# Vigor and the LDR in Parkinson disease

> **NIH NIH R21** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $390,000

## Abstract

Abstract
Dopamine replacement therapy (DRT) is the standard and very effective symptomatic treatment for early to
moderate Parkinson disease (PD). The most important DRT component is the Long Duration Response
(LDR), a pharmacodynamic effect that builds up over the course of weeks. DRT actions are poorly understood
and the basis of the LDR is unknown. As the LDR wanes in advancing disease, PD patients develop
troublesome motor fluctuations and increasing disability. LDR kinetics suggest long-term plastic changes in
striatal function. Studies of striatal dopamine actions indicate that striatal dopaminergic neurotransmission
regulates “vigor;” modulation of the velocity, amplitude, force, or frequency of movements. Vigor is closely
allied with the concept that striatal dopaminergic neurotransmission mediates motivation; assessment of act
utility and appropriate scaling of actions to perceived rewards. Recent theoretical and experimental results
suggest that tonic striatal dopamine signaling is a key determinant of movement vigor. Convergent clinical
pharmacologic and experimental data lead to a strong hypothesis that the LDR results from chronic DRT
partially restoring movement vigor. This model of the LDR requires stable “records” of action values. Recent
non-human primate work on saccadic eye movement vigor indicates the existence of striatal dopaminergic
neurotransmission stably encoding motor behavior values for prolonged periods – a potential mechanism for
the LDR. Prior experiments examining vigor in PD did not take the LDR into account, resulting in incomplete
examinations of the role of vigor deficits in PD. Our long-term goal is to understand the clinically relevant
actions of DRT. The primary objective of our proposal is to test the hypothesis that the LDR results from partial
restoration of normal movement vigor-motivation. Our secondary objective is to evaluate a potential
mechanism underlying the LDR. The rationale for these experiments is that better understanding of the LDR, a
clinically crucial component of DRT action, will lead to improved symptomatic therapy. We will study recently
diagnosed PD subjects. All subjects will undergo standard evaluations of clinical, cognitive, and motivational
features. Subjects will perform incentive motivation tasks assessing movement vigor – motivation coupling to
assess our primary hypothesis. A task assessing saccadic eye movement vigor in response to stable value
signals will be employed to evaluate our secondary hypothesis. They will perform all tasks before and after
LDR induction in both the “practical off” and post-acute treatment states. Validation of our hypotheses would
have considerable impact by identifying the functional process underlying the LDR and providing information
for uncovering the mechanisms of the LDR. This would facilitate research into LDR mechanisms, provide a
rational basis for developing valid animal models of the LDR, and open a new path towards improved
symptomatic ...

## Key facts

- **NIH application ID:** 9868676
- **Project number:** 1R21NS114749-01
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Roger L Albin
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $390,000
- **Award type:** 1
- **Project period:** 2019-12-01 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9868676

## Citation

> US National Institutes of Health, RePORTER application 9868676, Vigor and the LDR in Parkinson disease (1R21NS114749-01). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/9868676. Licensed CC0.

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