# Biological Determinants of Impulsivity in Parkinson's Disease

> **NIH NIH R01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2020 · $388,162

## Abstract

PROJECT SUMMARY
Motor symptoms in Parkinson's disease (PD) are effectively managed by dopamine-based therapies, yet
behavioral changes in patients can arise as an unintended consequence. Symptoms characterized by
persistent participation in reward-driven activities result in significant morbidity to patients and caregivers. The
descriptive term for these symptoms, impulsive and compulsive behaviors, captures the aberrant, goal-
directed, decision-making phenomenology typified in this clinical condition. Symptoms range from
hypersexuality to compulsive eating, gambling, shopping, and excessive participation in certain hobbies.
Impulsive and compulsive behaviors are more commonly manifest in patients taking dopamine agonist therapy,
and behaviors can abate with reduction or discontinuation of their use. Indeed, other therapeutic interventions,
including deep brain stimulation and levodopa, are associated with the genesis of maladaptive behaviors, and
overall, these symptoms appear to localize to a dysfunctional, or `overdosed', mesocorticolimbic dopamine
system. This proposal will characterize the biological determinants of impulsive and compulsive behaviors in
PD, with specific focus on the role of dopamine agonist therapy and the mesolimbic dopamine network. We
propose a series of experiments that will determine distinct functional brain changes in response to dopamine
agonist use in patients with and without impulsive and compulsive behaviors. Our first aim is to identify how the
cerebral hemodynamic response to dopamine agonists distinguishes patients with impulsive and compulsive
behaviors. We hypothesize that these patients have an exaggerated, or increased, mesolimbic hemodynamic
response to dopamine agonist therapy. Hemodynamic changes will be linked to neurocognitive assessments of
reward-based decision making and risk preference, emphasizing the coherence between physiologic brain
changes and the behavioral response to medication. Next, we aim to determine how dopamine therapy can
differentially alter inhibitory gamma-aminobutyric acid (GABA) neurotransmission in patients susceptible to
impulsive and compulsive behaviors. Finally, we will test the hypothesis that releasable dopamine stores in the
mesolimbic dopamine system are greater in patients susceptible these behaviors, thus linking a biological
mechanism the etiology of these maladaptive behaviors. Completion of this study will pave the way for the use
of non-invasive, quantitative outcomes in PD necessary for future target validation studies and early-phase
drug discovery. Also, we will provide direct evidence that dopamine therapy acts on extra-striatal neural
networks, linking regional changes in neural activity to dopamine-induced alterations to GABA levels. This work
will advance the field to engaging novel therapeutic targets essential to effective treatment of impulsive and
compulsive behaviors. Ultimately, this work will guide the development of improved, individualized ther...

## Key facts

- **NIH application ID:** 9928126
- **Project number:** 5R01NS097783-05
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Daniel Oliver Claassen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $388,162
- **Award type:** 5
- **Project period:** 2016-08-01 → 2021-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9928126

## Citation

> US National Institutes of Health, RePORTER application 9928126, Biological Determinants of Impulsivity in Parkinson's Disease (5R01NS097783-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9928126. Licensed CC0.

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