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）：拟议的研究将检查在过去2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。在这种事件之后，睡眠中断是非常常见的，特别是在REM睡眠的情况下，可以预测创伤后心理症状的后期发展。虽然睡眠中断通常被归类为觉醒过度的清醒症状，但即使是基线觉醒的轻微升高也会干扰睡眠，因为促进觉醒的回路和神经调质与正常睡眠-觉醒周期中有利于觉醒的回路和神经调质重叠。睡眠紊乱可能会干扰依赖于睡眠的情绪记忆过程，如消退记忆的巩固和泛化（记住曾经预测危险的能力不再如此），从而导致创伤后精神病理学。在拟议研究的参与者中，首先将使用复合分层抽样获得从高功能到高症状的心理健康范围。 指数来自3个精神病理学的跨诊断评估。在如此选择的参与者中，将评估过度觉醒的程度，以便在2个不同的分析水平上生成连续范围的值。首先，将根据3份经过验证的问卷计算规范的自我报告过度觉醒指标。其次，一个有效的听觉惊吓范例将测量从快速（最小唤醒）到缺乏或缓慢习惯（最大唤醒）的连续体的生理反应习惯。然后，参与者将完成2周的睡眠日记，手腕活动记录仪，然后是经过验证的恐惧条件反射和消退方案，包括2个晚上的会议，间隔24小时。恐惧条件反射和消退学习（第1阶段）和消退回忆（第2阶段）将使用皮肤电导反应（SCR）进行生理学测量。将使用3 T下的fMRI扫描来检查用于表达条件性恐惧（恐惧表达网络）和消除这种恐惧（恐惧记忆网络）的2个神经回路中的并行活动。动态多导睡眠图将在两次功能磁共振成像之间的适应夜、基线夜和记忆巩固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，与生理上表现为SCR持续升高的消退回忆差有关，与神经上表现为恐惧表达网络的激活较少和恐惧表达网络的激活较多有关。其次，自我报告和/或生理水平的过度觉醒将与较差的睡眠质量相关。第三，更大 过度觉醒与较少的灭绝回忆和较少的灭绝激活以及更多的恐惧网络有关。支持的假设组合将支持的可能性，创伤提高唤醒系统的基线活动，导致睡眠中断，这反过来又损害了灭绝记忆的巩固，可能降低入侵的恐惧记忆和其他创伤后症状的阈值。