Fear extinction and sleep across the spectrum of severity in post-traumatic hyperarousal

 描述(由申请人提供)：拟议的研究将研究在过去两年内(不包括过去一个月)经历过严重创伤事件的人中，过度觉醒、睡眠质量和消退记忆之间的相互关系。在这样的事件发生后，睡眠中断是非常常见的，特别是在快速眼动睡眠的情况下，可以预测创伤后心理症状的后来发展。尽管睡眠中断通常被归类为过度唤醒的清醒症状，但即使是轻微的基线唤醒升高也会干扰睡眠，因为在正常的睡眠-醒来周期中，促进唤醒的回路和神经调节器与有利于清醒的回路和神经调节器重叠。睡眠障碍可能会干扰依赖睡眠的情绪记忆过程，如消亡记忆的巩固和概括(记住曾经预测的危险不再发生的能力)，从而导致创伤后精神病理。在这项拟议研究的参与者中，首先将通过使用复合体的分层抽样获得从高度功能到高度症状的一系列心理健康 从3项跨诊断精神病理学评估中得出的指数。在这样选择的参与者中，将评估高度唤醒的程度，以便在两个不同的分析水平上产生连续的值范围。首先，将从3份有效问卷中计算出规范的自我报告高度唤醒测量。其次，经过验证的声音惊吓范式将测量从快速(最小唤醒)到缺席或缓慢习服(最大唤醒)的生理反应的连续体习惯化。然后，参与者将完成为期两周的睡眠日记，手腕动作图，然后是经过验证的恐惧条件调节和消除方案，包括两个晚上的会议，24小时。分开。恐惧条件反射和消退学习(课程1)和消退回忆(课程2)将使用皮肤电导反应(SCR)进行生理学测量。在3T时，将使用fMRI扫描来检查表达条件性恐惧(恐惧-表达网络)和消除这种恐惧(消退-记忆网络)的两个神经回路中的并发活动。动态多导睡眠图将在两次fMRI会议之间的适应之夜、基线之夜和消退-记忆巩固之夜测量睡眠质量和结构。首先，假设睡眠质量差，尤其是快速眼动睡眠质量差，在生理上与SCR持续升高表现出的消退回忆差有关，而在神经上则与消退记忆中的激活较少而恐惧表达网络中的激活较多有关。其次，自我报告和/或生理水平上的高度唤醒会与较差的睡眠质量相关。第三，更大 高度唤醒将与更少的灭绝回忆和更少的灭绝激活和更多的恐惧网络相关联。支持这两种假说的组合将支持这样一种可能性，即创伤提高唤醒系统的基线活动，导致睡眠中断，进而损害消亡记忆的巩固，可能降低恐惧记忆和其他创伤后症状的入侵阈值。

 DESCRIPTION (provided by applicant): Proposed research will examine interrelationships between hyperarousal, sleep quality and extinction memory among persons who have experienced a severe traumatic event within the past 2 years (excluding the past month). In the aftermath of such an event, sleep disruption is very common and, particularly in the case of REM sleep, can predict the later development of post-traumatic psychological symptoms. Although sleep disruption is commonly classified with waking symptoms of hyperarousal, even mild elevation of baseline arousal can disturb sleep because the circuits and neuromodulators that promote arousal overlap with those that favor wakefulness during the normal sleep-wake cycle. Disturbed sleep may contribute to post-traumatic psychopathology by interfering with sleep-dependent emotional memory processes such as the consolidation and generalization of extinction memory (the ability to remember that what once predicted danger no longer does so). Among participants in the proposed study, a range of psychological health from highly functioning to highly symptomatic will first be obtained with stratified sampling using a composite index derived from 3 trans- diagnostic assessments of psychopathology. Across participants thus selected, the degree of hyperarousal will be assessed so as to generate a continuous range of values at 2 different levels of analysis. First, a canonical self-report hyperarousal measure will be computed from 3 validated questionnaires. Second, a validated acoustic-startle paradigm will measure habituation of physiological reactivity across continuum from rapid (minimal arousal) to absent or slow habituation (maximal arousal). Participants will then complete 2 weeks of sleep diaries with wrist actigraphy followed by a validated fear conditioning and extinction protocol consisting of 2 evening sessions 24 hr. apart. Fear conditioning and extinction learning (Session 1) and extinction recall (Session 2) will be measured physiologically using skin conductance response (SCR). Concurrent activity in 2 neural circuits for the expression of conditioned fear (fear-expression network) and extinction of such fear (extinction-memory network) will be examined using fMRI scanning at 3T. Ambulatory polysomnography will measure sleep quality and architecture on an adaptation night, a baseline night and an extinction-memory consolidation night between the 2 fMRI sessions. Hypotheses are, first, that poor quality of sleep, especially of REM, will be associated with poor extinction recall expressed physiologically by maintained elevation of SCR, and neurally by less activation in extinction-memory and more activation in fear-expression networks. Second, greater hyperarousal at self-report and/or physiological levels will be associated with poorer sleep quality. And third, greater hyperarousal will be associated with less extinction recall and less activation in extinction and more in fear networks. Support for hypotheses in combination will support the possibility that trauma elevates baseline activity in arousal systems resulting in sleep disruption that, in turn, impairs consolidation of extinction memory possibly lowering thresholds for intrusion of fear memories and other post-traumatic symptoms.