# Fronto-insular network in cognitive-affective interactions during decision-making

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA SANTA CRUZ · 2023 · $484,279

## Abstract

PROJECT SUMMARY
 Complex decision-making often encompasses both cognitive and affective components. Cognitive and
affective processes engage distinct but interacting systems in the brain, and both systems are effected by stress,
a prevalent problem in modern society and a well-known risk factor for psychiatric disorders. Human brain
imaging studies suggest a network of brain regions as the potential interface between cognitive and affective
processing, particularly the medial prefrontal cortex (mPFC), the anterior insular cortex (aIC), and midbrain
dopamine (DA) regions such as the ventral tegmental area (VTA). However, these studies lack causality tests at
the neural circuit level. Comparative neuroanatomy and developmental genetics have identified in mice
evolutionarily related mPFC, aIC, and DA regions. The structure and function of these regions are also disturbed
by stress. These findings open the venue to use mouse as a model species for causal studies of the fundamental
functions of these brain regions with precise circuit manipulation tools. Our overall goal is to elucidate the
fronto-insular circuit mechanisms underlying cognitive-affective interactions during decision-making
and the impact of stress on such mechanisms in mice. Our proposal is based on published literature and
preliminary data showing: 1) mPFC, aIC and VTA are engaged in cognitive and affective decision-making; 2)
mPFC and aIC are directly connected and both receive DA inputs from VTA; 3) stress affects mPFC and aIC
neurons as well as DA release in these areas; 4) DA modulates mPFC and aIC activity and decision-making. By
combining projection-specific viral labeling of neural circuits with in vivo imaging/electrophysiology and
optogenetic/pharmacogenetic manipulations, we will test the central hypothesis that mPFC-aIC interaction is
crucial for decision-making, which is disrupted by chronic stress but rescuable via DA modulation.
Specifically, in Aim 1, we will determine the function of mPFC-aIC connections during decision-making in the
attentional set-shifting test. In Aim 2, we will examine how stress affects mPFC-aIC connectivity and function. In
Aim 3, we will define impact of stress on DA modulation of mPFC and aIC function, and explore the possibility
to rescuing decision-making by selectively restore DA modulation in mPFC or aIC in stressed mice. The
successful outcomes of this project will not only provide fundamental knowledge about the circuit mechanisms
underlying higher brain functions, but also point out potential therapeutic targets for alleviating the detrimental
effects of stress and psychiatric illnesses.

## Key facts

- **NIH application ID:** 10602555
- **Project number:** 5R01MH127737-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA SANTA CRUZ
- **Principal Investigator:** Kuan Hong Wang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $484,279
- **Award type:** 5
- **Project period:** 2022-04-05 → 2027-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10602555

## Citation

> US National Institutes of Health, RePORTER application 10602555, Fronto-insular network in cognitive-affective interactions during decision-making (5R01MH127737-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10602555. Licensed CC0.

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