# Emotion network dysfunction and decline in early frontotemporal dementia

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2024 · $789,467

## Abstract

ABSTRACT
Frontotemporal dementia (FTD) is a family of neurodegenerative syndromes characterized by progressive
decline in emotion, social behavior, and language. The behavioral variant of FTD is the most common clinical
subtype and is characterized by deficits in emotion, empathy, and social behavior. FTD is often sporadic but
can be caused by genetic mutations in C9orf72, GRN, and MAPT. Genetic forms of FTD offer a critical window
into the disease's early stages because individuals with genetic mutations can be identified, studied, and
followed when they are asymptomatic and as they enter the symptomatic stage of the disease. Our previous
laboratory-based studies have found alterations in autonomic nervous system activity, facial expression, and
experience occur early in FTD and reflect dysfunction in specific brain networks. Anatomically specific emotion
biomarkers could be used to monitor symptom progression or treatment response in clinical trials of
asymptomatic or mildly symptomatic individuals, but more scalable approaches are needed. The proposed
project will build on our prior laboratory-based studies of emotion in asymptomatic and symptomatic individuals
with FTD and will include longitudinal, multi-day assessments of emotion and behavior in the real world. These
data will allow us to test whether novel emotion biomarkers we have discovered in the laboratory can be
tracked with remote tools and will enable us to determine whether there are additional areas of change in early
FTD that have previously gone undetected. The central hypothesis of this proposal is that emotions are direct
readouts of vulnerable brain systems that can be used to monitor progression in the asymptomatic and early
symptomatic phase of FTD. We will conduct laboratory-based assessments of emotion in 100 mutation carriers
across the clinical spectrum, 50 mutation non-carrier family member controls, 50 people with sporadic
behavioral variant FTD, and 50 older healthy controls at three annual research visits that include a clinical
work-up and neuroimaging. We will also conduct five biannual remote assessments of emotion during which
we will measure real-world autonomic physiology (with wearable devices), behavior (with participants'
photographs and self-reported activities), and subjective feelings (with experience sampling methods). We will
address three key aims. In Aim 1, we will map the real-world landscape of emotion in asymptomatic mutation
carriers and early FTD and its associations with laboratory measures of emotion and affective symptoms. In
Aim 2, we will isolate the neural systems underlying FTD-relevant aberrations in emotion as measured in the
real world and laboratory. In Aim 3, we will quantify longitudinal emotion system decline in early FTD. By
integrating neuroimaging techniques with measures of emotion from the laboratory and the real world, this
project has the potential to advance current models of the biological basis of emotion dysfunction and...

## Key facts

- **NIH application ID:** 10795864
- **Project number:** 5R01AG052496-08
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Virginia Emily Sturm
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $789,467
- **Award type:** 5
- **Project period:** 2016-12-15 → 2027-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10795864

## Citation

> US National Institutes of Health, RePORTER application 10795864, Emotion network dysfunction and decline in early frontotemporal dementia (5R01AG052496-08). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10795864. Licensed CC0.

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