Mismatch vs. standard intervention during memory reconsolidation blockade with propranolol: effect on psychophysiological reactivity during traumatic imagery

普萘洛尔记忆再巩固阻断期间的不匹配与标准干预：对创伤性意象期间心理生理反应的影响

• 批准号: 10572643
• 负责人: SCOTT P. ORR
• 金额: $ 20.1万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-15 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10572643
• 关键词: Adrenergic beta-Antagonists; Aftercare; American; Animal Experimentation; Animals; Basic Science; Behavior; Biological; Biology; Clinical; Clinical Trials; Double-Blind Method; Elements; Exploratory/Developmental Grant; Face; Functional disorder; Galvanic Skin Response; Goals; Heart Rate; Human; Imagery; Intervention; Investigational Therapies; Journals; Laboratories; Measures; Memory; Mental Health; Mental disorders; Molecular; National Institute of Mental Health; Outcome; Parents; Participant; Pharmaceutical Preparations; PhenX Toolkit; Physiological; Placebo Control; Placebos; Post-Traumatic Stress Disorders; Predisposition; Process; Property; Propranolol; Psychiatry; Psychophysiology; Publishing; Randomized; Reading; Reporting; Research; Science; Specific qualifier value; Symptoms; Testing; Time; United States National Institutes of Health; Work; brain tissue; clinical application; cognitive task; design; experience; experimental study; falls; fear memory; improved; innovation; insight; memory consolidation; mental imagery; neural circuit; neuroimaging; novel; permissiveness; pharmacologic; post intervention; post-traumatic symptoms; psychologic; randomized placebo-controlled clinical trial; response; traumatic event; treatment arm

PROJECT SUMMARY / ABSTRACT The proposed R21 project will attempt to further develop a novel intervention for posttraumatic stress symptoms inspired by the science of memory reconsolidation. Work in normal humans has shown that when a stable, consolidated memory is reactivated (i.e., retrieved) under appropriate conditions, it reverts to an unstable state, a process referred to herein as deconsolidation. In such a state, the memory is susceptible to the action of various “amnestic” agents that may inhibit its reconsolidation, thereby weakening it. The β- adrenergic blocker propranolol (PPNL) possesses such amnestic properties. More recent research has found that in order to initiate deconsolidation, there must be a prediction error, or mismatch, between what is expected and what occurs when the memory is reactivated. Prior placebo-controlled, randomized clinical trials (PBO-RCT) from our laboratory have found that when propranolol is administered concomitant with the reactivation of a psychologically traumatic memory, the memory is weakened, as revealed by subsequent lower physiological (heart rate, skin conductance, facial electromyogram) responding during script-driven mental imagery. Clinical applicability was evaluated in a PBO-RCT, in which PTSD participants receiving propranolol underwent six weekly sessions of 10-20 min of “standard” (STD) traumatic memory reactivation stimulated by reading a narrative. At post-treatment, these participants showed a greater reduction of PTSD symptoms compared to participants who had taken PBO. The goal of the proposed study is to test whether intentionally incorporating innovative mismatch (MM) into traumatic memory reactivation can improve upon physiological responding during script-driven mental imagery. Participants will be randomized to one of 2 treatment arms: STD/PPNL and MM/PPNL. A baseline assessment will measure psychophysiological responsivity to script-driven mental imagery (target measure). PPNL will be administered 90-min prior to each of six weekly 10-20 min. traumatic memory reactivation sessions. In the MM condition, a different, unexpected mismatch (e.g., singing the narrative) will be incorporated into the reactivation. In the STD condition, the participant will read the narrative the same way each time. The focus of the R21 proposal will be to assess whether the MM/PPNL group shows lower subsequent physiological responses than the STD/PPNL group.

项目摘要 /摘要 拟议的R21项目将试图进一步开发一种新的干预措施，以缓解创伤后压力 受记忆重新整合科学启发的症状。在正常人中的工作表明，当 稳定，合并的内存被重新激活（即检索），在适当的条件下，它恢复为 不稳定的状态，此处称为解糖的过程。在这样的状态下，记忆容易受到影响 各种“柔滑”药物的作用可能会抑制其重新溶解，从而削弱它。 β- 肾上腺阻滞剂普萘洛尔（PPNL）具有这种柔韧性。最近的研究发现 为了启动解糖化，必须在什么之间存在预测错误或不匹配 预期以及内存重新激活时发生的情况。 先前的安慰剂对照，随机临床试验（PBO-RCT）来自我们的实验室，发现当 普萘洛尔与心理创伤记忆的重新激活相关， 记忆力削弱，如随后的较低的身体（心率，皮肤电导，面部的较低）所揭示 肌电图）在脚本驱动的心理图像中做出响应。在A中评估了临床适用性 PBO-RCT，PTSD参与者接受普萘洛尔的参与者进行了六次每周10-20分钟的课程 通过阅读叙述刺激了“标准”（STD）创伤性记忆重新激活。在治疗后，这些 与服用PBO的参与者相比，参与者显示出PTSD症状的减少更大。这 拟议的研究的目标是测试是否有意将创新不匹配（MM）提高到 创伤性记忆重新激活可以改善脚本驱动的心理图像期间的身体反应。 参与者将被随机分为两个治疗组之一：STD/PPNL和MM/PPNL。基线评估 将测量对脚本驱动的心理图像（目标测量）的心理生理反应。 PPNL会 在每周10-20分钟的每周六分钟之前，要进行90分钟。创伤性记忆重新激活会话。在毫米中 条件，不同的，意外的不匹配（例如，唱歌叙事）将被纳入 重新激活。在性病条件下，参与者每次都会以相同的方式阅读叙述。重点 R21提案将评估MM/PPNL组是否显示随后的生理 响应比STD/PPNL组。