PubMed · 2000 · 141 citations · 0 references
Life SciencesNeurologyNeuroscienceMotor NeuroscienceMovement DisordersNeurophysiologyBasal Ganglia PhysiologyMotor PathwaysNeurologic PathophysiologyNeurophysiology Of Movement DisordersParkinson DiseaseParkinsonian DisordersAnimal Disease ModelsBasal Ganglia FunctionBasal Ganglia Functional OrganizationBasal Ganglia Motor CircuitsBasal Ganglia Motor ControlGlobus Pallidus External SegmentGlobus Pallidus Internal SegmentNeuronal Synchronization
Basal ganglia have long been implicated in movement disorders, and advances such as the 1‑methyl‑4‑phenyl‑1,2,3,6‑tetrahydropyridine‑monkey model and renewed surgical therapies have clarified the pathophysiological mechanisms underlying hypokinetic and hyperkinetic disorders. This review examines the functional organization of the basal ganglia thalamocortical motor circuit and the neuronal activity changes that occur in these disorders. The authors present an alternative to the classic rate model for Parkinson’s disease that incorporates observed neuronal activity changes and additional pathways contributing to motor dysfunction. They propose that dyskinesias arise from excessive reductions in mean discharge rate, altered firing patterns, and increased synchronization in the internal globus pallidus, with the specific involuntary movement type depending on relative changes in direct, indirect, and alternative pathways, and they model drug‑induced dyskinesia, hemiballismus, and dystonia.
Although the basal ganglia have been implicated in the development of movement disorders since the 1940s, the exact role played by these structures has remained elusive. The development of the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-monkey model of parkinsonism, and the recent resurgence of surgical therapy for the treatment of hypokinetic and hyperkinetic movement disorders has, however, led to an improved understanding of the pathophysiological mechanisms that underlie their development. In this article, we review the functional organization and examine the changes in neuronal activity that occur in the basal ganglia thalamocortical 'motor' circuit in these disorders. An alternative to the classic 'rate' model for Parkinson's disease is presented that incorporates the observed changes in neuronal activity, as well as additional neuronal pathways that contribute to these changes. Based on studies in animal models and humans with hyperkinetic movement disorders, it is postulated that dyskinesias develop as the result of a combination of excessive reductions in the mean discharge rate, altered patterns and increased synchronization of neurons in the internal segment of the globus pallidus. It is further postulated that the particular type of involuntary movement which develops also depends on the relative change in neuronal activity in the direct, indirect and alternative pathways. Support for these postulates is examined, and models for drug-induced dyskinesia, hemiballismus and dystonia are proposed.