# Role of prefrontostriatal circuits in effort-based, cost-benefit decision making

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2023 · $536,764

## Abstract

PROJECT SUMMARY
Ongoing evaluation of cost-benefit tradeoffs guides action selection during adaptive decision making. When
outcomes change, the utility of potential actions is re-evaluated to determine whether to persist or deviate from
an existing strategy. Disturbances in the neural mechanisms underlying cost-benefit decision making can lead
to pathological behavior (e.g., addiction, OCD, depression/anxiety). Effort-based decision making is specifically
disrupted in patients with depression, schizophrenia and substance use disorders. Although pathological
behavior in these conditions is linked to dysfunction in the prefrontal cortex and striatum, we lack the detailed
neurobiological understanding necessary to design targeted therapeutic interventions. We will address this deficit
using cutting edge tools for measuring and manipulating neural activity in freely behaving animals. We will test
the specific hypothesis that anterior cingulate cortex (ACC) to nucleus accumbens (NAc) projection neurons
encode updates to action selection policies based on new effort-reward tradeoffs, and that inputs to the NAc
instantiate new, effortful choice strategies. In Aim 1, we will use miniaturized head-mounted microscopes to
determine how ACC and ACCàNAc projection neuron activity is organized to represent effort-related cost-
benefit computations influencing action selection. In Aim 2, we will manipulate the activity of ACCàNAc
projection neurons with optogenetics, during flexible decision making driven by changes in effort-related value.
Finally, in Aim 3, we will focus on prefrontal projections to the NAc, measuring and inhibiting activity at ACCàNAc
terminals and comparing with inputs from the orbitofrontal cortex (OFC). We will do this during decision making
in the context of both effort and delay-costs as a tool to further refine our understanding of how NAc integrates
prefrontal inputs and translates these into action selection. This proposal directly addresses a pressing need to
understand the cell-type and circuit-specific mechanisms that mediate cost-benefit decision making. Our
research can inform pharmacological, psychotherapeutic and brain stimulation interventions for a variety of
psychiatric conditions characterized by disordered cost-benefit evaluations and decision making.

## Key facts

- **NIH application ID:** 10737578
- **Project number:** 1R01MH131858-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Scott Allen Wilke
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $536,764
- **Award type:** 1
- **Project period:** 2023-08-01 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10737578

## Citation

> US National Institutes of Health, RePORTER application 10737578, Role of prefrontostriatal circuits in effort-based, cost-benefit decision making (1R01MH131858-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10737578. Licensed CC0.

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