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Deep brain stimulation mechanisms: beyond the concept of local functional inhibition

Authors

  • Jean-Michel Deniau,

    1. Institut National de la Santé et de la Recherche Médicale U.667, Dynamique et Physiopathologie des Réseaux Neuronaux, Collège de France, 11 Place Marcelin Berthelot, 75231 Paris Cedex 05 France, and Université Pierre et Marie Curie, 4 Place Jussieu, 75005 Paris, France
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  • Bertrand Degos,

    1. Institut National de la Santé et de la Recherche Médicale U.667, Dynamique et Physiopathologie des Réseaux Neuronaux, Collège de France, 11 Place Marcelin Berthelot, 75231 Paris Cedex 05 France, and Université Pierre et Marie Curie, 4 Place Jussieu, 75005 Paris, France
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  • Clémentine Bosch,

    1. Institut National de la Santé et de la Recherche Médicale U.667, Dynamique et Physiopathologie des Réseaux Neuronaux, Collège de France, 11 Place Marcelin Berthelot, 75231 Paris Cedex 05 France, and Université Pierre et Marie Curie, 4 Place Jussieu, 75005 Paris, France
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  • Nicolas Maurice

    1. Institut de Biologie du Développement de Marseille-Luminy (IBDML), UMR6216 (Centre National de la Recherche Scientifique/Université de la Méditerranée), Marseille Cedex, France
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Dr J.-M. Deniau, 1INSERM U 667, as above.
E-mail: jean-michel.deniau@college-de-france.fr

Abstract

Deep brain electrical stimulation has become a recognized therapy in the treatment of a variety of motor disorders and has potentially promising applications in a wide range of neurological diseases including neuropsychiatry. Behavioural observation that electrical high-frequency stimulation of a given brain area induces an effect similar to a lesion suggested a mechanism of functional inhibition. In vitro and in vivo experiments as well as per operative recordings in patients have revealed a variety of effects involving local changes of neuronal excitability as well as widespread effects throughout the connected network resulting from activation of axons, including antidromic activation. Here we review current data regarding the local and network activity changes induced by high-frequency stimulation of the subthalamic nucleus and discuss this in the context of motor restoration in Parkinson’s disease. Stressing the important functional consequences of axonal activation in deep brain stimulation mechanisms, we highlight the importance of developing anatomical knowledge concerning the fibre connections of the putative therapeutic targets.

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