# A Novel Bench-to-Bedside Translational Model of Anhedonia

> **NIH NIH R01** · UNIVERSITY OF NEW MEXICO · 2022 · $352,392

## Abstract

Although considered a trans-diagnostic phenotype, anhedonia can emerge from deficits in motivation,
valuation, or hedonic appreciation, each of which reflect different neural processes and are differently
expressed across individuals. There is a critical need to refine the construct of anhedonia in order to improve
treatment. Our long-term goal is to combine computational, imaging, and causal manipulations to define a
translational biomarker of diminished valuation in anhedonia. In this proposal we identify how the EEG
response known as the Reward Positivity (RewP) is a candidate biomarker specific to value-based deficiencies
in anhedonia. The RewP is only elicited by the presentation of a rewarding outcome, it is decreased in
depression, and it scales with the central feature of reinforcement learning models, the positive reward
prediction error (+RPE). Importantly, this same neural response can be elicited in rodents using the same
learning task as in humans. The objective of this proposal is to test whether induced emotion, depressed
mood, and learned helplessness (in mice) directly diminish +RPE coding in the RewP. The rationale for this
approach is that electrophysiology is a highly promising tool for identifying mechanisms of complex behaviors
and translating these mechanisms between species. In Aim 1, we will determine if induced emotion and +RPE
have independent or interactive effects on the RewP. In Aim 2 we will recruit depressed participants and
determine if anhedonia and +RPE have independent or interactive influences on the source-level generators
underlying the RewP (using MEG). In Aim 3 we will use the same task in a mouse model with infralimbic
recordings; we will then test the causal diminishment (learned helplessness) and recovery (fluoxetine) of this
mechanism. This proposed research is innovative because we have identified a computational function tightly
tied to a neural response that directly addresses the disease-specific phenotype in human patients and is
capable of being assessed, manipulated, and recovered within a rodent model. This contribution is expected to
be significant because it will advance a translational mechanism for deficient valuation in anhedonia. Upon
completion of these aims, the expected outcome will validate the RewP as a sensitive and specific mechanism
of aberrant valuation in anhedonia. In line with the RDoC framework, our use of computational modeling will
allow us to algorithmically contrast multiple sub-constructs of approach motivation in the positive valence
systems domain. The translational computational psychiatry approach advanced here links circuit-level
dysfunction, aberrant computations, and trans-diagnostic behavioral phenotype. The successful completion of
the aims advanced here will create what we think is the most promising path for combining these strengths into
a computationally-inspired, mechanistically tested, translatable model of aberrant valuation in anhedonia. This
novel candi...

## Key facts

- **NIH application ID:** 10337129
- **Project number:** 5R01MH119382-04
- **Recipient organization:** UNIVERSITY OF NEW MEXICO
- **Principal Investigator:** JAMES F CAVANAGH
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $352,392
- **Award type:** 5
- **Project period:** 2019-03-14 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10337129

## Citation

> US National Institutes of Health, RePORTER application 10337129, A Novel Bench-to-Bedside Translational Model of Anhedonia (5R01MH119382-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10337129. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*