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

• 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
• 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

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）：夸大或持续的恐惧是精神疾病中常见的现象。虽然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情况下的创伤记忆知之甚少，这是一个非常重要的临床问题。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，震惊）。在实验室环境中已经使用了两种范例（阻断再巩固和消退）来减少获得性恐惧（Nader等人，二○年; REF，YEAR）;然而，这些技术的临床效果有限：再巩固阻断需要潜在的毒性药物，而消退通常不是永久性的。我的初步研究结果表明，我们已经设计出一种新的行为模式，可以减弱和阻止恐惧记忆的回归。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大大改善结果，并降低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，我建议检查这种持续衰减恐惧的神经机制，以消除歧义，我们的新范式如何区分自己从标准的灭绝机制。我们将在大鼠和人类研究中平行进行这些实验，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体。 公共卫生相关性：夸大或持续的恐惧在精神疾病中很常见。两种范例（阻断再巩固和消退）已被用于在实验室设置，以减少获得性恐惧，然而，这些技术的临床疗效有限。在这里，我们提出了一种新的行为模式，衰减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大大改善结果，并降低患有创伤后应激障碍或特定恐惧症的个体复发的可能性。

项目成果

Learned together, extinguished apart: reducing fear to complex stimuli.

• DOI: 10.1101/lm.031740.113
• 发表时间: 2013-11-15
• 期刊: Learning & memory (Cold Spring Harbor, N.Y.)
• 作者: Jones CE;Ringuet S;Monfils MH
• 通讯作者: Monfils MH

Post-retrieval extinction as reconsolidation interference: methodological issues or boundary conditions?

• DOI: 10.1007/s00213-013-3004-1
• 发表时间: 2013-04
• 期刊: PSYCHOPHARMACOLOGY
• 影响因子: 3.4
• 作者: Auber, Alessia;Tedesco, Vincenzo;Jones, Carolyn E.;Monfils, Marie-H.;Chiamulera, Christian
• 通讯作者: Chiamulera, Christian

Fear conditioning by-proxy: social transmission of fear during memory retrieval.

• DOI: 10.1016/j.bbr.2010.04.047
• 发表时间: 2010-12-06
• 期刊: BEHAVIOURAL BRAIN RESEARCH
• 影响因子: 2.7
• 作者: Bruchey, Aleksandra K.;Jones, Carolyn E.;Monfils, Marie-H.
• 通讯作者: Monfils, Marie-H.

Updating appetitive memory during reconsolidation window: critical role of cue-directed behavior and amygdala central nucleus.

• DOI: 10.3389/fnbeh.2013.00186
• 发表时间: 2013
• 期刊: Frontiers in behavioral neuroscience
• 影响因子: 3
• 作者: Olshavsky ME;Song BJ;Powell DJ;Jones CE;Monfils MH;Lee HJ
• 通讯作者: Lee HJ

Extinction and Retrieval + Extinction of Conditioned Fear Differentially Activate Medial Prefrontal Cortex and Amygdala in Rats.

• DOI: 10.3389/fnbeh.2015.00369
• 发表时间: 2015
• 期刊: Frontiers in behavioral neuroscience
• 影响因子: 3
• 作者: Lee HJ;Haberman RP;Roquet RF;Monfils MH
• 通讯作者: Monfils MH