# Emotion network dysfunction and decline in early frontotemporal dementia

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $641,476

## Abstract

ABSTRACT
Frontotemporal dementia (FTD) is a neurodegenerative disease that is characterized by progressive decline in
social behavior, emotion, and language. In behavioral variant FTD (bvFTD), the most common FTD subtype,
impairment in emotion and empathy are hallmark features that arise due to degeneration of emotion circuits.
Although bvFTD begins in frontoinsula and anterior cingulate cortex, brain regions with known roles in
visceromotor emotion generation and autonomic integration, the earliest signs of emotion system dysfunction
are unknown. Approximately 40% of FTD cases are genetic and due to mutations in C9ORF72, GRN, and
MAPT. Gene-positive mutation carriers offer a novel inroad into early emotion alterations in FTD because
these individuals can be identified, studied, and followed during the asymptomatic, preclinical phase of disease
and in the early symptomatic clinical phase. Changes in emotion physiology and behavior may occur early in
the disease, reflect decline in emotion-relevant brain networks, and relate to affective symptoms. The proposed
studies will help to characterize preclinical emotion deficits and their underlying circuitry and to determine
whether these deficits are early indicators of decline in FTD. Anatomically-specific markers could be used to
monitor symptom progression or to track disease-related dysfunction in clinical trials of asymptomatic or mildly
symptomatic individuals. This proposal integrates laboratory measures of autonomic nervous system reactivity
and facial expression with multi-modal neuroimaging techniques to identify how emotion systems change in the
earliest stages of FTD. We will study 100 asymptomatic gene-positive subjects (50 C9ORF72+, 30 GRN+, and
20 MAPT+), 50 healthy controls (age-matched, gene-negative family members), 40 patients with bvFTD, and
40 older age-matched healthy controls at two annual research visits. Subjects will undergo laboratory testing of
emotion in addition to a clinical work-up and structural and functional connectivity magnetic resonance
imaging. The central hypothesis of this proposal is that objective measures of emotion physiology and behavior
are direct readouts of vulnerable brain systems that can be measured noninvasively and track progression in
the in preclinical and early symptomatic phase of FTD. We will address three key aims. In Aim 1, we will isolate
the domains of emotional dysfunction in early FTD and determine how specific emotional deficits relate to
behavioral and affective symptoms. In Aim 2, we will delineate the neural circuitry underlying identified
emotional deficits in bvFTD and preclinical FTD. In Aim 3, we will identify laboratory measures that track
emotion network decline over time in early FTD. This project has the potential to advance current models of the
biological basis of emotion dysfunction in FTD and other clinical disorders that have similar emotional
symptoms but lack obvious brain lesions.

## Key facts

- **NIH application ID:** 9833478
- **Project number:** 5R01AG052496-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Virginia Emily Sturm
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $641,476
- **Award type:** 5
- **Project period:** 2016-12-15 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9833478

## Citation

> US National Institutes of Health, RePORTER application 9833478, Emotion network dysfunction and decline in early frontotemporal dementia (5R01AG052496-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9833478. Licensed CC0.

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