Fear extinction memory in primary insomnia

原发性失眠的恐惧消退记忆

• 批准号: 8833338
• 负责人: Edward F. Pace-Schott
• 金额: $ 21.75万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-04-07 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8833338
• 关键词: Acclimatization; Address; Adult; Amygdaloid structure; Anterior; Anxiety; Anxiety Disorders; Area; Biological Markers; Brain; Chronic; Chronic Insomnia; Cognitive Therapy; Color; Comorbidity; Conditioned Reflex; Cues; Development; Diagnosis; Disease; Dorsal; Emotional; Emotions; Extinction (Psychology); Eye Movements; Fright; Functional Magnetic Resonance Imaging; Galvanic Skin Response; Generalized Anxiety Disorder; Health; Hippocampus (Brain); Hour; Human; Impairment; Individual; Learning; Measures; Memory; Memory impairment; Neurobiology; Outcome; Patients; Performance; Persons; Physiological; Physiology; Play; Polysomnography; Post-Traumatic Stress Disorders; Prefrontal Cortex; Primary Insomnia; Protocols documentation; Psychophysiology; Publishing; REM Sleep; Research; Risk Factors; Role; Shock; Signal Transduction; Sleep; Sleep Architecture; Sleep Stages; Sleep disturbances; Sleeplessness; Staging; Stimulus; Structure; Symptoms; Testing; Time; anxiety symptoms; base; cingulate cortex; clinically relevant; conditioned fear; conditioning; density; deprivation; emotion regulation; fear memory; indexing; learning extinction; memory consolidation; neuropsychiatry; non rapid eye movement; novel; rapid eye movement; relating to nervous system; response; sleep regulation; success; treatment strategy

DESCRIPTION (provided by applicant): Sleep aids in the consolidation of memory and also plays a key role in regulating emotions. Extinction is a form of emotional memory that promotes emotion regulation by inhibiting the expression of conditioned fear. Using a validated 2-day human protocol, we propose to compare extinction memory between persons with Primary Insomnia and normally sleeping controls to test the main hypothesis that those with insomnia will display poorer extinction memory. Conditioned fear will be established to two colors as conditioned stimuli (CS+) using a mild electric shock as an unconditioned stimulus (US) and skin conductance response (SCR) as the conditioned response (CR). A third color never paired with a shock (CS-) will confirm differential conditioning. Fear of one color (CS+E) will then be extinguished by its repeated presentation without the US. After 24 h, memory for this extinction learning as well as the conditioned fear memory for the unextinguished CS+ (CS+U) will be tested. The accompanying neural responses will be measured at each stage of this protocol (fear conditioning, extinction learning, extinction recall) using functional magnetic resonance imaging (fMRI). Sleep physiology will be measured using ambulatory polysomnography (PSG) on an acclimation night, a baseline night and on the night that will intervene between the day when conditioning and extinction are learned and when they are recalled 24 h later. Correlations of extinction memory performance with sleep physiology will be examined among sleep quality measures (e.g., sleep efficiency) as well as sleep architectural measures (e.g., sleep stage percentages) and measures specific to rapid eye movement (REM) sleep (e.g. REM continuity). It is hypothesized that extinction memory (the degree to which SCR to the CS+E remains suppressed after 24 h) will be poorer in insomniacs. Additionally, it is hypothesized that the degree to which extinction recall generalizes (i.e., the degree to which SCR to the CS+U as well as to the CS+E is reduced) will be greater in controls versus insomniacs. It is also hypothesized that, in insomniacs versus controls during extinction recall, the neural structures whose activity has been associated with extinction learning and memory (ventromedial prefrontal cortex and hippocampus) will be hypoactivated and those associated with the expression of conditioned fear (amygdala and dorsal anterior cingulate cortex) will be hyperactivated. Lastly, it is hypothesized that, in insomniacs, extinction memory will correlate positively with sleep quality as well as with the integrity of sleep architecture, especially during REM sleep, across the night intervening between extinction learning and extinction recall.

描述（由申请人提供）：睡眠有助于巩固记忆，在调节情绪方面也起着关键作用。消退是一种情绪记忆，通过抑制条件恐惧的表达来促进情绪调节。使用经过验证的2天人类协议，我们建议比较原发性失眠症患者和正常睡眠对照组之间的消退记忆，以检验失眠症患者的消退记忆较差的主要假设。条件性恐惧将被建立为两种颜色作为条件性刺激（CS+），使用轻度电击作为非条件性刺激（US）和皮肤电导反应（SCR）作为条件性反应（CR）。第三种颜色从未与电击（CS-）配对，将确认差异条件反射。对一种颜色（CS+E）的恐惧将在没有美国的重复呈现中消失。24小时后，将测试该消退学习的记忆以及未消退CS+（CS+U）的条件恐惧记忆。将在本方案的每个阶段（恐惧条件反射、消退学习、消退回忆）使用功能性磁共振成像（fMRI）测量伴随的神经反应。在适应夜、基线夜和将在学习条件反射和消退的白天与24小时后回忆条件反射和消退的白天之间进行干预的夜晚，将使用动态多导睡眠图（PSG）测量睡眠生理学。将在睡眠质量指标（例如，睡眠效率）以及睡眠结构测量（例如，睡眠阶段百分比）和快速眼动（REM）睡眠的特定测量（例如REM连续性）。据推测，消退记忆（24小时后CS+E的SCR保持抑制的程度）在失眠症患者中较差。此外，假设消退回忆的泛化程度（即，CS+U以及CS+E的SCR降低的程度）在对照组中比失眠症患者中更大。还假设，在失眠症患者与对照组在灭绝回忆期间，其活动与灭绝学习和记忆（腹内侧前额叶皮层和海马）相关的神经结构将被低激活，而与条件恐惧（杏仁核和背侧前扣带皮层）的表达相关的神经结构将被过度激活。最后，假设在失眠症患者中，消退记忆将与睡眠质量以及睡眠结构的完整性呈正相关，特别是在REM睡眠期间，在整个夜间介于消退学习和消退回忆之间。