Elsevier

Progress in Neurobiology

Volume 87, Issue 2, February 2009, Pages 118-131
Progress in Neurobiology

Primate models of dystonia

https://doi.org/10.1016/j.pneurobio.2008.10.003Get rights and content

Abstract

Several models of dystonia have emerged from clinical studies providing a comprehensive explanation for the pathophysiology of this movement disorder. However, several points remain unclear notably concerning the specific role of brainstem, basal ganglia nuclei and premotor cortex. We review data collected in sub-human primate to see whether they might provide new insights into the pathophysiology of dystonia. As in human patients, lesions of the putamen induce dystonia, as well as pharmacological manipulations of the dopaminergic system. In addition, primate studies revealed that lesions in brain stem areas involved in the control of muscular tone and GABAergic manipulations in various basal ganglia nuclei or thalamus also lead to dystonia. Moreover, there is a dramatic disruption in the processing of proprioceptive information with abnormal large receptive fields in the basal ganglia, thalamus, primary somesthetic cortex and premotor cortex of dystonic monkeys. These data highlight the idea that dystonia is associated with aberrant sensory representations interfering with motor control. Considering that the supplementary motor area (SMAp) is the target of basal ganglia projections within the motor loop, we propose a model of dystonia in which abnormal excitability, associated with alteration in sensory receptive fields within the SMAp, leads to an abnormal synchronization between primary motor cortex columns. Such a phenomenon might account for the co-contractions of antagonist muscles favored by action and the abnormal postures observed in dystonia.

Section snippets

Phenomenology and clinical models of dystonia

Dystonia is defined as a syndrome of sustained muscular contractions leading to repetitive movements and abnormal postures (Fahn, 1987). This broad definition has the advantage of including many clinical aspects of the disease, even though other frequently combined signs, such as bradykinesia (slowing of movement), myoclonia, tremor or troubles in action planning (apraxia), are not considered. From a phenomenological point of view, dystonia is the inability to select correctly the muscular

Lesions and pharmacological manipulations of the brainstem

Dystonia is characterized by muscular tonic spasms. In the early fifties, there emerged the idea that the brain stem region involved in the regulation of muscular tone could play a role in the genesis of dystonic symptoms.

Indeed, lesions of the red nucleus or the ventromedial mesencephalic tegmentum induce the onset of a spasmodic torticollis in the monkey (Battista et al., 1976, Carpenter, 1956, Foltz et al., 1959, Malouin and Bedard, 1982) (Table 1). The head turns to the side of the

Models of occupational dystonia in primates

Occupational dystonia is a particular form of focal dystonia appearing in body regions, generally the hand, and is involved in movements requiring high dexterity such as writing, playing music, professional activity, or the practice of skilled sports (Cohen and Hallett, 1988, Marsden and Sheehy, 1990). Evidence is accumulating from animal and human studies that focal hand dystonia could be the consequence of aberrant learning (Byl, 2003). A model of occupational hand dystonia has been developed

What do we learn from experimental models of dystonia?

Although we have some information about the cellular mechanisms subserving primary dystonia such as enzymatic defect (Illarioshkin et al., 1998) or the storing of non-functional protein, e.g., Torsin (Ozelius et al., 1997), in many cases the role of these biological phenomena, as well as the nature of the causal gene, remains unknown. Secondary dystonia means that a lesion in a particular region of the brain induces dystonia, although it is unknown whether this is the result of a direct effect

Acknowledgement

We wish to thank Ray Cooke for checking the English.

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