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| ID | Type | Description | Link |
|---|---|---|---|
| R01MH137445 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute of Mental Health (NIMH) | NIH |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| High-Intensity Exercise | Experimental | High intensity exercise on a seated cycle for 26 minutes |
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| Moderate-Intensity Exercise | Experimental | moderate intensity exercise on a seated cycle for 26 minutes |
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| Light-Intensity Exercise | Experimental | Light intensity exercise on a seated cycle for 26 minutes |
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| Quiet Rest | No Intervention |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Exercise | Behavioral | 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. |
| 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. |
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Josh M Cisler, PhD | Contact | 512-495-5162 | josh.cisler@austin.utexas.edu |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Health Discovery Building | Recruiting | Austin | Texas | 78712 | United States |
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| ID | Term |
|---|---|
| D013313 | Stress Disorders, Post-Traumatic |
| ID | Term |
|---|---|
| D040921 | Stress Disorders, Traumatic |
| D000068099 | Trauma and Stressor Related Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D015444 | Exercise |
| ID | Term |
|---|---|
| D009043 | Motor Activity |
| D009068 | Movement |
| D009142 | Musculoskeletal Physiological Phenomena |
| D055687 | Musculoskeletal and Neural Physiological Phenomena |
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|
| 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. |