# The Pathophysiology of Network Synchrony in Parkinson's Disease

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $212,441

## 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 DBS implantation surgery. This approach enables superior investigation of spatially specific cortical
phenomena 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
are 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 in PD 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 network coupling in PD....

## Key facts

- **NIH application ID:** 9997707
- **Project number:** 5R01NS097782-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** NADER POURATIAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $212,441
- **Award type:** 5
- **Project period:** 2016-09-30 → 2021-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9997707

## Citation

> US National Institutes of Health, RePORTER application 9997707, The Pathophysiology of Network Synchrony in Parkinson's Disease (5R01NS097782-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9997707. Licensed CC0.

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