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

• 批准号: 10630706
• 负责人: Kevin M Crombie
• 金额: $ 3.59万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-03-03 至 2023-08-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10630706
• 关键词: Address; Adult; Aerobic Exercise; Agonist; 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; Texas; Therapeutic; Training; Trauma; Treatment Efficacy; United States National Institutes of Health; Universities; Woman; Work; anandamide; anxiety reduction; austin; 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

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 Texas at Austin 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.

项目摘要 基于暴露的心理治疗（例如，长时间暴露）是最好的支持治疗方法之一 创伤后应激障碍（PTSD），但这些前线治疗的缓解率通常仅为50- 60％。这些疗法旨在通过启用治疗安全学习来减少对创伤提醒的焦虑， 假设通过恐惧扩展学习的机制起作用。因此，恐惧延伸 范式被广泛用作暴露疗法的实验室模型，这是在这种疗法的观念中 在实验室中增强扩展学习和回忆可能是提高效率的候选人 基于暴露的疗法。我们最近的临床初步研究（没有成像组件）的结果 前提是提示现代强度有氧运动的初步证据可以促进恐惧的巩固 扩展记忆并增强了扩展回忆的认知指数 - 这种效果是由 运动引起的anandamide（AEA；主要的内源性大麻素）的增加。那，这个K01项目涉及 一项随机对照fMRI实验室研究：1）测试不同剂量的有氧运动（光， 扩展训练后提供的中等和高强度）改善了认知，物理和中性 扩展召回索引，包括增强的扩展存储器编码多元模式的检索 （24小时后测试时）和2）通过确定剂量反应关系进一步探测AEA的作用 有氧运动强度和外围AEA浓度之间（以及运动引起的 在暴露于创伤的男人和女性中，AEA的增加介导了预测关系 没有PTSD（n = 120）。 PI将接受培训和心态，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学数据），2）临床暴露和临床专业知识 PTSD和动画障碍的模型和神经循环，3）在临床试验中获得专业知识，以便能够 设计，进行和分析药物和非药理学RCT作为独立研究者， 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德克萨斯大学奥斯汀分校进行，包括国内和 与顶尖研究人员的国际合作，所有这些都建立了广泛的NIH研究 投资组合跨越了几个领域，例如：计算神经科学，精神病学，临床心理学， 生物统计学和药理学。最终，从PI的指导和培训经历 Menorship Team以及从该K01奖获得的结果将成为PI成为PI的脚手架 能够在PTSD和临床上进行有影响力的心理健康研究的独立研究者 通过使用多学科镜头和不断增长的高级方法，焦虑群体 精神病学和计算神经科学领域。