# Neural correlates of active avoidance learning and their interactions with fear extinction mechanisms in PTSD patients

> **NIH NIH R01** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 2024 · $678,226

## Abstract

Project Summary
Primary characteristics of posttraumatic stress disorder (PTSD) include persistent fears and excessive
maladaptive avoidance behaviors. Preclinical models of PTSD have heavily investigated the brain
mechanisms of fear inhibition and active avoidance learning. Significant progress has been made in
translating fear conditioning and extinction data into the human brain and their implications have helped
further our understanding of PTSD psychopathology. The mechanisms of active avoidance, however, have
scarcely been examined in the human brain, especially within the context of maladaptive responses as in
the case of PTSD. The studies proposed in this application are designed to begin to fill this scientific gap.
We will use a novel conditioning and active avoidance paradigm (CAAP) to examine the neural
correlates of active avoidance and fear extinction learning and explore how extinction modulates
active avoidance responses in participants with and without a PTSD diagnosis using functional
magnetic resonance imaging (fMRI). PTSD psychopathology involves dysfunctional limbic-frontal activity
including the ventromedial prefrontal cortex (vmPFC), hippocampus (HPC), and amygdala. Studies of
avoidance in rodents and a few fMRI studies in healthy humans suggest that the vmPFC and striatum
mediate threat response by toggling the expression of fear vs. avoidance responses. Participants (healthy
controls with trauma exposure, and patients diagnosed with PTSD) will undergo the novel (validated) two-
day CAAP. On day 1, participants will undergo Pavlovian fear conditioning, immediately followed by an active
avoidance conditioning phase. Avoidance is achieved by pressing a button to prevent a shock from occurring
but will not terminate the conditioned stimulus (CS). Pavlovian fear extinction learning (button removed; no
avoidance possible) will follow. On day 2, recall of extinction learning will be tested. Before the start of the
recall test, participants will receive a small monetary endowment and will be told that this money could be
used to pay for shock avoidance during the recall test. The first aim is to Identify neural correlates of active
avoidance. The second aim is to study activations after the CS+ terminates that index the relief from the
avoided shock. The third aim is to examine neural correlates of extinction-to-avoidance transfer. The
proposed studies are expected to provide a more integrated mechanistic understanding of the
psychopathology of PTSD and reduce the gap between the rodent literature and human neuroimaging in
avoidance research.

## Key facts

- **NIH application ID:** 10908049
- **Project number:** 7R01MH123736-04
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
- **Principal Investigator:** Mohammed R Milad
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $678,226
- **Award type:** 7
- **Project period:** 2023-09-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10908049

## Citation

> US National Institutes of Health, RePORTER application 10908049, Neural correlates of active avoidance learning and their interactions with fear extinction mechanisms in PTSD patients (7R01MH123736-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10908049. Licensed CC0.

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