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

创伤后过度觉醒中不同严重程度的恐惧消退和睡眠

• 批准号: 9080870
• 负责人: Edward F. Pace-Schott
• 金额: $ 69.12万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-03-17 至 2020-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9080870
• 关键词: Acclimatization; Acoustics; Acute; Adopted; Amygdaloid structure; Anterior; Architecture; Area; Arousal; Arousal and Regulatory Systems; Brain; Cells; Chronic; Data; Development; Diagnosis; Diagnostic; Dorsal; Emotional; Ensure; Event; Extinction (Psychology); Fright; Functional Magnetic Resonance Imaging; Future; Galvanic Skin Response; Hippocampus (Brain); Individual; Intervention; Measures; Memory; Mental Health; Military Personnel; Modeling; Negative Reinforcements; Neuromodulator; Participant; Patient Self-Report; Peripheral; Persons; Physiological; Polysomnography; Post-Traumatic Stress Disorders; Prefrontal Cortex; Prospective Studies; Protocols documentation; Psychopathology; Psychophysiology; Psychotherapy; Questionnaires; REM Sleep; Research; Research Domain Criteria; Sampling; Scanning; Severities; Sleep; Sleep Disorders; Sleep Wake Cycle; Sleep disturbances; Stress; Symptoms; System; Testing; Trauma; Wakefulness; Wrist; actigraphy; base; blood oxygen level dependent; cingulate cortex; conditioned fear; diaries; experience; fear memory; habituation; indexing; learning extinction; member; memory consolidation; memory process; neural circuit; neural correlate; psychological symptom; public health relevance; relating to nervous system; response; stressor; traumatic event

 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.

 描述（由申请人提供）：拟议的研究将检查过去两年内（不包括过去一个月）经历过严重创伤事件的人的过度觉醒、睡眠质量和消退记忆之间的相互关系。睡眠中断非常常见，尤其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期发展。扰乱睡眠，因为促进唤醒的回路和神经调节剂与正常睡眠-觉醒周期中促进觉醒的回路和神经调节剂重叠。睡眠紊乱可能会干扰睡眠依赖性情绪记忆过程（例如消退的巩固和泛化），从而导致创伤后精神病理学。记忆（记住曾经预测危险的东西不再具有这种能力）在拟议研究的参与者中，首先将通过使用复合材料的分层抽样来获得从高功能到高症状的一系列心理健康状况。 来自 3 个病理学跨诊断评估的指数将在选定的参与者中进行评估，以便在 2 个不同的分析水平上生成连续范围的心理值。其次，经过验证的声音惊吓范式将测量从快速（最小唤醒）到缺乏或缓慢习惯（最大）的连续生理反应习惯。然后，参与者将通过腕部活动记录仪完成 2 周的睡眠日记，然后进行经过验证的恐惧调节和消退方案，其中包括 2 次晚间的恐惧调节和消退学习（第 1 节）和消退回忆（第 2 节）。将使用皮肤电导反应 (SCR) 来测量 2 个神经回路的并发活动，以表达条件性恐惧（恐惧表达网络）和消除这种恐惧（消除记忆）。网络）将使用 3T 的功能磁共振成像扫描进行检查，动态多导睡眠图将测量两次功能磁共振成像期间的适应夜、基线夜和消退记忆巩固夜的睡眠质量和结构。 ，特别是快速眼动睡眠，与生理上通过持续升高的 SCR 表达的消退记忆不良有关，在神经上通过消退记忆的激活较少和恐惧表达网络的激活较多而表达。自我报告和/或生理水平将与较差的睡眠质量相关。 过度觉醒与较少的消退记忆和较少的消退激活以及更多的恐惧网络有关。对假设的支持将支持这样一种可能性：创伤提高了觉醒系统的基线活动，导致睡眠中断，进而损害消退记忆的巩固。可能会降低恐惧记忆和其他创伤后症状侵入的阈值。