# Reward Encoding and Anxiety

> **NIH NIH R01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2020 · $480,428

## Abstract

PROJECT
SUMMARY/ABSTRACT
Anxiety
is
a
debilitating symptom of most psychiatric disorders including PTSD, major depression,
schizophrenia, autism and addiction. Treatment of anxiety is mostly limited to benzodiazepines, which have
abuse potential and produce multiple cognitive and behavioral side effects, including increased propensity to
develop dementia. Design of alternative treatments or prevention strategies is contingent upon a better
understanding of the neuronal basis of anxiety. While animal studies have so far informed us about the
functional neuroanatomy of fear and anxiety, the negative impact of real-life anxiety extends beyond aversive
feelings and involves disruptions in ongoing goal-directed behaviors. For example, anxiety is associated with
deficits in flexible control of reward-driven actions and expression of motivated behavior when it is subject to
the risk of an aversive outcome. The neural basis of these behavioral deficits is largely unknown. Thus, the
overarching research question that drives the experimental aims of this application is: How does anxiety affect
neuronal encoding of goal-directed behaviors? To address this question, a major challenge of the experimental
approach is to create a background state of anxiety that does not prohibit animals to perform goal-oriented and
rewarded tasks during electrophysiological recordings from multiple regions. With this in mind, we propose to
use two complementary experimental models of anxiety in combination with innovative and clinically relevant
behavioral tasks while measuring dynamic coordination between neurons of two regions implicated in reward
processing and flexible control of behavior: ventral tegmental area (VTA) and dorsomedial prefrontal cortex
(dmPFC). Specific aims are designed based on a computational-style model with assumptions that are
supported by preliminary data: (1) behavioral differences (between control and anxiety states) are specific to
conditions that involve action selection under conflict or the risk of an aversive outcome; (2) differences
(between control and anxiety states) in neuronal activity are observed during conflict/aversive outcomes and
involve diminished recruitment of action encoding neurons in dmPFC and disrupted coordination between
dmPFC neural activity and VTA dopamine neurons. This approach is novel and significant because a
neurocomputational understanding of aberrant neural activity relevant to symptoms such as anxiety can help
identify biological markers and clinical measures that delineate etiology and physiology of those symptoms.

## Key facts

- **NIH application ID:** 9878131
- **Project number:** 5R01MH115027-03
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** BITA MOGHADDAM
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $480,428
- **Award type:** 5
- **Project period:** 2018-06-01 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9878131

## Citation

> US National Institutes of Health, RePORTER application 9878131, Reward Encoding and Anxiety (5R01MH115027-03). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9878131. Licensed CC0.

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