Fear extinction memory in primary insomnia

原发性失眠的恐惧消退记忆

• 批准号: 8699371
• 负责人: Edward F. Pace-Schott
• 金额: $ 24.62万
• 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/8699371
• 关键词: Acclimatization; Address; Adult; Amygdaloid structure; Anterior; Anxiety; Anxiety Disorders; Area; Biological Markers; Brain; Chronic; Chronic Insomnia; Cognitive Therapy; Color; Comorbidity; Cues; Development; Diagnosis; Disease; Dorsal; Emotional; Emotions; Extinction (Psychology); Eye Movements; Fright; Functional Magnetic Resonance Imaging; Galvanic Skin Response; Generalized Anxiety Disorder; Hippocampus (Brain); Hour; Human; Impairment; Individual; Learning; Measures; Memory; Memory impairment; Metric; 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; base; cingulate cortex; clinically relevant; conditioned fear; conditioning; density; deprivation; emotion regulation; indexing; learning extinction; neuropsychiatry; non rapid eye movement; novel; public health relevance; 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，通过抑制条件性恐惧的表达来促进情绪调节。使用一个经过验证的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，以验证失眠症患者会表现出较差的消退记忆的主要假设。条件恐惧将以两种颜色作为条件刺激（CS+），使用轻度电击作为非条件刺激（US）和皮肤电导反应（SCR）作为条件反应（CR）。第三种颜色从未与电击配对（CS-）将确认差异条件。对一种颜色（CS+E）的恐惧将在没有美国的情况下反复出现。24小时后，测试这种消退学习的记忆以及未消退CS+ (CS+U)的条件恐惧记忆。使用功能磁共振成像（fMRI）测量该方案每个阶段（恐惧条件反射、消退学习、消退回忆）的伴随神经反应。睡眠生理学将使用动态多导睡眠记录仪（PSG）在适应之夜、基线之夜以及在学习条件反射和消失的白天和24小时后回忆它们之间的夜晚进行测量。消退记忆表现与睡眠生理学的相关性将在睡眠质量测量（如睡眠效率）、睡眠结构测量（如睡眠阶段百分比）和快速眼动（REM）睡眠特定测量（如REM连续性）中进行检验。据推测，失眠症患者的消失记忆（24小时后SCR对CS+E的抑制程度）会更差。此外，据推测，与失眠症患者相比，对照组中消失回忆普遍化的程度（即CS+U和CS+E的SCR减少的程度）将更大。还有一种假设是，失眠症患者与对照组相比，在消退记忆过程中，与消退学习和记忆相关的神经结构（腹内侧前额叶皮层和海马体）活性降低，而与条理性恐惧表达相关的神经结构（杏仁核和背前扣带皮层）活性升高。最后，假设失眠症患者的消退记忆与睡眠质量和睡眠结构的完整性呈正相关，特别是在快速眼动睡眠期间，整个晚上在消退学习和消退回忆之间进行干预。