# Pathophysiology-based approaches to deep brain stimulation for Parkinson's disease

> **NIH NIH P50** · UNIVERSITY OF MINNESOTA · 2021 · $367,644

## Abstract

ABSTRACT (Project 1)
Parkinson’s disease (PD) is a progressive neurodegenerative disease affecting over 10 million people world-
wide. It can be a debilitating disorder and although studied for decades the physiological changes in the basal
ganglia thalamocortical (BGTC) circuit that underlie its development remain under debate. Deep brain stimulation
(DBS) of the subthalamic nucleus (STN) and internal globus pallidus (GPi) has been a highly effective therapy
for many patients with PD, however, the results have been highly variable and may be associated with cognitive
compromise in some patients. To advance DBS therapies for PD we require a deeper understanding of the local
and network-wide circuit dynamics and their relationship to motor signs and cognitive function. This
understanding will provide the rationale for optimizing STN and GPi DBS, targeting specific regions within the
STN and GPi, and development of patient-specific DBS based on the patients’ motor signs and cognitive profile.
The goals of this study are to advance our understanding of the role of BGTC (subcortical-cortical) and
cortical-cortical circuits in the development of PD, the changes that occur with DBS and L-dopa, and to
use this understanding to advance current and develop new DBS approaches for its treatment. We will
define the relationship between synchronized oscillations, coherence and connectivity within the broader BGTC
circuit (STN, GPi, sensory, motor, premotor and dorsolateral prefrontal cortices) to the development of PD motor
signs, define their role in motor performance (SA1,2), cognitive function (SA1,2,3), and corresponding changes
with DBS, L-dopa and DBS+L-dopa (SA2). By defining the strength and direction of connectivity patterns at rest
and during movement we will characterize the role of individual circuits within the BGTC network and define their
respective roles in motor performance and cognitive function paving the way for future development of
optimization algorithms for DBS that take advantage of this understanding (SA1,2,3,4). By correlating the degree
of coherence between multiple single cells and local field potential (LFP) activity we will also advance our
understanding of the role of spike-phase locking to the development of motor signs. Through high resolution
imaging techniques and parcellation analyses we will define the optimal site for DBS within the STN and GPi
(SA2,3,4) correlating motor and cognitive outcomes to biomarker activity and lead location, leading to patient-
specific DBS and development of automated programming algorithms based on each patient’s phenotype and
lead location. The proposed aims will be conducted using directional DBS leads, multiple independent current
controlled (MICC) devices, high resolution imaging and electrophysiological recordings in PD patients with
electrocorticography (ECoG) arrays undergoing microelectrode mapping (SA1,3), postoperatively in patients
with ECoG arrays and externalized leads (SA2,3), a...

## Key facts

- **NIH application ID:** 10282962
- **Project number:** 1P50NS123109-01
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Jerrold L Vitek
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $367,644
- **Award type:** 1
- **Project period:** 2021-09-17 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10282962

## Citation

> US National Institutes of Health, RePORTER application 10282962, Pathophysiology-based approaches to deep brain stimulation for Parkinson's disease (1P50NS123109-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10282962. Licensed CC0.

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