Novel paradigm attenuates traumatic memories and prevents return of fear

描述(由申请者提供)：夸大或持续的恐惧是精神障碍的常见现象。虽然巴甫洛夫条件反射的研究在揭示恐惧学习的神经基础方面取得了很大的进展，但对于如何减少或消除病理性病例中的创伤记忆却知之甚少，这是临床上非常关注的问题。当最初的中性刺激(条件刺激，CS；例如，音调)在与无条件刺激(US；例如，电击)配对后获得引起恐惧反应的能力时，可以形成联想情绪记忆。实验室环境中使用了两种模式(阻断再巩固和消除)来减少获得性恐惧(Nader等人，2000年；参考文献，年份)；然而，这些技术的临床疗效有限：再巩固阻断需要潜在的有毒药物，而灭绝通常不是永久性的。我的初步发现表明，我们已经设计出一种新的行为范式，可以减弱和防止恐惧记忆的回归。我们的结果表明，对常用的临床治疗(暴露疗法)进行细微的修改可以极大地改善结果，并降低患有创伤后应激障碍或特定恐惧症的个人复发的可能性。在拟议的研究中，我建议检查这种持续的恐惧衰减背后的神经机制，以澄清我们的新范式如何区别于标准的消退机制。我们将在大鼠和人类研究中并行进行这些实验，然后测试这种形式的疗法是否可以用于治疗患有特定恐惧症的个人。 与公共卫生相关：夸大或持续的恐惧在精神障碍中是常见的。实验室环境中使用了两种模式(阻止重新巩固和消除)来减少获得性恐惧；然而，这些技术的临床效果有限。在这里，我们提出了一种新的行为范式，它可以减弱和防止恐惧记忆的回归。我们的发现表明，对常用的临床治疗(暴露疗法)进行细微的修改可以极大地改善结果，并降低患有创伤后应激障碍或特定恐惧症的个人复发的可能性。

DESCRIPTION (provided by applicant): Exaggerated or persistent fear is a common occurrence in psychiatric disorders. Although much progress has been made in uncovering the neural basis of fear learning through studies of Pavlovian conditioning, little is known about how to reduce or eliminate traumatic memories in pathological cases, which is of great clinical concern. Associative emotional memories can be formed when an initially neutral stimulus (conditioned stimulus, CS; e.g., a tone) acquires the ability to elicit fear responses after being paired with an unconditioned stimulus (US; e.g., a shock). Two paradigms (blockade of reconsolidation and extinction) have been used in the laboratory setting to reduce acquired fear (Nader et al., 2000; REF, YEAR); however, the clinical efficacy of these techniques has been limited: reconsolidation blockade requires potentially toxic drugs, while extinction is not typically permanent. My preliminary findings indicated that we have devised a novel behavioral paradigm that attenuates and prevents the return of fear memories. Our results indicate that subtle modifications to a commonly employed clinical treatment (exposure therapy) could greatly improve outcome, and reduce the potential for relapse in individuals suffering from post-traumatic stress disorder or specific phobias. In the proposed studies, I propose to examine the neural mechanisms that underlie this persistent attenuation of fear, in order to disambiguate how our novel paradigm distinguishes itself from standard extinction mechanisms. We will perform these experiments in rat and human studies in parallel, and then test whether this form of therapy can be used to treat individuals that suffer from specific phobias. PUBLIC HEALTH RELEVANCE: Exaggerated or persistent fear is a common occurrence in psychiatric disorders. Two paradigms (blockade of reconsolidation and extinction) have been used in the laboratory setting to reduce acquired fear; however, the clinical efficacy of these techniques has been limited. Here, we present a novel behavioral paradigm that attenuates and prevents the return of fear memories. Our findings indicate that subtle modifications to a commonly employed clinical treatment (exposure therapy) could greatly improve outcome, and reduce the potential for relapse in individuals suffering from post-traumatic stress disorder or specific phobias.