Restoration of locomotive function in Parkinson’s disease by spinal cord stimulation: mechanistic approach

Authors

  • Romulo Fuentes,

    1. Department of Neurobiology, Duke Medical Center, 311 Research Drive, Durham, NC 27710, USA
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    • R.F. and P.P. contributed equally to this work.

  • Per Petersson,

    1. Department of Experimental Medical Science, NRC, Lund University, Lund, Sweden
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    • R.F. and P.P. contributed equally to this work.

  • Miguel A. L. Nicolelis

    1. Department of Neurobiology, Duke Medical Center, 311 Research Drive, Durham, NC 27710, USA
    2. Center for Neuroengineering, Duke University, Durham, NC, USA
    3. Department of Biomedical Engineering, Duke University, Durham, NC, USA
    4. Department of Psychology and Neuroscience, Duke University, Durham, NC, USA
    5. Edmond and Lily Safra International Institute of Neuroscience of Natal (ELS-IINN), Natal RN, Brazil
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Romulo Fuentes, as above.
E-mail: fuentes@neuro.duke.edu

Abstract

Specific motor symptoms of Parkinson’s disease (PD) can be treated effectively with direct electrical stimulation of deep nuclei in the brain. However, this is an invasive procedure, and the fraction of eligible patients is rather low according to currently used criteria. Spinal cord stimulation (SCS), a minimally invasive method, has more recently been proposed as a therapeutic approach to alleviate PD akinesia, in light of its proven ability to rescue locomotion in rodent models of PD. The mechanisms accounting for this effect are unknown but, from accumulated experience with the use of SCS in the management of chronic pain, it is known that the pathways most probably activated by SCS are the superficial fibers of the dorsal columns. We suggest that the prokinetic effect of SCS results from direct activation of ascending pathways reaching thalamic nuclei and the cerebral cortex. The afferent stimulation may, in addition, activate brainstem nuclei, contributing to the initiation of locomotion. On the basis of the striking change in the corticostriatal oscillatory mode of neuronal activity induced by SCS, we propose that, through activation of lemniscal and brainstem pathways, the locomotive increase is achieved by disruption of antikinetic low-frequency (<30 Hz) oscillatory synchronization in the corticobasal ganglia circuits.

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