Preventing the return of fear in humans: Reconsolidation and control

防止人类恐惧卷土重来：重新巩固和控制

• 批准号: 8661034
• 负责人: Elizabeth Anya Phelps
• 金额: $ 37.87万
• 依托单位: NEW YORK UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-06-11 至 2017-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8661034
• 关键词: Adrenergic beta-Antagonists; Adult; Amygdaloid structure; Animal Model; Animals; Anxiety Disorders; Behavioral; Clinical; Disease; Drug usage; Effectiveness; Event; Extinction (Psychology); Fright; Functional Magnetic Resonance Imaging; Future; Goals; Human; Intervention; Laboratory Procedures; Lead; Learning; Link; Literature; Measures; Memory; Methods; Modeling; Molecular; Nature; Patients; Population; Post-Traumatic Stress Disorders; Prefrontal Cortex; Prevalence; Procedures; Propranolol; Recovery; Research; Rodent; Specificity; Stress; System; Techniques; Time; Training; Translations; Update; base; conditioned fear; effective therapy; experience; improved; learning extinction; neural circuit; neuromechanism; novel; prevent; psychologic; relating to nervous system; resilience; stressor; success

DESCRIPTION (provided by applicant): The prevalence of anxiety disorders is estimated to be up to 18% of the US adult population. A primary treatment for anxiety disorders is exposure therapy, which is based on the principles of fear extinction. Although extinction based therapies can be effective, their efficacy is limited, in part due to the nature of extinction learning itsel. There is abundant evidence that extinction learning does not result in a significant alteration of the original fear memory, but rather results in new learning that the previously feared event is now safe. One consequence is that the original fear memory and the extinction memory may compete for expression. A range of circumstances, such as the passage of time (spontaneous recovery), alterations in context (renewal), and stress (reinstatement), can result in the fear returning. This potential for fear memory recovery even after extensive extinction training highlights the need to discover more persistent and robust techniques to diminish fear. Using simple classical fear conditioning paradigms, research in non-human animals has identified two potential mechanisms to prevent the return of fear. The first is by manipulating the reconsolidation or re-storage of the original fear memory. The second is by allowing the animal experience with control over the stressor, which has been shown to have lasting effects on reducing the likelihood of fear recovery. The goal of the proposed research is to assess in humans the efficacy, specificity, and underlying neural mechanisms of techniques that have been shown to prevent the return of fear in non- human animals. Studies under Aim 1 examine techniques to disrupt or alter the reconsolidation of conditioned fear in humans. Specifically, the pharmacological disruption of reconsolidation is explored and the specificity and the psychological and neural consequences of behavioral interference techniques used to alter the reconsolidation of conditioned fear are examined. Aim 2 examines whether experience with control over a stressor can diminish the likelihood that a fear memory returns. Finally, the studies under Aim 3 examine the success of these techniques in patients who suffer from PTSD to determine if the neural consequences of this anxiety disorder alters the effectiveness of these procedures. The overarching goal of all the proposed studies is to discover how and when we might be able to prevent the return of fear in humans, which has the potential to lead to novel and more effective treatments for anxiety disorders.

描述（由申请人提供）：据估计，美国成年人口中焦虑症的患病率高达 18%。焦虑症的主要治疗方法是暴露疗法，它基于恐惧消除的原理。尽管基于消退的疗法可能有效，但其功效有限，部分原因在于消退学习本身的性质。有大量证据表明，消退学习不会导致原始恐惧记忆的显着改变，而是导致新的学习，即以前害怕的事件现在是安全的。后果之一是原始恐惧记忆和消退记忆可能会竞争表达。一系列情况，例如时间的流逝（自然恢复）、环境的改变（更新）和压力（恢复），都可能导致恐惧再次出现。 即使在广泛的消除训练之后，恐惧记忆恢复的潜力也凸显出需要发现更持久和更强大的技术来减少恐惧。使用简单的经典恐惧调节范式，对非人类动物的研究发现了两种防止恐惧卷土重来的潜在机制。第一种是通过操纵原始恐惧记忆的重新巩固或重新存储。第二种是让动物体验对压力源的控制，这已被证明对降低恐惧恢复的可能性具有持久的影响。 本研究的目的是评估已被证明可以防止非人类动物再次出现恐惧的技术在人类中的功效、特异性和潜在神经机制。目标 1 下的研究考察了破坏或改变人类条件性恐惧重新巩固的技术。具体来说， 探讨了重新巩固的药理学破坏，并检查了用于改变条件性恐惧重新巩固的行为干扰技术的特异性以及心理和神经后果。目标 2 检查控制压力源的经验是否可以减少恐惧记忆恢复的可能性。最后，目标 3 下的研究检验了这些技术在患有 PTSD 的患者中是否成功，以确定这种焦虑症的神经后果是否会改变这些手术的有效性。所有拟议研究的总体目标是发现我们如何以及何时能够阻止人类恐惧的回归，这有可能为焦虑症带来新的、更有效的治疗方法。