Using Exercise to Enhance Fear Extinction Learning

Efficacy and Mechanisms of Exercise-Enhanced Fear Extinction

The goal of the current project is to establish the efficacy and mechanisms of exercise-enhanced fear extinction retrieval and generalization in posttraumatic stress disorder (PTSD). Exposure therapy is the gold standard treatment for PTSD, yet is only associated with remission rates of ~55% and in clear need of improvement. Exposure therapy is hypothesized to work through mechanisms of fear extinction learning, and as such, laboratory-based fear extinction paradigms are widely used as models of exposure therapy. Recent data demonstrates that moderate-intensity aerobic exercise, delivered specifically during or after fear extinction learning, can boost the consolidation of fear extinction learning. Consistent with emerging models of exercise's pro-extinction effect, our pilot data among women with PTSD found that moderate intensity aerobic exercise delivered after fear extinction learning leads to a reduction in subsequent fear responding 24hrs later, an effect that was mediated by exercise-induced increases in peripheral brain derived neurotrophic factor (BDNF). Our pilot data using multivariate pattern analyses (MVPA) also identified divided neurocircuitry organization of fear vs safety memories, and that this divided neural organization was altered in PTSD. Building on our pilot data, the current project would 1) compare the impact of different intensities of exercise delivered following fear extinction learning on multimodal measures of fear extinction retrieval and generalization, 2) identify the impact of exercise on MVPA representations of fear vs safety memories, and 3) demonstrate that spontaneous reactivations of extinction encodings in the acute consolidation window operate as candidate mechanisms by which exercise enhances extinction retrieval and generalization. Using a 3-day fear conditioning, fear extinction, and fear extinction retrieval and recognition task during functional magnetic resonance imaging (fMRI), 200 adults with PTSD would be randomly assigned to either resting control or 30min of either light, moderate, or high intensity exercise. Testing dose-response relationships between exercise intensity and fear extinction will inform translation of this research to clinical settings. A one week-follow-up extinction retrieval test would investigate the impact of exercise on longer-term retention. This project would provide a critical evaluation of the impact of aerobic exercise on consolidation and recall of extinction learning in PTSD samples, thereby providing a strong foundation to translate this research to clinical care and enhance clinical outcomes for PTSD. The project would also provide general knowledge regarding dose-response relationships and neural mechanisms that support enhanced extinction, thereby informing development of additional novel treatments.

Study Overview

• Status: Recruiting
• Conditions: PTSD; Exercise Intensity; Fear Extinction; Fear Conditioning
• Intervention / Treatment: Behavioral: Exercise

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Josh M Cisler, PhD; Phone Number: 512-495-5162; Email: josh.cisler@austin.utexas.edu

Study Locations

• United States
  • Texas
    • Austin, Texas, United States, 78712
      • Recruiting
      • Health Discovery Building
      • Contact: Josh M Cisler, PhD; Phone Number: 512-495-5162; Email: josh.cisler@austin.utexas.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 18 - 55 years of age
• Currently experiencing at least 4 PTSD symptoms with at least 1 re-experiencing symptom (e.g., trauma memory intrusion, trauma nightmares, trauma flashbacks, intense emotional distress related to trauma, or marked physiological reactivity related to trauma) from criterion B.
• English speaking
• Medically healthy

Exclusion Criteria:

• being pregnant
• having a history of light headedness or fainting during physical activity
• having a history of chest pain during physical activity
• having a bone, joint, cardiac, or other medical condition that a doctor has said may be worsened by physical activity
• responding 'Yes' to any of the seven questions on the Physical Activity Readiness Questionnaire (PAR-Q; unless they provide a doctor's note indicating that it is safe for them to engage in aerobic exercise )
• percutaneous coronary intervention or acute myocardial infarction in the last 6 weeks
• unstable arrhythmias/implanted cardiac defibrillator shocks in the last 3 months
• Internal ferromagnetic objects (such as electronic devices, surgical implants, shrapnel, etc.)
• Nonremovable dental implants, such as braces or upper permanent retainers, as these will distort the MRI images we collect (note: filings, crowns, and silver or gold teeth are OK)
• Any other condition, medication, or implant that the investigator believes would degrade image quality or render data unusable
• psychotic disorders
• Permanent makeup or tattoos with metallic dyes,
• A self-reported history of loss of consciousness (greater than 30 minutes)
• physical disabilities that prohibit task performance (such as blindness or deafness)
• Any other condition that the investigator believes might put the participant at risk
• Claustrophobia
• History of cardiovascular disease
• on-going traumatic event exposure (e.g., living with an abusive partner)
• Severe substance use disorder.
• unstable medication (changes within the past ~4 weeks)
• Acute sedatives/pain killers (e.g., benzodiazepines, Vicodin) and prescription stimulants (e.g., Adderall) would not be permitted for 6 hours prior to the study visit.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High-Intensity Exercise; High intensity exercise on a seated cycle for 26 minutes	Behavioral: Exercise; Exercise consists of a total duration of 26 minutes on a seated exercise cycle. Exercise begins with a 3min warm-up, 20min of exercise at the desired intensity range, and then a 3min cool-down. During exercise, heart rate is monitored and perceived effort is assessed every 2 minutes.
Experimental: Moderate-Intensity Exercise; moderate intensity exercise on a seated cycle for 26 minutes	Behavioral: Exercise; Exercise consists of a total duration of 26 minutes on a seated exercise cycle. Exercise begins with a 3min warm-up, 20min of exercise at the desired intensity range, and then a 3min cool-down. During exercise, heart rate is monitored and perceived effort is assessed every 2 minutes.
Experimental: Light-Intensity Exercise; Light intensity exercise on a seated cycle for 26 minutes	Behavioral: Exercise; Exercise consists of a total duration of 26 minutes on a seated exercise cycle. Exercise begins with a 3min warm-up, 20min of exercise at the desired intensity range, and then a 3min cool-down. During exercise, heart rate is monitored and perceived effort is assessed every 2 minutes.
No Intervention: Quiet Rest

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Threat Expectation	Threat expectation is a cognitive process and measure of fear towards conditioned stimuli	Threat expectation to conditioned stimuli is measured with a 4pt Likert Scale (range 0-3) in response to conditioned stimuli, using self-report, as a measure of cognitive features of fear, one day after intervention and 7-13 days after intervention.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Skin Conductance Responses (SCRs)	skin conductance response is a measure of sympathetic arousal and is measured on the palms using BIOPAC equipment	SCR is assessed on the palms in response to conditioned stimuli, using BIOPAC equipment, as a measure of sympathetic arousal, one day after intervention and 7-13 days after intervention.
BOLD Activation to CS+ and CS-	blood oxygen level dependent (BOLD) response measured during fMRI provides an assessment of neural activity	BOLD activity to conditioned stimuli is measured during fMRI in response to conditioned stimuli, using 3T Siemens Prisma, as a measure of neural activity, one day after intervention and 7-13 days after intervention.

Collaborators and Investigators

• Sponsor: Josh Cisler
• Collaborators: National Institute of Mental Health (NIMH)

Study record dates

Study Major Dates

• Study Start (Actual): September 2, 2025
• Primary Completion (Estimated): May 1, 2030
• Study Completion (Estimated): May 1, 2030

Study Registration Dates

• First Submitted: April 14, 2026
• First Submitted That Met QC Criteria: April 20, 2026
• First Posted (Actual): April 23, 2026

Study Record Updates

• Last Update Posted (Actual): April 23, 2026
• Last Update Submitted That Met QC Criteria: April 20, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Trauma and Stressor Related Disorders; Mental Disorders; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Exercise
• Other Study ID Numbers: STUDY00006895; R01MH137445 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No