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

项目摘要 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只有50- 百分之六十这些疗法旨在通过使治疗安全学习， 这被假设为通过恐惧消退学习机制起作用。因此，恐惧灭绝 范例被广泛用作暴露疗法的实验室模型， 在实验室中增强消退学习和回忆可能是提高 基于安全的治疗。我们最近的临床初步研究结果（无成像组件） 初步证据表明，中等强度的有氧运动可以促进恐惧的巩固 灭绝记忆和增强灭绝回忆的认知指数-一种由 运动诱导的大麻素增加（AEA;一种主要的内源性大麻素）。因此，K 01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（轻度， 中强度和高强度），改善了认知、生理和神经功能。 灭绝回忆指数，包括灭绝记忆编码的多变量模式的增强检索 (when 24小时后检测），2）通过确定剂量-反应关系进一步探索AEA的作用 有氧运动强度和外周AEA浓度之间的关系（以及运动诱导的 AEA的增加介导了上述关系）在创伤暴露的男性和女性中， 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，多变量成像分析和计算 建模以分析心理生理学和神经成像数据），2）临床暴露和临床专业知识 创伤后应激障碍和焦虑症的模型和神经回路，3）获得临床试验的专业知识， 作为独立研究者设计、实施和分析药理学和非药理学RCT， （四）专业及事业发展活动，以促进跨学科的研究合作。的 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 投资组合跨越几个领域，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获得的指导和培训经验 导师团队，以及从这个K 01奖获得的结果，将作为一个脚手架的PI成为 一个独立的调查员能够进行有影响力的心理健康研究创伤后应激障碍和临床 焦虑人群通过利用多学科透镜和先进的方法，从不断进步的 精神病学和计算神经科学领域。

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.