# The Pathophysiology of Network Synchrony in Parkinson's Disease

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 2024 · $635,036

## Abstract

Project Summary/Abstract
The physiological underpinning of motor symptoms in Parkinson disease (PD) remains incompletely understood.
We propose that the dynamic nature of basal ganglia thalamocortical (BGTC) network activity accounts for and
is critical for understanding the dynamic symptomatology of PD and the pathophysiology of disease. We believe
that the failure to focus on and investigate the non-stationarity of BGTC physiology and movement kinematics
significantly contributes to inconsistency in published results and has impeded progress. We propose and
investigate a novel model that accounts for the underexplored temporally dynamic cascade of physiological
events occurring between nodes in the BGTC motor circuit. We hypothesize that transient exaggerations in
network-level coupling that result in impaired information flow trigger pathophysiological and motor sequelae of
PD, including rigidity and bradykinesia, allowing for and differentiating pathological and non-pathological
synchrony. We hypothesize that the likelihood of pathological synchrony resulting in impaired information flow
depends on the “movement” state, accounting for disproportionate difficulty with movement initiation in PD. We
also hypothesize that treatment (dopaminergic and deep brain stimulation [DBS]) decreases the probability of a
synchrony-triggered pathological cascade, with some common final changes in the network (e.g., cortical phase
amplitude coupling) but with specific differences in physiological effects due to distinct sites of therapeutic action.
We will build on prior success of investigating PD network physiology in patients undergoing DBS implantation
surgery by simultaneously assessing population level activity from multiple BGTC nodes, including motor cortex,
dorsal premotor cortex (to where pallidal-receiving thalamic regions project), subthalamic nucleus (STN), and
globus pallidus (GPi, in separate patients), in relation to clinical symptoms and behavior. We now also integrate
single unit physiology and synchronized dynamic tasks to test our model. In Aim 1, we will establish the dynamic
relationship between network synchronization, local oscillations, and pathophysiologic sequelae under different
therapeutic conditions, including STN and GPi DBS and dopaminergic therapy. We hypothesize an increased
probability of synchrony leading to pathologic sequelae in the “off” state and test specific hypotheses about both
common and distinct physiological effects of the different therapies, depending on site of action. In Aim 2, we
hypothesize and aim to demonstrate that movement-related brain states affect sequelae of network synchrony
both physiologically and behaviorally, differentially impacting movement initiation and ongoing activity. Finally,
in Aim 3, we will distinguish normal and pathologic synchrony (across therapeutic and movement conditions)
using a novel information theoretic frameowrk, with a focus on the impact of criticality, complexity matchin...

## Key facts

- **NIH application ID:** 10890880
- **Project number:** 5R01NS097782-08
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** NADER POURATIAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $635,036
- **Award type:** 5
- **Project period:** 2016-09-30 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10890880

## Citation

> US National Institutes of Health, RePORTER application 10890880, The Pathophysiology of Network Synchrony in Parkinson's Disease (5R01NS097782-08). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10890880. Licensed CC0.

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