Direct activation of primary motor cortex during subthalamic but not pallidal deep brain stimulation

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Deep brain stimulation (DBS) of the subthalamic nucleus (STN) and globus pallidus internus (GPi) is an effective treatment for parkinsonian motor signs. Though its therapeutic mechanisms remain unclear, it has been suggested that antidromic activation of the primary motor cortex (M1) plays a significant role in mediating its therapeutic effects. This study tested the hypothesis that antidromic activation of M1 is a prominent feature underlying the therapeutic effect of STN and GPi DBS. Single-unit activity in M1 was recorded using high-density microelectrode arrays in two parkinsonian nonhuman primates each implanted with DBS leads targeting the STN and GPi. Stimulation in each DBS target had similar therapeutic effects, however, antidromic activation of M1 was only observed during STN DBS. Although both animals undergoing STN DBS had similar beneficial effects, the proportion of antidromic-classified cells in each differed, 30 versus 6%. Over 4 h of continuous STN DBS, antidromic activation became less robust, whereas therapeutic benefits were maintained. Although antidromic activation waned over time, synchronization of spontaneous spiking in M1 was significantly reduced throughout the 4 h. Although we cannot discount the potential therapeutic role of antidromic M1 activation at least in the acute phase of STN DBS, the difference in observed antidromic activation between animals, and target sites, raise questions about its hypothesized role as the primary mechanism underlying the therapeutic effect of DBS. These results lend further support that reductions in synchronization at the level of M1 are an important factor in the therapeutic effects of DBS. SIGNIFICANCE STATEMENT Recently there has been great interest and debate regarding the potential role of motor cortical activation in the therapeutic mechanisms of deep brain stimulation (DBS) for Parkinson's disease. In this study we used chronically implanted high density microelectrode arrays in primary motor cortex (M1) to record neuronal population responses in parkinsonian nonhuman primates during subthalamic nucleus (STN) DBS and globus pallidus internus (GPi) DBS. Our results suggest a contribution of antidromic activation of M1 during STN DBS in disrupting synchronization in cortical neuronal populations; however, diminishing antidromic activity over time, and differences in observed antidromic activation between animals and target sites with antidromic activation not observed during GPi DBS, raise questions about its role as the primary mechanism underlying the therapeutic effect of DBS.

Original languageEnglish (US)
Pages (from-to)2166-2177
Number of pages12
JournalJournal of Neuroscience
Issue number10
StatePublished - Mar 4 2020

Bibliographical note

Funding Information:
Received Oct. 17, 2019; revised Jan. 23, 2020; accepted Jan. 28, 2020. Author contributions: L.A.J., J.W., M.D.J., and J.L.V. designed research; L.A.J., J.W., S.D.N., and J.Z. performed research;L.A.J.andJ.W.contributedunpublishedreagents/analytictools;L.A.J.,J.W.,S.D.N.,andJ.Z.analyzeddata; L.A.J., J.W., and J.L.V. wrote the paper. This work was supported by NIH NINDS: R01NS037019, R37NS077657, P50 NS098573, R01NS110613; and by MnDRIVE (Minnesota’s Discovery, Research and Innovation Economy) Brain Conditions Program, Engdahl Family Foundation. Conflicts of interest: J.L.V. serves as a consultant for Medtronic, Boston Scientific, and Abbott, and serves on the scientific advisory board for Surgical Information Sciences. The remaining authors declare no competing financial interests. *L.A.J. and J.W. contributed equally to this work. Correspondence should be addressed to Jerrold L. Vitek at

Publisher Copyright:
Copyright © 2020 the authors.


  • Basal ganglia
  • Deepbrainstimulation
  • Hyperdirectpathway
  • Nonhumanprimate
  • Parkinson'sdisease
  • Primarymotorcortex
  • Parkinsonian Disorders
  • Globus Pallidus/physiology
  • Macaca mulatta
  • Deep Brain Stimulation/methods
  • Motor Cortex/physiology
  • Animals
  • Female
  • Subthalamic Nucleus/physiology

PubMed: MeSH publication types

  • Research Support, Non-U.S. Gov't
  • Journal Article
  • Research Support, N.I.H., Extramural


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