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

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA SANTA CRUZ · 2023 · $377,338

## Abstract

ABSTRACT
 Alzheimer’s Disease (AD) is one of the most prevalent age-related neurodegenerative disorders with
devastating effects on a broad range of brain functions from memory to decision making. While it is well known
that AD impairs cognitive functions, neuropsychiatric symptoms are common in those at risk of or with AD and
predict the incidence of cognitive impairment. Human brain imaging studies have highlighted a network of brain
regions, particularly the medial prefrontal cortex (mPFC), the anterior insular cortex (aIC), and midbrain
dopamine (DA) regions, as the potential interface between cognitive and affective processing. Furthermore,
comparative neuroanatomy and developmental genetics have identified in mice brain regions evolutionarily
related to human mPFC, aIC, and DA regions. The overall objective of our parent grant (R01MH127737) is to
elucidate the fronto-insular circuit mechanisms underlying cognitive-affective interactions during flexible
decision-making and the impact of stress on such mechanisms in mice. Frontal cortical association areas
typically show early appearance of amyloid pathology during AD progression. However, how amyloid pathology
impacts long-range cortical projections mediating cognitive-affective interactions during decision-making has not
been investigated. This administrative supplement extends our mechanistic investigation of fronto-insular
network in cognitive-affective interactions during decision-making to mouse genetic models of AD. We
hypothesize that the balanced neural communication in mPFC-aIC-DA circuits is progressively impaired
by amyloidosis, leading to the impairment of cognitive flexibility. Using amyloidosis mice (APP/PS1 and
5xFAD), we propose two aims. Aim 1 determines how amyloidosis affects mPFC-aIC connectivity and function;
Aim 2 defines the impact of amyloidosis on DA modulation of mPFC and aIC function. With preliminary data
obtained through this supplement, we will apply for NIA funding to further investigate the mechanistic links among
progressive changes in neural activity, synaptic morphology, and amyloid pathology in fronto-insular circuits in
AD mouse models, and to explore fronto-insular circuit modulation paradigms to protect against the pathological
progression and cognitive decline associated with AD.

## Key facts

- **NIH application ID:** 10715606
- **Project number:** 3R01MH127737-02S1
- **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:** $377,338
- **Award type:** 3
- **Project period:** 2022-04-05 → 2027-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10715606

## Citation

> US National Institutes of Health, RePORTER application 10715606, Fronto-insular network in cognitive-affective interactions during decision-making (3R01MH127737-02S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10715606. Licensed CC0.

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