# Characterizing the pathophysiological role of the pallido-thalamocortical motor pathway in Parkinson's disease

> **NIH NIH R01** · UNIVERSITY OF MINNESOTA · 2024 · $615,116

## Abstract

ABSTRACT
Although studied for decades, the physiological changes in the basal ganglia thalamocortical (BGTC) circuit that
underlie the development of motor signs of Parkinson’s disease (PD) remain under debate. Excessive
synchronization and coherence in neural activity has been demonstrated within the internal segment of the
globus pallidus (GPi) and between GPi - motor cortex (M1). However, the relationship of coherence within and
across subcortical-cortical regions to severity of motor signs of PD, specifically bradykinesia, is not well
understood. Deep brain stimulation (DBS) targeting the posterolateral sensorimotor region of GPi has been
shown to be an effective location for reducing clinical motor signs, however, there is debate around the optimal
subregion (e.g. ventral vs. dorsal) within GPi for stimulation. There is evidence that stimulating the
pallidothalamic pathway, specifically the lenticular fasciculus, is associated with improved motor severity. There
is also evidence that GPi-M1 coherence reduces with DBS and is associated with improved bradykinesia.
However, the relationship between pathways and neurophysiological activity, is unknown. This project will
explore the spatial distribution of pathophysiological activity within the GPi and across the pallidothalamocortical
network, how it modulates with movement and changes stimulation directed toward regions of GPi exhibited
relatively high level of coherence with M1. This information will provide the rationale for the development of
precise, patient-specific stimulation paradigms and lay the groundwork for novel closed-loop stimulation
algorithms. The goals of this study are: 1) to describe the characteristics of low/high beta and high
frequency oscillations that underlie bradykinesia. 2) describe the characteristics and dynamics of
coherence in the beta band between GPi-M1 and their relationship to quantified measures of
bradykinesia, and 3) describe the relationship between pallidothalamic pathway activation and measures
of bradykinesia using real-time measure of GPi-M1 coherence to direction stimulation in GPi. This project
will leverage access to recordings in the operating room during DBS lead implant surgery to record simultaneous
local field potentials (LFP) from microelectrodes, segmented DBS leads and electrocorticography (ECoG) strips
while the patient performs a self-initiated reach-to-target task in order to examine the modulation of GPi-M1
coherence during movement (SA1,2). We will use high field 7T imaging and biophysical computational models
to correlate activated pallidothalamic pathways to changes in quantified measures of bradykinesia using real-
time measures of GPi-M1 coherence to direct stimulation toward regions of GPi showing relatively high or low
GPi-M1 coherence while the patients performs a self-initiated reach task (SA3). This study will provide the
rationale for precise biomarkers and pathway-based stimulation targeting within the sensorimotor region of...

## Key facts

- **NIH application ID:** 10800402
- **Project number:** 1R01NS128029-01A1
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Joshua E Aman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $615,116
- **Award type:** 1
- **Project period:** 2024-01-01 → 2028-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10800402

## Citation

> US National Institutes of Health, RePORTER application 10800402, Characterizing the pathophysiological role of the pallido-thalamocortical motor pathway in Parkinson's disease (1R01NS128029-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10800402. Licensed CC0.

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