Dysfunction of the subthalamic nucleus induces behavioral and movement disorders in monkeys

Authors

  • Carine Karachi MD, PhD,

    Corresponding author
    1. INSERM, UMR_S679, Neurology and Experimental Therapeutics, Paris, France
    2. UPMC Univ Paris 6, UMR_S679, Paris, France
    3. Assistance Publique-Hôpitaux de Paris, Groupe Pitié-Salpêtrieère, Paris, France
    • INSERM U679, Hôpital de la Salpêtrière, 47 Bd de l'Hôpital, 75651 Paris Cedex 13, France
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  • David Grabli MD, PhD,

    1. INSERM, UMR_S679, Neurology and Experimental Therapeutics, Paris, France
    2. UPMC Univ Paris 6, UMR_S679, Paris, France
    3. Assistance Publique-Hôpitaux de Paris, Groupe Pitié-Salpêtrieère, Paris, France
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  • Nicolas Baup MD,

    1. INSERM, UMR_S679, Neurology and Experimental Therapeutics, Paris, France
    2. UPMC Univ Paris 6, UMR_S679, Paris, France
    3. Department of Psychiatry, Centre Hospitalier Saint-Anne, Paris, France
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  • Stéphanie Mounayar PhD,

    1. INSERM, UMR_S679, Neurology and Experimental Therapeutics, Paris, France
    2. UPMC Univ Paris 6, UMR_S679, Paris, France
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  • Dominique Tandé,

    1. INSERM, UMR_S679, Neurology and Experimental Therapeutics, Paris, France
    2. UPMC Univ Paris 6, UMR_S679, Paris, France
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  • Chantal François PhD,

    1. INSERM, UMR_S679, Neurology and Experimental Therapeutics, Paris, France
    2. UPMC Univ Paris 6, UMR_S679, Paris, France
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  • Etienne C. Hirsch PhD

    1. INSERM, UMR_S679, Neurology and Experimental Therapeutics, Paris, France
    2. UPMC Univ Paris 6, UMR_S679, Paris, France
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  • Potential conflict of interest: None reported.

Abstract

High-frequency stimulation of the subthalamic nucleus (STN) in parkinsonian patients is reported to induce psychiatric effects. The likely explanation for these effects is the partitioning of the STN into sensorimotor, associative, and limbic anatomo-functional territories. Thus, a specific neuronal dysfunction of the STN sensorimotor territory could lead to abnormal movements, whereas a dysfunction of the associative or limbic territory could lead to behavioral disturbances. To test this hypothesis, neuronal dysfunction of the STN was induced by microinjections of the GABA agonist muscimol, or antagonist bicucculline, in various parts of the nucleus in three monkeys. Stereotyped behaviors (licking and biting fingers) and/or violent hyperactivity were obtained with bicuculline injected into the anteromedial, associative, and limbic territories, whereas injections of muscimol induced no major effects. Abnormal limb movements (contralateral ballism) were obtained after muscimol or bicuculline injections into the posterolateral, sensorimotor territory. Control injections localized around the STN induced other effects (mainly torticollis), which underlines the specificity of STN injection effects. Our study supports the hypothesis that the anteromedial part of the STN is involved in behavioral control. © 2009 Movement Disorder Society

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