The influence of aerobic exercise on consolidation of fear extinction learning in PTSD

有氧运动对PTSD患者恐惧消退学习巩固的影响

基本信息

批准号：
10840496
负责人：
Kevin M Crombie
金额：
$ 13.84万
依托单位：
UNIVERSITY OF ALABAMA IN TUSCALOOSA
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-03-03 至 2028-02-29
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10840496
关键词：
Address Adult Aerobic Exercise Agonist Alabama American Amygdaloid structure Animal Model Anxiety Disorders Biometry Clinical Clinical Psychology Clinical Trials Cognitive Collaborations Computer Models Control Groups Dangerousness Data Diagnosis Disease remission Dose Endocannabinoids Enzymes Exercise Exhibits Expectancy Extinction FAAH inhibitor Fostering Fright Functional Magnetic Resonance Imaging Galvanic Skin Response Goals Hippocampus Image Individual Interdisciplinary Study International Knowledge Laboratories Laboratory Study Learning Light Mediating Memory Mental Health Mentored Research Scientist Development Award Mentorship Methodology Modeling Outcome Participant Pathway interactions Pattern Peripheral Pharmacology Physiological Pilot Projects Population Post-Traumatic Stress Disorders Prefrontal Cortex Process Psychiatry Psychophysiology Psychotherapy Randomized Regulation Research Research Personnel Retrieval Role Safety Sampling Signal Transduction Techniques Testing Therapeutic Training Trauma Treatment Efficacy United States National Institutes of Health Universities Woman Work anandamide anxiety reduction career development clinical anxiety cognitive enhancement computational neuroscience design endogenous cannabinoid system exercise intensity experience fatty acid amide hydrolase improved indexing learning extinction lens memory consolidation memory encoding men multidisciplinary neural neural circuit neural patterning neurobiological mechanism neuroimaging notch protein pharmacologic response scaffold theories trauma exposure

项目摘要

PROJECT SUMMARY Exposure-based psychotherapies (e.g., prolonged exposure) are among the best supported treatments for posttraumatic stress disorder (PTSD), yet remission rates for these front-line treatments are typically only 50- 60%. These therapies aim to reduce anxiety towards trauma reminders by enabling therapeutic safety learning, which is hypothesized to work via the mechanisms of fear extinction learning. As such, fear extinction paradigms are widely used as laboratory models of exposure therapy, under the notion that treatments that enhance extinction learning and recall in the lab may be promising candidates for improving the efficacy of exposure-based therapies. Results from our recent clinical pilot studies (without an imaging component) provided preliminary evidence suggesting moderate-intensity aerobic exercise can boost consolidation of fear extinction memories and enhance cognitive indices of extinction recall – an effect that was mediated by exercise-induced increases in anandamide (AEA; a primary endocannabinoid). Thus, this K01 project involves a randomized controlled fMRI laboratory study to: 1) test whether different doses of aerobic exercise (light-, moderate-, and high-intensity) delivered after extinction training improves cognitive, physiological, and neural indices of extinction recall including enhanced retrieval of multivariate patterns of extinction memory encoding (when tested 24hrs later), and 2) further probe the role of AEA by determining dose-response relationships between aerobic exercise intensities and peripheral AEA concentrations (and whether the exercise-induced increases in AEA mediate the aforementioned relationships) in trauma-exposed men and women with and without PTSD (N=120). The PI will receive training and mentorship including: 1) training in computational neuroscience theory and statistical techniques (e.g., multivariate imaging analyses and computational modeling to analyze psychophysiological and neuroimaging data), 2) clinical exposure and expertise in clinical models and neurocircuitry of PTSD and anxiety disorders, 3) gaining expertise in clinical trials to be able to design, conduct, and analyze pharmacological and non-pharmacological RCTs as an independent investigator, and 4) professional and career development activities to foster multi-disciplinary research collaborations. The proposed training and research will occur at The University of Alabama and includes domestic and international collaborations with top-notch researchers, all of which have established extensive NIH research portfolios spanning several fields such as: computational neuroscience, psychiatry, clinical psychology, biostatistics, and pharmacology. Ultimately, the guidance and training experiences gained from the PI’s mentorship team, and the results obtained from this K01 award, will serve as a scaffolding for the PI to become an independent investigator capable of conducting impactful mental health research in PTSD and clinical anxiety populations by utilizing a multidisciplinary lens and advanced methodologies from the ever-advancing fields of psychiatry and computational neuroscience.

项目概要基于暴露的心理疗法（例如，长期暴露）是最受支持的治疗方法之一创伤后应激障碍 (PTSD)，但这些一线治疗的缓解率通常仅为 50- 60% 这些疗法旨在通过实现治疗安全学习来减少对创伤提醒的焦虑，这是通过恐惧消退学习机制来实现的，因此，恐惧消退。范式被广泛用作暴露疗法的实验室模型，其理念是治疗在实验室中增强消退学习和回忆可能是提高消退效果的有希望的候选者基于暴露的疗法。我们最近的临床试点研究的结果（没有成像成分）提供了初步证据表明中等强度的有氧运动可以促进恐惧的巩固灭绝记忆并增强灭绝回忆的认知指数——这种效应是由运动引起的 anandamide（AEA；一种主要内源性大麻素）的增加因此，这个 K01 项目涉及到。一项随机对照功能磁共振成像实验室研究，旨在：1) 测试是否进行不同剂量的有氧运动（轻、中强度和高强度）在消退训练后进行可改善认知、生理和神经消退回忆指数，包括消退记忆编码多元模式的增强检索（24 小时后测试时），2) 通过确定剂量反应关系进一步探讨 AEA 的作用有氧运动强度和外周 AEA 浓度之间的关系（以及运动引起的在遭受创伤的男性和女性中，AEA 的增加介导了这些关系）没有 PTSD（N=120）。 PI 将接受培训和指导，包括： 1) 计算培训。神经科学理论和统计技术（例如，多元成像分析和计算建模以分析心理生理学和神经影像数据），2）临床接触和临床专业知识 PTSD 和焦虑症的模型和神经回路，3) 获得临床试验方面的专业知识，以便能够作为独立研究者设计、进行和分析药理学和非药理学随机对照试验， 4) 专业和职业发展活动，以促进多学科研究合作。拟议的培训和研究将在阿拉巴马大学进行，包括国内和与顶尖研究人员进行国际合作，所有这些研究人员都在 NIH 进行了广泛的研究作品集涵盖多个领域，例如：计算神经科学、精神病学、临床心理学、最终，从 PI 那里获得的指导和培训经验。导师团队以及从 K01 奖项获得的成果将作为 PI 成为的脚手架能够对 PTSD 和临床进行有影响力的心理健康研究的独立研究者通过利用多学科视角和不断进步的先进方法来缓解焦虑人群精神病学和计算神经科学领域。