# The Pathophysiology of Network Synchrony in Parkinson's Disease

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 2020 · $246,462

## Abstract

Project Summary/Abstract
The pathophysiology underlying the motor symptoms of Parkinson’s disease (PD) remains incompletely
understood with recent conflicting reports of changes in neuronal activity in distinct nodes within the basal
ganglia-thalamocortical (BGTC) motor circuit. A unified approach that accounts for conflicting results is
needed. Emphasizing the relatively underexplored dynamic relationship between nodes in the circuit, we build
upon the hypothesis that exaggerated network-level coupling is the pathophysiologic process underlying the
rigidity and bradykinesia of PD by impeding effective information flow. Accordingly, we propose that modulation
of network coupling is the common therapeutic mechanism across pharmacologic and surgical therapies; other
physiologic sequelae are specific to the target of therapeutic intervention and account for disparate results in
the literature. We will simultaneously assess cortical and subcortical physiology in relation to clinical symptoms
and in response to deep brain stimulation (DBS), cortical stimulation and pharmacologic therapy in patients
undergoing deep brain stimulation (DBS) implantation surgery. This approach enables superior investigation of
spatially specific cortical phenomenon compared to extraoperative studies. We propose that it is critically
important to understand the functional connectivity of the extended BGTC network, including not only the motor
cortex with subthalamic nucleus (STN) as most studies do, but also connectivity with globus pallidus internus
(GPi, the final common output of the basal ganglia) and the supplementary motor area (SMA) and dorsal
premotor cortex (PMd), which is to where pallidal-receiving thalamic regions dominantly project. Moreover, our
analyses will focus on the differential physiological significance of low vs high β oscillations with respect to
normal motor function, disease, and therapeutic intervention. In Specific Aim 1, we aim to understand the
clinical correlates of the untreated BGTC motor network both at rest and with movement, taking specific
advantage of temporal variation in disease symptomatology (as measured with objective clinical rating scales
and comprehensive kinematics) with simultaneously recorded measures of network connectivity. In Specific
Aim 2, we will use subcortical and cortical stimulation to specifically perturb distinct nodes in the BGTC motor
network, in order to confirm that network coupling is the common mechanism underlying therapeutic brain
stimulation, regardless of target, and to also identify target specific effects that can account for known clinical
differences in DBS at STN vs GPi. Finally, in Specific Aim 3, we will evaluate pharmacologic modulation of the
BGTC motor network, with an aim to understand the temporal relationships between symptom amelioration
and network modulation. Taken together, we will significantly enhance the existing BGTC motor network wiring
diagram by elucidating the role of motor netw...

## Key facts

- **NIH application ID:** 10429875
- **Project number:** 7R01NS097782-06
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** NADER POURATIAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $246,462
- **Award type:** 7
- **Project period:** 2021-04-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10429875

## Citation

> US National Institutes of Health, RePORTER application 10429875, The Pathophysiology of Network Synchrony in Parkinson's Disease (7R01NS097782-06). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10429875. Licensed CC0.

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