Novel paradigm attenuates traumatic memories and prevents return of fear

新颖的范例可以减轻创伤记忆并防止恐惧再次出现

基本信息

批准号：
8011230
负责人：
Marie H. Monfils
金额：
$ 17.89万
依托单位：
UNIVERSITY OF TEXAS AT AUSTIN
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-01-01 至 2012-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8011230
关键词：
Amygdaloid structure Attenuated Behavioral Behavioral Paradigm Biochemical Markers Brain region Chemosensitization Clinical Clinical Treatment Conditioned Stimulus Electrophysiology (science)Emotional Extinction (Psychology)Fright Functional Magnetic Resonance Imaging Hour Human Individual Laboratories Lateral Learning Memory Mental disorders Modification Outcome Pharmaceutical Preparations Phase Phosphorylation Post-Traumatic Stress Disorders Process Protocols documentation Public Health Rattus Relapse Research Retrieval Sampling Sensory Shock Specific Phobia Stimulus Synapses Techniques Testing Time Training Update Variant Work attenuation base blood oxygenation level dependent response classical conditioning clinical efficacy conditioned fear follow-up improved in vivo neural circuit neuromechanism novel prevent public health relevance relating to nervous system research study response

项目摘要

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.

描述（由申请人提供）：过度或持续的恐惧在精神疾病中很常见。尽管通过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进展，但对于如何减少或消除病理病例中的创伤记忆却知之甚少，而这正是临床所关心的。当最初的中性刺激（条件刺激，CS；例如音调）与非条件刺激（US；例如电击）配对后获得引发恐惧反应的能力时，可以形成联想情绪记忆。实验室环境中使用了两种范式（封锁再巩固和消退）来减少获得性恐惧（Nader 等，2000；REF，YEAR）；然而，这些技术的临床功效有限：再巩固封锁需要潜在有毒的药物，而灭绝通常不是永久性的。我的初步发现表明，我们设计了一种新颖的行为范式，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，并减少患有创伤后应激障碍或特定恐惧症的个体复发的可能性。在拟议的研究中，我建议检查这种恐惧持续减弱背后的神经机制，以消除我们的新范式如何与标准灭绝机制区分开来的歧义。我们将在大鼠和人体研究中并行进行这些实验，然后测试这种疗法是否可以用于治疗患有特定恐惧症的个体。公共卫生相关性：过度或持续的恐惧在精神疾病中很常见。实验室环境中使用了两种范例（封锁再巩固和消退）来减少获得性恐惧；然而，这些技术的临床疗效有限。在这里，我们提出了一种新颖的行为范式，可以减弱和防止恐惧记忆的回归。我们的研究结果表明，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，并减少患有创伤后应激障碍或特定恐惧症的个体复发的可能性。