Shuffling Improves the Acute and Carryover Effect of Subthalamic Coordinated Reset Deep Brain Stimulation

Jing Wang, Sinta P. Fergus, Luke A Johnson, Shane D Nebeck, Jianyu Zhang, Shivaputra Kulkarni, Hemant Bokil, Gregory F Molnar, Jerrold L. Vitek

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17 Scopus citations

Abstract

Coordinated reset deep brain stimulation (CR DBS) in the subthalamic nucleus (STN) has been demonstrated effective for the treatment of the motor signs associated with Parkinson's disease (PD). A critical CR parameter is an order in which stimulation is delivered across contacts. The relative effect of alternating vs. not alternating this order, i.e., shuffling vs. non-shuffling, however, has not been evaluated in vivo. The objective of this study is to compare the effect of shuffled vs. non-shuffled STN CR DBS on Parkinsonian motor signs. Two Parkinsonian non-human primates were implanted with a DBS lead in the STN. The effects of STN CR DBS with and without shuffling were compared with the traditional isochronal DBS (tDBS) using a within-subject design. For each stimulation setting, DBS was delivered for 2 or 4 h/day for 5 consecutive days. The severity of PD was assessed using a modified clinical rating scale immediately before, during, and 1 h after DBS, as well as on days following the discontinuation of the 5 days of daily stimulation, i.e., carryover effect. Shuffled STN CR DBS produced greater acute and carryover improvements on Parkinsonian motor signs compared with non-shuffled CR. Moreover, this difference was more pronounced when more effective stimulation intensity and burst frequency settings were used. tDBS showed limited carryover effects. Given the significant effect of shuffling on the effectiveness of CR DBS, it will be critical for future studies to further define the relative role of different CR parameters for the clinical implementation of this novel stimulation paradigm.

Original languageEnglish (US)
Article number716046
JournalFrontiers in Neurology
Volume13
DOIs
StatePublished - Feb 18 2022

Bibliographical note

Funding Information:
This study was supported by the National Institutes of Health (R01NS117822, P50NS098573, R01NS037019, and R37NS077657), a research grant from Boston Scientific, the Engdahl Family Foundation, and a fellowship award from the Parkinson’s Foundation. These funding sources played no additional role in the collection, analysis, or interpretation of the

Publisher Copyright:
Copyright © 2022 Wang, Fergus, Johnson, Nebeck, Zhang, Kulkarni, Bokil, Molnar and Vitek.

Keywords

  • Parkinson's disease
  • coordinated reset
  • deep brain stimulation
  • non-human primates
  • subthalamic nucleus

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