# Neural mechanisms of extinction generalization in human

> **NIH NIH F31** · UNIVERSITY OF TEXAS AT AUSTIN · 2021 · $36,374

## Abstract

PROJECT SUMMARY/ABSTRACT
Post-Traumatic Stress Disorder (PTSD) is a serious detriment to mental health in the United States, with a
lifetime prevalence of 6.8%. The most commonly used clinical technique in the treatment of PTSD is exposure
therapy, however this strategy is imperfect, and the results obtained during exposure therapy in a clinical setting
repeatedly fail to generalize to novel real-world situations. The Aims of this application are to characterize the
neural mechanisms of the return of fear and to test a novel strategy to prevent this return. Pavlovian fear
conditioning and extinction serve as useful laboratory models of PTSD and exposure therapy respectively. The
observed lapses in exposure therapy can be explained by the role of context in fear and extinction learning and
recall. Extinction is expressed in a contextually specific manner, while fear readily generalizes to new contexts
in a phenomenon called renewal. The renewal of fear and the specificity of extinction explain why many
treatments fail to produce lasting benefits. In laboratory settings, context is often defined as physical space, but
advancements in episodic memory research have shown that mental context plays a significant role in the
learning and recall of memories in humans. It is currently unknown how a mental context framework can be
applied to enhance understanding of the neural and cognitive mechanisms of emotional learning and memory.
In line with NIMH Strategic Objective 1 to define the mechanism of complex behaviors, Aim 1 of this proposal
will investigate the neural mechanisms of fear and extinction mental context reinstatement in both healthy
participants and patients with PTSD. Advanced fMRI neuroimaging techniques will be used to quantify the
reactivation of mental contexts during a renewal test. Previous attempts to overcome the contextual specificity
of extinction focus on contextual manipulations such as extinguishing in multiple contexts, cue reminders, or
pharmacologically inhibiting contextual processing. These techniques have been implemented to mixed success,
and in the case of pharmacological treatments are not always practical solutions. Accordingly, Aim 2 will test a
novel behavioral strategy designed to diminish contextual processing during extinction learning, safely facilitating
extinction generalization. This simple manipulation, known as directed forgetting, has previously been shown to
diminish hippocampal activity. Healthy subjects will engage in directed forgetting during extinction learning. We
will then test if extinction learning augmented with directed forgetting results in extinction generalization to new
contexts. This Aim supports NIMH Strategic Objective 3 to develop new treatments through advancements in
neuroscience and behavioral sciences. The combined Aims laid out in this proposal will significantly bolster
current knowledge of the neural and cognitive mechanisms of successful extinction following fear learning and
wil...

## Key facts

- **NIH application ID:** 10172859
- **Project number:** 5F31MH124360-02
- **Recipient organization:** UNIVERSITY OF TEXAS AT AUSTIN
- **Principal Investigator:** Augustin Cole Hennings
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $36,374
- **Award type:** 5
- **Project period:** 2020-09-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10172859

## Citation

> US National Institutes of Health, RePORTER application 10172859, Neural mechanisms of extinction generalization in human (5F31MH124360-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10172859. Licensed CC0.

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