# The motor network in Parkinson's disease: Mechanisms of therapy

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $352,917

## Abstract

Our long-term goal is to understand the brain rhythms underlying specific signs and symptoms of
movement disorders at fast time scales, determine the effects of deep brain stimulation (DBS) on these brain
rhythms, and utilize this knowledge to develop closed loop or “adaptive” stimulation. DBS of the globus pallidus
(GP) is increasingly performed for Parkinson's disease (PD), based on its greater safety with respect to
cognition and mood compared with subthalamic nucleus (STN) DBS, but its mechanism is not well understood.
Invasive field potential recordings in the basal ganglia in humans has led to the influential hypothesis that
specific patterns of abnormal oscillatory synchronization underlie the motor signs of PD. Abnormal rhythms in
the beta band (13-30 Hz) are thought to be “antikinetic” while higher frequency (60-90 Hz) rhythms are
“prokinetic.” Other frequencies may be “tremorogenic”. Our general approach is to extend this conceptual
foundation to motor cortex and utilize network analyses from simultaneous cortical and subcortical recordings.
 In the initial grant period 2014-18, we focused on STN and its cortical interactions. Here, we will study
pallidal and pallidocortical responses to levodopa and pallidal DBS, utilizing the technical approach developed
in the previous grant period: chronic multisite field potential recording from basal ganglia and cortical
electrodes, utilizing a totally implantable bidirectional neural interface. We employ a newly available second
generation interface, RC+S (Medtronic) which holds substantial advantages with respect to recording quality
and programmability over the first generation device (PC+S). We will use this device to understand
electrophysiologic effects of antiparkinsonian medications (Aim 1) and of therapeutic pallidal DBS (Aim 2) on
the basal-ganglia thalamocortical circuit; and build on these results to prototype algorithms for adaptive
stimulation in which brain signals are utilized to adjust stimulation parameters according to changing brain
needs (Aim 3). In addition to in-clinic recordings in defined medication states (on or off), we will use home
recordings, with continuous “data streaming” from the implanted device and from wearable monitors, to
increase the odds of biomarker identification.
 The impact of these studies will be to: 1) Provide a mechanistic understanding of the effects of
therapeutic pallidal DBS on the basal ganglia-thalamocortical circuit. This may translate into improved
physiological criteria for electrode placement and to rational and streamlined programing strategies. 2) Create
a foundation for the development of “adaptive” DBS, perhaps the first major technical advance in DBS therapy
since its introduction 25 years ago. 3) Develop a novel paradigm in human neuroscience, that of chronic
ambulatory brain network recording in totally naturalistic environments, providing a platform for answering
fundamental questions on basal ganglia-cortical interactions. Mechani...

## Key facts

- **NIH application ID:** 9873075
- **Project number:** 5R01NS090913-06
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** PHILIP Andrew STARR
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $352,917
- **Award type:** 5
- **Project period:** 2014-09-30 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9873075

## Citation

> US National Institutes of Health, RePORTER application 9873075, The motor network in Parkinson's disease: Mechanisms of therapy (5R01NS090913-06). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9873075. Licensed CC0.

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