# Inhibitory Learning as a Novel Mechanism of Prolonged Exposure: An Investigation of Laboratory and Mobile Health Measures

> **NIH VA IK2** · VA SAN DIEGO HEALTHCARE SYSTEM · 2024 · —

## Abstract

Prolonged exposure (PE) is a gold standard treatment for posttraumatic stress disorder (PTSD), but it
fails to fully resolve PTSD in approximately half of Veterans who initiate it. Better understanding the
mechanisms underlying PE could increase Veteran response rates by informing new therapeutic strategies to
enhance PE and more accurate methods for identifying who will benefit from PE. The main interventions
components in PE are a) imaginal exposures, which involve repeatedly describing the memory of a previous
trauma, and b) in-vivo exposures, which involve confronting safe yet distressing situations that resemble the
trauma. The effectiveness of PE exposures at ameliorating PTSD appears to largely depend upon their ability to
facilitate fear extinction, as operationalized by reduced fear when the exposure is performed again. In PE,
clinicians attempt to facilitate fear extinction (i.e., lower fear in future exposures) by focusing on within-session
habituation (WSH) – an acute decline in fear during the current exposure. However, WSH tends to poorly
predict future fear levels in the laboratory and symptom reduction during PE, suggesting it is an insufficient
marker of exposure effectiveness. Instead, fear extinction appears to be driven by inhibitory learning (IL),
wherein the memory of a feared outcome not occurring during a feared situation inhibits fear when the same
situation is encountered again. Within exposures, IL can be measured by how much the patient's conscious
expectation of their feared outcome (i.e., threat expectancy) decreases after the outcome fails to occur. IL, as
indexed by reduced threat expectancy following each exposure, has shown promise as a mechanism of
exposure therapy for anxiety disorders. However, the role of IL in PE for Veterans has yet to be investigated.
 To address this gap, the proposed study will use a multimodal collection of clinical, laboratory, and
mobile health measures to systematically evaluate whether IL is predictive of fear extinction and symptom
reduction during PE for Veterans. 80 Veterans with PTSD will complete a standard course of PE over
telehealth. Mobile health technologies will be used to assess IL (i.e., changes in threat expectancy ratings from
pre- to post-exposure) and fear-related responses (i.e., peak levels of subjective distress and physiological
arousal during each exposure). Participants will also complete a behavioral fear extinction task prior to PE that
will assess their capacity to experience IL, as measured by how much their expectancy for an aversive stimulus
decreases following instances where it does not occur. Our overarching hypothesis is that each measure of IL
will predict better fear extinction during exposures and more improvement in PTSD symptoms during PE. We
will specifically examine whether greater reductions in threat expectancy during each exposure type (imaginal
and in-vivo) predict lower peak levels of subjective fear and physiological fear during subseque...

## Key facts

- **NIH application ID:** 10799530
- **Project number:** 1IK2CX002640-01A1
- **Recipient organization:** VA SAN DIEGO HEALTHCARE SYSTEM
- **Principal Investigator:** Christopher Hunt
- **Activity code:** IK2 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2024-03-01 → 2029-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10799530

## Citation

> US National Institutes of Health, RePORTER application 10799530, Inhibitory Learning as a Novel Mechanism of Prolonged Exposure: An Investigation of Laboratory and Mobile Health Measures (1IK2CX002640-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10799530. Licensed CC0.

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