# Project 2:  Contribution of Traumatic Brain Injury to Fear Extinction and Avoidance

> **NIH NIH P20** · UNIVERSITY OF PUERTO RICO MED SCIENCES · 2021 · $220,741

## Abstract

Project Summary / Abstract
Traumatic brain injury (TBI) affects about 4 million civilians and soldiers each year, many of whom are
diagnosed with mental health conditions like post-traumatic stress disorder (PTSD). There are common
mechanisms that contribute to the neurobiology of TBI and PTSD, and both conditions can impair learning,
neuroplasticity, and emotional regulation. Epidemiological studies of veterans show a strong correlation
between sustaining TBI and developing PTSD. However, animal studies show conflicting results. To determine
whether a relationship exists between TBI and PTSD, a biological link must be established using reliable brain
injury models and behavioral tests. Clinically, there are two broad classes of TBI in which research models
exist: focal (e.g. contusion), produced by controlled cortical impact (CCI), and diffuse (e.g. concussion),
produced by weight drop onto the closed head. With CCI, injury level and extent of tissue deformation
resemble physiological parameters related to contusion. In concussion, impact to the head plus angular
acceleration produces neurological and cognitive dysfunction. Furthermore, repeat concussions as seen in
sports and combat, result in axonal damage that disrupts communication and activity between brain regions,
potentially impairing emotional regulation. A form of emotional regulation that may be modified by TBI is fear
extinction, a type of learning that reduces fear expression. Extinction is the basis of exposure therapy for fear
and anxiety disorders. In addition to impaired extinction, PTSD patients display excess avoidance, which
reduces the attainment of goals and rewards. Notably, there are homologous brain regions in rodents and
humans needed for extinction and avoidance. We will use CCI or repeat closed head injury (rCHI; model of
repeat concussion) to test the hypotheses that TBI impairs fear extinction (causing high fear), and impairs the
extinction of avoidance (causing excess avoidance). After TBI, we propose that dysfunction in the amygdala,
hippocampus, and medial prefrontal cortex (mPFC) will underlie impaired extinction, whereas dysfunction in
the amygdala, mPFC, and ventral striatum will underlie excess avoidance. This work will increase the base of
scientific and public health evidence about the effects of TBI to extinction and avoidance. Principal techniques
in this project include neuronal tract tracing and immunohistochemical approaches that identify activity in brain
areas. These protocols rely heavily on the instrumentation and expertise available in the COBRE
Neuroimaging and Electrophysiology Facility. The microscopy equipment and image analysis support at the
Molecular Sciences Research Center will provide essential tools for achieving the objectives of this project.

## Key facts

- **NIH application ID:** 10212404
- **Project number:** 5P20GM103642-09
- **Recipient organization:** UNIVERSITY OF PUERTO RICO MED SCIENCES
- **Principal Investigator:** Demetrio Sierra
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $220,741
- **Award type:** 5
- **Project period:** 2013-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10212404

## Citation

> US National Institutes of Health, RePORTER application 10212404, Project 2:  Contribution of Traumatic Brain Injury to Fear Extinction and Avoidance (5P20GM103642-09). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10212404. Licensed CC0.

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