A Theory of the Basal Ganglia and Their Disorders

The Basal ganglia, to adopt a phrase of Churchill's, are "a riddle wrapped in a mystery, inside an enigma." And although there is a wealth of information available on them, this research field remains controversial due in part to the diverse number of disciplines involved. A Theory of the Basal Ganglia and Their Disorders provides a clear, coherent view of basal ganglia that integrates evidence from the basic neurosciences, neurology, and psychiatry. The author explores the basal ganglia within a context of the function of the mammalian forebrain as a whole.Divided into two parts, the book explores the basic framework in which normal functions of the basal ganglia can be understood, and then moves on to discuss major disorders. It explains, as far as possible, symptoms and related clinical facts in terms of the underlying pathology and pathophysiology. With this goal in mind, the author includes only disorders of the basal ganglia for which there are already clear ideas about the underlying neuropathology or pathophysiology. He also conveys the human experience of these disorders as well as their scientific basis. While many books cover cutting-edge research, none have addressed large-scale questions about the role of the basal ganglia as a whole. Until now. This is arguably the only book published in the last 50 years that has attempted to provide an overall theory of the basal ganglia, as well as relevant areas of neurology and psychiatry. It concisely presents the theory, rather than comprehensively covering all the literature, and places the essential clinical facts within a framework formulated for normal operations of the basal ganglia. Presenting a unified view, the book takes several steps toward unraveling the riddle that is basal ganglia.

THE FRAMEWORK FOR NORMAL BASAL GANGLIONIC FUNCTIONIntroduction: Background to the Dynamics of the Basal GangliaThe Cortico-Thalamo-Hippocampal Excitatory Network: Substrate for Cell Assemblies and Associative Operations Definition of Executive Functions The "Motor Thalamus": Target of Executive Decisions?The Striatum: Functional Significance and "Direct" Connectivity to Output Nuclei of the Basal GangliaThe Striatum: Detector and Encoder of Motivationally Significant Outcomes of Behavior and Deployer of Motivationally Favorable Behaviors Functional Subdivisions within Each Component of the Basal Ganglia The "Credit Assignment Problem" Morphological Evidence about the Fine Distribution of Connections in the Basal Ganglia Cybernetic Interpretations Derived from Quantitative Synaptology Collateral Inhibition in the Striatum The "Indirect" Pathways from Striatum to Basal Ganglia Output Nuclei, and Their Relation to the "Direct" Pathway Overall Patterns of Connectivity Segregation versus Overlap of "Direct" and "Indirect" Pathways from Striatum to Thalamus The "Credit Assignment Problem" in the Indirect Pathway Evidence on the Relative Role of "Direct" and "Indirect" Pathways Theories of Basal Ganglionic Function Early Theories Synopsis of Key Issues The "Scaling of Movement" Hypothesis The "Focused Selection" Hypothesis A More Complete Version of the "Focused Selection" Theory, Including Predictions Comparison with an Earlier Theory of the Basal Ganglia: Significance of Cell Assemblies Dynamics of Neural Activity in Structures of the Basal Ganglia and the Nature of the Neural Code in These Structures Synopsis of Part I and Predictions Derived from It INTERPRETATION OF SYMPTOMS OF DISEASES OF THE BASAL GANGLIAIntroduction General Comments Neuropathology and Pathophysiology of Disorders of the Basal Ganglia Huntington's Disease Parkinson's Disease and Parkinsonian Syndromes Introduction The "Goad and the Halter" in Parkinson's Disease Coactivation of Striatal Neurons and Cognitive Problems Associated with Parkinsonian Syndromes Inflexibility of Adjustments of Posture and Gait in Parkinson's DiseaseThe Role of the Subthalamus in Production of Parkinsonian Symptoms Burst Firing in Components of the Basal Ganglia and Parkinsonian Tremor Direct Connections from Basal Ganglia to Brain Stem, and Their Role in Parkinsonian Akinesia and Rigidity Parkinson's Disease: Summary Dopamine-Dependent Psychosis Introduction Development of the Dopamine Hypothesis of Psychosis Neural Dynamics in the Basal Ganglia When Dopaminergic Tone is Elevated Overactivity of Striatal Dopamine in Relation to the Symptoms of Psychosis Pharmacology of Psychosis Positive Feedback between Striatum and Cortex in the Generation of Psychosis Syndromes Arising as Complications of Prolonged Underactivity of Striatal Dopamine Mechanism, and Other Disorders of the Basal Ganglia Introduction Reasons for Identifying Striatal Cholinergic Cell Loss as the Origin of the Four Syndromes Phenomenology of Peak Dose Dyskinesia and Tardive Dyskinesia Dyskinesias, Stereotypy, Refractory Psychosis and Other Behavioral Pathologies Related to High-Dopamine States without a Prior History of Prolonged Dopaminergic Underactivity Pharmacological Theory: Involvement of Dopaminergic and Cholinergic Receptor Subtypes Other Disorders Involving the Basal Ganglia Synopsis of Part II and Predictions Derived from It Appendix 1: Abbreviations Appendix 2: Pharmacological Agents and Their Actions References Index