# Fronto-subthalamic modulation of movement inhibition in Parkinson's disease

> **NIH NIH F31** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $30,794

## Abstract

PROJECT ABSTRACT
Parkinson’s disease patients experience excessive motor inhibition when they are off dopaminergic
medications. Common symptoms include slowness in movements, rigidity, and freezing of gait. Dopaminergic
medication can lead to insufficient inhibition, producing involuntary movements. The circuit mechanisms of
motor inhibition in Parkinson’s disease, and how they are modulated by medication, are not fully understood. A
hyderdirect pathway between the inferior frontal cortex (IFC) and subthalamic nucleus (STN) has been
hypothesized to modulate rapid stopping. However, there is still no evidence of an IFC-STN hyperdirect
pathway in humans. Furthermore, spatiotemporally precise characterization of stopping-related activity in both
sites has never been studied in patients due to methodological constraints. The goal of this study is to use
multisite, high-resolution electrophysiology, in both acute and chronic settings, to assess the role of the IFC
and STN during movement inhibition in Parkinson’s patients. First, we will characterize the topography of
fronto-STN connectivity using acute, intraoperative, high-resolution electrocorticography in the prefrontal cortex
and penetrating deep brain electrodes in the STN. We will use short-latency evoked potentials to confirm a
monosynaptic hyperdirect pathway between the IFC and STN. Then, using the same intraoperative recording
paradigm, we will characterize the circuit’s role in rapid movement inhibition. Patients will perform a stop signal
task, and we will assess task-related IFC-STN coherence as a measure of connectivity during stopping. We
will perturb stopping-related activity by stimulating in task-relevant areas of the prefrontal cortex. Finally, we will
use a chronically implanted bidirectional neural interface, which has simultaneous recording and stimulation
capabilities, to assess how dopaminergic medications affect the IFC-STN circuit as patients fluctuate in
symptomatology. These experiments will be the first to characterize: 1) IFC-STN hyperdirect circuit anatomy,
2) IFC-STN circuit activity during stopping, and 3) IFG-STN network modulation by medication. This work will
inform pathophysiology for symptoms of abnormal movement inhibition, such as freezing of gait. It may lead to
the development of feedback-driven, therapeutic stimulation to perturb network activity and improve symptoms.

## Key facts

- **NIH application ID:** 9813518
- **Project number:** 5F31NS103410-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Witney Chen
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $30,794
- **Award type:** 5
- **Project period:** 2018-12-01 → 2020-02-02

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9813518

## Citation

> US National Institutes of Health, RePORTER application 9813518, Fronto-subthalamic modulation of movement inhibition in Parkinson's disease (5F31NS103410-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9813518. Licensed CC0.

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