# Functional Dissection of Neural Circuitry in Temporally Patterned Deep Brain Stimulation

> **NIH NIH R15** · MICHIGAN TECHNOLOGICAL UNIVERSITY · 2020 · $463,747

## Abstract

Deep brain stimulation (DBS) is an established treatment for various neurological and psychiatric disorders
including Parkinson’s disease (PD). Subthalamic nucleus (STN) and globus pallidus interna (GPi) are current
anatomical targets and clinically effective for DBS in PD. Clinical studies reported no significant difference in
effective treatment between these two targets, although additional interest has been prompted in GPi-DBS due
to increased concerns about cognitive and behavioral side effects of STN-DBS. The therapeutic effects of DBS
are highly dependent on stimulation parameters. With the selection of appropriate stimulation amplitude and
pulse duration, high frequencies of DBS alleviate PD motor symptoms. Recent studies demonstrated that the
effects of DBS were also strongly dependent on the timing between stimulation pulses (temporal pattern).
Optimized temporal patterns of stimulation at a lower average frequency could relieve motor deficits and reduce
adverse side effects. Despite the promising clinical benefits, the lack of understanding of the effects of temporal
patterns of DBS on neuronal and behavioral dynamics limits the development of this promising treatment strategy
as well as optimal selection of DBS targets. The goal of our research is to reveal the relationships between
specific temporal patterns of DBS in STN and GPi and (i) neural activity in STN and GPI associated circuits and
(ii) motor function in PD. We will combine computational design, optogenetic manipulation, electrophysiological
recording, and behavioral assays to dissect and optimize the therapeutic effects of temporally patterned STN-DBS and GPi-DBS in a rodent model of PD. Our specific aims are to: (1) Design and validate temporal patterns
of optogenetic STN-DBS and GPi-DBS to treat parkinsonian motor symptoms; (2) Determine the relationship
between neural activity in the STN-thalamic or GPi-thalamic neural circuits and motor function during temporally
patterned optogenetic STN-DBS and GPi-DBS. The results from this proposed research will shed light on the
functional role of the temporal patterns of DBS in PD treatment. A better understanding of how temporally
patterned DBS exerts its therapeutic effects will make a significant contribution to optimal target selection and
the development of novel treatment strategies to improve the efficacy and efficiency of DBS in PD and other
neurological and psychiatric disorders.

## Key facts

- **NIH application ID:** 10046820
- **Project number:** 1R15NS115032-01A1
- **Recipient organization:** MICHIGAN TECHNOLOGICAL UNIVERSITY
- **Principal Investigator:** Chunxiu Yu
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $463,747
- **Award type:** 1
- **Project period:** 2020-09-15 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10046820

## Citation

> US National Institutes of Health, RePORTER application 10046820, Functional Dissection of Neural Circuitry in Temporally Patterned Deep Brain Stimulation (1R15NS115032-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10046820. Licensed CC0.

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