# Neural correlates of fear conditioning and extinction in veterans with PTSD and alcohol use disorder

> **NIH VA I01** · VA SAN DIEGO HEALTHCARE SYSTEM · 2024 · —

## Abstract

Approximately half of all treatment seeking Veterans with posttraumatic stress disorder (PTSD) have
problems with alcohol, yet it is unclear how current alcohol use affects critical processes mediating recovery from
trauma. Despite strong preclinical evidence that recent, heavy alcohol exposure adversely impacts fear
extinction, and that fear extinction is central to recovery from PTSD, the direct effects of current, problematic
alcohol use on fear extinction have not been characterized in those with PTSD and alcohol use disorders
(PAUD). Similarly, contextual fear processing, or the accurate discrimination of threat in the environment, is
implicated in the maintenance of PTSD but has never been explored in PAUD. Severe symptom profiles, small
treatment gains, and high treatment dropout rates in Veterans with PAUD underscore the need to understand
the effects of current heavy drinking on the mechanisms of fear extinction and contextual fear processing.
Without studies accounting for the influence of alcohol on processes central to PTSD recovery, treatment
innovation for PAUD is likely to remain limited.
 Previous work and preliminary data from our lab suggest that individuals with PTSD have specific deficits in
fear extinction and recall, and that the ventromedial prefrontal cortex (vmPFC), hippocampus (HPC), amygdala,
insula, and dorsal anterior cingulate cortex (dACC) play critical roles in the inhibition and expression of fear
processing. Moreover, our preliminary data show that current problematic alcohol use in the context of PTSD is
associated with higher treatment drop-out and fewer treatment gains from exposure-based relative to coping
skills therapy, potentially suggesting an extinction-specific impact of alcohol use on clinical outcomes. While
preclinical models provide compelling mechanistic evidence that chronic alcohol exposure disrupts fear
extinction and recall, as yet there is no clinical analogue to this work. Relatedly, contextual fear processing
is abnormal in PTSD, and damage to the hippocampus (HPC) impairs this process. Tasks used previously to
assess contextual fear processing may not reliably invoke HPC dependent processes, and none have assessed
the impact of alcohol despite the known deleterious impact of alcohol on HPC structure and function.
 In the proposed design, we will compare Veterans with PTSD and ongoing, heavy alcohol use (“Drinking” or
D-PAUD) to those with 30- to 90-days of sustained abstinence (A-PAUD) using a validated 2-day protocol of
concurrent psychophysiological and functional brain imaging measures of fear acquisition, extinction learning,
extinction recall, as well as a newly validated configural threat learning measure of contextual fear processing
that invokes HPC dependent processes. We predict that Veterans with D-PAUD will show physiological response
indicative of greater fear recovery, and neural response consistent with decreased fear inhibition (i.e., less
vmPFC activation) during fear extin...

## Key facts

- **NIH application ID:** 10910997
- **Project number:** 5I01CX002397-02
- **Recipient organization:** VA SAN DIEGO HEALTHCARE SYSTEM
- **Principal Investigator:** ANDREA SPADONI TOWNSEND
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2023-04-01 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10910997

## Citation

> US National Institutes of Health, RePORTER application 10910997, Neural correlates of fear conditioning and extinction in veterans with PTSD and alcohol use disorder (5I01CX002397-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10910997. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*