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.

项目概要/摘要 拟议的 R21 项目将尝试进一步开发针对创伤后应激障碍的新型干预措施 受记忆再巩固科学启发，对正常人的研究表明，当出现这种症状时。 稳定的、巩固的记忆在适当的条件下被重新激活（即检索），它恢复到 不稳定状态，这里称为分解的过程，在这种状态下，存储器容易受到影响。 各种“记忆删除”剂的作用可能会抑制其重新巩固，从而削弱它。 最近的研究发现，肾上腺素能阻滞剂普萘洛尔（PPNL）具有这种遗忘特性。 为了启动拆分，必须存在预测错误或不匹配 预期的情况以及记忆重新激活时会发生什么。 我们实验室之前的安慰剂对照随机临床试验 (PBO-RCT) 发现，当 普萘洛尔与心理创伤记忆的重新激活同时施用， 记忆力减弱，如随后较低的生理（心率、皮肤电导、面部电导率）所揭示的那样 肌电图）在脚本驱动的心理意象过程中的反应进行了临床适用性的评估。 PBO-RCT，其中接受普萘洛尔的 PTSD 参与者每周接受六次每次 10-20 分钟的治疗 在治疗后，通过阅读叙述刺激“标准”（STD）创伤记忆重新激活。 与服用 PBO 的参与者相比，参与者的 PTSD 症状明显减轻。 拟议研究的目标是测试是否有意将创新错配（MM）纳入 创伤性记忆重新激活可以改善脚本驱动的心理意象期间的生理反应。 参与者将被随机分配到 2 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意象的心理生理反应（目标测量）。 在 MM 中，每次 10-20 分钟的创伤记忆重新激活课程之前 90 分钟进行。 在这种情况下，不同的、意想不到的不匹配（例如，唱叙事）将被纳入 在 STD 条件下，参与者每次都会以相同的方式阅读叙述的焦点。 R21提案将评估MM/PPNL组是否表现出较低的后续生理 反应高于 STD/PPNL 组。