# Mechanisms and pathways mediating the motor effects of pallidal deep brain stimulation

> **NIH NIH P50** · UNIVERSITY OF MINNESOTA · 2020 · $366,672

## Abstract

Project Summary/Abstract
Deep brain stimulation (DBS) in the region of the globus pallidus (GP) or subthalamic nucleus (STN) has been
demonstrated to provide clinically meaningful improvements in motor function and improve patient quality of life
in people with Parkinson’s disease (PD). While the STN is the typical target of choice at most neurosurgical
centers, there has been a resurgence of interest in selecting the GP as a target. This interest is based on
evidence that the overall clinical effects are comparable to those of STN DBS, but GP DBS may have fewer
neuropsychological side-effects and affords greater flexibility for programming and adjustment of medications.
Yet, there is considerable variability in response to GP DBS across patients, levodopa dose typically remains
high, and, like STN DBS, is it ineffective for levodopa-resistant motor features such as postural instability, gait
disturbances and freezing of gait. We argue that significant improvements in the efficacy of GP DBS can be
gained through an increased understanding of the mechanisms, locations and pathways mediating the motor
effects of DBS in the human pallidum. The premise of this project is that the motor effects of conventional GP
DBS are compromised by a balance between the need to suppress levodopa-induced dyskinesias (akinetic)
and reduce bradykinesia (prokinetic). We will test the hypothesis that the mechanisms and locations mediating
these “opposite effects” are in functionally and topographically separate regions of the GP. This hypothesis will
be tested by conducting a systematic study of the effects of GP stimulation location on both levodopa-
responsive (rigidity and bradykinesia) and levodopa-resistant (balance, gait, freezing) motor features of PD
(Aim 2), and the topography of movement-related oscillatory activity within the pallidum (GPi and GPe) and
STN by recording local field potentials in people with chronically implanted electrodes (Aim 3). State-of-the-art
high-field MRI (7T) and patient-specific tractography-activation models will be used to focus stimulation to the
region of interest (ventral GPi, dorsal GPi, ventral GPe) and estimate the pallidofugal pathways activated by
stimulation (Aim 1). The results of these experiments will provide critical information about the stimulation
location and axonal pathways mediating improvement or deterioration of motor signs with GP DBS, the
neurophysiological biomarkers of disordered movement, and how these biomarkers are changed by
medication and DBS. This knowledge can be translated to the next generation of DBS devices that provide
current steering and closed-loop control to provide optimal therapeutic outcomes.

## Key facts

- **NIH application ID:** 9971613
- **Project number:** 5P50NS098573-05
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** COLUM D MACKINNON
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $366,672
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9971613

## Citation

> US National Institutes of Health, RePORTER application 9971613, Mechanisms and pathways mediating the motor effects of pallidal deep brain stimulation (5P50NS098573-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9971613. Licensed CC0.

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