Progress in brain research, volume 218

Serial Editor Vincent Walsh Institute of Cognitive Neuroscience University College London 17 Queen Square London WC1N 3AR UK Elsevier Radarweg 29, PO Box 211, 1000 AE Amsterdam, Netherlands The Boulevard, Langford Lane, Kidlington, Oxford OX5 1GB, UK 225 Wyman Street, Waltham, MA 02451, USA First edition 2015 Copyright # 2015 Elsevier B.V All rights reserved No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher Details on how to seek permission, further information about the Publisher’s permissions policies and our arrangements with organizations such as the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/permissions This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein) Notices Knowledge and best practice in this field are constantly changing As new research and experience broaden our understanding, changes in research methods, professional practices, or medical treatment may become necessary Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds, or experiments described herein In using such information or methods they should be mindful of their own safety and the safety of others, including parties for whom they have a professional responsibility To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors, assume any liability 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 ISBN: 978-0-444-63565-5 ISSN: 0079-6123 For information on all Elsevier publications visit our website at store.elsevier.com Contributors Joseph Alarcon Biophotonics and Bioengineering Laboratory, Department of Electrical and Computer Engineering, Ryerson University, Toronto, ON, Canada Olivier Alluin Department of Neuroscience and Groupe de Recherche sur le Syste`me Nerveux Central (GRSNC), Faculty of Medicine, Universite´ de Montre´al, and SensoriMotor Rehabilitation Research Team of the Canadian Institute of Health Research, Montreal, Quebec, Canada Lea Awai €rich, Switzerland Spinal Cord Injury Center, Balgrist University Hospital, Zu Stuart N Baker Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK Dorothy Barthe´lemy School of Rehabilitation, Universite´ de Montre´al, and Centre for Interdisciplinary Research in Rehabilitation of Greater Montreal, Institut de re´adaptation GingrasLindsay de Montre´al, SensoriMotor Rehabilitation Research Team of the Canadian Institute of Health Research, Montreal, Canada Fin Biering-Sørensen Clinics for Spinal Cord Injuries, Rigshospitalet and Glostrup hospital, Hornbæk, Denmark Kathrin B€ osl HELIOS Klinik Kipfenberg, Kipfenberg, Germany David W Cadotte Division of Neurosurgery, Department of Surgery, Faculty of Medicine, University of Toronto, and Toronto Western Hospital, University Health Network, Toronto, ON, Canada Jaehoon Choe Departments of Integrative Biology and Physiology, and Department of Neuroscience, University of California, Los Angeles, CA, USA Julien Cohen-Adad Institute of Biomedical Engineering, Ecole Polytechnique de Montre´al, SensoriMotor Rehabilitation Research Team of the Canadian Institute of Health Research, Montreal, QC, Canada Dale Corbett Heart & Stroke Foundation Canadian Partnership for Stroke Recovery and Department of Cellular & Molecular Medicine, University of Ottawa, Ottawa, Canada v vi Contributors Armin Curt €rich, Switzerland Spinal Cord Injury Center, Balgrist University Hospital, Zu Numa Dancause De´partement de Neurosciences, and Groupe de Recherche sur le Syste`me Nerveux Central (GRSNC), Faculty of Medicine, SensoriMotor Rehabilitation Research Team of the Canadian Institute of Health Research, Universite´ de Montre´al, Montre´al, QC, Canada Hugo Delivet-Mongrain Department of Neuroscience and Groupe de Recherche sur le Syste`me Nerveux Central (GRSNC), Faculty of Medicine, Universite´ de Montre´al, Montreal, Quebec, Canada V Reggie Edgerton Departments of Integrative Biology and Physiology; Department of Neurobiology; Department of Neurosurgery, and Brain Research Institute, University of California, Los Angeles, CA, USA Steve A Edgley Department of Physiology, Development and Neuroscience, Cambridge University, Cambridge, UK Manuel Escalona Department of Neuroscience and Groupe de Recherche sur le Syste`me Nerveux Central (GRSNC), Faculty of Medicine, Universite´ de Montre´al, Montreal, Quebec, Canada Hamza Farooq Biophotonics and Bioengineering Laboratory, Department of Electrical and Computer Engineering, Ryerson University, Toronto, ON, Canada James W Fawcett Department of Clinical Neuroscience, John van Geest Centre for Brain Repair, University of Cambridge, Robinson Way, CA, UK Michael G Fehlings Department of Genetics and Development, Toronto Western Research Institute, Toronto Western Hospital, University Health Network, Division of Neurosurgery, Department of Surgery, Faculty of Medicine, Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada Eberhard E Fetz Department of Physiology and Biophysics, Washington National Primate Research Center, University of Washington, Seattle, WA, USA Edelle C Field-Fote Crawford Research Institute, Shepherd Center, Atlanta, GA, USA Karen M Fisher Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK Contributors Joyce Fung School of Physical and Occupational Therapy, McGill University, Montreal; Feil/Oberfeld Research Centre, Jewish Rehabilitation Hospital, Laval, and Montreal Centre for Interdisciplinary Research in Rehabilitation (CRIR), SensoriMotor Rehabilitation Research Team of the Canadian Institute of Health Research, Montreal, Quebec, Canada Parag Gad Departments of Integrative Biology and Physiology, University of California, Los Angeles, CA, USA Helen Genis Biophotonics and Bioengineering Laboratory, Department of Electrical and Computer Engineering, Ryerson University, Toronto, ON, Canada Yury Gerasimenko Departments of Integrative Biology and Physiology, University of California, Los Angeles, CA, USA; Pavlov Institute of Physiology, St Petersburg, and Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russia Mariana Gomez-Smith Faculty of Medicine, and Canadian Partnership for Stroke Recovery, University of Ottawa, Ottawa, Ontario, Canada Monica A Gorassini Department of Biomedical Engineering; Faculty of Medicine and Dentistry, and Neuroscience and Mental Health Institute, University of Alberta, Edmonton, Alberta, Canada Jean-Pierre Gossard Department of Neuroscience and Groupe de Recherche sur le Syste`me Nerveux Central (GRSNC), Faculty of Medicine, Universite´ de Montre´al, and SensoriMotor Rehabilitation Research Team of the Canadian Institute of Health Research, Montreal, Quebec, Canada Matthew Jeffers Faculty of Medicine, and Canadian Partnership for Stroke Recovery, University of Ottawa, Ottawa, Ontario, Canada Jamil Jivraj Biophotonics and Bioengineering Laboratory, Department of Electrical and Computer Engineering, Ryerson University, Toronto, ON, Canada Dorsa Beroukhim Kay Division of Biokinesiology and Physical Therapy, Ostrow School of Dentistry, and Neuroscience Graduate Program, University of Southern California, Los Angeles, CA, USA Mohamad Khazaei Department of Genetics and Development, Toronto Western Research Institute, University Health Network, Toronto, Ontario, Canada vii viii Contributors Aritra Kundu Department of Neuroscience and Groupe de Recherche sur le Syste`me Nerveux Central (GRSNC), Faculty of Medicine, Universite´ de Montre´al, Montreal, Quebec, Canada Anouk Lamontagne School of Physical and Occupational Therapy, McGill University, Montreal; Feil/Oberfeld Research Centre, Jewish Rehabilitation Hospital, Laval, and Montreal Centre for Interdisciplinary Research in Rehabilitation (CRIR), SensoriMotor Rehabilitation Research Team of the Canadian Institute of Health Research, Montreal, Quebec, Canada Jessica Livingston-Thomas Faculty of Medicine, and Canadian Partnership for Stroke Recovery, University of Ottawa, Ottawa, Ontario, Canada Jitka L€ udemann-Podubecka´ HELIOS Klinik Kipfenberg, Kipfenberg, Germany Henrik Lundell Department of Exercise and Sport Sciences; Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, and Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark Francine Malouin Faculty of Medicine, Department of Rehabilitation, Universite´ Laval; Centre interdisciplinaire de recherche en re´adaptation et inte´gration sociale (CIRRIS), Institut de re´adaptation en de´ficience physique de Que´bec (IRDPQ), and SensoriMotor Rehabilitation Research Team of the Canadian Institute of Health Research, Quebec, Canada Babak K Mansoori De´partement de Biologie mole´culaire, Biochimie me´dicale et pathologie, Universite´ Laval, Que´bec, QC, Canada Marina Martinez Department of Neuroscience and Groupe de Recherche sur le Syste`me Nerveux Central (GRSNC), Faculty of Medicine, Universite´ de Montre´al, and SensoriMotor Rehabilitation Research Team of the Canadian Institute of Health Research, Montreal, Quebec, Canada Sylvie Nadeau  Ecole de re´adaptation, Universite´ de Montre´al, Centre de recherche interdisciplinaire en re´adaptation de Montre´al me´tropolitain (CRIR), Institut de re´adaptation Gingras-Lindsay-de-Montre´al (IRGLM), and SensoriMotor Rehabilitation Research Team of the Canadian Institute of Health Research, Quebec, Canada Mandheeraj Singh Nandra Department of Electrical Engineering, California Institute of Technology, Pasadena, CA, USA Contributors Carine Nguemeni Faculty of Medicine, and Canadian Partnership for Stroke Recovery, University of Ottawa, Ottawa, Ontario, Canada Jens Bo Nielsen Department of Exercise and Sport Sciences, and Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark Dennis Alexander Nowak HELIOS Klinik Kipfenberg, Kipfenberg, and Department of Neurology, University Hospital, Philips University, Marburg, Germany Carol L Richards Faculty of Medicine, Department of Rehabilitation, Universite´ Laval; Centre interdisciplinaire de recherche en re´adaptation et inte´gration sociale (CIRRIS), Institut de re´adaptation en de´ficience physique de Que´bec (IRDPQ), and SensoriMotor Rehabilitation Research Team of the Canadian Institute of Health Research, Quebec, Canada Serge Rossignol Department of Neuroscience and Groupe de Recherche sur le Syste`me Nerveux Central (GRSNC), Faculty of Medicine, Universite´ de Montre´al, and SensoriMotor Rehabilitation Research Team of the Canadian Institute of Health Research, Montreal, Quebec, Canada Francois D Roy Neuroscience and Mental Health Institute; Department of Physical Therapy, and Faculty of Rehabilitation Medicine, University of Alberta, Edmonton, Alberta, Canada Roland R Roy Departments of Integrative Biology and Physiology, and Brain Research Institute, University of California, Los Angeles, CA, USA Samir Sangani School of Physical and Occupational Therapy, McGill University, Montreal; Feil/Oberfeld Research Centre, Jewish Rehabilitation Hospital, Laval, and Montreal Centre for Interdisciplinary Research in Rehabilitation (CRIR), SensoriMotor Rehabilitation Research Team of the Canadian Institute of Health Research, Montreal, Quebec, Canada Ahad M Siddiqui Department of Genetics and Development, Toronto Western Research Institute, University Health Network, Toronto, Ontario, Canada Demetris S Soteropoulos Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK John D Steeves ICORD (International Collaboration On Repair Discoveries), Blusson Spinal Cord Centre, Vancouver General Hospital, University of British Columbia (UBC), Vancouver, BC, Canada ix x Contributors Yu-Chong Tai Department of Electrical Engineering, California Institute of Technology, Pasadena, CA, USA Aiko K Thompson Department of Health Sciences and Research, College of Health Professions, Medical University of South Carolina, Charleston, SC, and Helen Hayes Hospital, NYS Department of Health, West Haverstraw, NY, USA Boris Touvykine De´partement de Neurosciences, Pavillon Paul-G-Desmarais, Universite´ de Montre´al, Montre´al, QC, Canada Barry Vuong Biophotonics and Bioengineering Laboratory, Department of Electrical and Computer Engineering, Ryerson University, Toronto, ON, Canada Maria Willerslev-Olsen Department of Exercise and Sport Sciences, and Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark Carolee J Winstein Division of Biokinesiology and Physical Therapy, Ostrow School of Dentistry; Department of Neurology, Keck School of Medicine, and Neuroscience Graduate Program, University of Southern California, Los Angeles, CA, USA Jonathan R Wolpaw National Center for Adaptive Neurotechnologies, Wadsworth Center, NYS Department of Health, Albany, NY, USA Jaynie F Yang Faculty of Medicine and Dentistry; Department of Surgery, and Neuroscience and Mental Health Institute, University of Alberta, Edmonton, Alberta, Canada Victor X.D Yang Biophotonics and Bioengineering Laboratory, Department of Electrical and Computer Engineering, Ryerson University; Physical Science—Brain Sciences Research Program, Sunnybrook Research Institute; Division of Neurosurgery, Sunnybrook Health Sciences Centre, and Division of Neurosurgery, Department of Surgery, Faculty of Medicine, University of Toronto, Toronto, ON, Canada Boubker Zaaimi Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK Ephrem T Zewdie Department of Biomedical Engineering, and Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada Hui Zhong Departments of Integrative Biology and Physiology, University of California, Los Angeles, CA, USA Preface This book regroups the proceedings of a Symposium held in May 2014 in Montreal entitled “Rehabilitation: At the Crossroads of Basic and Clinical Sciences.” This was the 36th meeting of the Groupe de Recherche sur le Syste`me Nerveux Central funded by the Fond de la Recherche du Que´bec-Sante´ (FRQ-S) and was jointly organized with the SensoriMotor Rehabilitation Research Team funded by the Canadian Institutes for Health Research (CIHR) The Symposium was designed with two major goals in mind First, we wanted to bring together basic and clinical scientists interested in neurorehabilitation Translational research should design models and conduct experiments that address pressing clinical questions, while clinical researchers and clinicians integrate new knowledge to design better treatments and platforms A continuous dialogue between basic scientists, clinical researchers, and clinicians is necessary for these objectives to be reached Second, we wanted a meeting where scientists working on spinal cord injury (SCI) and on stroke could share recent advances in their respective fields and find commonality Although these two fields are often separate in clinical and laboratory settings, our thoughts were that the mechanisms of recovery following central nervous lesions, in the spinal cord or in the brain, follow similar rules and that emerging treatments likely as well We devoted one day to SCI and one day to stroke recovery On each day, we designed the sessions to discuss clinical impairments, ongoing clinical trials, the investigation of novel techniques currently being tested in humans, and finally, potential mechanisms involved in spontaneous recovery and how they can be best targeted through therapeutic approaches From our discussions, it was obvious that the treatments of both SCI and stroke face important clinical challenges The translation of findings from clinical research, and even more from animal research, to patient care is not a trivial task Despite the challenges, we have seen great progress over the years Perhaps most importantly, the infrastructures to handle future changes of practice are much improved Clinical research has also been thriving with the improvement of noninvasive imaging techniques and the development of stimulation methods Both after SCI and stroke, clinical scientists are developing promising treatments using transcranial magnetic stimulation, transcranial direct current stimulation, or galvanic stimulation Although these are exciting times for neurorehabilitation, many questions remain Our current understanding of principles of plasticity and mechanisms of postlesion recovery is far from complete Much of this knowledge can be more efficiently and precisely obtained with research on animal models, which allow better control of confounding factors and the use of invasive techniques and serve to establish proofs of concepts In the last decade, basic scientists have increasingly directed their experiments toward providing complementary information to human studies In these animal models, potential treatments of the future, such as neural prostheses, are conceived, developed, and improved Our guest Plenary Speaker (Eberhard E Fetz) introduced concepts of closed-loop brain–computer interface xix xx Preface to produce activity-dependent stimulation of the brain, spinal cord, or muscles Such methods may eventually be used as therapeutic aids in several conditions and enable us to further improve the recovery of patients with SCI and stroke Whereas basic and clinical research scientists represented two completely isolated populations just a few years ago, our Symposium, as reflected in this collection of contributions from our speakers, sends the clear message that translation is becoming much more a reality than a vague concept Our discussions highlighted the remarkable consistency in the key conclusions between basic and clinical research as well as between the fields of SCI and stroke Perhaps the strongest take-home message was that each individual, either after stroke or SCI, is different Plasticity between patients varies with, for example, lesion size and location, initial impairments resulting from the lesion, prelesion lifestyle, and cardiovascular condition and neuropsychological profiles In these heterogeneous populations, it is unlikely that a single treatment will apply to all Instead, to design better therapies, we need a clear understanding of the basic mechanisms through which these different factors affect plasticity and recovery With this knowledge, perhaps some day, it will be possible to individualize the treatment of each patient based on his or her clinical profile and surrogate markers of postlesion plasticity We believe this colossal task will be achieved through close collaboration between basic and clinical scientists, something that must be nurtured through events such as this symposium We wish to acknowledge Manon Dumas and Rene´ Albert of the GRSNC for their daily implication in the organization of this meeting as well as Claude Gauthier and Tania Rostane for their support Many thanks also to reviewers who took the time to assess the abstracts and to comment on the manuscripts Finally, our special thanks to the funding organizations: CIHR, FRQ-S, Rick Hansen Institute, Wings for Life, Eli Lilly, Institute of Neurosciences and Mental Health and Addiction of CIHR, the Universite´ de Montre´al, and the Faculty of Medicine as well as the Quebec Rehabilitation Research Network (REPAR) for the student poster Awards N Dancause S Nadeau S Rossignol 434 CHAPTER 19 Stroke recovery Yamashita, T., Ninomiya, M., Hernandez Acosta, P., Garcia-Verdugo, J.M., Sunabori, T., Sakaguchi, M., Adachi, K., Kojima, T., Hirota, Y., Kawase, T., Araki, N., Abe, K., Okano, H., Sawamoto, K., 2006 Subventricular zone-derived neuroblasts migrate and differentiate into mature neurons in the post-stroke adult striatum J Neurosci 26 (24), 6627–6636 Zagrebelsky, M., Schweigreiter, R., Bandtlow, C.E., Schwab, M.E., Korte, M., 2010 Nogo-A stabilizes the architecture of hippocampal neurons J Neurosci 30 (40), 13220–13234 Zhong, J., Chan, A., Morad, L., Kornblum, H.I., Fan, G., Carmichael, S.T., 2010 Hydrogel matrix to support stem cell survival after brain transplantation in stroke Neurorehabil Neural Repair 24 (7), 636–644 Zorner, B., Schwab, M.E., 2010 Anti-Nogo on the go: from animal models to a clinical trial Ann N Y Acad Sci 1198 (Suppl 1), E22–E34 Index Note: Page numbers followed by f indicate figures and t indicate tables A Abductor hallucis brevis (AHB), 133, 136 Accelerated Skill Acquisition Program (ASAP), 342, 348, 350t Activities of daily living (ADL), 256 Acute phase, SCI apoptosis, 19–20 cell death and demyelination, 19–20 excitotoxicity, 19 Fas receptors, 19–20 glial scar, 20 glutamate receptor, 19 hemorrhage and ischemia, 18 inflammatory cytokines, 18 ionic dysregulation and excitotoxicity, 19 ischemia and immune infiltration, 19 macrophages, 18–19 microglia, 18–19 neuroprotective interventions, 18 neutrophils, 18–19 oligodendrocyte cell death, 19–20 Aerobic glycolysis, 66 AHB See Abductor hallucis brevis (AHB) Allen Institute for Brain Sciences, 65–66 AlphaFIM, 264 Alzheimer’s disease, 66–67, 217–219, 424 American Spinal Injury Association (ASIA) Impairment Scale, 3, 24, 233 5-aminolevulinic acid (5-ALA) glioblastomas, 60 medulloblastoma, 60 meningiomas, 60 Amyotrophic lateral sclerosis (ALS), 23–24, 25 Analgesia, 203 Animal models ChABC, 174–176 FGF-2, 26 locomotor control systems, 175f preclinical research in, 373–374 stroke recovery, 415–417 anti-NogoA, 214–215 Anti-stokes, 61 Arm Motor Ability Test, 343–344 ASAP See Accelerated Skill Acquisition Program (ASAP) ASIA Impairment Scale, 35 Axon regeneration, 214–215 B Barnes maze, 423 BART See Bilateral Arm Reaching Test (BART) BBCI See Bidirectional brain–computer interfaces (BBCI) BBS See Berg Balance Scale (BBS) Berg Balance Scale (BBS), 83, 93, 97 Bidirectional brain–computer interfaces (BBCI) activity-dependent intracranial DBS, 247–249 bridging lost connections brain-controlled intraspinal stimulation, 244f cognitive prosthesis, 245 electrical stimulation, 242–245 FES, paralyzed muscles, 242 neural activity, 242 noncontingent stimulation, 245 VLSI models, 245 strengthening weak synaptic connections cortical conditioning experiments, 246f corticomotoneuronal (CM) cells, 247 electrocorticographic potentials, 247 Hebbian plasticity, 245 intracortical microstimulation, 245 Mrec muscle, 246 Nrec site, 245 Nstim site, 245 spike-triggered stimulation, 247 Bilateral Arm Reaching Test (BART), 341 Bilateral arm training, 339 Bilateral motor cortex, rTMS effectiveness, 303 follow-up, 303 patients characteristics lesion location, 303 stroke etiology, 303 time after stroke, 302 upper limb impairment, severity of, 303 stimulation parameters, 303 Bipedal locomotor control, Blood–brain-barrier (BBB), 18, 188 Blood-spinal cord barrier (BSCB), 18 Body-weight-supported treadmill training (BWSTT), 128, 259–260 435 436 Index Brain-derived neurotrophic factor (BDNF), 34–35, 419–420 Brain imaging technology, 333 Bright field microscopy, 60–61 BSCB See Blood-spinal cord barrier (BSCB) C Canadian Best Practice Recommendations for Stroke Care (CBPRSC), 261–262 Canadian Neurological Stroke Scale (CNSS), 257 Caudal forelimb area (CFA), 364–365 CBPRSC See Canadian Best Practice Recommendations for Stroke Care (CBPRSC) Central nervous system (CNS) adult NPCs, 30 plasticity and rehabilitation anti-NogoA treatments, 216 chondroitinase ABC, 214 rehabilitation, 216 spinal cord injury, 216 RhoA, 34 Central pattern generator (CPG), 174–176, 175f Cerebrospinal fluid (CSF), 83 Cerefy Neuroradiology Atlas, 63 Cervical spinal cord, 393f Cethrin, 34 Chondroitin ABC (ChABC) chondroitin sulfate proteoglycans, 188–189 growth factors (GFs) cocktail, 188–189 Chondroitinase, 215 Chondroitin sulfate proteoglycans (CSPGs), 214–215, 219 Ciliary neurotrophic factor (CNTF), 35 CIMT See Constraint-Induced Movement Therapy (CIMT) Cingulate motor areas (CMAs), 363–364 Clinical trials, SCI preclinical development phase allometric scaling, 229 animal model, 228 dose scaling, 229 GMP facility, 230 intellectual property development and investor funding, 228 oral/systemic administration, 229 safety, 228 therapy, formulation of, 229 “window of opportunity,”, 228 yin and yang interaction, 229–230 SCI clinical studies AIS grade classification, 234–235 EMSCI, 232 FIM, 237 ISNCSCI, 233 limb-specific outcome tools, 237 motor function, 233t neurological and functional measurement tools, 232 NLI, 233 SCOPE, 232 sensory awareness, 234 translational requirements CNS disorder, 230 CONSORT, 230 neurological improvement, 231 therapeutic interventions, 231 World Medical Association, 230 Closed-loop brain–computer interfaces, 241–242 Clostridium botulinum, 34 CNS See Central nervous system (CNS) CNSS See Canadian Neurological Stroke Scale (CNSS) Coherent Anti-Stokes Raman Scattering (CARS) microscopy astrocytoma, 61 Commissural interneurons, 393f Common peroneal nerve (CPN), 128–129 Community-dwelling stroke survivors, 256 Computed tomography (CT), 57 Consolidated Standards of Reporting Trials (CONSORT), 230 Constraint-Induced Movement Therapy (CIMT), 339 Continuous theta burst stimulation (cTBS), 285 Contralateral effects, 390–392 Contralesional cortex, 403 Contralesional hemisphere inhibition animal models, preclinical research in, 373–374 cortical motor network monkeys, 363–364 rats, 364–365 hyperexcitability, 372–373 interhemispheric connections callosal connections, 366 homotopic callosal connections, 366–368 ipsilateral motor network, 366 parietal cortex, 366 PMv, 367f sensorimotor cortex, 369f trajectory errors, 368–370 interhemispheric interactions, healthy adults, 371–372 Index ipsilateral corticospinal projections, 370–371 neurorehabilitation, 373 noninvasive brain stimulation methods, 377–378 onset time and duration, 374–375 rat model, cortical stroke GABA-A agonist Muscimol, 375 inhibition duration, 377 lesion size, 377 paretic forelimb, 376f rehabilitative therapies, 362 rTMS, 362 stroke patients, clinical studies in, 373–374 tDCS, 362 TMS, 362 Contralesional motor cortex, rTMS effectiveness stimulation protocol-dependent efficiency, 299 stimulation sessions, 299 follow-up, 298–299 patients characteristics lesion location, 297 stroke etiology, 297 time after stroke, 297 upper limb impairment, severity of, 297–298 stimulation parameters adjunct therapies, 298 stimulated area, 298 stimulation protocol, 298 stimulation sessions, number of, 298 Cortical activation, 390 Cortical motor network monkeys CMAs, 363–364 corticospinal neurons, 364 motoneurons, 364 SMA, 363–364 ventral and dorsal premotor cortex, 363–364 rats CFA, 364–365 corticoreticulospinal network, 365 corticospinal and rubrospinal tract lesions, 365 pyramidal tract lesions, 365 reticulospinal tract, 365 RFA, 364–365 Cortical neurons, 220–221, 242 Cortical stimulation (CS), 70–71, 120 Corticomotoneuronal (CM) cells, 247, 402f Corticomotoneuronal (CM) connections, 391, 401, 405 Corticospinal neurons, 364 Corticospinal tract contralateral effects, 390–392 ipsilateral effects, 392–394 Corticospinal tract (CST), 6, 81, 158–159 CPG See Central pattern generator (CPG) Crystalloids, 21–22 CSPGs See Chondroitin sulfate proteoglycans (CSPGs) Cutaneomuscular reflex (CMR), 128–129 Cyclogram, 6–7 D Deep brain stimulation (DBS), 242, 247–249 Deformable anatomic template (DAT), 71 Demyelination, 19–20, 61 Diffusion tensor imaging (DTI), 70–71, 95–96 Direct electrical stimulation (DES), 71 Dobutamine, 21–22 DOPA injection, 185–186 Dopamine, 21–22 Dorsal premotor cortex (dPMC), 283–284, 363–364 DTI See Diffusion tensor imaging (DTI) Dysphagia, 254 E Early supported discharge (ESD), 264–265 ECM See Extracellular matrix (ECM) Electrical enabling motor control (eEmc), 200 Electrocorticographic (ECoG) potentials, 247 Electrode array, spinal rat model clinical and physiological assessments, 208–209 control box and multiplexer circuit board, 202 data collection and analysis, 205 head connector and intramuscular EMG electrode implantation, 202 implant fabrication, 201–202 lumbosacral spinal cord, 200–201 methods, 201 motor evoked responses, 205 neural networks, 207 neurophysiological mechanisms and specific sensorimotor integration, 209–210 sMEPs, 200 soleus muscle, 205 spinal cord transection and array implantation, 203 stimulation and testing procedures, 203–204 wired electrodes vs multielectrode arrays, 209 Electromyographic (EMG) activity, 83, 158 Eloquent cortex (EC), 70–71 Embryonic stem cells (ESCs), 28–29 Endothelin-1 (ET-1), 415–417 437 438 Index Enriched rehabilitation (ER), 415–417, 420f Epidural stimulation, 210 EPSP See Excitatory postsynaptic potential (EPSP) ESCs See Embryonic stem cells (ESCs) European Multicenter study about Spinal Cord Injury (EMSCI), 232 Excitatory postsynaptic potential (EPSP), 393f, 395f, 397f EXCITE clinical trial, 339 Extracellular matrix (ECM) chondroitin sulfate proteoglycans, 219–221 CNS plasticity and rehabilitation anti-NogoA treatments, 216 chondroitinase ABC, 214 rehabilitation, 216 spinal cord injury, 216 plasticity, memory, and alzheimer’s disease, 216–219 F Fast-firing interneurons, 220–221 FES See Functional electrical stimulation (FES) Fibroblast growth factor-2 (FGF-2), 26 Flaccid paralysis, 389–390 Flat treadmill (FTM), 182 Fluorescence-guided surgery, 59–60 FMAS See Fugl-Meyer Assessment Scale (FMAS) fNIRS See Functional near-infrared spectroscopy (fNIRS) Fugl-Meyer Assessment Scale (FMAS), 257, 343–344 Functional ambulation profile (FAP), 133 Functional electrical stimulation (FES), 242, 243f Functional independence measure (FIM), 4, 237, 263–264 Functional magnetic resonance imaging (fMRI) cortical changes, 318–319 maladaptive plasticity theory, 282–283 neuronal activity, 70–71 Functional near-infrared spectroscopy (fNIRS) fiber optic cables, 319 hemoglobin, 319 medial PFC activity, 320 optical imaging, 319–320 oxygenated Hb, 319–320 treadmill walking, 319–320 G Gait quality, 2f Galvanic vestibular stimulation (GVS), 85 Gastrocnemius medialis (GM) muscle, 87 Geron Corporation, 29 Glycosaminoglycan (GAG), 219 Graded redefined assessment of strength, sensibility, and prehension (GRASSP), 237 Granulocyte colony stimulating factor (G-CSF), 25–26 Greenhouse–Geisser correction factor, 137 GVS See Galvanic vestibular stimulation (GVS) H Hand function, 400–402 Hand, spinal systems, 399–400 Hebb–Williams maze, 424 Heparin, 21–22 High-resolution imaging methods CARS microscopy, 60–61 clinical applications ependymomas, 68 leptomeningea, 67–68 medulloblastoma, 67 microvasculature, 68 neurosurgical oncology imaging, 67 OCT-OA, 67–68 patient prognosis, 67 SV-OCT, 68 fluorescence-guided surgery, 59–60 histological/stain atlases, 62–63 human brain and spinal cord, 56–58 imaging atlases, 62 neuronavigation, 70–71 OCT, 58–59 RNA and subcellular imaging atlases, 65–66 Hip–knee cyclograms, 8f Huntington’s disease, 424 Hyaluronan, 220–221 Hypotension, 21–22 I Image-guidance systems (IGS), 70–71 Incomplete spinal cord injury (iSCI) CMRs, 136 CPN conditioning, TA MEP, 143–145 cutaneomuscular reflexes, 145–148 demographic, injury and clinical measures before training, 130t electrophysiological measures EMG recordings and peripheral nerve stimulation, 133 maximum compound action potential (Mmax), 134 MVC, 133–134 endurance training, 148–149 functional implications, 151–152 Index intervention endurance training, 132 MMT, 133 6MWT, 132 10MWT(ss), 133 precision training, 132 SCI-FAP, 133 maximum voluntary contractions, 142–143 MEPmax, 138–141 movement accuracy, participants, 137–138 sensorimotor training, 128 spinal cord after training, descending activation of, 149–150 spinal inhibition after SCI, 150–151 statistical analysis, 137 study design, 129–132 TA MEPS, CPN stimulation, 135–136 TMS recruitment curve, 135 walking, 1–2 walking training, 128–129 Induced pluripotent stem cells (iPSCs), 29–30 Inhibitory postsynaptic potentials (IPSPs), 151, 393f Interdisciplinary Comprehensive Arm Rehabilitation Evaluation (ICARE), 349 Interhemispheric imbalance model, 285 Intermittent theta burst stimulation (iTBS), 285 International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI), 84, 233 Intracortical microstimulation (ICMS) mapping, 368 Intraluminal suture model, 415–417 Ipsilateral corticospinal tract, 392–394, 395f Ipsilateral effects, 392–394 Ipsilateral motor output, 403–404 Ipsilesional motor cortex, rTMS effectiveness stimulation protocol-dependent efficiency, 302 stimulation sessions, 302 follow-up, 301 patients characteristics lesion location, 300 stroke etiology, 300 time after stroke, 300 upper limb impairment, severity of, 300 stimulation parameters adjunct therapies, 301 stimulated area, 301 stimulation protocol, 301 stimulation sessions, number of, 301 IPSP See Inhibitory postsynaptic potential (IPSP) Ischemic injury, 414–415 iSCI See Incomplete spinal cord injury (iSCI) K Kolmogorov–Smirnov test, 88 L Ladder treadmill (LTM), 182 Lateral gastrocnemius soleus (LGS), 186 LEMS See Lower extremity motor score (LEMS) Liberation, absorption, distribution, metabolism and excretion (LADME), 229 Light haptic cues cortical mapping block trial, 322 CAREN (Motek Medical), 320–321 fingertip contact, 320–321 laterality index, 322–323 mixed-reality system, 321f NIRS measurement, 322–323 RSMC, 324 self-paced treadmill, 323–324 standing and walking tasks, 322f steady-state walking phase, 323–324 topographical maps, 324f postural control locomotion, 315–316 quiet stance, postural stability, 315 Locomotor experience applied poststroke trail (LEAPS), 270 Locomotor training after complete SCI clonidine, 176–177 CPG, 174–176 fictive locomotion, 174–176 locomotor control systems, animal models, 175f lumbosacral intrinsic neuronal circuitry, 176 monoaminergic agonists, 176 oxymetazoline, 176–177 tizanidine, 176–177 cats, skilled locomotion in cortical activity, 181 FTM, 182 LTM, 182 motor cortex, 182 paw placement, 182 supraspinal and spinal pathways, 183 training paradigms, 181 complete spinal cord transection frequency-dependent depression, 185–186 hindlimb movements, 185 LGS, 186 plasticity, 185 reflex pathways, 184–185 439 440 Index Locomotor training (Continued) spinalization and treadmill training, 185 tibial nerve stimulation, 186 incomplete SCI locomotor recovery, 177–179 mechanisms, 179–181 partial SCI, 186–187 rodents (robot and manual training) after complete SCI paradigm, 189–190 after incomplete SCI paradigm, 187–189 Long-term depression (LTD), 284–285 Long-term potentiation (LTP), 284–285 Lower extremity motor score (LEMS), 3, 84, 234 Lupus/hypersensitivity syndrome, 25 M Magnesium (Mg), 26–27 Magnetic resonance imaging (MRI) Cerefy Neuroradiology Atlas, 63 coordinate brain mapping system, 63 MNI-Poly-AMU template, human spinal cord, 65f MNI template, 63 online imaging toolbox, 64–65 spinal cord segmentation techniques, 64–65 Talairach and Tournoux atlas, 63 tumor detection and treatment, 57 Maladaptive overactivity theory, 284 Maladaptive plasticity theory, 282–283, 337–338 Mann–Whitney Rank Sum test, 88 Manual muscle test (MMT), 133 Matlab program, 135 Mauchly’s test, 137 Maximum voluntary contraction (MVC), 133–134 Medial gastrocnemius (MG), 202 Medial longitudinal fasciculus (MLF), 397f, 399f Medium-latency response (MLR), 87 Memory, 216–217 MEPs See Motor-evoked potentials (MEPs) Mesenchymal stromal cells (MSCs), 31 Metabolic syndrome, 414 10-meter walk test (10MWT), 4, 133 Methylprednisolone, 22–23 6-Min Walking Test (6MWT), 4, 83 Mirror neuron system, 345 MLF See Medial longitudinal fasciculus (MLF) Modified Barthel Index, Montoya staircase test, 415–417 Montreal Neurological Institute (MNI) brain template, 63 Morris water maze, 423 Motoneurons proportions of, 393f response of, 393f Motor cortex nonprimary, 390 primate, 390 Motor cortex stimulation, 343–344 Motor-evoked potentials (MEPs), 5, 134, 158, 261 Motor system, 389–390 MRI See Magnetic resonance imaging (MRI) MSCs See Mesenchymal stromal cells (MSCs) MVC See Maximum voluntary contraction (MVC) N National Acute Spinal Cord Injury Study (NASCIS), 22–23 National Institute of Health Guide for the Care and Use of Laboratory Animals, 201 National Institutes of Health Stroke Scale (NIHSS), 257 National Spinal Cord Injury Statistical Center (NSCSC), 232 Near-infrared spectroscopy (NIRS), 259–260, 314 Negotiated equilibrium hypothesis, 168 Neural excitability bimanual training cortical excitability, 113 delayed-intervention control study, 113–114 descending corticospinal pathways, 114 functional electrical stimulation, 113 upper extremity tasks, 112–113 impaired hand function after SCI excitatory influences, loss of, 108 learned nonuse, 107–108 rate of transmission, 106–107 tetraplegia, 107 improved hand function after SCI corticomotor excitability, 110–111 functional electrical stimulation, 109–110 paired associative stimulation, 112 PNSS, 108–109 rTMS, 112 thenar muscles, 108 vibration, 110 nervous system cortical plasticity, 104 learning task, 105–106 PNSS, 104 somatosensory cortex, 104 spinal cord stimulation, 105 tDCS, 105 Index walking function cortical circuits, 117–120 spinal reflexes and spinal central pattern generator circuits, 115–117 Neural progenitor cells (NPCs), 30 Neural stem cells, 30 Neurodegenerative disease, 217–219 Neurological level of injury (NLI), 233 Neuronal tracing techniques, 368 Neuroplasticity BDNF, 419–420 constraint-induced movement therapy, 419 contralesional motor reorganization, 417–418 cortical synaptic density, 417 enriched rehabilitation, 418 growth inhibitory gene expression, 419–420 ionic imbalance and cell death, 417–418 ipsilesional cortex, 418 monocular deprivation, 417 myelination, 417 Nogo-A, 420–421 perilesional cortex, 418 poststroke interventions, 418 TMS, 419 two-photon fluorescence microscopy, 417–418 use-dependent neuronal activity, 417 Val66Met, 419–420 Neuroprotectant efficacy, 414–415 Neurorehabilitation, brain damage adjunct therapies, 362 arm and hand movements, 333–334 behavioral demands and motor skill acquisition, 333–334 challenging situation difficult task, 334–335 intensity, 336 specificity effects, 335–336 neuroplasticity food-retrieval practice paradigm, 332–333 hand representation (distal forelimb) area, 332–333 neurorehabilitation, 333 paretic arm and hand, 351 primimg the brain, methods for direct cortical stimulation, rehabilitation, 342–344 noninvasive cortical stimulation, 344–345 problem-solving strategies, 333–334 progressive and optimally adapted over practice practice timimg, 338–339 repetition without repetition, 337–338 solicit motivation and active participation motivation, motor learning, 339–342 salient and meaningful tasks, 342 use it or lose it, 339 therapy dose, 336 Neurospec scripts, 86–87 NINDS stroke priorities, 342–343 Nitrogen (NO), 19 Noninvasive cortical stimulation ASAP, 348–350 hypothesis-driven multimodal combination therapies, 344–345 intrinsic motivation circuits, 346–347 motor learning and neurorehabilitation, action observation, 345–346 rTMS stimulation, 344–345 skill, capacity and motivation, 348–350 Noninvasive stimulation protocols, 362 NPCs See Neural progenitor cells (NPCs) O Object recognition memory, 216–217, 218f Occupational therapy (OT), 267 OCT See Optical coherence tomography (OCT) OCT optical attenuation imaging (OCT-OA), 67–68 Ocular dominance plasticity, 214 OECs See Olfactory ensheathing cells (OECs) Olfactory ensheathing cells (OECs), 29, 31–32 Oligodendrocyte precursor cells (OPCs), 29 Optical coherence tomography (OCT), 58–59, 67–68 P Paralysis, flaccid, 389–390 Parkinson’s disease, 347, 424 Parvalbumin (PV) interneurons, 216–217 Parylene-based platinum electrode arrays, 209 Parylene-metal-parylene, 201–202 Pearson’s correlation coefficient, 88 Perineuronal nets (PNNs), 216–217, 220–221 Peripheral nerve somatosensory stimulation (PNSS), 104, 108–110 Phenylephrine, 21–22 Physical therapy (PT), 267 PNNs See Perineuronal nets (PNNs) PNSS See Peripheral nerve somatosensory stimulation (PNSS) Polyethylene glycol (PEG), 26–27 Poly-lactic-co-glycolic acid (PLGA), 33–34 Population-based atlas, 66–67 Positron emission tomography (PET), 57, 318–319 Postlesion plasticity, 362 Poststroke Checklist tool, 268–269 Poststroke depression (PSD), 422 441 442 Index Poststroke neuroplasticity, 415 Potassium-chloride cotransporters (KCC2), 151 Predicting recovery potential (PREP), 261 Prefrontal cortices (PFC), 319–320 Premotor cortices (PMC), 319–320 Primate cervical spinal cord, 393f ipsilateral corticospinal tract in, 395f motor cortex, 390 reticular formation, 397f, 404f Primate models vs rodent models, 405 Propriospinal neurons, 399–400 Proteus vulgaris, 33 PT See Pyramidal tract (PT) PTN See Pyramidal tract neuron (PTN) PubMed research database, 286 Pulse-width modulation (PWM), 202 Pyramidal tract (PT), 395f Pyramidal tract neuron (PTN), 402f Q Quebec Rehabilitation Stroke Strategy, 262, 268–269 R Radial arm maze, 423 Raman scattering-based microscopy techniques, 60–61 Randomized control trials (RCTs), 258 Rasch analysis, 237 Reactive oxygen (ROS), 19 Repetitive transcranial magnetic stimulation (rTMS) cortical excitability, 284–285 effectiveness patient characteristics-dependent efficiency, 305 stimulated hemisphere-dependent efficiency, 304–305 stimulation parameter-dependent efficiency, 305 follow-up, 304 hand motor assessment, 286 methods, 286 motor recovery, 285 motor recovery, affected hand after stroke bilateral, 295t contralesional motor cortex, 287t ipsilesional motor cortex, 291t neural correlates, motor recovery, 282–284 neuromodulatory techniques, 282 noninvasive stimulation techniques, 282 patient characteristic-dependent efficiency lesion location, 306 stroke etiology, 305 time since stroke, 305 upper limb impairment, severity of, 306 patients characteristics lesion location, 304 stroke etiology, 304 time after stroke, 303–304 upper limb impairment, severity of, 304 stimulation parameter-dependent efficiency stimulated area, 306 stimulation protocol, 306 stimulation sessions, number of, 306 stimulation parameters adjunct therapies, 304 stimulated area, 304 stimulation protocol, 304 stimulation sessions, number of, 304 Reticular formation, 394–396, 397f, 404f Reticulospinal connections, 399f Reticulospinal tract, 394–398 Rho-associated kinase (ROK), 34 Rick Hansen SCI Registry, 232 Right lateral sensorimotor cortex (RSMC), 324 Riluzole in Spinal Cord Injury Study (RISCIS), 24 Rodent corticospinal tract, 405 Rodent models vs primate models, 405 Rostral forelimb area (RFA), 364–365 rTMS See Repetitive transcranial magnetic stimulation (rTMS) S Schwann cells (SCs), 27–28 SCI See Spinal cord injury (SCI) Self-assembling peptides (SAPs), 33 Self-efficacy, 341–342 Semaphorin 3A (Sema3A), 221 Sensorimotor cortex (SMC), 259–260, 319–320 Sensorimotor enhancement cortical mapping fMRI, 318–319 fNIRS, 319–320 noninvasive neuroimaging techniques, 318–319 PET, 318–319 integrated sensory information, 316 light haptic touch CNS, 314 functional locomotor recovery, 314 hemiplegia, 314 mobility problems, 314 postural control, 314–316 Index NIRS, 314 rehabilitation techniques, 316 virtual environments, 314 virtual reality, 314 virtual reality technology context-sensitive VEs, 317 ecological client-specific contexts, 317 experience-dependent neuroplasticity, 317 external sensory cues, 318 gait stability, 318 haptic strip, 318 mixed-reality system, 318 stroke rehabilitation, 317–318 therapeutic interventions, 317 Sensorimotor Rehabilitation Research Team (SMRRT), 270 Sensory axon plasticity, 214 Shaprio–Wilk test, 137 Short-latency response (SLR), 87 Shoulder abduction finger extension (SAFE), 261 Single pellet reaching task, 415–417 SIRROWS trial, 346–347 SMC See Sensorimotor cortex (SMC) Sodium succinate (MPSS), 22–23 Soleus muscles, 202 Somatosensory cortex, 104 Somatosensory-evoked potentials (SSEPs), Specific descending pathways, clinical gait deficits BBS, 97 beta and gamma coherence, 96–97 clinical assessment, 83 CST, 81 data analysis coherence, 86–87 GVS, 87–88 MEP, 86 spinal cord segmentation, 85–86 statistics, 88 diffusion anisotropy, 95–96 electrophysiological assessment, 83–85 GVS, 85 MEPs and coherence, 84–85 MRI, 83 participants, 81–83 results gait and balance function, 92–93 GVS, 88–89 spinal cord atrophy and electrophysiological and clinical measures, 93–95 vestibular responses, characterization of, 90–91 TA EMG activity, 96 Speckle variance OCT (SV-OCT), 68 Spike-timing-dependent plasticity (STDP), 245 Spinal cord independence measure (SCIM)), 2f, Spinal cord injury (SCI) acute phase apoptosis, 19–20 cell death and demyelination, 19–20 excitotoxicity, 19 Fas receptors, 19–20 glial scar, 20 glutamate receptor, 19 hemorrhage and ischemia, 18 inflammatory cytokines, 18 ionic dysregulation and excitotoxicity, 19 ischemia and immune infiltration, 19 macrophages, 18–19 microglia, 18–19 neuroprotective interventions, 18 neutrophils, 18–19 oligodendrocyte cell death, 19–20 cell-based therapies ESCs, 28–29 iPSCs, 29–30 MSCs, 31 NPCs, 30 OECs, 31–32 Schwann cells, 27–28 clinical intervention hemodynamic control, 21–22 immobilizing patients, 21 steroids, 22–23 surgical decompression, 21 combinatorial therapy cotherapy, multiple cell types, 36 neuroprotection, 35 neuroregeneration, 36 epidemiology, 16 motor function, 2–3 neuroprotective strategies FGF-2, 26 G-CSF, 25–26 minocycline, 25 PEG, 26–27 riluzole, 23–24 neuroregenerative strategies bioengineering scaffolds, regeneration, 33–34 CSPGs, glial scar, 33 Rho inhibition, 34 primary phase, 16–17 rehabilitation, 23, 34–35 secondary phase acute phase, 18–20 443 444 Index Spinal cord injury (SCI) (Continued) chronic phase, 20 immediate phase, 18 intermediate phase, 20 walking performance and functional independence, 2–3 Spinal Cord Outcomes Partnership Endeavor (SCOPE), 232 Spinal motor evoked potentials (sMEPs), 200 Spinal stretch reflex (SSR), 158 Spinal systems, control of hand, 399–400 SSEPs See Somatosensory-evoked potentials (SSEPs) Stroke recovery animal models, 415–417 cognitive dysfunction animal stroke models, 422–423 cortical excitability, 423–424 environmental enrichment, 424 focal ischemic models, 424 Hebb–Williams maze, 424 long-term poststroke disability, 422 music therapy, 423–424 PSD, 422 rehabilitation, 423 spatial learning and memory, 423 exogenous and endogenous stem cell approaches functional benefits, 421 immunosuppressive drugs, 421–422 neural precursor cells, 421–422 post-stroke cognitive impairments, 422 neuroplasticity, 417–421 prevention and acute treatment, 414–415 problem of, 413–414 silver bullet approach, 424 Stroke rehabilitation community poststroke, 254–256 EBRSR, 262 recovery after stroke human brain changes, rehabilitation interventions, 259–260 predictive functional recovery, 260–261 stroke severity, 257–259 rehabilitation continuum poststroke, 262–266 statistics and consequences, 254 subacute and community reintegration phase community rehabilitation interventions, 268 economic analysis, 269 intensity of rehabilitation, 267 secondary prevention, periodic reevaluations and maintenance, 268–269 sensorimotor rehabilitation research team, 269–271 type of therapy, 267 Stroop Task, 423 Supplementary motor area (SMA), 319–320, 363–364 Surgical Timing in Acute Spinal Cord Injury Study (STASCIS), 21 Syste`me de mesure d’autonomie fonctionnelle (SMAF), 264 T Talairach and Tournoux atlas, 63 Targeted neuroplasticity, rehabilitation CNS pathways, humans conditioning trials, 164–165 control trials, 164 CST activity, 163 good coaching, 165 maximum voluntary contraction measurement, 164 recruitment curve measurements, 164 skill acquisition, 161–163 skin preparation and electrode placement, 163 spinal pathway, H-reflex, 163 stimulus test, 164 conditioning, functional impact of plasticity, targeted pathway, 166–169 soleus H-reflex, 166 operant-conditioning, 158 plasticity, reflex conditioning sites of, 158–159 time course of change, 159–161 Tetraplegia, 107 Thrombolysis, 414 Thromboprophylaxis, 21–22 Tibialis anterior (TA) muscles, 83, 202 Tibial nerve (TN), 133 Timed-Up and Go (TUG), 4, 83 Tissue plasminogen activator (t-PA), 414 T-maze Win/Shift-Win/Stay tests, 423 TMS See Transcranial magnetic stimulation (TMS) Trail Making Test, 423 Transcranial direct current stimulation (tDCS), 105, 282, 362 Transcranial magnetic stimulation (TMS), 81, 128–129, 158, 259–260, 362, 403, 419 Treadmill training, 176, 184–185, 191f Triage methodology, 263–264 Tumorigenicity, 30 Index U W Ultrasonography, 57 Upper extremity motor score (UEMS), 234, 236–237 US National Institute on Disability and Rehabilitation Research (NIDRR), 232 Walking competency, 255–256 Walking function clinical neurophysiology spinal cord integrity, spinal neural circuits, 5–6 gait analysis, 6–7 motor function, 2–3 neural control, 7–10 recovery, clinical assessments of functional assessments, 4–5 neurological assessments, Walking index for spinal cord injury (WISCI), 2f, Whole-body vibration (WBV), 116–117 Wisconsin Card Sorting Task, 423 World Health Organization (WHO), 254 World Medical Association, 230 V Ventral premotor cortex (PMv), 363–364, 367f Virtual environments (VEs), 314 Virtual reality (VR), 314 context-sensitive VEs, 317 ecological client-specific contexts, 317 experience-dependent neuroplasticity, 317 external sensory cues, 318 gait stability, 318 haptic strip, 318 mixed-reality system, 318 stroke rehabilitation, 317–318 therapeutic interventions, 317 445 Other volumes in PROGRESS IN BRAIN RESEARCH Volume 167: Stress Hormones and Post Traumatic Stress Disorder: Basic Studies and Clinical Perspectives, by E.R de Kloet, M.S Oitzl and E Vermetten (Eds.) – 2008, ISBN 978-0-444-53140-7 Volume 168: Models of Brain and Mind: Physical, Computational and Psychological Approaches, by R Banerjee and B.K Chakrabarti (Eds.) – 2008, ISBN 978-0-444-53050-9 Volume 169: Essence of Memory, by W.S Sossin, J.-C Lacaille, V.F Castellucci and S Belleville (Eds.) – 2008, ISBN 978-0-444-53164-3 Volume 170: Advances in Vasopressin and Oxytocin – From Genes to Behaviour to Disease, by I.D Neumann and R Landgraf (Eds.) – 2008, ISBN 978-0-444-53201-5 Volume 171: Using Eye Movements as an Experimental Probe of Brain Function—A Symposium in Honor of Jean B€uttner-Ennever, by Christopher Kennard and R John Leigh (Eds.) – 2008, ISBN 978-0-444-53163-6 Volume 172: Serotonin–Dopamine Interaction: Experimental Evidence and Therapeutic Relevance, by Giuseppe Di Giovanni, Vincenzo Di Matteo and Ennio Esposito (Eds.) – 2008, ISBN 978-0-444-53235-0 Volume 173: Glaucoma: An Open Window to Neurodegeneration and Neuroprotection, by Carlo Nucci, Neville N Osborne, Giacinto Bagetta and Luciano Cerulli (Eds.) – 2008, ISBN 978-0-444-53256-5 Volume 174: Mind and Motion: The Bidirectional Link Between Thought and Action, by Markus Raab, Joseph G Johnson and Hauke R Heekeren (Eds.) – 2009, 978-0-444-53356-2 Volume 175: Neurotherapy: Progress in Restorative Neuroscience and Neurology — Proceedings of the 25th International Summer School of Brain Research, held at the Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands, August 25–28, 2008, by J Verhaagen, E.M Hol, I Huitinga, J Wijnholds, A.A Bergen, G.J Boer and D.F Swaab (Eds.) –2009, ISBN 978-0-12-374511-8 Volume 176: Attention, by Narayanan Srinivasan (Ed.) – 2009, ISBN 978-0-444-53426-2 Volume 177: Coma Science: Clinical and Ethical Implications, by Steven Laureys, Nicholas D Schiff and Adrian M Owen (Eds.) – 2009, 978-0-444-53432-3 Volume 178: Cultural Neuroscience: Cultural Influences On Brain Function, by Joan Y Chiao (Ed.) – 2009, 978-0-444-53361-6 Volume 179: Genetic models of schizophrenia, by Akira Sawa (Ed.) – 2009, 978-0-444-53430-9 Volume 180: Nanoneuroscience and Nanoneuropharmacology, by Hari Shanker Sharma (Ed.) – 2009, 978-0-444-53431-6 Volume 181: Neuroendocrinology: The Normal Neuroendocrine System, by Luciano Martini, George P Chrousos, Fernand Labrie, Karel Pacak and Donald W Pfaff (Eds.) – 2010, 978-0-444-53617-4 Volume 182: Neuroendocrinology: Pathological Situations and Diseases, by Luciano Martini, George P Chrousos, Fernand Labrie, Karel Pacak and Donald W Pfaff (Eds.) – 2010, 978-0-444-53616-7 Volume 183: Recent Advances in Parkinson’s Disease: Basic Research, by Anders Bj€orklund and M Angela Cenci (Eds.) – 2010, 978-0-444-53614-3 Volume 184: Recent Advances in Parkinson’s Disease: Translational and Clinical Research, by Anders Bj€orklund and M Angela Cenci (Eds.) – 2010, 978-0-444-53750-8 Volume 185: Human Sleep and Cognition Part I: Basic Research, by Gerard A Kerkhof and Hans P.A Van Dongen (Eds.) – 2010, 978-0-444-53702-7 Volume 186: Sex Differences in the Human Brain, their Underpinnings and Implications, by Ivanka Savic (Ed.) – 2010, 978-0-444-53630-3 Volume 187: Breathe, Walk and Chew: The Neural Challenge: Part I, by Jean-Pierre Gossard, Re´jean Dubuc and Arlette Kolta (Eds.) – 2010, 978-0-444-53613-6 Volume 188: Breathe, Walk and Chew; The Neural Challenge: Part II, by Jean-Pierre Gossard, Re´jean Dubuc and Arlette Kolta (Eds.) – 2011, 978-0-444-53825-3 Volume 189: Gene Expression to Neurobiology and Behaviour: Human Brain Development and Developmental Disorders, by Oliver Braddick, Janette Atkinson and Giorgio M Innocenti (Eds.) – 2011, 978-0-444-53884-0 447 448 Other volumes in PROGRESS IN BRAIN RESEARCH Volume 190: Human Sleep and Cognition Part II: Clinical and Applied Research, by Hans P.A Van Dongen and Gerard A Kerkhof (Eds.) – 2011, 978-0-444-53817-8 Volume 191: Enhancing Performance for Action and perception: Multisensory Integration, Neuroplasticity and Neuroprosthetics: Part I, by Andrea M Green, C Elaine Chapman, John F Kalaska and Franco Lepore (Eds.) – 2011, 978-0-444-53752-2 Volume 192: Enhancing Performance for Action and Perception: Multisensory Integration, Neuroplasticity and Neuroprosthetics: Part II, by Andrea M Green, C Elaine Chapman, John F Kalaska and Franco Lepore (Eds.) – 2011, 978-0-444-53355-5 Volume 193: Slow Brain Oscillations of Sleep, Resting State and Vigilance, by Eus J.W Van Someren, Ysbrand D Van Der Werf, Pieter R Roelfsema, Huibert D Mansvelder and Fernando H Lopes da Silva (Eds.) – 2011, 978-0-444-53839-0 Volume 194: Brain Machine Interfaces: Implications For Science, Clinical Practice And Society, by Jens Schouenborg, Martin Garwicz and Nils Danielsen (Eds.) – 2011, 978-0-444-53815-4 Volume 195: Evolution of the Primate Brain: From Neuron to Behavior, by Michel A Hofman and Dean Falk (Eds.) – 2012, 978-0-444-53860-4 Volume 196: Optogenetics: Tools for Controlling and Monitoring Neuronal Activity, by Thomas Kn€opfel and Edward S Boyden (Eds.) – 2012, 978-0-444-59426-6 Volume 197: Down Syndrome: From Understanding the Neurobiology to Therapy, by Mara Dierssen and Rafael De La Torre (Eds.) – 2012, 978-0-444-54299-1 Volume 198: Orexin/Hypocretin System, by Anantha Shekhar (Ed.) – 2012, 978-0-444-59489-1 Volume 199: The Neurobiology of Circadian Timing, by Andries Kalsbeek, Martha Merrow, Till Roenneberg and Russell G Foster (Eds.) – 2012, 978-0-444-59427-3 Volume 200: Functional Neural Transplantation III: Primary and stem cell therapies for brain repair, Part I, by Stephen B Dunnett and Anders Bj€orklund (Eds.) – 2012, 978-0-444-59575-1 Volume 201: Functional Neural Transplantation III: Primary and stem cell therapies for brain repair, Part II, by Stephen B Dunnett and Anders Bj€orklund (Eds.) – 2012, 978-0-444-59544-7 Volume 202: Decision Making: Neural and Behavioural Approaches, by V.S Chandrasekhar Pammi and Narayanan Srinivasan (Eds.) – 2013, 978-0-444-62604-2 Volume 203: The Fine Arts, Neurology, and Neuroscience: Neuro-Historical Dimensions, by Stanley Finger, Dahlia W Zaidel, Franc¸ois Boller and Julien Bogousslavsky (Eds.) – 2013, 978-0-444-62730-8 Volume 204: The Fine Arts, Neurology, and Neuroscience: New Discoveries and Changing Landscapes, by Stanley Finger, Dahlia W Zaidel, Franc¸ois Boller and Julien Bogousslavsky (Eds.) – 2013, 978-0-444-63287-6 Volume 205: Literature, Neurology, and Neuroscience: Historical and Literary Connections, by Anne Stiles, Stanley Finger and Franc¸ois Boller (Eds.) – 2013, 978-0-444-63273-9 Volume 206: Literature, Neurology, and Neuroscience: Neurological and Psychiatric Disorders, by Stanley Finger, Franc¸ois Boller and Anne Stiles (Eds.) – 2013, 978-0-444-63364-4 Volume 207: Changing Brains: Applying Brain Plasticity to Advance and Recover Human Ability, by Michael M Merzenich, Mor Nahum and Thomas M Van Vleet (Eds.) – 2013, 978-0-444-63327-9 Volume 208: Odor Memory and Perception, by Edi Barkai and Donald A Wilson (Eds.) – 2014, 978-0-444-63350-7 Volume 209: The Central Nervous System Control of Respiration, by Gert Holstege, Caroline M Beers and Hari H Subramanian (Eds.) – 2014, 978-0-444-63274-6 Volume 210: Cerebellar Learning, Narender Ramnani (Ed.) – 2014, 978-0-444-63356-9 Volume 211: Dopamine, by Marco Diana, Gaetano Di Chiara and Pierfranco Spano (Eds.) – 2014, 978-0-444-63425-2 Volume 212: Breathing, Emotion and Evolution, by Gert Holstege, Caroline M Beers and Hari H Subramanian (Eds.) – 2014, 978-0-444-63488-7 Volume 213: Genetics of Epilepsy, by Ortrud K Steinlein (Ed.) – 2014, 978-0-444-63326-2 Volume 214: Brain Extracellular Matrix in Health and Disease, by Asla Pitkaănen, Alexander Dityatev and Bernhard Wehrle-Haller (Eds.) 2014, 978-0-444-63486-3 Other volumes in PROGRESS IN BRAIN RESEARCH Volume 215: The History of the Gamma Knife, by Jeremy C Ganz (Ed.) – 2014, 978-0-444-63520-4 Volume 216: Music, Neurology, and Neuroscience: Historical Connections and Perspectives, by Franc¸ois Boller, Eckart Altenm€uller, and Stanley Finger (Eds.) – 2015, 978-0-444-63399-6 Volume 217: Music, Neurology, and Neuroscience: Evolution, the Musical Brain, Medical Conditions, and Therapies, by Eckart Altenm€uller, Stanley Finger, and Franc¸ois Boller (Eds.) – 2015, 978-0-444-63551-8 449 ... locomotor training in individuals with SCI regardless of training approach J Neuroeng Rehabil 6, 36 Pepin, A., Norman, K.E., Barbeau, H., 2003 Treadmill walking in incomplete spinal-cordinjured subjects:... elicited during epidural spinal cord stimulation in motor complete spinal cord injured patients following intensive training (Angeli et al., 2014; Harkema et al., 2011) These findings suggest... by the intralimb coordination, which may depend predominantly on intact supraspinal input, making intralimb coordination a valuable measure for recovery beyond spontaneous/conventionally induced