The Hidden Life of the Basal Ganglia: At the Base of Brain and Mind

Contents
Preface
Acknowledgments
I. Introduction and Background
	1. The Basal Ganglia: Why and Where?
		Why Should We Study the Basal Ganglia?
		Gross Anatomy of the Basal Ganglia
		Basal Ganglia Volumes
		“Tell Me Who Are Your Friends?”: The Cortex and Thalamus
		A Cord of Three Motor Strands Is Not Quickly Broken: The Cerebellum
		Emotion and Motion: The Papez Limbic Circuit
		Form and Function
		Chapter Summary
	2. Cellular Anatomy and Biochemistry of the Basal Ganglia
		The Cortex
		The Striatum
		The Subthalamic Nucleus
		GPe, GPi, and SNr
		The Thalamus
		The Basal Ganglia in Numbers
		Number of Neurons outside the Hard Core of the Basal Ganglia
		The Other Half: The Glia
		Chapter Summary
	3. The Synaptic Connections of the Basal Ganglia Network
		The Synaptic Map of the Feedforward Connectivity of the Basal Ganglia
		Lateral Connectivity in the Basal Ganglia
		Feedback and Reciprocal Connectivity in the Main Axis of the Basal Ganglia
		Convergence/Divergence of Basal Ganglia Connectivity
		Convergence, Divergence, Again and Again
		Chapter Summary
	4. Computational Modeling of Brain and Behavior
		Top-Down versus Bottom-Up Approaches
		Hierarchical Levels of Understanding of the Nervous System
		Chapter Summary
	5. Principles of Neurophysiological Data Acquisition
		Electrodes, Frequency Domains, and Types of Neurophysiological Data
		The Black Magic of Neurophysiology Recording
		Spike Detection, Spike Sorting, and Isolation Quality
		Electrical Stimulation of the Brain
		Inactivation of Brain Activity
		What Was Left Out?
		Chapter Summary
	6. Principles of Neurophysiological Analysis
		Temporal and Frequency Domains and Neurophysiological Data Analysis
		Time Domain Analysis of Rate and Pattern of Spontaneous Activity
		Frequency Domain Analysis of Discharge Pattern
		Pairwise Correlations Analysis of Synchronization of Spontaneous Activity
		Effective Connectivity in the Brain and the Sensitivity of Cross-Correlation Analysis
		Cross-Correlation Analysis of Spike Trains of Neighboring Neurons
		Coherence: Frequency Domain Analysis of Neuronal Synchronization
		Analysis of Evoked Activity
		Advanced Analysis Topics
		Chapter Summary
II. Computational Physiology of the Healthy Basal Ganglia
	7. Physiology of the Basal Ganglia
		Spontaneous Discharge Rate
		Spontaneous Discharge Pattern
		Synchronization of Spontaneous Discharge
		Synchronization of GPe Pauses and Spiking Activity
		Basal Ganglia–Evoked Activity: Polarity and Amplitude
		Basal Ganglia–Evoked Activity: Temporal Structure
		Synchronization of Basal Ganglia–Evoked Activity
		Chapter Summary
	8. Basal Ganglia Physiology: The Roads Less Traveled
		The Basal Ganglia and the Sleep/Wake Cycle
		Right/Left Brain and Basal Ganglia Asymmetry
		Biological Sex and the Basal Ganglia
		Age Effects in the Basal Ganglia
		Evolution and Comparative Biology of the Basal Ganglia
		Chapter Summary
	9. Box-and-Arrow Rate Models of the Basal Ganglia
		D1/D2 Direct/Indirect Pathways Box-and-Arrow Model of the Basal Ganglia
		Computational Physiology of the D1/D2 Direct/Indirect Pathways Box-and-Arrow Model of the Basal Ganglia
		The D1/D2 Saga
		The Two Pallidal Segments: Friends or Foes?
		Thalamo/Cortical versus Dopamine Drive of the Striatum and the Basal Ganglia Network
		Anatomical Updates of the D1/D2 Direct/Indirect Pathways Box-and-Arrow Model of the Basal Ganglia
		The Three-Layer Model of the Basal Ganglia
		The Pitfalls of Box-and-Arrow Models of the Basal Ganglia
		Focusing versus Scaling: Action Selection in the Basal Ganglia
		Computational Physiology and Pitfalls of Action-Selection Models of the Basal Ganglia
		Chapter Summary
	10. Reinforcement-Learning Actor/Critic Models of the Basal Ganglia
		Principles of Reinforcement Learning
		Reinforcement Learning in Equations
		Reinforcement Learning in the Basal Ganglia Networks
		Encoding of Reward Prediction Error by Dopaminergic Neurons
		Homogeneous Dopamine Innervation of the Striatum
		Dopamine Modulates the Efficacy of the Corticostriatal Synapses
		Who Is the Teacher of the Teacher?
		Computational Physiology of the Reinforcement-Learning Actor/Critic Model of the Basal Ganglia
		Pitfalls of the Reinforcement-Learning Actor/Critic Model of the Basal Ganglia
		Chapter Summary
	11. Multiple-Critics, Multiobjective Optimization Models of the Basal Ganglia
		Multiobjective Optimization
		The Cholinergic Critic
		Basal Ganglia Critics Modulate Both Striatal Excitability and Afferent Synaptic Efficacy
		Freestanding (Outside the Striatum) Neuromodulation in the Basal Ganglia
		Computational Physiology of the Multiple-Critics, Multiobjective Optimization Model of the Basal Ganglia
		Pitfalls of the Multiple-Critics, Multiobjective Optimization Model of the Basal Ganglia
		Chapter Summary
	12. The Basal Ganglia as One of Many State-to-Action Loops
		Brain Networks and Kahneman’s Systems 1 and 2
		Bottleneck Dimensionality Reduction in the Basal Ganglia
		Linear and Nonlinear Neuronal Input-Output RELATIONSHIPS in the Basal Ganglia
		Computational Physiology of the Basal Ganglia: The Current Status
		Computational Physiology of the Basal Ganglia: Second-Order Questions
		Chapter Summary
III. Computational Physiology of Basal Ganglia Disorders and Their Therapy
	13. Parkinson’s Disease and Other Basal Ganglia–Related Human Disorders
		The Pyramidal versus the Extrapyramidal Systems
		Parkinson’s Disease
		Other Basal Ganglia–Related Disorders
		Why Are Basal Ganglia Disorders So Poorly Compensated by Other Brain Structures?
		Chapter Summary
	14. Animal Models of Parkinson’s Disease
		The 6-OHDA Rodent Model of Parkinson’s Disease
		The MPTP Model of Parkinson’s Disease
		Animal Models Are Lies That Help Us to Reveal the Truth and to Reduce Human Suffering
		Chapter Summary
	15. Physiology of Parkinson’s Disease: Animal Models
		Discharge Rate
		Discharge Pattern and Synchronization
		On Oscillations and Synchronization
		Changes in the Spiking Activity of the Motor Cortex in MPTP-Treated Monkeys
		Local Field Potentials and Their Correlation with Spiking Activity in the Basal Ganglia of MPTP-Treated Monkeys
		Beta Oscillations in the MPTP Monkey Do Not Go to Sleep
		Chapter Summary
	16. Physiology of Parkinson’s Disease: Human
		Theta and Beta Oscillations in the Basal Ganglia of Parkinson’s Patients
		Subthalamic Beta Oscillations Are Synchronized
		The Functional Roles of Beta and Theta Oscillations
		LFP Studies
		Chapter Summary
	17. Pharmacotherapy of Parkinson’s Disease
		Anticholinergic Treatment of Parkinson’s Disease
		Dopamine Therapy for Parkinson’s Disease
		Amantadine Therapy for Parkinson’s Disease
		The Built-In Problems of Pharmacotherapy for Parkinson’s Disease Symptoms
		Alpha-Synuclein Therapy for Parkinson’s Disease
		Lifestyle Therapy for Parkinson’s Disease
		Chapter Summary
	18. Deep Brain Stimulation Therapy for Parkinson’s Disease
		DBS Technology
		DBS Clinical and Adverse Effects
		Mechanism of DBS
		Optimization of DBS Therapy for Parkinson’s Disease
		Better DBS Navigation
		“Asleep” DBS
		What Is the Best Target in Space for DBS for Parkinson’s Disease?
		Chapter Summary
	19. Closing the Loop on Parkinson’s Disease and Basal Ganglia–Related Disorders
		Closed-Loop DBS
		Not All Betas Are Created Equal: On Bad and Good Beta Oscillations
		A Basal Ganglia–Cortex Holistic View of Beta Oscillations
		The Other Side of the Moon: Ketamine, Hyperkinetic States, and Gamma Oscillations
		Dreams May Come True: Phase-Specific Closed-Loop DBS
		Learning from the Basal Ganglia: Machine-Learning DBS
		On Dreams and Delusions in the Basal Ganglia: Closed-Loop DBS for Schizophrenia
		If Your Dreams Don’t Scare You, They Aren’t Big Enough
		Chapter Summary
IV. From the Basal Ganglia and Brain to the Mind
	20. The Basal Ganglia, Free Will, and Human Responsibility
		State-to-Action Loops and Free Will
		Escaping the Tyranny of Biological State-to-Action Loops
		If You Don’t Know Where You’re Going, Then It Doesn’t Much Matter Which Way You Go
Notes
	Chapter 1
	Chapter 2
	Chapter 3
	Chapter 4
	Chapter 5
	Chapter 6
	Chapter 7
	Chapter 8
	Chapter 9
	Chapter 10
	Chapter 11
	Chapter 12
	Chapter 13
	Chapter 14
	Chapter 15
	Chapter 16
	Chapter 17
	Chapter 18
	Chapter 19
	Chapter 20
References
Index