# Optimizing coordinated reset deep brain stimulation for Parkinson's disease

> **NIH NIH R01** · UNIVERSITY OF MINNESOTA · 2022 · $625,645

## Abstract

PROJECT SUMMARY/ABSTRACT
Parkinson’s disease (PD) is a neurodegenerative disorder affecting 6-7 million people worldwide. Traditional
high frequency, isochronal deep brain stimulation (DBS) is an effective treatment for the motor signs associated
with PD. Clinical outcomes, however, vary across centers and within centers across patients. Adverse effects
can be induced by “current-spread” to unintended brain areas when the DBS lead is sub-optimally placed which
limits clinical benefits. Coordinated reset (CR) DBS is a promising novel DBS approach that has the potential to
overcome the limitations of traditional DBS. By alternating lower intensity stimulation delivered in a burst pattern
across different contacts of the DBS lead, CR DBS is associated with less current spread, thus reducing the
incidence of adverse effects, and improvement in motor signs that persist for days to weeks after cessation of
stimulation, i.e. carryover effect. Although the effectiveness of CR DBS has been demonstrated in both preclinical
and clinical studies, the selection of CR parameters that provide the greatest carryover effect has been
challenging. The optimal target for CR DBS must also be identified. The proposed study using a within-subject
experimental design will 1) optimize the critical parameter (cycle rate) of CR DBS, (2) compare the effect of CR
DBS in the subthalamic nucleus (STN) and internal segment of the globus pallidus (GPi), and (3) characterize
the changes in cortical and subcortical neuronal activities associated with its therapeutic effect. The nonhuman
primate model of PD will be used with each animal implanted with DBS leads in the STN and GPi and high-
density Utah arrays placed over the primary motor, dorsal premotor and dorsolateral prefrontal cortices.
Objective and quantitative motor assessments will be performed to measure the acute and carryover effect of
CR DBS with different cycle rates and in different targets (STN and GPi). The central hypothesis is that the
therapeutic effect of CR DBS is greatest when the cycle rate is based on subject-specific pathophysiological
biomarkers associated with the PD state. We further hypothesize that CR DBS in GPi will provide greater acute
benefits in motor signs and induce significantly longer carryover effects. We predict that motor improvements
induced by CR DBS will correlate with a reduction in synchronized neuronal activity within and across cortical
and subcortical nodal points in the basal-ganglia-thalamocortical (BGTC) circuit. The results of this study will
provide a time efficient approach for the selection of CR DBS cycle rate based on subject-specific biomarker
activity in the BGTC circuit, identify the optimal target for CR DBS and enhance our understanding of the
mechanism(s) underlying the therapeutic effect of CR DBS. Results of the study will significantly advance the
development of CR DBS for the treatment of PD that will enhance clinical outcomes, prolong battery life and
induce fe...

## Key facts

- **NIH application ID:** 10413216
- **Project number:** 5R01NS117822-03
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Jing Wang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $625,645
- **Award type:** 5
- **Project period:** 2020-09-30 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10413216

## Citation

> US National Institutes of Health, RePORTER application 10413216, Optimizing coordinated reset deep brain stimulation for Parkinson's disease (5R01NS117822-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10413216. Licensed CC0.

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