the circuitry of the human spinal cord:...

THE CIRCUITRY OF THEHUMAN SPINAL CORD: SPINALAND CORTICOSPINALMECHANISMS OF MOVEMENT

Studies of human movement have proliferated in recent

years. This greatly expanded and thoroughly updated refer-

ence surveys the literature on the corticospinal control of

spinal cord circuits in human subjects, showing how differ-

ent circuits can be studied, their role in normal movement

and how they malfunction in disease states. Chapters are

highly illustrated and consistently organised, reviewing, for

each pathway, the experimental background, methodol-

ogy, organisation and control, role during motor tasks

and changes in patients with central nervous system

lesions. Each chapter concludes with a helpful résumé

that can be used independently of the main text to provide

practical guidance for clinical studies. The final four chap-

ters bring together the changes in transmission in spinal

and corticospinal pathways during movement and how

they contribute to the desired movement. This book is

essential reading for research workers and clinicians

involved in the study, treatment and rehabilitation of

movement disorders.

Emmanuel Pierrot-Deseilligny is Emeritus Professor of

Clinical Neurophysiology and Rehabilitation at the

Université Pierre et Marie Curie, Paris.

David Burke is the Bushell Professor of Neurology at Royal

Prince Alfred Hospital and Associate Dean (Research),

Sydney Medical School, The University of Sydney.

www.cambridge.org© in this web service Cambridge University Press

Cambridge University Press978-0-521-19258-3 - The Circuitry of the Human Spinal Cord: Spinal and Corticospinal Mechanisms of MovementEmmanuel Pierrot-Deseilligny and David BurkeFrontmatterMore information

http://www.cambridge.org/9780521192583

http://www.cambridge.org


THE CIRCUITRY

OF THE HUMAN

SPINAL CORD

Spinal and CorticospinalMechanisms of Movement

Emmanuel Pierrot-DeseillignyUniversité Pierre et Marie Curie

David BurkeThe University of Sydney






CAMB R I DG E UN I V E R S I T Y P R E S S

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© Emmanuel Pierrot-Deseilligny and David Burke, 2012

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First published 2012

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Contents

Acknowledgements page xvi

Preface xvii

List of abbreviations xxi

1 General Methodology 1

H Reflex and Tendon Jerk 1

Basic Methodology (H reflex) 4

H and M Recruitment Curve 7

Tendon Jerk 8

Random Alternation of Control and

Conditioned Reflexes 8

Time Resolution of the Method 8

Recovery Cycle of the H Reflex 9

Threshold Tracking of the H Reflex 11

Mechanisms Acting on the Afferent Volley 11

Alterations in the Excitability of Ia Afferents 11

Presynaptic Inhibition of Ia Terminals 11

Homosynaptic Depression 12

Curtailment of the Compound EPSP by a

Disynaptic Ib IPSP 12

‘Pool Problems’ 15

Non-linearity in the Input–Output Relation 15

Changes in the Recruitment Gain of the

Motoneurone Pool 16

Plateau Potentials and Amplification of

Synaptic Input 17

Quantitative Data 20

Clinical Value 21

The F wave 21

Modulation of the On-Going EMG Activity 24

Underlying Principles and Methodology 24

Discrepant Changes in the On-Going EMG

and in the H Reflex 26

Advantages, Limitations and Conclusions 27

Investigations on Single Motor Units 28

v






Post-stimulus Time Histograms (PSTHs) 28

Underlying Principles 28

Basic Methodology 30

Timing of the Changes in Firing Probability 31

Size and Significance of the Peaks and

Troughs in the PSTH 32

Critique: Limitations, Advantages and

Conclusions 33

Post-stimulus Time Frequencygrams (PSFs) 34

Unitary H Reflex 35

Stimulation of the Motor Cortex 36

Caveats in Interpreting Studies Using

Transcranial Stimulation 38

Transcranial Stimulation by Single Pulses 39

Paired-Pulse Stimulation of the Motor Cortex 44

Short-Interval Intracortical Inhibition (SICI) 44

Long-Interval Intracortical Inhibition (LICI) 45

Cortical Silent Period 45

Short-Interval Intracortical Facilitation

(SICF) 45

Long-Interval Intracortical Facilitation

(LICF) 46

Interhemispheric Interactions 46

Combined Peripheral and Cortical

Stimulation 46

Prolonged Stimulation of the Motor Cortex

(rTMS, TBS, tDCS) 47

Spatial Facilitation 48


Spatial Facilitation in the PSTH 48

Spatial Facilitation of Monosynaptic Reflexes 50

Coherence Analyses and Motor Control 51

Résumé 52

References 59

2 Monosynaptic Ia Excitation,

Homosynaptic Depression and

Transcortical Ia Excitation 65

Monosynaptic Ia Excitation of Motoneurones 65

Background from Animal Experiments 65

Methodology 67

Homonymous Monosynaptic Ia Excitation 67

Heteronymous Monosynaptic Ia Excitation 69

Range of Electrical Thresholds and CV of

Ia Afferents 74

Organisation and Pattern of Connections 76

Homonymous Monosynaptic Ia

Excitation 76

Heteronymous Ia Connections in the Lower

Limb 77

Heteronymous Ia Connections in the

Upper Limb 78

Equivocal Data Obtained with

Conditioning Tendon Taps 80

Motor Tasks and Physiological Implications 80

Short-Latency Ia Spinal Stretch Reflex 80

Heteronymous Connections in the Lower

Limb 82

Heteronymous Connections in the Upper

Limb 84

Studies in Patients and Clinical Implications 84

Homosynaptic Depression (HD) 85


Methodology 85

Organisation and Physiological Implications 87

Strength of HD at Different Synapses 87

HD during Voluntary Contraction 88

Use-Dependent Plasticity 89

Functional Significance 89

HD in Patients 90

Spasticity 90

Parkinson’s Disease 90

Transcortical Ia Excitation 90

History of Transcortical LLSRs

in Humans 91

Denouement 93

Patients with Mirror Movements 93

Motor Cortex Stimulation 93

Transcortical LLSRs in the Upper Limb 94

LLSRs in Distal and Proximal Muscles 94

Overlap with Voluntary M3 Response 94

Group II Medium-Latency

Responses 95

Sensory Pathway of M2 Responses 95


Transcortical LLSRs in the Lower Limb 96

Evidence for Transcortical LLSRs 96


Résumé 99

References 103

vi Contents






3 Fusimotor Mechanisms, Muscle Spindles

and Their Role in the Control of

Movement 110

Background 110

Methodology 114

Comparisons of Tendon Jerk and H Reflex 114

Nerve Blocks 115

Microneurography 115

Exploiting the Thixotropic Properties of

Intrafusal Fibres 117

Critique of the Tests to Study Fusimotor

Drive 117


Background Drive to Relaxed Muscles 118

Discharge Rates 118

Effect of Muscle Vibration on Human

Spindles 119

Reflex Activation of Fusimotor Neurones 121

Supraspinal Activation of Fusimotor

Neurones 123


Remote Muscle Contraction 123

Motor Preparation and Imagery 124

Deliberate Voluntary Effort 125

Isometric (Restrained) Contractions 125

Concentric and Eccentric Contractions 127

Activation of γ and β Motoneurones 127

Natural Unrestrained Movements 127

Possible Role of the Fusimotor System

during Movement 128


Spasticity 129


Résumé 130

References 133

4 Recurrent Inhibition 138


Methodology 140

Arguable Techniques 140

The Paired H Reflex Technique 141


Conditioning Reflex and H’ Test Reflex 142

Evidence for Recurrent Inhibition 142

Validation 146

Critique: Limitations, Cautions,

Conclusion 146

Heteronymous Recurrent Inhibition 147


Orthodromic (Reflex) Discharge 148

Antidromic Motor Volley 148

Evidence for Recurrent Inhibition 148

Critique: Limitations, Conclusions 152


Homonymous Recurrent Inhibition 152

Heteronymous Recurrent Inhibition in the

Lower Limb 153

Heteronymous Recurrent Inhibition in the

Upper Limb 154

Projections to Ia Inhibitory Interneurones 155

Cortical Control 157

Peripheral Control 157


Voluntary Contractions of the Test Muscle 158

Methodology 158

Various GS Voluntary Contractions 158

Mechanisms Underlying the Changes

in H’ 160


Conclusions and Functional Implications 162

Contraction of the Antagonistic Muscle 163

Co-contraction of Antagonistic Muscles 163

Stance 165

Homonymous Recurrent Inhibition 165


Heteronymous Recurrent Inhibition during

Gait 167


Spasticity: Recurrent Inhibition at Rest 169

Stroke and Spinal Cord Injury 169

Progressive Spastic Paraparesis 169

Spasticity: Changes in Recurrent

Inhibition during Motor Tasks 170

Patients with Other Movement Disorders 170

Résumé 170

References 174

5 Reciprocal Ia Inhibition 178


Methodology 180

Contents vii






Methods to Investigate Reciprocal Ia

Inhibition at Hinge Joints 180

Inhibition of the Monosynaptic Reflex 180

Modulation of the On-going EMG 181

PSTHs for Single Units 181

Evidence for Reciprocal Ia Inhibition 181

Evidence for Ia-Induced Inhibition 181

Evidence for Disynaptic Transmission 184

Recurrent Inhibition of the Relevant

Interneurones 185

Critique of the Tests to Study Reciprocal

Ia Inhibition 185


Pattern and Strength of Reciprocal Ia

Inhibition at Rest at Hinge Joints 187

Other Inputs to Ia Interneurones 188

Cutaneous Facilitation of Reciprocal Ia

Inhibition 188

Corticospinal Facilitation of Reciprocal

Ia Inhibition 190

Vestibulospinal Facilitation of Reciprocal

Ia Inhibition 190

Absence of ‘True’ Reciprocal Ia Inhibition at

Wrist Level 190

Inhibition at Wrist Level Does Not Fulfil

the Criteria for Reciprocal Ia Inhibition 190

Convergence of Group I Afferents from

Several Different Muscles 192

Homosynaptic Depression 193


Voluntary Contraction of the Antagonist 194

Soleus H Reflex Depression 194

Reciprocal Ia Inhibition during Voluntary

Ankle Dorsiflexion 194

Mechanisms Underlying Changes in

Reciprocal Ia Inhibition 197

Functional Implications 198


Voluntary Activation of the Agonist Muscle 199

Reciprocal Ia Inhibition during

Co-contraction of Antagonistic Muscles 200

Postural Activity 202

Gait 204


Spasticity 205

Stroke 205

Spinal Cord Lesions 205

Underlying Mechanisms 206

Cerebral Palsy 206

Hyperekplexia 206


Résumé 206

References 210

6 Ib Pathways 214


Methodology 217

Methods to Investigate Ib Inhibition 217

Inhibition of the H Reflex at Rest 218

Inhibition in the PSTHs for Single Units 218

Evidence for Ib Inhibition 218

Evidence for a Ib Conditioning Input 218

Evidence for Disynaptic Transmission 221

Ib vs. Reciprocal Ia Inhibition 223

Short Duration 223

Oligosynaptic Group I Excitation 224

Critique of the Tests to Reveal Ib Effects 224


Pattern and Strength of Ib Inhibition 225

Homonymous Ib Inhibition 225

Heteronymous Ib Inhibition 225

Oligosynaptic Group I Excitation 226

Convergence with Ia Afferents 227

Effects of Low-Threshold Cutaneous

Afferents 227

Cutaneous Suppression 227

Cutaneous Facilitation 229

Facilitation of Ib Inhibition by Joint

Afferents 230

Effects from Nociceptive Afferents 230

Descending Effects 232

Convergent Inputs 232


Voluntary Contraction of the Agonist 234

Evidence for Suppression of Ib Inhibition 234

Possible Mechanisms 234

Possible Functional Role of Ib Inhibition 237

Facilitation by Other Afferent Discharges 237

Ib Inhibition to Motoneurones not Involved

in the Voluntary Contraction 238

viii Contents






Inactive Synergists 238

Voluntary Contraction of Antagonists 238

Changes in Ib Inhibition during Walking 238


Ib Inhibition 241

Spasticity 241

Hyperekplexia 241


Restless Leg Syndrome, Supranuclear Palsy 241

Mechanisms Underlying the Decreased Ib

Inhibition 241

Ib Excitation in Spastic Patients 242

Résumé 242

References 245

7 Group II Pathways 249


Methodology 252


Stretch-Induced Homonymous Group II

Excitation 252

Responses in Standing Subjects 252

Responses in Subjects Reclining Supine 254

Electrically Induced Heteronymous Group II

Excitation 254

Late High-Threshold H Reflex Facilitation 254

PSTHs of Single Units 254

Modulation of the On-going EMG 254

Evidence for Muscle Group II Excitation 257

Late Excitation is not Due to Motor or

Fusimotor Axon Stimulation 257

Evidence for Slowly Conducting Afferents 257

Differential Effects of Vibration 257

Pharmacological Validation 260

Origin of Group II Afferents 260

Critique of the Tests Used to Reveal

Group II Actions 260

Contamination by Group I Effects 260

Contamination by Transcortical

Long-Latency Responses 261

Other Limitations 261


Peripheral Pathway 261

Conduction Velocity of Group II Afferents 261

Group II–Ia Ratio 262

Central Pathway of Group II Excitation 262

Estimates of the Central Delay 262

Rostral Location of the Relevant

Interneurones 263

Distribution of Group II Excitation 264

Stretch-Induced Responses in Ipsilateral

and Contralateral Muscles

(Lower Limb) 264

Heteronymous Group II Excitation

(Lower Limb) 264

Group II Excitation in the Upper Limb 264

Convergence with Other Peripheral

Afferents 265

Group I Afferents 265

Absence of Evidence for Cutaneous

Projections 266

Peripheral Inhibitory Input to Interneurones 266

Absence of Group II Inhibition of

Motoneurones 266

Corticospinal Control of Group II Excitation 267

Corticospinal Facilitation of Group II

Excitation 267

Corticospinal Control of Inhibitory

Interneurones 267


Voluntary Contractions 270

Postural Tasks 271

Homonymous Group II Excitation 271

Heteronymous Group II Excitation in

Postural Tasks 273

Monoaminergic Control System? 273


Gait 274

Contribution to Soleus Activation 274

Contribution to Quadriceps Activation 276

Group II-Mediated Responses to

External Perturbations 276


Peripheral Neuropathies 279

Spasticity 279

Increased Propriospinally Mediated

Group I–Group II Excitation 279

Possible Underlying Mechanisms 280

Is Increased Group II Excitation

Sufficient to Cause Spasticity? 282

Contents ix







Dystonia 284

Résumé 284

References 288

8 Presynaptic Inhibition of Ia Terminals 292


Methodology 295

H Reflex vs. MEP 295

Assessing the Excitability of PAD

Interneurones 297

Flawed Technique: Prolonged Vibration

of the Homonymous Tendon 297

Short Vibration of a Heteronymous

Tendon 298

Electrically Induced ‘D1’ and ‘D2’

Inhibitions 298

Critique 299

Assessing Monosynaptic Ia Facilitation

of the H Reflex 300

Experimental Paradigm 300

Validation 300

Critique 302

Techniques Using Single Motor Units 302

Opposite Changes in Ia Facilitation and

Heteronymous Inhibition 302


Projections to Different Motoneurone Types 302

Organisation of PAD INs in Subsets 303

Peripheral Projections to PAD INs 304

Excitatory Effects 304

Depression from Tactile Cutaneous

Afferents 304

Corticospinal Projections 304

Vestibulospinal Projections 307

Tonic Level of Presynaptic Inhibition of la

Terminals 307

Sensitivity of Stretch-Induced Ia Volleys

to Presynaptic Inhibition 307


Ia Terminals on Voluntarily Activated Lower

Limb Motoneurones 308

Evidence for Decreased Presynaptic

Inhibition 308

Changes during Various Contractions 310

Origin and Functional Implications 312


Ia Terminals on Motoneurones of Inactive

Synergists 313

Evidence for Increased Presynaptic

Inhibition 313

Origin and Functional Implications 314

Ia terminals to Motoneurones of

Antagonists 314

Selective Contraction of the Antagonist 314

Co-contraction of Antagonists 314


Contraction of Remote Muscles 316

Ia Terminals on Upper Limb

Motoneurones 317

Active Standing 317

Walking 319

Running 320

Bicycling 321


Changes in Tests Assessing Presynaptic

Inhibition with Ageing 321

Spasticity 322

Over-interpretation of Decreased

Homonymous Vibratory Inhibition 322

Patients with Spinal Cord Lesions 322

Stroke Patients 322

Changes during Voluntary Movement 323


Dystonia 324

Résumé 324

References 329

9 Cutaneomuscular, Withdrawal and

Flexor Reflex Afferent (‘FRA’) Responses 334


Cutaneous Responses through ‘Private’

Pathways 335

FRA Pathways 337

Methodology 339


Stimulation 340

Electrical Stimuli 340

Mechanical Stimuli 340

Assessing the Effects of Cutaneous Stimuli 341

Responses Recorded at Rest 341

Modulation of Motoneurone Excitability 343

x Contents






Critique of the Tests to Study Cutaneous

Effects 343

Withdrawal Reflexes 344

Afferent Pathway of Withdrawal Reflexes 344

Parallel between Pain Sensation and the

RIII Reflex 344

Afferent Volleys Involved in the

RIII Reflex and Pain 346

Central Pathway of Early Withdrawal

Responses 347

Central Delay 347

Conclusion 349

Functional Organisation of Early

Withdrawal Reflexes 349

Trunk Skin Reflexes 349

Plantar Responses 351

Other Withdrawal Responses in the

Lower Limb 352

Withdrawal Responses in the Upper Limb 353

Late Withdrawal Responses 353

Late Withdrawal Responses in Patients

with Complete SCI 355

Late Responses in Normal Subjects 357

Interactions between Different Inputs 358

Painful Homonymous Cutaneous Volleys 358

Effects of Other Peripheral Inputs 359

Descending Effects 359

Changes during Motor Tasks 361

Voluntary Contraction 361

Postural Tasks 362

Gait 362

Cutaneomuscular Reflexes Evoked by

Non-noxious Stimuli 362

The Different Responses 362

RII Reflex at Rest 362

Cutaneomuscular Reflexes during

Voluntary Contraction 363

Modulation of the Monosynaptic Reflex 363

Afferent Pathway 365

Central Pathway of Early Responses 365

Spinal Origin of the Early Effects? 365

Oligo- or Poly-synaptic Spinal Pathways? 367

‘Private’ Pathway or Changes in

Transmission in Another Pathway? 367

Presynaptic Inhibition of Ia Terminals 368

Central Pathway for Long-Latency Effects 368

Pattern of the Facilitation of

Monosynaptic Reflexes 368

Latencies of the Responses 369

Observations in Patients 369

Maturation 369

Which Supraspinal Pathway in Lower

Limbs? 369

Which Supraspinal Pathway in Upper

Limbs? 371

Projections to Different Types of

Motoneurones 372

Functional Role of Cutaneomuscular

Responses 374

Cutaneomuscular Responses in the

Upper Limb 374

Cutaneomuscular Responses in the

Lower Limb 376

Interlimb Cutaneomuscular Responses 377

Gait 377

Changes in Patients and Clinical

Implications 379

Complete Spinal Transection 380

Upper Motoneurone Lesions Other

Than Complete SCI 380

Abolition of Normal Cutaneous Reflexes 380

Babinski Response 381

Withdrawal Reflexes in the Lower Limb 381

Flexor Spasms 381

Withdrawal Reflexes in the Upper Limb 382

Cutaneomuscular Responses 382

Grasp Reflex 382


Restless Leg Syndrome 382

Cerebellar Patients 383

Peripheral Neuropathies 383

Diagnostic Uses 383

Résumé 383

References 389

10 Propriospinal Transmission of

Descending Motor Commands 395


The C3–C4 Propriospinal System in

the Cat 395

Contents xi






The C3–C4 Propriospinal System in

the Monkey 397

Methodology 398

Propriospinally Mediated Peripheral

Excitation 398

Cutaneous Suppression of Descending

Excitation 400


Interneurones 400


Excitatory Inputs to Propriospinal

Neurones 401

Peripheral Excitatory Input 401

Corticospinal Excitation of

Propriospinal Neurones 402

Feedback Inhibition of Propriospinal

Neurones 405

Peripheral Inhibition of Propriospinal

Neurones 405

Corticospinal Excitation of

Feedback Inhibitory Interneurones 407

Possible Existence of Inhibitory

Propriospinal Interneurones 408

Interaction between Excitatory and

Inhibitory Inputs 408

Propriospinal Neurones and

Inhibitory Interneurones 408

Can Transmission via Segmental

Interneurones Explain the Results? 408

Cervical Activity Visualised with

BOLD fMRI 410

Explanation for the Conflicting

Conclusions 410

Natural vs. Artificial Activation of

Corticospinal Projections 411

Organisation of the Cervical

Propriospinal System 411

Organisation in Subsets 411

Convergence and Divergence 411

Projections to Different Types of

Motoneurones 412


Transmission of a Part of the

Descending Command 414


Evidence for Disfacilitation 414

Site of Disfacilitation 416

Effect on Various Motor Nuclei 416

Quantitative Aspects of the Cutaneous

Suppression 416

Changes during Muscle Fatigue 417

Propriospinal Excitation during Simple

Tasks 418

Reflex Facilitation at the Onset of

Contraction 418

Descending Facilitation of

Propriospinal Neurones 418

Factors Limiting the Increase in

Reflex Facilitation 418

Further Insights on the Organisation

of the System 419

Handedness-Related Asymmetry 419

Task-Dependent Changes 420

Grip 420

Reach-to-Grasp Movements 420

Grip–Lift Task 422


Integration of Group I and

Descending Inputs 422

Cutaneous Suppression of the

Descending Command 423

In Which Movements Is the

Propriospinal System Involved? 425


Lesion at the Junction C6–C7 Spinal Level 425

Stroke Patients 427

Cutaneous Suppression of the

On-Going EMG 427

Correlation with Recovery from

Hemiplegia 429


Dystonia 431

The Lumbar Propriospinal System 431


Methodology 431


Interneurones 432


Peripheral Excitatory Input 432

Peripheral Inhibitory Inputs 433

xii Contents






Peripheral Inhibition of Motoneurones 433

Corticospinal Control 434


Résumé 436

References 442

11 Spinal and Corticospinal Pathways in

Different Movements 446

Complex Limb Mechanics in Multi-joint

Movements 447

Spinal Pathways in Voluntary Isometric

Contractions 448

Recruitment of Motoneurones 448

Spinal Mechanisms Help Maintain

Contractions 450

PIC-Induced Plateau Potentials in

Motoneurons 450

Fusimotor-Driven Inflow from Spindle

Endings 450

FRA Hypothesis 451

Propriospinally Mediated Excitation 451

Cutaneomuscular Responses 451

Suppression of Transmission in

Inhibitory Pathways 451

Control of Different Features during the

Contraction 452

Contribution of Spinal Pathways 452

Timing of the Effects 453

Spinal Pathways in Flexion–Extension

Movements 453

Afferent Discharges 453

Shortening and Lengthening Contractions 454

Differences in Muscle Activation 454

Recruitment Order of Motor Units 456

Presynaptic Inhibition of Ia Terminals? 456

Decreased Excitability of Motoneurones 456

Which Mechanism? 457

Movements Involving Hinge Joints 458

Pathways Contributing to Inhibition

of the Antagonists 458

Absence of Redundancy 459

Movements Involving Ball Joints 460

Human Spinal Circuitry at Wrist Level 460

Non-reciprocal Group I Inhibition

during Movements 462

Presynaptic Inhibition of Ia Terminals

during Movements 464

Recurrent Inhibition during Movements 464

Propriospinal Pathways during

Movements 465

Different Strategies for Proximal and

Distal Movements 465

Rapid Concentric Movements 465

Coordinated Activation of Various Synergies 466

The Case for and against Muscle

Synergies 467

Rationale 467

Arguments for the Hypothesis 467

Arguments against the Hypothesis 467

Conclusion 468

Where Are Motor Synergies Laid Down? 468

Spinal Origin? 468

Hierarchical Control Schema 469

Synergies Based on ‘Hardwired’

Spinal Connections 469

State-Dependent Modulation of

Spinal Pathways 470

CPG 471

C3–C4 Propriospinal System 471

Co-contraction of Antagonists 472

Changes in Spinal Pathways 472

Hinge Joints 472

Ball Joints 473

Control of the Decreased Inhibition

between Antagonists 473

Spinal Mechanisms 473

Specific Corticospinal Drive for

Co-contractions 474

Joint Stiffness 475

Control of the Stretch Reflex at Hinge

Joints 475

Control of the Excitation at Ball Joints 475

Involvement of Transcortical Reflexes in

Movement 476

Task-Dependent Responses 476

Postural Responses 476

Co-ordinated Functional Responses 478

LLSRs vs. Volitional Activity and Group

II-Mediated Responses 478

Voluntary Intent and Single Joint LLSRs 478

Contents xiii






Flexion–Extension and Supination–

Pronation at Elbow Level 478

Elbow–Wrist Coupling 479

Elbow–Shoulder Coupling 479

Conclusion 481

Efference Copy and Internal Models 481

Efference Copy 481

Concept 481

Evidence for Efference Copy in Limb

Movements 482

Where Are Efference Copy Signals

Generated? 484

Internal Models 484

Concept 484

Optimal Feedback Control and

Minimal Intervention Principle 485

C3–C4 Propriospinal System 485

Involvement of the Primary Motor Cortex

(M1) in Voluntary Movements 486

Changes in Excitability of Corticospinal

Neurones 486

Change in Corticospinal or

Motoneurone Excitability? 486

Inactivity 486

Isometric Tonic Contractions 487

Phasic Contractions 488

Motor Resonance 490

Isometric Sinusoidal Contractions 490

Lengthening Contractions 491

Period Preceding the Contraction 491

Contraction of the Antagonists 492

Cortical Reciprocal Inhibition 493

Task-Related Changes in Motor

Cortex Excitability 493

Conclusions 494

Changes in Short-Interval Intracortical

Inhibition (SICI) 494

Changes in SICI during Contraction 494

Period Preceding Movement 495

Termination of Movement 495

Conclusion 495

Spinal and Supraspinal Factors in

Human Muscle Fatigue 496

Methodology 496

Evidence for Central Fatigue 496

Which Mechanisms? 497

Conclusion 497

Résumé 497

References 508

12 Spinal and Corticospinal Pathways in

Stance and Gait 515

Bipedal Stance 515

Quiet Standing 515

The Inverted Pendulum 515

Multi-Sensory Feedback 516

Intrinsic Stiffness of the Ankle 517

Stretch Reflex 517

Paradoxical Muscle Movement 518

Predictive Response 518

Conclusion 520

Unstable Postures Requiring Prolonged

Contractions 520

Responses to Fast Transient

Perturbations in the Pitch Plane 520

Reflex Responses in Ankle Muscles 520

Ankle and Hip Strategies 522

‘Change in Support’ Strategy 523

Responses to Fast Transient Pitch–Roll

Perturbations 523

Changes with Training and with Ageing 524

Gait 525

Characteristics of Human Walking 525

Biomechanical Characteristics 525

Is There a CPG in Humans? 526

Pattern of Muscle Activation 527

Spinal Pathways in Unperturbed Walking 527

Contribution of Different Spinal

Pathways 527

Mechanisms Operating at Ankle Level 528

Stabilisation of the Knee 528

Transition 529

Reactions to External Perturbations 529

Stretch-Induced Responses 529

Cutaneous Reflexes 531

Responses in or from

Upper Limbs 531

Complex Responses 531

Conclusions 532

Running, Hopping, Landing 532

Résumé 533

References 537

xiv Contents






13 Plasticity in Spinal and Corticospinal

Pathways 541

The H Reflex: A Tool to Study Synaptic

Plasticity 541

Spinal Cord Plasticity 542

Evidence for Spinal Plasticity 543

‘Spinal Fixation’ in Animal

Experiments 543

Training and Disuse 543

H Reflex Operant Conditioning 543

Maturation and Spinal Plasticity 546

Data from Animal Experiments 546

Human Cutaneous Reflexes 546

Proprioceptive Reflexes 547

Stance and Gait 547

Spinal Plasticity in the Elderly 548

Monosynaptic Reflex 548

Transmission in Spinal Pathways 548

Training Corrective Balance Reactions 548

Short-term Spinal Plasticity 549

Disuse 549

Specific Training 549

From Short- to Long-term Spinal

Plasticity 550

Long-term Spinal Plasticity 551

Long-term Spinal Plasticity following

CNS Lesions 552

Spontaneous Plasticity after SCI 552

Changes in Transmission in Spinal

Pathways after CNS Lesion 552

Which Protocol for Rehabilitation

of SCI? 552

Corticospinal Plasticity 553

Short-term Motor Cortex Plasticity 553

‘Use-Dependent’ Plasticity of the

Motor Cortex 553

TMS-Induced Plasticity of the

Motor Cortex 553

Peripheral-Induced Plasticity of the

Motor Cortex 554

Corticospinal Plasticity Induced by

Disuse or Specific Training 555

Long-term Motor Cortex Plasticity 555

Skill-Related Long-term Motor

Cortex Plasticity 555

Reorganisation of the Motor Cortex

Representation 555

Age-Related Changes 556

Brain Plasticity after Lesions 556

Take-over by the Ipsilateral

Hemisphere? 556

Affected Hemisphere 557

Résumé 557

References 561

14 Contribution of Spinal Pathways to

the Pathophysiology of Movement

Disorders 565

Spinal Pathways in Spasticity 565

What Is Spasticity? What Is not? 565

Definition 565

Spasticity vs. Animal Decerebrate

Rigidity 566

Spasticity vs. ‘Contracture’ 566

Contribution to Motor Impairment 566

Spinal Pathways at Rest 567

Why Do Spinal Pathways

Malfunction? 570

Changes in Spinal Pathways during

Movement 571

Spasticity after Cerebral Lesions 572

Affected Side of Stroke Patients 572

Unaffected Side of Stroke Patients 572

Synkinetic Movements 572

Cerebral Palsy 572

Spasticity after Spinal Lesions 573

Spinal Pathways in Parkinson’s Disease 573

Possible Mechanisms Underlying

Parkinsonian Rigidity 573

Increased Passive Muscle Stiffness 573

Exaggerated Long-Latency Responses to

Stretch 574

Transmission in Spinal Pathways at

Rest 574

Transmission in Spinal Pathways during

Motor Tasks 575

Spinal Pathways in Dystonia 575

Résumé 576

References 577

Index 580

Contents xv






Acknowledgements

This book is dedicated to the memory of Anders

Lundberg, whose work and personal support have pro-

vided the inspiration behind most of the research

described here.

Writing this book would not have been possible with-

out the understanding, life-long support and benign

tolerance that we have received throughout our careers

from Evelyne and Katre, who have allowed us to pursue

our interests even when the demands placed on them

were unreasonable and who have, in recent year, put

much on hold while we completed this work.

Geneviève Bard and Mary Sweet have provided us

with invaluable assistance in collating references and

getting the text into presentable order. We are grateful

for the friendship, loyalty and meticulous attention to

detail that has characterised their association with us

over more than two decades.

The studies reported here represent the intellectual

achievements of collaborators, colleagues and stu-

dents. We are grateful to everyone whose work is

reported here, and to our colleagues and collaborators

and their publishers who have allowed us to reproduce

figures from their original work.

Finally, we are indebted to L’Institut National de la

Santé et de la Recherche Médicale (INSERM) and the

National Health & Medical Research Council of

Australia (NHMRC) for recognising the value of

research into human motor control and its disorders.

xvi






Preface

This book is the direct descendant of our book entitled

The Circuitry of the Human Spinal Cord: Its Role in

Motor Control and Movement Disorders, published in

2005 by Cambridge University Press. A revised and

updated edition was needed because in 7 years new

and more recent data have changed views about the

role of the spinal cord in the control of limb movement.

This revised edition also takes into account the devel-

opment and rapid uptake of investigations using trans-

cranial stimulation of the motor cortex. Thus, much

more attention has been put on the corticospinal con-

trol of movement and transcortical pathways. Neural

plasticity, whether underlying learning a new skill by

healthy subjects or compensatory mechanisms for the

neural changes associated with ageing or disease, has

also been the subject of many recent investigations that

deserve to be considered.

The book is dedicated to Anders Lundberg (1920–

2009). Anders Lundberg is rightfully seen as the father

of modern spinal cord neurophysiology, on how spinal

circuitry is mobilised by descending commands and

how feedback modifies the command at spinal cord

level. Anders Lundberg was an outstanding leader, an

intense and focused researcher, a tough critic, a good

listener and inspiring mentor. He and his students

provided much of the background data from animal

experiments for the human studies which this book

attempts to summarise. Above all, not only did he

lead the world in the definition of interneuronal mech-

anisms in the spinal cord but he also developed

hypotheses about how these mechanisms would be

used in the intact organism. In later years, having

defined the C3–C4 propriospinal system in the cat, he

undertook behavioural experiments to confirm its role

xvii






in movement, and it remains the only carefully docu-

mented interneuronal system for which a functional

purpose has been clearly identified. His enthusiasm

and enormous intellect have provided an impetus for

us to show how discoveries from animal experiments

have benefited the human condition, despite the adap-

tations that are necessary to cater for the greater motor

repertoire of human subjects.

In the preface to our previous book, we wrote: Over

recent years, reappraisal of the role of direct cortico-

motoneuronal projections in higher primates including

humans has led to the view that the control of move-

ment resides in the motor cortical centres that drive

spinal motoneurone pools to produce the supraspinally

crafted movement. This view belies the complex inter-

neuronal machinery that resides in the spinal cord. It is

a thesis of this book that the final movement is only

that part of the supraspinally derived programme that

the spinal cord circuitry deems appropriate. This

statement remains, we believe, as true today as it was

in 2005 and it is also a driving motivation behind this

volume. As research interest shifts to the complexities

of the cortical mechanisms in the control of move-

ment, so too has the thrust of this new book shifted

to encompass transcortical reflexes, motor cortex excit-

ability and corticospinal mechanisms in greater detail.

Nevertheless, it is timely to remind the reader that

limb movements can be planned and their programs

initiated by the brain but they cannot be performed

without a spinal cord and they cannot be performed

gracefully without the intricate feedback systems that

reside within it.

As mentioned above, there has been an explosion of

literature on motor control over the past 7 years, much

of it devoted to cortical mechanisms preceding and

associated with movement, and even some that do

not have any direct influence on spinal circuitry.

However, even in the latter instance, the state of the

spinal cord is important when the procedures involved

in testing the cortical circuitry depend on the modula-

tion of a response that is transmitted through spinal

mechanisms. In reviewing the literature for this book,

we have become concerned that so simple a fact has

been so often ignored in publications, even in presti-

gious journals.

However, the justification for a new book ultimately

resides not in restating the obvious but in whether there

is anything new to say, and accordingly it should be

asked, precisely what is new in this book?

� To understand the influence of cortical mechanisms

on the spinal motoneurone pools it is necessary to

understand, first, how segmental mechanisms can

modulate the command signal and, second, the lim-

itations of techniques that can be used in human

subjects to demonstrate appropriate changes.

Accordingly, the structure of the initial chapters in

this new book recapitulates that of the previous

book – but each has been updated to cover new

findings, new techniques and new appreciations of

advantages and disadvantages.

� In a new chapter, the largest in this volume, we focus

more fully on the techniques (and their limitations)

used to study cortical and corticospinal mechanisms

in the control ofmovement and on the results of such

studies. It thereby provides an overview that integra-

tes spinal and cortical mechanisms so that those who

work at one end of the neuraxis can appreciate the

importance of the other.

� A further major advance over the last decade has

been on the plastic changes in connectivity that

occur with development, senescence, motor learn-

ing, disease and recovery from it. An understanding

of how the nervous system can adapt to changed

circumstances is the key to understanding, on the

one hand, acquired differences in motor skill and, on

the other hand, the compensations, sometimes dys-

functional, that occur when the nervous system is

damaged. Accordingly appropriate data are high-

lighted in chapters focussed on specific circuits,

and there is a new chapter that specifically addresses

the short- and long-standing adaptations of the func-

tion of spinal and corticospinal circuits to altered

demands and pathology.

Organisation of Individual Chapters

We have retained the same format as for the previous

book, with consideration first of the different spinal

pathways for which there are reliable and non-invasive

xviii Preface






methods of investigation. Accordingly, after an exten-

sive chapter on Methodology, we consider spinal cir-

cuitry in Chapters 2–10 with, for each circuit:

1. A brief background from animal experiments.

Human investigations are indirect and it is crucial

to know the essential characteristics of each path-

way described in animal experiments with record-

ings from motoneurones and/or interneurones.

Caution should always be taken in extrapolating

from data obtained in ‘reduced preparations’

(anaesthetised, decerebrate or spinalised animals)

to awake intact human subjects, but the validation of

a technique for exploring a given pathway may

require controls only possible in animal experi-

ments, and the results in human subjects are more

credible when there is a close analogy with animal

experiments.

2. A critical description of the available method(s) that

have been used to explore the relevant pathways

selectively. For those who wish to know how meth-

ods and concepts have evolved over the years and

why some interpretations were erroneous even if, at

the time, influential, the methods are described in

detail, with their limits and caveats, and the results

obtained and their interpretation(s) are critically

evaluated in each chapter. Because human studies

are fraught with technical difficulties, much space

has been allotted to methods and potential pitfalls.

3. The organisation and descending control (in partic-

ular corticospinal) of these pathways in human sub-

jects. The basic organisation of each pathway may

well be the same in humans and cats, but the

strength of the projections of individual spinal path-

ways on different motoneurone pools and their

descending control have been the subject of phylo-

genetic adaptations to different motor repertoires.

For the human lower limb, more elaborate reflex

assistance is required for bipedal stance and gait.

That there has been this phylogenetic adaptation

argues that spinal pathways have a functional role

in human subjects and are not evolutionary relics.

4. The changes in transmission in these pathways dur-

ing various motor tasks. How spinal reflex pathways

are used in motor control cannot be deduced from

experiments on ‘reduced’ animal preparations. It

requires experiments performed during natural

movements, as can be done in humans. This has

been one major contribution of human studies to

the understanding of motor control physiology.

Thus, even though many of the conclusions are

speculative, this book gives a large place to the

probable functional implications of the described

changes in transmission in spinal pathways during

movement.

5. Changes in transmission in these pathways in

patients with various lesions of the CNS. This has

provided new insights about the pathophysiology

of the movement disorder in these patients.

Overall Organisation of the Book

We have again adopted much the same organisation as

previously.

Methodology. The general methodologies which are

used for investigating pathways are considered in a first

chapter with the advantages and disadvantages of each

technique. There is a risk that starting with a technical

chapter would dissuade the non-specialist reader from

delving further into the book. However, this initial

chapter is useful to understand the rationale, advan-

tages and limitations of the different techniques used to

investigate different pathways, and we consider it

important for those who have no experience with a

particular technique but wish to use it in human sub-

jects. Nevertheless it is not essential for the compre-

hension of subsequent chapters.

Résumés. For those who want to get to the gist of the

matter reasonably quickly each chapter terminates with

a résumé of its salient points. The résumés can be used

on their own without reference to the detailed text.

They give a practical ‘recipe’ on the choice of the

appropriate technique and its proper use in routine

clinical studies, together with data on the possible func-

tional role of the particular pathway in motor control

and in the pathophysiology of movement disorders.

Overviews. The final four chapters summarise and

synthesise the changes in transmission in spinal and

corticospinal pathways during movement, and how

these changes contribute to motor control, and spinal

Preface xix






mechanisms underlying spasticity and motor impair-

ment in patients with Parkinson’s disease and dystonia.

The physiological and pathophysiological roles of

spinal and corticospinal pathways are presented using

a different approach to that in the previous chapters.

With respect to the previous book, these overviews

have been greatly developed.

A long chapter (Chapter 11) is focussed on purpose-

ful movements and involves:

(i) an overview of the contribution made by the differ-

ent spinal pathways in various kinds of movement,

(ii) an attempt to unravel the relationships between

volitional control, afferent feedback (in particular

through transcortical reflexes), and possible effer-

ence copy,

(iii) a description of the changes in motor cortex excit-

ability and short interval intracortical inhibition

(SICI) during the different phases of variousmove-

ment, and

(iv) the role of spinal and supraspinal factors in muscle

fatigue.

Chapter 12 considers the contribution of spinal and

transcortical pathways in unperturbed and perturbed

stance and gait.

Plastic changes in spinal and corticospinal circuits

are considered in Chapter 13.

In a brief summary, Chapter 14 collates data in pre-

ceding chapters on spinal mechanisms underlying

spasticity and the motor impairment in patients with

Parkinson’s disease and dystonia.

xx Preface






Abbreviations

Ach acetylcholine

ACT afferent conduction time

ADM abductor digiti minimi

AG1 first agonist burst

AG2 second agonist burst

AHP afterhyperpolarisation

ALS amyotrophic lateral sclerosis

ANT antagonist burst

APB abductor pollicis brevis

APL abductor pollicis longus

BB biceps brachii

BF biceps femoris

BR brachioradialis

CMEP cervicomedullary motor evoked

potential

CNS central nervous system

CoM centre of mass

CPG central pattern generator

CPN common peroneal nerve

CS corticospinal tract

CSP contralateral silent period

CSP cutaneous silent period

CT conduction time

CUSUM cumulative sum

CV conduction velocity

D-wave direct wave of the corticospinal volley

DPN deep peroneal nerve

E1 early cutaneomuscular excitation

E2 late cutaneomuscular excitation

ECR extensor carpi radialis

ECT efferent conduction time

ECU extensor carpi ulnaris

ED extensor digitorum

xxi






EDB extensor digitorum brevis

EDL extensor digitorum longus

EEG electroencephalogram

EHB extensor hallucis brevis

EHL extensor hallucis longus

EMG electromyogram

EPSP excitatory post-synaptic potential

FA fractional anisotropy

FCR flexor carpi radialis

FCU flexor carpi ulnaris

FDB flexor digitorum brevis

FDI first dorsal interosseous

FDP flexor digitorum profundus

FDS flexor digitorum superficialis

FHB flexor hallucis brevis

fMRI functional magnetic resonance imaging

FN femoral nerve

FPL flexor pollicis longus

FRA flexion reflex afferents

GABA gamma-aminobutyric acid

GL gastrocnemius lateralis

GM gastrocnemius medialis

GS gastrocnemius–soleus

GTO Golgi tendon organ

H’ test reflex, paired H reflex

technique for recurrent inhibition

H1 conditioning H reflex, paired H reflex


HD homosynaptic depression

Hmax maximal H reflex

I-wave indirect wave of the corticospinal volley

I1 cutaneomuscular inhibition

Ia IN Ia inhibitory interneurone

Ib IN Ib interneurone

ICF intracortical facilitation

IHI interhemispheric inhibition

IN interneurone

IPSP inhibitory post-synaptic potential

ISI interstimulus interval

iSP ipsilateral cortical silent period

L-Ac L-acetylcarnitine

LAI long-latency afferent inhibition

LICF long-interval intracortical facilitation

LICI long-interval intracortical inhibition

LL response long-latency response

LLSR long-latency stretch reflex

Loc Coer locus coeruleus

LRN lateral reticular nucleus

LTD long-term depression

LTI linear-time-invariant

LTP long-term potentiation

M wave direct motor response

M1 primary motor cortex

M1 short-latency stretch response

M2 long-latency stretch response (upper

limb)

M2 medium-latency stretch response

(lower limb)

M3 long-latency stretch response

MC musculo-cutaneous

MEP motor evoked potential

MLSR medium-latency stretch response

Mmax maximal direct motor response

MN motoneurone

MS multiple sclerosis

MT motor threshold

MU motor unit

MVC maximal voluntary contraction

NA noradrenergic

NRM nucleus raphe magnus

PAD primary afferent depolarisation

PAD IN interneurone mediating primary

afferent depolarisation

PAS paired associative stimulation

PB peroneus brevis

PD posterior deltoid

PET positron emission tomography

PIC persistent inward current

PL peroneus longus

PM pectoralis major

PN propriospinal neurone

PSF post-stimulus frequencygram

PSP post-synaptic potential

PSTH post-stimulus time histogram

PT perception threshold

PTN posterior tibial nerve

PTP post-tetanic potentiation

RC Renshaw cell

xxii List of abbreviations






REM rapid eye movements

RF rectus femoris

rTMS repetitive TMS

S1 conditioning stimulus, paired H reflex


SAI short-latency afferent inhibition

SCI spinal cord injury

SD standard deviation

SEM standard error of the mean

SICF short-interval intracortical

facilitation

SICI short-interval intracortical inhibition

SLSR short-latency stretch reflex

SM test stimulus, paired H reflex


SPN superficial peroneal nerve

SR superficial radial

SSEP somatosensory evoked potential

ST semitendinosus

TA tibialis anterior

TBS theta burst stimulation

tDCS transcranial direct current stimulation

TENS transcutaneous electrical nerve

stimulation

TES transcranial electrical stimulation

TFL tensor fascia latae

TMS transcranial magnetic stimulation

TN tibial nerve

Tri triceps brachii

TT tendon jerk threshold

TVR tonic vibration reflex

UMN upper motoneurone

V1 reflex response following Mmax during

voluntary contraction

VL vastus lateralis

VM vastus medialis

VS vestibulospinal tract

VSCT ventral spinocerebellar tract

List of abbreviations xxiii






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