Broken Movement: The Neurobiology of Motor Recovery after Stroke

by John W. Krakauer, S. Thomas Carmichael

Overview

An account of the neurobiology of motor recovery in the arm and hand after stroke by two experts in the field.

Stroke is a leading cause of disability in adults and recovery is often difficult, with existing rehabilitation therapies largely ineffective. In Broken Movement, John Krakauer and S. Thomas Carmichael, both experts in the field, provide an account of the neurobiology of motor recovery in the arm and hand after stroke. They cover topics that range from behavior to physiology to cellular and molecular biology. Broken Movement is the only accessible single-volume work that covers motor control and motor learning as they apply to stroke recovery and combines them with motor cortical physiology and molecular biology. The authors cast a critical eye at current frameworks and practices, offer new recommendations for promoting recovery, and propose new research directions for the study of brain repair.
Krakauer and Carmichael discuss such subjects as the behavioral phenotype of hand and arm paresis in human and non-human primates; the physiology and anatomy of the motor system after stroke; mechanisms of spontaneous recovery; the time course of early recovery; the challenges of chronic stroke; and pharmacological and stem cell therapies. They argue for a new approach in which patients are subjected to higher doses and intensities of rehabilitation in a more dynamic and enriching environment early after stroke. Finally they review the potential of four areas to improve motor recovery: video gaming and virtual reality, invasive brain stimulation, re-opening the sensitive period after stroke, and the application of precision medicine.

Product Details

ISBN-13:	9780262545839
Publisher:	MIT Press
Publication date:	06/07/2022
Pages:	288
Product dimensions:	7.00(w) x 9.00(h) x (d)

About the Author

John W. Krakauer is John C. Malone Professor and Professor of Neurology, Neuroscience, and Physical Medicine and Rehabilitation at the Johns Hopkins University School of Medicine.

S. Thomas Carmichael is Professor and Chair and Frances Stark Endowed Chair in the Department of Neurology at the David Geffen School of Medicine at the University of California, Los Angeles, and Codirector of UCLA's Broad Stem Cell Center.

Table of Contents

Preface xi

Acknowledgment xiii

1 The Current Landscape of Upper Limb Neurorehabilitation 1

1.1 Introduction 1

1.2 The Many Faces of Motor Recovery 1

1.3 True Recovery versus Compensation 3

1.4 (Mis)measures of Arm Paresis 3

1.5 Current Upper Limb Neurorehabilitation: What Is Done, and Does it Work? 8

1.6 Conclusions 10

2 Upper Limb Paresis: Phenotype, Anatomy, and physiology 13

2.1 Introduction 13

2.2 The Modern History of Hemiparesis (Part 1): Sherrington, Tower, and Walshe 13

2.3 The Modern History of Hemiparesis (Part 2): The Lawrence and Kuypers Studies in the Macaque 17

2.4 Weakness 20

2.5 Residual Motor Control and the Idea of Synergies 24

2.6 The Dissociation between Strength and Motor Control 27

2.7 The Contributions of the Corticospinal and Reticulospinal Tracts to Strength and Control 33

2.8 Poststroke Resting Posture 36

2.9 Abnormal Postural Control Mechanisms during Movement 37

2.10 Spasticity 41

2.11 The Relationship between Lesion Location and Arm Paresis Phenotype after Stroke 46

2.12 Remote Physiological Effect: Diaschisis 47

2.13 Remote Physiological Effect: The Interhemispheric Competition Model and the Use of Noninvasive Brain Stimulation for Treatment Hemiparesis 50

2.14 The Ipsilateral "Unaffected" Arm 53

2.15 Conclusions 57

3 Acute Hemiparesis: Spontaneous Biological Recovery, the Effect of Training, Sensitive Periods, and Reorganization 59

3.1 Introduction 59

3.2 The Modern History of Motor Recovery after Stroke: Hughlings Jackson, Leyton and Sherrington. Ogden and Franz 59

3.3 The Modern History of Motor Recovery after Stroke: Twitchell and Brunstrom 64

3.4 The Natural History of Recovery of Hand and Arm Impairment 67

3.5 The Proportional Recovery Rule 68

3.6 The Recovery of Motor Control in the Arm and Hand: Kinematic and Kinetic Measurement 77

3.7 The Interactions between Spontaneous Recovery and Training: Repair versus Learning 84

3.8 A Sensitive Period of Increased Responsiveness to Training 95

3.9 Relevance of Rodent Models to Human Stroke 98

3.10 Recovery and Brain Recorganization 100

3.11 Conclusion 106

4 The Molecular and Cellular Biology of the Peri-Infarct Cortex and Beyond Repair versus recorganization 111

4.1 Introduction 111

4.2 Regions of Stroke Damage 112

4.3 Triggers for Neural Repairs Radiate Outward from the Infarct core 116

4.4 Excitatory/Inhibitory Balance in Peri-Infarct Cortex 119

4.5 Dendritic Spine Alterations in Peri-Infarct Cortex 122

4.6 Reactive Astrocytes and Extracellular Matrix Change in Peri-Infarct Cortex 123

4.7 The Effects of Ischemia on Distant Connected Brain Regions 125

4.8 Axonal Sprouting 126

4.9 Does Axonal Regeneration Recapitulate Development? 133

4.10 Neuronal and Glial Progenitor Response after Stroke (Neurogenesis and Gliogenesis) 135

4.11 Reconciling Regeneration with (Behavioral) Recovery 137

4.12 Does Activity in the Injured Brain Make The Injury Worse? 138

4.13 Conclusions 139

5 A Hierarchical Framework for Tissue Repairs after Stroke 141

5.1 First-and Second-Order Principles of Repair 141

5.2 Stroke is Not just an Acute Killer but a Chronic Disabling Disease 142

5.3 Behavioral Activity an Shapes Tissue Regeneration 143

5.4 The Suffered Is the Learned 145

5.5 The Motor Recovery Engram and CREB 147

5.6 Plasticity Is a Risk for Cell Death: Timing for a Neural Repair Therapy after Stroke 152

5.7 The Brain Forms Regenerative Cellular Niches during Repairs and Recovery 153

5.8 Engaging CNS Tissue Regeneration Is Like Activating a Cancer 155

5.9 Neural Repair Therapies Must be Focused in Time and Space 155

5.10 Regeneration Does Not Recapitulate Development: The Meaning of "Phenotype" 156

5.11 Neuronal Networks in Motor Recovery: Second-Order Principles Interact 157

5.12 Conclusion 159

6 Chronic Hemiparesis: Motor Learning, Compensation, and the Challenge of Reversing Impairment in Late Stroke 161

6.1 Introduction 161

6.2 Motor Learning Principles for Neurorehabilitation 162

6.3 Compensation 171

6.4 Repetitive Task-Oriented Training 172

6.5 Constraint-Induced Movement Therapy 177

6.6 Robotic Therapy 180

6.7 Conclusion 183

7 Pharmacological and Cell Therapies for Recovery from Stroke 185

7.1 Introduction 185

7.2 Brief Overview of Stem Cell Therapy in Stroke 185

7.3 What Is a Stem Cell? 186

7.4 Types of Stems and Progenitor Cells in Brain Therapy 187

7.5 Mechanisms of Stem Cell Preclinical Studies to the Clinic 193

7.7 Pharmacological Therapies for Stroke Recovery 198

7.8 Molecelar Neurorehabilitation 207

8 A Future Approach to Neurorehabilitation after Stroke: If Humans Had Wings 209

8.1 Introduction 209

8.2 Video Games and Virtual Reality 209

8.3 Direct Physiological Interventions 211

8.4 Reopending the Sensitive Period 214

8.5 Precision Health and Recovery after Stroke 220

8.6 Conclusions 222

References 223

Index 265

What People are Saying About This

Daniel Wolpert

This elegant book provides a critical re-examination of stroke recovery, and by providing a mechanistic understanding sets the stage for new and more effective therapies.

John Rothwell

It is an enormous pleasure to read such a deeply researched and meticulous monograph by two outstanding scientists. At last we get informed, considered opinions that are combined with a unified intellectual thread, rather than the usual multi-authored catechism that intones the literature without questioning the content. It will irritate and delight in equal measure, but is never dull.

Endorsement

This elegant book provides a critical re-examination of stroke recovery, and by providing a mechanistic understanding sets the stage for new and more effective therapies.

—Daniel Wolpert, Royal Society Research Professor; Professor of Engineering, Department of Engineering, University of Cambridge

From the Publisher

It is an enormous pleasure to read such a deeply researched and meticulous monograph by two outstanding scientists. At last we get informed, considered opinions that are combined with a unified intellectual thread, rather than the usual multi-authored catechism that intones the literature without questioning the content. It will irritate and delight in equal measure, but is never dull.

—John Rothwell, Professor of Human Neurophysiology, University College London Institute of Neurology

This elegant book provides a critical re-examination of stroke recovery, and by providing a mechanistic understanding sets the stage for new and more effective therapies.

—Daniel Wolpert, Royal Society Research Professor; Professor of Engineering, Department of Engineering, University of Cambridge

Editorial Reviews

My hope is that Broken Movement leads the brightest and best to be impressed with what we already know about stroke recovery, be curious as to why clinical outcomes are still poor and then join the cause to make things better.--Brain--

From the Publisher