For more than a century, physicians and scientists have struggled to understand the mechanism by which the central nervous system controls movement and the origins of the many conditions that disrupt it. Since Kinnear Wilson’s first description of hepatolenticular degeneration in 1912, studies of the basal ganglia have been central to these efforts. For the most part, researchers have attempted to extrapolate data from animal studies to build general models of basal ganglia function and have then applied these to explain the pathophysiology of human movement disorders. However, with the development of more sophisticated functional imaging and electrophysiologic technologies to investigate brain function in animal models and human disease states, a number of paradoxes have been identified. This has prompted a reevaluation of the classic model of basal ganglia function.
This article focuses on the mechanisms of altered motor control in movement disorders, with special emphasis on conditions affecting the basal ganglia and their movement-related network. By convention, movement disorders have been grouped on the basis of their clinical phenomenology into hypokinetic and hyperkinetic conditions. The hypokinetic disorders primarily include the various forms of parkinsonism, both the typical and atypical, the majority of which are produced by neurodegenerative processes. The hyperkinetic movement disorders are far more diverse, both in terms of phenomenology and etiology, and include dystonias, chorea and hemiballismus, tics, stereotypies, myoclonus, and tremor.
With few exceptions, the basal ganglia are known to play an essential role in the manifestation of most of the disorders that fall within this classification. In this article, each of these disorders are, therefore, evaluated and interpreted primarily within the context of one or more of the existing models of the basal ganglia. Although tremor is also present in Parkinson disease, its pathophysiology is thought to differ from that of bradykinesia. Therefore, parkinsonian tremor will be discussed separately in this article. Disorders such as ataxia (as well some forms of tremor) localize to the cerebellum and related circuits whereas the various forms of myoclonus may localize to virtually all levels of the central nervous system. A group of rare disorders that include the apraxias and alien limb phenomenon localize primarily to cortical-subcortical circuits. The latter disorders will not be considered in this summary. A brief introduction to the theories and organization of motor control in the central nervous system provides a wider context within which to view the specific disorders that affect it. This topic has been extensively reviewed elsewhere (40; 59; 103; 22; 298), and the following is intended to orientate the reader.
Over the last few years the role of the cerebellum in these “basal ganglia” disorders has been better characterized, particularly in Parkinson disease and dystonia. In addition, further evidence is available to understand the oscillation model of the basal ganglia. These topics will be updated in this article.
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• With few exceptions, the basal ganglia are known to play an essential role in the manifestation of most hyper- and hypokinetic movement disorders. The role of the cerebellum is also increasingly being recognized.
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• The pathophysiology of tremor, however, is generally felt to differ from that of other hyperkinetic movement disorders, and likely varies according to the etiology.
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• One of the earliest and most basic models of basal ganglia function is based on Albin and colleagues’ 2-circuit model of “direct” and “indirect” pathways within the basal ganglia (04). However, the reliance on neuronal firing rate to explain the manifestation of movement disorders was found to be insufficient. Over the last decade, a number of modifications have been made to the basic model to account for more recent findings.
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• The oscillation model of the basal ganglia is an emerging concept that attempts to address the limitations of the basic rate model of basal ganglia functions.
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• Driven largely by postoperative local field potential and intraoperative microelectrode recordings from patients undergoing deep brain stimulation, oscillations of the basal ganglia have been increasingly applied to the analysis of movement disorders.
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• A growing interest in the neurophysiology of movement has led to a renewal of surgical interventions for movement disorders, which have, in turn, enhanced our knowledge of both normal and abnormal motor control.