The Basal Ganglia IX (eBook)

Preface 5
Contents 9
You Cannot Have a Vertebrate Brain Without a Basal Ganglia 26
1 Introduction 27
2 Where is the Basal Ganglia in Nonmammals? 28
3 By What Pathways Does the Basal Ganglia Control Movement in Nonmammals 38
4 Major Evolutionary Steps in Basal Ganglia Organization 42
References 43
The Involvement of Corticostriatal Loops in Learning Across Tasks, Species, and Methodologies 48
1 Introduction 48
2 Basal-Ganglia-Dependent Learning Tasks 49
2.1 Tasks from the Rodent Literature 49
2.1.1 Instrumental Conditioning 49
2.2 Tasks from the Monkey Literature 50
2.2.1 Visual Discrimination 50
2.2.2 Arbitrary Visuomotor Learning/Conditional Response 50
2.2.3 Rule Learning 51
2.3 Tasks from the Human Literature 51
2.3.1 Categorization and Classification 51
2.3.2 Decision Making 52
3 Roles of Corticostriatal Loops in Learning 52
3.1 Corticostriatal Loops: Anatomy 53
3.2 Corticostriatal Loops: Function 54
3.3 Visual Corticostriatal Loop 55
3.4 Motor Corticostriatal Loop 56
3.5 Executive Corticostriatal Loop 57
3.6 Motivational Corticostriatal Loop 58
4 Interactions between Corticostriatal Loops 58
References 59
Information Processing in the Striatum of Behaving Monkeys 63
1 Introduction 63
2 Methods 64
3 Results 65
4 Discussion 67
References 69
What Controls the Timing of Striatal Spiny Cell Action Potentials in the Up State? 71
1 Up and Down States 71
2 What Kind of Synaptic Input Could Trigger Spiking in the Up State? 72
3 A Role for Inhibition? 73
4 Measurement of Excitatory and Inhibitory Conductances in the Up State 74
5 Fast Membrane Fluctuations Are Mostly Inhibitory 77
References 82
Asymmetric Encoding of Positive and Negative Expectations by Low-Frequency Discharge Basal Ganglia Neurons 84
1 Introduction 84
2 Methods 86
3 Results 86
3.1 Monkey Behavior Reflects Expectation of Rewarding and Aversive Events 86
3.2 PANs and GPe LFD Activity Are Asymmetrically Modulated by Expectation of Aversive and Reward Outcomes 88
4 Discussion 90
References 92
Stimulation Effect on Neuronal Activity in the Globus Pallidus of the Behaving Macaque 94
1 Introduction 94
2 Methods 95
3 Results 96
4 Discussion 101
References 103
High-Frequency Stimulation of the Globus Pallidus External Segment Biases Behavior Toward Reward 105
1 Introduction 105
2 Methods 107
2.1 General 107
2.2 Behavioral Task 107
2.3 Data Analysis 109
3 Results 110
3.1 High-Frequency Stimulation Changes the Monkey’s Licking Response 110
3.2 Progression of the Stimulation Effect 112
4 Discussion 113
4.1 High-Frequency Stimulation Alters Expectation of Reward 113
4.2 High-Frequency Stimulation is Associated with Synaptic Plasticity 113
4.3 Therapeutic Implications 114
References 114
The Subthalamic Region of Luys, Forel, and Dejerine 117
1 Introduction 117
2 Research by Luys on Brain structure 118
2.1 Brain Atlases 118
2.2 Methods of Preparation 118
2.3 The Subthalamic Region in the Atlases 118
3 Research by Luys on Brain Functions 120
3.1 Neurology 120
3.2 Psychiatry 121
3.3 Hypnotism and Other Psychic Phenomena 122
4 The Subthalamus Following Luys 123
4.1 Meynert 123
4.2 Auguste Forel (1848–1931) 123
4.3 Joseph-Jules Dejerine (1849–1917) 124
5 Conclusions 126
5.1 Luys as Discoverer of the STN 126
5.2 Establishment of Basic Subthalamic Structure 126
References 126
Organization of Motor Cortical Inputs to the Subthalamic Nucleus in the Monkey 128
1 Introduction 129
2 Methods 129
3 Results 130
4 Discussion 134
References 135
A Subpopulation of Mesencephalic Dopamine Neurons Interfaces the Shell of Nucleus Accumbens and the Dorsolateral Striatum in 137
1 Introduction 138
2 Materials and Methods 139
2.1 Anatomical Tracing Studies 139
2.1.1 Surgical Procedures 139
2.1.2 Tracer Injections 139
2.1.3 Histological Procedures 139
2.2 Electrophysiological Studies 140
3 Results 141
3.1 Anatomical Tracing Studies 141
3.2 Effect of Shell Stimulation on the Activity of VTA/SNC Dopaminergic Neurons Projecting to the Sensorimotor Territory of th 143
4 Discussion 143
4.1 Mesencephalic Dopamine Neurons as a Link Between the Shell and the Dorsolateral Striatum 145
4.2 Functional Considerations 146
4.3 Conclusion 147
References 147
Synchrony of the Rat Medial Prefrontal Cortex Network During Isoflurane Anaesthesia 149
1 Introduction 149
2 Materials and Methods 151
2.1 Surgery and Placement 151
2.2 Isoflurane Manipulations 151
2.3 Data Acquisition and Analysis 152
2.4 Histological Evaluation 152
3 Results 152
3.1 Definition of Up- and Down-States 152
3.2 Up- and Down-State Transitions are Reversibly Influenced by Isoflurane Anaesthesia 153
3.3 Prelimbic Neurons Fire Action Potentials Only During Up-States 154
4 Discussion 155
4.1 Synaptic Effects of Isoflurane 156
4.2 Isoflurane Modulates Mechanisms Underlying Up-Down-State Transitions 157
4.3 Final Considerations 158
References 158
On the Relationships Between the Pedunculopontine Tegmental Nucleus, Corticostriatal Architecture, and the Medial Reticular Fo 161
1 The Pedunculopontine Tegmental Nucleus 162
2 How does the PPTg Interact with the Anatomy of Corticostriatal Loops? 162
3 Corticostriatal Systems, Instrumental Responding and the PPTg 165
4 Does PPTg Integrate Processing Between Corticostriatal and Brainstem Systems? 169
5 Conclusions 171
References 172
Microcircuits of the Pedunculopontine Nucleus 176
1 Past and Present Notions of the PPN 176
2 Ultrastructural Analysis 177
3 Local Connectivity 178
4 Local Network Model 179
References 181
The Effects of Dopaminergic Modulation on Afferent Input Integration in the Ventral Striatal Medium Spiny Neuron 184
1 Introduction 184
2 Striatal Anatomy 185
2.1 Anatomy of the Nucleus Accumbens 185
3 Functional Role of MSP Cells and DA Modulation 187
3.1 Intrinsic Properties and Membrane Behavior of MSP Neurons 188
4 Computational Model 189
4.1 Current Injection Responses 190
4.2 Synaptic Input Responses 193
5 Bistability or Bimodality? 196
5.1 Effect of NMDA:AMPA Ratio Changes 197
5.2 Local Inhibition 200
6 Afferent Ensembles and Integration 200
7 Implications of the Model for Disease States 201
References 202
A Spiking Neuron Model of the Basal Ganglia Circuitry that Can Generate Behavioral Variability 206
1 Introduction 206
2 Computational Hypotheses for Basal Ganglia Function 207
3 Simulation Results 209
3.1 Selection and Timing Mechanisms for Exploration in the Basal Ganglia Network 210
3.2 Modulation of Selection Probability and Timing for Exploitation 213
4 Discussion 214
References 214
Learning with an Asymmetric Teacher: Asymmetric Dopamine-Like Response Can Be Used as an Error Signal for Reinforcement Learn 216
1 Introduction 217
1.1 Reinforcement Learning and the Basal Ganglia 217
1.2 Dopaminergic Signal Is Truncated at Zero 218
2 Methods 219
3 Results 222
3.1 Error Signal with Lower Gain for the Negative Domain 222
3.2 Error Signal with a Constant Negative Value for the Negative Domain 223
3.3 Error Signal Set to Zero for the Negative Domain 223
4 Discussion 223
References 225
A Theoretical Information Processing-Based Approach to Basal Ganglia Function 226
1 Introduction 226
2 The Functional Perspective 228
3 The Neurophysiologic Basis 229
4 The Informational Theoretical Construct 230
4.1 Ionic Mechanisms 231
4.2 Application to Behavior 232
5 Can We Make Any Real Sense of This? 233
References 237
The Cellular Localisation of GABAA and Glycine Receptors in the Human Basal Ganglia 239
1 Introduction 239
2 Methods 240
2.1 Brain Tissue 240
2.2 Immunohistochemical Procedures 240
2.2.1 Primary Antibodies 240
2.2.2 Single Immunoperoxidase Labelling 241
2.2.3 Immunofluorescent Double Labelling 242
3 Results 242
3.1 Striatum 242
3.2 Globus Pallidus 245
3.3 Lateral Medullary Lamina and Medial Medullary Lamina 245
3.4 Substantia Nigra 245
3.4.1 Substantia Nigra Pars Compacta 245
3.4.2 Substantia Nigra Pars Reticulata 246
4 Discussion 246
4.1 Striatum 246
4.2 Globus Pallidus 247
4.3 Substantia Nigra 248
4.4 Functional Considerations 249
References 249
Comparative Ultrastructural Analysis of D1 and D5 Dopamine Receptor Distribution in the Substantia Nigra and Globus Pallidus 252
1 Introduction 253
2 Materials and Methods 254
2.1 Animals 254
2.2 MPTP Administration and Behavioral Assessment 254
2.3 Tissue Preparation 254
2.4 Primary Antisera 254
2.5 Immunoperoxidase Procedure 255
2.6 Immunogold Procedure 255
2.7 Ultrastructural Analysis 256
3 Results 256
3.1 Ultrastructural Localization of D1 Receptor Immunoreactivity in GPi and SNr 256
3.2 Ultrastructural Localization of D5 Receptor Immunoreactivity in GPi and SNr 258
4 Discussion 260
4.1 Localization of D1/D5 Receptors in GPi and SNr 260
4.2 Functional Consequences of Dopamine D1/D5 Receptor Activation 260
4.3 Dopamine D1/D5 Receptor Activation May Influence Behavior 261
4.4 Functional Significance of D1LRs-Mediated Effects in Parkinsonism 262
References 263
Motor-Skill Learning in a Novel Running-Wheel Paradigm: Long-Term Memory Consolidated by D1 Receptors in the Striatum 267
1 Introduction 267
2 Motor-Skill Learning in the Running Wheel 269
2.1 Wheel-Skill Training and Test 269
2.2 Practice is Essential for Wheel-Skill Learning 269
2.3 Wheel-Skill Memory Lasts for Months 270
2.4 Effects of Cocaine and D1 Receptor Stimulation in the Striatum on Wheel-Skill Learning 271
2.5 Critical Role for Striatum in Wheel-Skill Consolidation and Stabilizing Effects of Cocaine 273
3 Discussion 275
3.1 Wheel-Skill Learning 275
3.2 Role of Striatal D1 Receptors and Effects of Cocaine on Skill Consolidation 276
3.3 Dissociation of Early- and Late-Stage Long-Term Skill Memory 277
References 278
Discriminative Stimulus- vs. Conditioned Reinforcer-Induced Reinstatement of Drug-Seeking Behavior and arc mRNA Expression i 280
1 Introduction 280
1.1 Neural Substrates Mediating the Effects of Conditioned Stimuli on Reinstatement 281
1.2 Cellular Compartment Analysis of Temporal Activity by Fluorescence In Situ Hybridization 282
2 Materials and Methods 283
2.1 Subjects 283
2.2 Surgical Procedure 283
2.3 Cocaine Self-Administration Training 284
2.3.1 DS Self-Administration Training 284
2.3.2 CR Self-Administration Training 284
2.3.3 Extinction Training 285
2.3.4 Reinstatement Test Day 285
2.4 In Situ Hybridization 285
2.5 Imaging and Cellular Compartment Analysis of Gene Expression 286
3 Results 286
3.1 Rats Can be Trained to Self-Administer Cocaine Under the Dual DS/CR Paradigm 286
3.2 Rats Trained Under Dual Paradigm Conditions Exhibit Cue-Induced Reinstatement of Drug-Seeking Behavior 287
3.3 Cellular Compartment Analysis of arc mRNA Expression in Neurons of Dorsolateral Striatum 287
3.4 Arc mRNA Expression Was Correlated with Cue-Induced Reinstatement of Drug-Seeking Behavior 289
4 Discussion 291
References 294
Preferential Modulation of the GABAergic vs. Dopaminergic Function in the Substantia Nigra by 5-HT2C Receptor 296
1 Introduction 296
2 Serotonin2C Receptor Distribution Within the Basal Ganglia Nuclei 297
2.1 Serotonin2c Receptor Distribution Within the Substantia Nigra 298
2.2 Serotonin2c Receptor Regulation in PD 298
3 Serotonin2C Modulation of the Substantia Nigra 299
3.1 Electrophysiological Data 299
3.1.1 Substantia Nigra Pars Compacta 299
3.1.2 Substantia Nigra Pars Reticulata 299
3.2 Neurochemical Data 302
3.2.1 Striatum 302
3.2.2 Substantia Nigra Pars Reticulata 302
4 Conclusions 303
References 305
Blockade of GABA Transporter (GAT-1) Modulates the GABAergic Transmission in the Rat Globus Pallidus 308
1 Introduction 308
2 Material and Methods 309
2.1 Electron Microscopic Immunocytochemistry 309
2.2 Whole-Cell Patch Clamp Recording 310
3 Results 311
3.1 Expression of GAT-1 in the GP 311
3.2 Effects of GAT-1 Transporter Inhibitor on Evoked IPSCs in the GP 311
3.2.1 Parasagittal Striatopallidal Slice Preparation 311
3.2.2 Coronal Striatopallidal Slice Preparation 312
3.3 Blockade of GAT-1 Has No Effect on mIPSCs 314
4 Discussion 315
References 317
Nitric Oxide Modulation of the Dopaminergic Nigrostriatal System: Focus on Nicotine Action 319
1 Introduction 319
2 Nitric Oxide Distribution in the Basal Ganglia 320
3 Involvement of NO in Neurodegeneration of Dopaminergic Nigrostriatal System 322
4 Nitric Oxide Modulation of the Activity of Dopaminergic Nigrostriatal System 323
5 NO/DA Interaction: Focus on Nicotine Effect 324
5.1 Experimental Data 324
5.2 Discussion 327
6 Conclusions 328
References 329
Regulation of Dopamine Release by Striatal Acetylcholine and Nicotine Is via Distinct Nicotinic Acetylcholine Receptors in Dor 332
1 Introduction 332
2 Materials and Methods 334
2.1 Slice Preparation and Voltammetry 334
2.2 Electrical Stimulation 334
2.3 Experimental Design and Analysis 335
3 Results 335
3.1 Identification of Different nAChR Subtypes in CPu and NAc 335
3.2 a6b2*-nAChRs Can Account for All Frequency Filtering of DA Release by nAChRs in NAc but Not CPu 335
3.3 Regional Differences in a6-nAChR Function Are Not Due to Confounding Differences in Endogenous ACh Tone or DA Rele 338
4 Discussion 339
4.1 b2*-nAChRs and Their Subtypes: A Filter on DA Release Probability in CPu and NAc 339
4.2 Dominant Role for a6 Subunit in NAc but Not CPu 340
5 Conclusions 341
References 341
Nitrergic Tone Influences Activity of Both Ventral Striatum Projection Neurons and Interneurons 345
1 Introduction 345
2 Materials and Methods 346
2.1 Animal Preparation 346
2.2 Microelectrodes and PFC Activation 346
2.3 Electrophysiological Recordings and Microiontophoresis 347
2.4 Juxtacellular Labelling and Histochemistry of Single Neurons 348
3 Results 349
3.1 Effects of the NO Manipulation VST Neurons 349
3.2 Anatomical Identification of Neurons 350
4 Discussion 350
4.1 Modulation of Striatal Activity by Alterations of Nitrergic Tone 350
4.2 Nitrergic Modulation of VST Interneurons 353
References 354
Kainic Acid-Induced Cell Proliferation in the Striatum Is Not Estrogen Dependent 357
1 Introduction 357
1.1 Organization of the Subventricular Zone in the Adult Mammalian Nervous System 358
1.2 The Role of Estrogen in Adult Neurogenesis 358
2 Methods 360
3 Results 361
4 Discussion 362
References 364
Striatal Dopaminergic Denervation and Spine Loss in MPTP-Treated Monkeys 366
1 Introduction 366
2 Materials and Methods 367
2.1 Animals and Tissue Preparation 367
2.1.1 MPTP Injections and Parkinsonism 367
2.1.2 Animal Perfusion 368
2.2 Golgi Impregnation 368
2.3 Immunocytochemistry 368
2.3.1 Primary Antibodies 368
2.3.2 Immunoperoxidase Labeling for Light and Electron Microscopy 368
2.4 Data Analysis 369
2.4.1 Quantitative Analysis of Dendritic Spine Density in Golgi-Impregnated Neurons 369
2.4.2 Immunolabeled Spine Analysis 369
2.4.3 Statistical Analysis and Photomicrograph Production 369
3 Results 370
3.1 Striatal Spine Loss: Golgi Analysis 370
3.1.1 Severely Dopamine-Depleted Striatum 370
3.1.2 Partially Dopamine-Depleted Striatum 370
3.2 Density of D1-Immunoreactive Spines in the Striatum 370
3.3 Calbindin Immunolabeling in the Striatum 372
4 Discussion 376
References 378
Prevention of Calbindin Recruitment into Nigral Dopamine Neurons from MPTP-Induced Degeneration in Macaca fascicularis 381
1 Introduction 381
2 Methods 382
2.1 Animals 382
2.2 Surgical Procedures 382
2.3 MPTP Treatment 384
2.4 Behavioral Analysis 384
2.5 Immunohistochemistry 384
2.6 Histological Analysis 385
3 Results 385
4 Discussion 386
References 387
Changes in the Subcellular Localization and Functions of GABA-B Receptors in the Globus Pallidus of MPTP-Treated Monkeys 390
1 Introduction 390
2 Materials and Methods 392
2.1 Animals and MPTP Treatment 392
2.2 Immunohistochemical Localization of GABA-B Receptors 392
2.3 Local Administration of GABA-B Compounds and Extracellular Recording of Pallidal Units 393
2.3.1 Surgery 393
2.3.2 Recording and Injection Sessions 393
2.3.3 Drugs 394
2.3.4 Data Analysis 394
3 Results 394
4 Summary and Conclusions 397
4.1 Effects of Dopaminergic Depletion on GABA-B Receptor Expression in the GP 397
4.2 Pharmacological Activation and Blockade of GABA-B Receptors in GPe and GPi of Parkinsonian Monkeys 398
References 398
Morphogenesis of Rodent Neostriatum Following Early Developmental Dopamine Depletion 401
1 Introduction 401
2 Methods 403
3 Results 404
4 Discussion and Perspectives 406
4.1 Neostriatal DA Afferents in ak Mice Are Reduced in a Dorsal to Ventral Manner 408
4.2 Reduced Neostriatal DA Afferents in ak Mice Reduce Patchy MOR Expression 409
4.3 Developmental Dopamine Depletion in ak Mice Does Not Alter Neostriatal Neuron Numbers but Reduces Neostriatal Volume and 410
References 410
Upregulation of NAD(P)H:Quinone Oxidoreductase (NQO1) in Glial Cells of 6-Hydroxydopamine-Lesioned Substantia Nigra in the Rat 413
1 Introduction 414
2 Materials and Methods 415
2.1 Animals 415
2.2 Intracerebral Injections of 6-Hydroxydopamine 415
2.3 Immunohistochemistry 415
2.4 LY 83583-Mediated Enzyme Histochemistry 416
2.5 Fluorojade Histochemistry 416
2.6 Digital Images 416
3 Results 417
3.1 Degeneration Pattern of DA Neurons After 6-OHDA Administration 417
3.2 Fluorojade-B 417
3.3 Autofluorescence 418
3.4 Activation of Microglia 419
3.5 Upregulation of NQO1 Immunoreactivity and NQO1 Enzyme Activity in Glial Cells 420
3.6 Induction of Reactive Glial Cells and Upregulation of GFAP Immunoreactivity in Reactive Glial Cells 425
3.7 Comparison of the Temporal Patterns of the Stainings Used 425
4 Discussion 426
References 430
Clioquinol Protects Against Cell Death in Parkinson’s Disease Models In Vivo and In Vitro 432
1 Introduction 432
2 Methods 433
2.1 Mice 433
2.2 6-OHDA Toxin Lesioning 434
2.3 Clioquinol Feeding 434
2.4 Histology, Estimation of Lesion Size and Stereological Cell Counts 434
2.5 MTT Assay for Determination of Human Neuroblastoma M17 Cell Viability 435
3 Results 435
3.1 Effects of CQ on Mice Lesioned with 6-OHDA 435
3.2 Effects of DA, Metals and CQ in an In Vitro Cellular Model 436
4 Discussion 438
References 441
Oscillatory Activity and Synchronization in the Basal Ganglia Network in Rodent Models of Parkinson’s Disease 444
1 Introduction 444
2 Results 447
2.1 Beta Frequency Activity in Paired GP-STN Recordings: Firing Rate and Pattern 447
2.2 Beta Frequency Activity in Paired GP–STN Recordings: LFP Power 449
2.3 Beta Frequency Activity in Paired GP–STN Recordings: Coherence and Spike–Triggered LFP Waveforms 449
3 Discussion 452
3.1 Loss of Dopamine and Emergence of Synchronized Activity in Basal Ganglia 452
3.2 Beta Activity in Additional Awake Rodent Models of PD 454
3.3 Observations in Rodent Models Consistent with Changes Observed in PD Patients: Conclusions 455
References 456
Behavioural Correlates of Dopaminergic Agonists’ Dyskinetic Potential in the 6-OHDA-Lesioned Rat 461
1 Introduction 461
2 Experimental Procedures 463
2.1 Subjects and 6-OHDA Lesion 463
2.2 Drugs 463
2.3 Assessment of Nigrostriatal Lesion: Adjusting Steps and Cylinder Test 463
2.4 Drug Treatment and Behavioural Tests 464
2.5 Statistics 464
3 Results 464
4 Discussion 466
4.1 High Dyskinetic Response After D1 Receptor Stimulation by SKF38393 467
4.2 Low Dyskinetic Response After D2 Receptor Stimulation by Ropinirole 467
5 Conclusions 468
References 468
Basal Ganglia and Behaviour: Behavioural Effects of Deep Brain Stimulation in Experimental Neurological and Psychiatric Disor 471
1 Introduction 471
2 Deep Brain Stimulation for Non-motor Symptoms of Movement Disorders 472
3 Deep Brain Stimulation in Psychiatric Disorders 476
3.1 Obsessive-Compulsive Disorder 476
3.2 Animal Models of Depression 477
3.3 Animal Models of Panic Disorder 478
4 Discussion 478
References 480
Modeling Nonmotor Symptoms of Parkinson’s Disease in Genetic Mouse Models 483
1 Introduction 483
2 Thy1-aSyn Mice 484
2.1 Neuropathological Alterations in Thy1-aSyn Mice 484
2.2 Nonmotor Deficits in Thy1-aSyn Mice 485
2.2.1 Olfactory Deficits 485
2.2.2 Anomalies in Circadian Rhythm 486
2.2.3 Anxiety and Depression 486
2.2.4 Cognitive Deficits 486
2.2.5 Gastrointestinal Dysfunction 487
2.2.6 Cardiovascular Dysfunction 487
2.3 Progressive Sensorimotor Dysfunction in Thy1-aSyn Mice 487
3 Conclusion 488
References 489
Differential Expression of Doublecortin-Like Kinase Gene Products in the Striatum of Behaviorally Hyperresponsive Rats 492
1 Introduction 493
2 Materials and Methods 494
2.1 Animals and Tissue Preparation 494
2.2 Unilateral Depletion of Dopamine and Exposure to Dopamine Agonists 495
2.3 Psychomotor Sensitization to Amphetamine or Morphine 495
2.4 Tyrosine Hydroxylase Immunostaining 496
2.5 In Situ Hybridization 496
2.6 Measurements and Quantifications 496
3 Results 497
3.1 Extent and Effect of the 6-OHDA Lesions 497
3.2 Changes in Levels of DCLK mRNA 497
3.3 Changes in Levels of CARP mRNA 499
4 Discussion 501
4.1 Apoptosis 502
4.2 Neuronal Morphology 503
4.3 Mechanisms 504
5 Conclusions 505
References 506
Paradox of the Basal Ganglia Model: The Antidyskinetic Effect of Surgical Lesions in Movement Disorders 511
1 Introduction 511
2 Pallidotomy in Parkinson’s Disease: Summary of Clinical Effects 512
3 Pallidotomy and Dyskinesias 513
4 The First Paradox of the Basal Ganglia Model: How Does Pallidotomy Eliminate Dyskinesias? 513
5 Conclusions 516
References 516
The Dynamic Relationship Between Voluntary and Involuntary Motor Behaviours in Patients with Basal Ganglia Disorders 519
1 Introduction 520
1.1 The Problem of Recording Whole-Body Involuntary Motor Behaviours 520
1.2 The Problem of Recording ‘Core’ Bradykinesia 521
1.3 The Dynamic Relationship Between Involuntary and Voluntary Motor Behaviours in Patients with PD Having LID and in Patien 522
2 Methods 523
2.1 Participants 523
2.2 Whole-Body Involuntary Movements Quantification 523
2.3 Bradykinesia Quantification Using a Rapid Alternating Movements Task 524
2.4 Statistics 524
3 Results 524
3.1 Whole-Body Involuntary Movements 524
3.2 Rapid Alternating Movement 526
4 Discussion 527
4.1 The Bradykinesia Issue in HD 527
4.2 Implications of the Present Results for Basal Ganglia Pathophysiology 527
4.3 Clinical Implications of the Present Results 529
5 Conclusions 530
References 530
Reduced and Modified Neuronal Activity in the Subthalamic Nucleus of Parkinson’s Disease Patients with Prior Pallidotomy 533
1 Introduction 533
2 Methods 535
2.1 Patients 535
2.2 Data Acquisition and Analysis 536
2.3 The Root Mean Square: An STN Raw Activity Measure 536
2.4 The Mean Successive Difference: A Measure of Irregularity 537
2.5 Statistical Analysis 538
2.6 Spectral Analysis 538
2.7 Software 538
3 Results 539
3.1 Average Normalized RMS 539
3.2 Variance of Normalized RMS 540
3.3 Irregularity (MSD) of Normalized RMS 540
3.4 Ipsilateral vs. Contralateral STN Activity in Cases with Unilateral Pallidotomy 540
3.5 Spectral Analysis 541
4 Discussion 541
5 Conclusions 544
References 545
Inhibition of Neuronal Firing in the Human Substantia Nigra Pars Reticulata in Response to High-Frequency Microstimulation Aid 548
1 Introduction 549
1.1 Parkinson’s Disease and the Basal Ganglia 549
1.2 Effects of High-Frequency Stimulation 549
2 Methods 550
2.1 Surgery and Recordings 550
2.2 Analysis 551
3 Results 552
4 Discussion 554
4.1 SNr Inhibition 554
4.2 STN Inhibition 555
4.3 Determining STN Borders 556
5 Conclusion 557
References 557
Activity of Thalamic Ventralis Oralis Neurons in Rigid-Type Parkinson’s Disease 559
1 Introduction 559
2 Subjects and Methods 560
3 Results 562
4 Discussion 563
References 566
Motor and Non-motor Effects of PPN-DBS in PD Patients: Insights from Intra-operative Electrophysiology 568
1 Introduction 569
2 Methods 570
2.1 Neurosurgery 570
2.2 Patient Evaluation 570
2.3 Peri-operative Recordings 572
3 Results 573
3.1 Acute and Long-Lasting Motor Effect 573
3.2 Cognitive Effects 574
3.3 Effects on Sleep 574
3.4 Effects of PPN-DBS on STN Neurons 575
4 Discussion 576
4.1 Motor Effects 576
4.2 Non-motor Effects 577
5 Conclusions 578
5.1 Is PPN-DBS (at 10–25 Hz in Our Protocol) Re-activating Impaired Pathways? 578
5.2 Is PPN-DBS Mostly Affecting Non-motor and Not Strictly Dopamine-Centred Functions? 579
References 580
Observation of Involuntary Movements Through Clinical Effects of Surgical Treatments 583
1 Introduction 583
2 Methods 584
2.1 Subjects 584
2.2 Surgery 584
2.3 Stereotactic Targets 584
2.4 EMG Analysis 584
3 Results 585
3.1 Tremor 585
3.1.1 Essential Tremor 585
3.1.2 Multiple Sclerosis 585
3.2 Dystonia 585
3.2.1 Generalized Dystonia 585
3.2.2 Focal Dystonia 586
3.3 Choreoballistic Involuntary Movements 586
4 Discussion 587
5 Conclusions 589
References 589