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Closed-loop spinal cord stimulation is superior in restoring locomotion in rodent models of Parkinson’s Disease

Benjamin Rees, Eleonora Borda, Miguel A. L. Nicolelis, View ORCID ProfileAmol P. Yadav
doi: https://doi.org/10.1101/2022.09.19.508432
Benjamin Rees
1Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA
2Paul and Carole Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA
3Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
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Eleonora Borda
4Center for Neuroprosthetics and Institute of Bioengineering, School of Engineering, École Polytechnique Fédérale de Lausanne, Chemin des Mines 9, 1202 Geneva, Switzerland
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Miguel A. L. Nicolelis
5Department of Neurobiology, Duke University, Durham, NC 27710, USA
6Center for Neuroengineering, Duke University, Durham, NC 27710, USA
7Department of Biomedical Engineering, Duke University, Durham, NC 27710, USA
8Department of Psychology and Neuroscience, Duke University, Durham, NC 27710, USA
9Department of Neurosurgery, Duke University, Durham, NC 27710, USA
10Department of Neurology, Duke University, Durham, NC 27710, USA
11Edmond and Lily Safra International Institute of Neuroscience, Natal, Brazil 59066060
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Amol P. Yadav
1Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA
2Paul and Carole Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA
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  • ORCID record for Amol P. Yadav
  • For correspondence: apyadav@iu.edu
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Abstract

Dorsal column stimulation (DCS) of the spinal cord is emerging as a promising new technology to treat Parkinson’s disease (PD). However, optimal stimulation settings that maximize its therapeutic effect on PD symptoms are yet to be determined. Here we demonstrate a closed-loop DCS (CLDCS) paradigm – a substantial advancement from previously tested continuous high-frequency DCS – in a bilateral intrastriatal 6-hydroxydopamine (6-OHDA) rodent model of PD. Firstly, CLDCS, triggered by corticostriatal beta frequency oscillations facilitated a pro-locomotion brain state that restored locomotion and reduced akinesia. Secondly, CLDCS was better at disrupting ongoing beta oscillations and achieved it with lesser overall charge delivery than continuous open-loop stimulation. These results indicate that CLDCS is markedly better than traditional spinal cord stimulation methods and can potentially be highly effective in treating PD symptoms. We envision that the CLDCS approach can be beneficial in the treatment of other neurological disorders which showcase similar pathological neuronal oscillations.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • Fig 1 was updated for clarity. Error in references to figure 2 within the main text was corrected.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted October 21, 2022.
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Closed-loop spinal cord stimulation is superior in restoring locomotion in rodent models of Parkinson’s Disease
Benjamin Rees, Eleonora Borda, Miguel A. L. Nicolelis, Amol P. Yadav
bioRxiv 2022.09.19.508432; doi: https://doi.org/10.1101/2022.09.19.508432
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Closed-loop spinal cord stimulation is superior in restoring locomotion in rodent models of Parkinson’s Disease
Benjamin Rees, Eleonora Borda, Miguel A. L. Nicolelis, Amol P. Yadav
bioRxiv 2022.09.19.508432; doi: https://doi.org/10.1101/2022.09.19.508432

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