools, for DOC assessment, 233–234 Biostatistics censored versus non-censored survival data, 114 Bispectral index, 204 Blindsight, 14, 15 Blood flow–based neuroimaging methods See Functional magnetic resonance imaging (fMRI) Blood oxygen level dependent (BOLD) signal, 157 BOLD See Blood oxygen level dependent (BOLD) signal Botulinum toxin, 128 BRAC See Basic-rest activity cycle (BRAC) Brain potential recovery of, 65 Brain-computer interfaces (BCI) techniques classification, 278 fMRI-based, 278–290 anatomical measurements, 284 clinical applications, 288 communication and control, 288 communication experiment, 283, 285 customize procedure, 289 efficiency and accuracy, 289 functional measurements, 284 future research path in, 288–289 localizer experiment, 282–285 mobility, 289 MRI data acquisition, 284 offline data analysis, 285 online data analysis, 284–286 online detection of consciousness, 288 procedure of study, 281–282 real-time data analysis, 284–285 stimulus presentation in scanner, 283–284 fNIRS-based, 279 for severely motor-disabled patients, 277–279 Brain-damaged patients, 266 Brain death alternative formulations of, 25–27 biological phenomenon of, 23 biophilosophical analysis of, 22 criteria for, 22–25 current controversy in, 22 defined, 22–25 determining circulatory tests, 27–29 determining respiratory tests, 27–29 differential diagnosis of, 36 neurological examination of, 22 overview, 21–22 paradigm of, 23–24 whole-brain criterion of, 27 Brain electrical activity in coma, 34 Brain imaging for DOC assessment, 235–236, 238 for TBI patient, 241 Brain injury See also Severe brain damage challenges, 301–302 ischemia and anoxia, 301 neuroanatomic and neurotransmitter function, 297, 299–302 TBI, 297, 299–300 Brain spontaneous activity, by fMRI studies, 270–271 Brainstem stroke, 339–341 Braintree scale, 77 of neurologic stages of recovery from brain injury, 75 Broca complex, 159, 162 Broca’s area, 50 415 Bromocriptine, 301, 304, 308 Brown–Peterson paradigm of short-term memory, 94 California Verbal Learning Test (CVLT), 91 cluster analysis, 91–92 Cambridge assessment approach, for DOC, 236–237, 245 Cardiopulmonary resuscitation (CPR), 128 Caveats on interpreting survival data studies, 115 CC See Consciousness consortium (CC) Censored survival time defined, 112 Cerebral cortex with TMS, 205 Chemical shift imaging (CSI), 221 Cholinergic pontine tegmentum, and arousal, 294–295 CI See Confidence interval (CI) Circadian rhythms, 180–182 of consciousness, 181 defined, 180 in mental performance, 180 prognostic marker in DOC, 182 Circulatory tests for determining brain death, 27–29 Classical LIS, 276–277, 290 Classic scale, 156 Cluster analysis with CVLT, 91–92 Cognitive deficits in TBI, 89 Cognitive electrophysiology, for TBI patient, 241 Coma, 12 brain electrical activity in, 34 and consciousness science, 399–408 defined, 34 diagnosis and prognosis, 405–406 DTI technique and, 400–404 fMRI technique and, 400–404 neuroimaging and ethics, 407–408 in patients, 12 therapeutic advances, 406–407 TMS in, 193–194 Coma recovery scale (CRS), 38 record sheet for, 39 Coma Recovery Scale-Revised (CRS-R), 77, 184 to assess DOC, 231–234, 237, 241, 243 Comatose patients assessment DTI, 225–226 MRI, 223–224 MRS, 224–225 Computerized tomography/ magnetic resonance imaging (CT/MRI), 127 Confidence interval (CI), 112 Confusional state/post-traumatic amnesia (CS/ PTA), 75 Conscious awareness state, 250 Consciousness, access, 361–364, 366–369, 385 capacity for, between cognitive modules, concept of, 6–8, 362–364 content of, 148 in context of blindsight, defined, 147 detection of aphasia in altered states of, 52–56 disorders See Disorders of consciousness (DOC) ethics of measuring and modulating, 371–381 etymology of, evaluating a brain’s capacity for, 202–203 evaluating a subject’s level of, 201–202 evidence, 364–366, 377 instruction probes, 364–366 processing of ambiguous words, 364 implications for behavioral assessment of level of, 56–57 integrated information theory of, 386–392 level of, 148 moral significance of, 366–368 need for scientific theory, 384–386 neural basis of, neural complexity of, recovery after ITB, 317, 319–320 science and coma, 399–408 science of, signs of, 13–14 with some philosophical approaches, stages of, 12 state, 249–250, 293–294 theoretical approaches to diagnosis of altered states, 383–396 undeniable complexity in, 416 Consciousness consortium (CC), 66 participants in, 66–67 Conscious states, 14–15 Contralateral biceps motor-evoked potentials in, 134 Cortical activation, 131–133 Cox Proportional Hazard Model, 68, 114 CPR See Cardiopulmonary resuscitation (CPR) CRS See Coma recovery scale (CRS) CRS-R See Coma Recovery Scale-Revised (CRSR) CT/MRI See Computerized tomography/ magnetic resonance imaging (CT/MRI) CVLT See California Verbal Learning Test (CVLT) Dantrolene, 318 DBS See Deep brain stimulation (DBS) DCD See Donation after circulatory death (DCD) DDR See Dead donor rule (DDR) Dead donor rule (DDR), 22 Death See Brain death Deep brain stimulation (DBS), 126 for arousal, 306, 310, 406–407 postoperative course, 137 results of intraoperative, 135 Desipramine, 305, 308 Dextroamphetamine, 303, 310 Diagnostic decision-making, 240 in DOC assessment feedback to referral team and family members, 240 process implication, 243 for TBI patient, 243 Diffuse axonal injury (DAI), 297, 300 Diffuse brain damage, 318 Diffusion tensor imaging (DTI) and coma, 404–405 comatose patients assessment by, 225–226 to evaluate TBI, 219–221, 242 prognosis values of, 217–218 Diffusion weighted imaging (DWI), 218–220 Digit span task, 93 Disability Rating Scale (DRS), 67, 76 data analysis for, 68–69 data collection, 67–68 predictors plus etiology in, 69 predictor variables in, 68 score at week 13, 69 score improvement over the weeks postenrollment, 69 time to follow commands in, 69–70 Disorders of consciousness (DOC), 34, 64, 112, 172 See also Minimally conscious states (MCS); Traumatic brain injury (TBI) patient; Vegetative state (VS) behavioral scales, 173 clinical assessment, 377–379 CRS-R to assess, 232–234, 237, 241, 243 cultural and historical perceptions, 373–377 diagnostic criteria for, 34 diagnostic decision making feedback to referral team and family members, 240 process implication, 243 event-related potentials to assess, 234–236, 238 existing criteria to assess, 233–236 additional brain imaging tools, 236 behavioural assessment tools, 233–234 brain imaging assessment tools, 235–236 electrophysiological assessment tools, 234–235 need of tools to facilitate, 233 fMRI relevance to assess, 219, 235–236, 239, 261–271 high extrinsic and intrinsic functionality systems, 263–266 hypoactive intrinsic system, 266–267 hypofunctional extrinsic system, 267–268 locked-in syndrome patients, 263–266 self-centered absorption patient, 267–268 spontaneous fMRI activity patterns, 268–271 information and support for families, 245–246 multimodal approach to assess, 236–240 application, 240–243 auditory fMRI paradigm, 239 brain imaging, 238 Cambridge assessment approach, 236–237 diagnostic decision making, 240 electrophysiology, 237–238 feedback to referral team and family members, 240 visual fMRI paradigm, 239–240 and pain perception, 329–336 417 personal injury for non-communicative patients, 353–358 SMART to assess, 232–234, 237, 240, 243 standard assessment protocol, 243–245 time of discovery, 371–373 Diurnal rhythms in mental performance, 180 Divided attention, 97–99 dual task performance, 98 of working memory, 97 DOC See Disorders of consciousness (DOC) Donation after circulatory death (DCD), 22 Dopamine, 295, 298, 300–304, 308, 310 Dopaminergic agents, to enhance arousal, 303–305, 307–308 Dorsal pathway, and arousal, 296 DRS See Disability Rating Scale (DRS) Dysautonomic attacks in homeostasis, 183 ECG See Electrocardiographic (ECG) recording Echo-planar imaging (EPI), 284 EDR See Excess death rate (EDR) EEG See Electroencephalographic recordings (EEG) Electrocardiographic (ECG) recording, 127 Electrocorticography (ECoG), 277 Electroencephalogram (EEG) spike-wave discharges on, 148 Electroencephalographic recordings (EEG), 126 desynchronization of, 127 Electroencephalography (EEG), 234, 237, 257, 277, 394–395 Electromyographic activation, 133–135 Electrooculography (EOG), 179 Electrophysiological assessment tools, for DOC, 234–235, 237–238 Emotional Brain, The, Encephalitis, 276 Endocrine circadian rhythms, 181 End-of-life decisions, 335, 339, 347, 376 EOG See Electrooculography (EOG) Epilepsy, 148 ERP See Event-related potentials (ERP) Ethics of measuring and modulating consciousness, 371–381 neuroimaging and, 407–408 Euthanasia, 216, 339, 346–347 Event-related potentials (ERP), 13, 54 for DOC assessment, 234–236, 238, 257 Excess death rate (EDR), 112 Executive functions, 250, 255, 384 in absence of behavior, 249–258 anosognosia, 103 behavioral aspects, 100 conceptualization and set-shifting, 100–101 heterogeneity after TBI, 102–103 lack of insight, 103 mental flexibility, 101 in naturalistic setting, 102 planning for, 101 theoretical aspects, 100 Exposure time defined, 112 Fahn–Tolosa–Mar´ n Tremor Rating Scale, 128, 137 Fatigue Severity Scale (FSS), 99 Fisher’s Exact Test, 79 Fluid attenuated inversion recovery (FLAIR), 216, 219, 221, 224 Fluoxetine, 303 FMRI See Functional magnetic resonance imaging (fMRI) Focused attention, 97 FOUR See Full Outline of UnResponsiveness (FOUR) Fractional anisotropy (FA), 220, 242, 405 Framingham Study on heart disease, 115 FSS See Fatigue Severity Scale (FSS) Full Outline of UnResponsiveness (FOUR), 37 Functional magnetic resonance imaging (fMRI), 40, 65, 153 based BCI techniques, 278–290 anatomical measurements, 284 clinical applications, 288 communication and control, 288 communication experiment, 283, 285 customize procedure, 289 efficiency and accuracy, 289 functional measurements, 284 future research path in, 288–289 localizer experiment, 282–285 mobility, 289 418 MRI data acquisition, 284 offline data analysis, 285 online data analysis, 284–286 online detection of consciousness, 288 procedure of study, 281–282 real-time data analysis, 284–285 stimulus presentation in scanner, 283–284 and coma, 400–404 as form of communication, 402–403 IITC and, 395 MCS patient assessment, 249–258 passive paradigms to assessment of awareness, 400–402 relevance to DOC, 219, 235–236, 239, 261–271 high extrinsic and intrinsic functionality, 263–266 hypoactive intrinsic system, 266–267 hypofunctional extrinsic system, 267–268 locked-in syndrome patients, 263–266 spontaneous fMRI activity patterns, 268–271 resting state, 403–404 Functional near-infrared spectroscopy (fNIRS), based BCIs, 275, 277, 279, 289 Fuzzy sets, 26 GABA See Gamma-aminobutyric acid (GABA) GABAergic basal forebrain cells, 127 Galveston Orientation and Amnesia Test (GOAT), 75 See also Amnesia Gamma-aminobutyric acid (GABA), 160 Gamma-aminobutyric acid (GABA)-agonist, 296, 298, 301, 406 intrathecal administration in vegetative state, 317–324 Gaussian distribution, 113 GBS See Guillain Barre syndrome (GBS) GCS See Glasgow Coma Scale (GCS); Glasgow Outcome Scale (GCS) General anaesthesia, 127, 137, 138, 328 Glasgow Coma Scale (GCS), 37, 178, 195 Glasgow Outcome Scale (GCS), 193, 194, 224 Global aphasia, 51 Globus pallidus internus (GPi), 127 Glutamate, 294, 296, 298–299, 301, 303, 305 Glycine, 324 GOAT See Galveston Orientation and Amnesia Test (GOAT) GPi See Globus pallidus internus (GPi) Guillain Barre syndrome (GBS), Head tremor, 127 anaesthetic procedure for, 128 autonomic activation in, 133–135 behavioural arousal, 130–131 cortical activation in, 131–133 electromyographic activation in, 133–135 electrophysiological monitoring and analysis, 129–130 microelectrode-guided delineation of, 130 microelectrode recordings, 129 stereotactic intervention, 128–129 stereotactic reconstruction of, 135–137 test simulation of, 129 Health insurance, 77 Health service use (HSU), 122 Heart rate (HR), 128 Histamine, 296, 299, 305 Homeostasis, 182–183 dysautonomic attacks in, 183 Hospital-level rehabilitation facilities for patients, 76 HR See Heart rate (HR) HRSA See U.S Health Resources and Services Administration (HRSA) HSU See Health service use (HSU) Hyperthermia, 36 Hypothalamic arousal systems, and arousal, 296–297 Hypothalamic lesion, 183 Hypothalamus behavioral and neocortical effects of, 162 Ictal automatisms, 152 Ictal neocortical slow oscillations, 162 ICU See Intensive care unit (ICU) IITC See Information integration theory of consciousness (IITC) Imidazopiridines, 305 Implicit memory, 92 Incomplete LIS, 276–277, 290 Information integration theory of consciousness (IITC), 202 theoretical guidelines, 203–204 Injury severity score (ISS), 122 419 Inpatient rehabilitation best outcome prediction variables and models, 84 discharge setting, 82 of duration CS/PTA, 82 of duration MCS, 82 of duration VS, 82 emergence from CS/PTA to post-confusional levels, 80–82 emergence from MCS to CS/PTA, 80 emergence from VS to MCS, 79–80 outcome measures for, 79 outcome 1–4 years post-injury (DRS scores), 82 return to household independence, 82–83 return to work and school, 83–84 for TBI patients, 77 Integrated information theory of consciousness (IITC), 386–392 brain imaging techniques and applications, 394–396 EEG, 394–395 fMRI, 394 framework to investigate brain function, 395–396 perturbational approaches, 395 positron emission tomography, 394 camera thought experiment, 389–392 conditions for low levels of consciousness prediction, 392–393 location of main complex and, 393–394 neuroanatomy and, 392 neurophysiology and, 392–393 photodiode thought experiment, 387–389 Intensive care unit (ICU), 172 Intracortical recordings (ICoR), 277 Intrathecal baclofen therapy (ITB) case reports, 320–324 consciousness recovery after, 319–320 for spasticity, 318–324 Intuitions, Ischemia and anoxia, neuroanatomic and neurotransmitter function, 301 ISS See Injury severity score (ISS) Kaplan–Meier method for analyze survival time data, 114 Language disorders of brain lesion, 51 Language processing cognitive architecture of, 50–51 with impaired consciousness, 50 phonology of, 50 with sound-based analysis processes, 50 speech production, 50 Laser Doppler flowmetry (LDF), 157 LDF See Laser Doppler flowmetry (LDF) Life expectancy clinical experience and, 115–116 determination, 114 literature in STBI, 116–118 prediction of survival time, 116 Life expectancy tables etiology of, 114 Life tables, 113–114 Limbic seizures, 151 GABAergic inhibitory influence, 162 neuroimaging studies of, 157–159 preliminary mechanistic studies in, 160 LIS See Locked-in syndrome (LIS) Locked-in syndrome (LIS), 34 differential diagnosis of, 36 Locked-in syndrome (LIS) patients, 261–266, 270, 275–277, 279, 368, 380, 399, 402, 404, 408 adaptation to, 343 alternative communication devices, 346 answering multiple-choice questions based on single-trial BOLD responses, 279–288 fMRI experiments, 282–283 MRI data acquisition, 284 offline data analysis, 285 online data analysis, 284–286 procedure of study, 281–282 real-time data analysis, 284–285 stimulus presentation in scanner, 283–284 BCI techniques, 277–279, 346 care and treatment, 277 classical, 276–277, 290, 340 communication device, 346 complete, 276–277, 279, 340 depression rate, 344–345 diagnosis, 276–277, 288, 290, 333 fMRI relevance to, 263–266 incomplete, 276–277, 290, 340 life, 339–348 420 psychological adaptations, 343–344 psychosocial adjustment to, 339 quality of life assessments in, 277, 339, 341–344, 403, 408 social participation, 345–346 wish to die, 346–347 Long-term depression (LTD), 193 Long-term memory, 90 with PTA patients, 90 in TBI patients, 90 Long-term potentiation (LTP), 193 LTD See Long-term depression (LTD) LTP See Long-term potentiation (LTP) and TBI, 215, 231, 236, 250 TMS in, 194–195 Modafinil, to enhance arousal, 305, 309 Mortality probability, 113 rate, 113 tables, 113 Motor evoked potentials (MEP), 192 MRI-compatible Zamorano– Dujovny frame, 128 MSTF See Multisociety Task Force (MSTF) Multiple regression analysis, 77 Multisociety Task Force (MSTF), 117 on PVS, 172 Magnetic resonance imaging (MRI) comatose patients assessment by, 223–224 to evaluate TBI, 219 prognosis values of, 217–218 Magnetic resonance spectroscopy (MRS) comatose patients assessment by, 224–225 to evaluate TBI, 221 prognosis values of, 217–218 Magnetoencephalography (MEG), 277 MCS See Minimally conscious states (MCS) MCS patient See also Minimally conscious states (MCS) behavioral assessment, 251 experimental design, 251–252 fMRI data acquisition and analysis, 252–258 functional imaging, 249–258 target detection task, 251–257 Median survival time, 112 Memory impairment, 90 Mental fatigue, 99 MEP See Motor evoked potentials (MEP) Methylphenidate, 301–302, 304, 307–308 Microelectrode-guided delineation of stimulation sites, 130 Midazolam, 128 Mind wandering conditions, 267 Minimally conscious states (MCS), 11, 34, 35–36, 119, 174 See also MCS patient behavioral assessment methods, 36–37 behavioral scales, 37–38 differential diagnosis, 36 functional imaging of, 249–258 pain perception in, 329–336 prognosis of, 36 Naltrexone, to enhance arousal, 306, 309 n-back task, 94 NBM See Nucleus basalis Meynert (NBM) NCC See Neural correlates of consciousness (NCC) N400 components, 55 Necessarily indicate deep nonrapid eye movement (NREM), 174 Network inhibition hypothesis revisited, 160–163 ictal neocortical slow activity during, 160–163 in TLE, 148–149 Neural correlates of consciousness (NCC), 14 Neuroanatomic and neurotransmitter function, following brain injury, 297, 299–302 Neuroanatomy of arousal, 294–299 basal forebrain, 297–299 cholinergic pontine tegmentum, 294–295 dorsal pathway, 296 hypothalamic arousal systems, 296–297 noradrenergic locus ceruleus, 295 reticular formation, 294 serotonergic raphe nuclei, 295 thalamo-cortical activating system, 296 ventral pathway, 296–299 and IITC, 392 Neuroethics, 371 Neuroimaging techniques comatose patients assessment, 223–226 and ethics, 407–408 to evaluate TBI, 216–221 conventional MRI, 219 diffusion tensor imaging, 219–221 421 magnetic resonance spectroscopy, 221 prognosis values, 217–218 Neuroleptic malignant syndrome, 304 Neurolitigators, 117 Neurophysiology and IITC, 392–393 Neuropsychological assessment in long-term memory, 93 Neurostimulants, to enhance arousal, 302–303, 307 Non-communicating patients injury, 270 as personal injuries conditions of liability, 353 damage, 353–354 evaluation, 354 objective thesis, 356 purpose of compensation, 357–358 recognition, 354–356 scope of compensation, 356–357 subjective thesis, 354–356 Noninvasive brain stimulation, for arousal, 306, 309–310 Nonpharmacologic technique for arousal, 306, 309–310 deep brain stimulation, 306 noninvasive brain stimulation, 306, 309–310 Non-traumatic etiology (NTBI), 65 Nonword stimuli, 55 Noradrenergic locus ceruleus, and arousal, 295 Norepinephrine, 295, 298–302, 305 NREM See Necessarily indicate deep nonrapid eye movement (NREM) NTBI See Non-traumatic etiology (NTBI) Nucleus basalis Meynert (NBM), 127 Oddball paradigm, 13 Orexin, 295–297, 299–300 Paced Auditory Serial Addition Test (PASAT), 94 Pain perception attitudes toward, 332–336 influenced by religious beliefs, 333–335 neuroimaging, 331–332 in vegetative and minimally conscious states, 329–336 Parity age, 113 PASAT See Paced Auditory Serial Addition Test (PASAT) P300 components, 55 Perceptual Awareness Scale (PAS), 15 Persistent vegetative state (PVS), 12, 34, 65, 117, 224, 317–318, 361 See also Vegetative state (VS) metaanalysis of, 75 Perturbational approaches, and IITC, 395 PET See Positron emission tomography (PET) Pharmacotherapy to enhance arousal, 302–309 antidepressants, 305, 308 dopaminergic agents, 303–305, 307–308 modafinil, 305, 309 naltrexone, 306, 309 neurostimulants, 302–303, 307 zolpidem, 305–306, 309 Phasic alertness attention, 96–97 Phenomenal consciousness See also Consciousness moral significance, 361–368 Philosophy, 27, 366 Phonetic processing, 50 Polysomnography sleep detection in, 174 Polyspike electrographic signals in seizures, 152 Positron emission tomography (PET), 39, 52, 153, 219, 235, 394, 399 Postconfusional/emerging independence, 75 Postoperative course of DBS, 137 Post-traumatic amnesia (PTA), 90 Posttraumatic amnesia syndrome (PTA), 13 Pramipexole, 304, 308 Predicted age at death, 113 President’s Council on Bioethics, 25 Primary auditory cortex, 53 Proactive interference, 91 Product-limit method, 114 Prognosis values, of neuroimaging techniques, 217–218 Prospective memory, 92 Pseudo locked-in cases, 268 422 PTA See Post-traumatic amnesia (PTA); Posttraumatic amnesia syndrome (PTA) PVS See Persistent vegetative state (PVS) Quality of life (QoL) assessments, in LIC patients, 277, 339, 341–344, 403, 408 Quantitative assessment protocol, 78 Quinlan, 371, 376 Rancho Los Amigos (RLA) Scale, 74 Random item generation, 94, 95 Rapid eye movement (REM) sleep, 178, 295–297 Rating Scale of Attentional Behaviour, 96 Relative risk (RR), 113 REM See Rapid eye movement (REM) sleep Repetitive TMS (rTMS), 193 Respiratory tests for determining brain death, 27–29 Reticular formation (RF), and arousal, 294 Retroactive interference, 91 Retrograde amnesia, 92 Retrograde memory, 92 deficits after TBI, 92 Rhythm robustness, 182 Right-to-die, 371, 407 Right-to-life, 367–368, 376 Riluzole, 340 RLA See Rancho Los Amigos (RLA) Scale RR See Relative risk (RR) RTMS See Repetitive TMS (rTMS) SCN See Suprachiasmatic nuclei (SCN) Script generation, 102 Seizure disorders in human, 148 Seizures subcortical-diencephalic structures in, 154 Semantic encoding, 91 Sensitivity to interference associated with TBI, 91 Sensory electrophysiology, for TBI patient, 241 Sensory Modality Assessment and Rehabilitation Technique (SMART), 38 to assess DOC, 231–234, 237, 240, 243 Septal nuclei, 157, 159, 160, 164, 296 Serotonergic raphe nuclei, and arousal, 295 Serotonin, 295, 297–298, 300–301, 303, 305 Sertraline, 305, 308 Severe brain damage defining personal loss after, 353–358 conditions of liability, 353 damage, 353–354 evaluation and compensation, 354 as personal injuries objective thesis, 356 purpose of compensation, 357–358 recognition, 354–356 scope of compensation, 356–357 subjective thesis, 354–356 Severely motor-disabled patients answering multiple-choice questions based on single-trial BOLD responses, 279–288 fMRI-based BCI techniques, 278–290 anatomical measurements, 284 clinical applications, 288 communication and control, 288 communication experiment, 283, 285 customize procedure, 289 efficiency and accuracy, 289 functional measurements, 284 future research path in, 288–289 localizer experiment, 282–285 mobility, 289 MRI data acquisition, 284 offline data analysis, 285 online data analysis, 284–286 online detection of consciousness, 288 procedure of study, 281–282 real-time data analysis, 284–285 stimulus presentation in scanner, 283–284 Severe traumatic brain injury (STBI), 111 life expectancy literature in, 116–118 morbidity in, 116 mortality in, 116 overview, 111–112 prediction of survival time, 115–116 quality of care and, 116 recent literature on survival time, 118–123 Short-term memory, 90 Simple regression test, 79 Single photon emission computed tomography (SPECT), 153, 305 Single photon emission tomography (SPECT), 36 Single-pulse TMS (spTMS), 192 423 Single-voxel 1H spectroscopy (SVS), 221 Sleep patterns, 174–180 abnormalities in, 174 on coma, 176 in DOC patients, 178 minor sleep alterations in, 178 monitor sleep–wake cycles and circadian rhythms, 174 physiological point of view, 176 Sleep–wake cycle, 34, 127, 174, 176 Slow-wave sleep (SWS), 173 SMART See Sensory Modality Assessment and Rehabilitation Technique (SMART) SMR See Standardized mortality ratio (SMR) Spasticity, 317–324 definition, 317–318 intrathecal baclofen therapy (ITB), 318–324 case reports, 320–324 consciousness recovery after, 319–320 selective dorsal rhizotomy, 318 selective peripheral neurotomy, 318 treatment, 318 SPECT See Single photon emission computed tomography (SPECT); Single photon emission tomography (SPECT) Speech perception literature, 54 processing, for TBI patient, 241 production, level of, 50 therapies, 77 Speed of processing See Attention Spiketrain-analysis, 129 Spinal cord stimulation (SCS), 317, 324 SpTMS See Single-pulse TMS (spTMS) Standardized mortality ratio (SMR), 113 STBI See Severe traumatic brain injury (STBI) Stereotactic reconstruction of stimulation sites, 135–137 Stroop test, 102 Structural magnetic resonance imaging, prognosis values of, 217–218 Subcortical arousal systems anatomy of, 126 Subjectivity, 336 Sub-second time scale, 205 Suffering, defined, 330 Suprachiasmatic nuclei (SCN), 180 Survival curve, 114 interpretation of, 115 Survival data analysis methods for, 114–115 Survival time, 113 Sustained attention, 97 SWS See Slow-wave sleep (SWS) Target detection, 251–257 and working memory, 249, 255, 402 TBI See Traumatic brain injury (TBI) Temporal lobe epilepsy (TLE), 148 animal models of, 156–160 consciousness system and, 164–165 EEG correlates of impaired consciousness in human, 151–153 future studies to, 163–164 ictal unconsciousness in, 155 loss of consciousness, 149 network inhibition hypothesis in, 148–149 network inhibition hypothesis revisited, 160–163 neuroimaging insights into impaired consciousness in human, 153–156 rodent models of, 156 seizures in, 148 video-EEG analyses of complex partial seizures and, 149 Temporal lobe seizures behavioral semiology of, 149–151 network effects in animal model, 156–160 Terri Schiavo case, 335, 361, 371, 376 Tetraplegia, 36 Thalamo-cortical activating system, and arousal, 296 Therapeutic advances and coma, 406–407 TLE See Temporal lobe epilepsy (TLE) TMS See Transcranial magnetic stimulation (TMS) TMS-evoked activations in brain, 212 in coma, 211 TMS-evoked slow waves of cortical neurons, 209 TMS/hd-EEG See Transcranial magnetic stimulation and electroencephalography (TMS/hd-EEG) Tonico-clonic seizures, 384–385, 394 424 Toronto Western Spasmodic Torticollis Rating Scale, 128 Trail Making Test, 101 Transcranial magnetic stimulation and electroencephalography (TMS/hd-EEG), 203 advantages of, 206 detects changes in brain’s capacity for integrated information during sleep, 206–211 in DOC patients, 211 evaluate information capacity, 204–206 evaluate thalamocortical integration, 204–206 during slow-wave sleep, 207 Transcranial magnetic stimulation (TMS), 191 in coma, 193–194 in DOC, 193 future research for, 196–197 general principles of, 192 MCS in, 194–195 paired-pulse, 192 possible confounding variables influencing in DOC, 195–196 repetitive, 193 single-pulse, 192 VS in, 194–195 Traumatic brain injury (TBI), 51, 65, 74, 89, 216, 225, 231, 236, 240, 276, 297, 299–301, 317–319, 377, 404–405 coma, 217 natural history of, 74 neuroanatomic and neurotransmitter function, 297, 299–300 neuroimaging techniques, 216–221 conventional MRI, 219 diffusion tensor imaging, 219–221, 242 magnetic resonance spectroscopy, 221 prognosis values of, 217–218 vegetative state (VS), 215, 217, 224 Traumatic brain injury (TBI) patient behavioural assessment, 240–241 brain imaging, 241 clinical history, 240 cognitive electrophysiology, 241 diagnostic decision-making process, 243 discrimination of visual information, 242 DTI, 242 multimodal assessment approach to, 240–243 respond to command, 242 sensory electrophysiology, 241 speech processing, 241 Tremulous cervical dystonia, 128 T-tests, 79 Unconscious injury as personal injuries to non-communicating patients conditions of liability, 353 damage, 353–354 evaluation, 354 objective thesis, 356 purpose of compensation, 357–358 recognition, 354–356 scope of compensation, 356–357 subjective thesis, 354–356 U.S Health Resources and Services Administration (HRSA), 29 VAS-F See Visual Analog Scale for Fatigue (VAS-F) Vegetative state (VS), 11, 34–35, 74, 232–233, 250, 262, 269–270, 353, 355–357, 361, 376–378, 402–407 See also Persistent vegetative state (PVS) brain activity, 383 brain imaging studies in, 13 effect of GABA agonists in, 317–324 misdiagnosis of LIS as, 276–277 pain perception in, 329–336 and TBI, 215, 217, 224 TMS in, 194–195 Ventral pathway, and arousal, 296–299 Visual Analog Scale for Fatigue (VAS-F), 99 Visual fMRI paradigm, for DOC assessment, 239–240 Visual memory, 90 VS See Vegetative state (VS) Wada tests, 151 Wakefulness, 172, 233, 239, 250, 262, 295–296, 305, 330, 362, 384, 386, 394 assessment of, 183–185 for DOC patients, 184 sleep evaluation of, 184 defined, 172 key feature in DOC, 172 425 WCST See Wisconsin Card Sorting Test (WCST) Wechsler memory scale revised (WMS-R), 90 Wessex Head Injury Matrix (WHIM), 38 WHIM See Wessex Head Injury Matrix (WHIM) Whole-brain death British formulation of, 25 Wisconsin Card Sorting Test (WCST), 101 Wish to die, 346–347 See also End-of-life decisions WMS-R See Wechsler memory scale revised (WMS-R) Working memory, 252, 257–258, 405 case studies for, 93 concept of, 93 and conscious access, 238, 241 experimental studies, 93–96 target detection and, 249, 255, 402 Wrist actimeter, 174 Written language processing, 56 Yerkes–Dodson Law, 173 Zolpidem, to enhance arousal, 305–306, 309, 378 Zombie systems, 363–365 ...PROGRESS IN BRAIN RESEARCH VOLUME 177 COMA SCIENCE: CLINICAL AND ETHICAL IMPLICATIONS EDITED BY STEVEN LAUREYS Coma Science Group, Cyclotron Research Center and Department of Neurology, `ge, Lie... Neuroscience, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, The Netherlands; Maastricht Brain Imaging Centre (M-BIC), Maastricht, ` ` The Netherlands; Coma Science. .. Society and co-funded by the Mind Science Foundation It brought together a distinguished small group of neuroscientists and clinical investigators engaged in the study of coma and consciousness and