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的巩固，并且在调节情绪中也起着关键作用。灭绝是一种情绪记忆的一种形式，它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天人协议，我们建议比较主要失眠症患者和通常睡眠控制的人之间的灭绝记忆，以测试失眠症患者的灭绝记忆较差的主要假设。有条件的恐惧将以两种颜色作为条件刺激（CS+），使用轻度的电击作为无条件的刺激（US）和皮肤电导反应（SCR）作为条件反应（CR）。第三种从未与冲击（CS-）配对的颜色将确认差分条件。然后，对一种颜色（CS+e）的恐惧将被没有美国的重复呈现来消灭。 24小时后，将测试这种灭绝学习以及未验证的CS+（CS+ U）条件恐惧记忆的记忆。伴随的神经反应将在该方案的每个阶段（恐惧条件，灭绝学习，灭绝回忆）使用功能磁共振成像（fMRI）进行测量。睡眠生理学将在适应之夜，基线之夜和夜晚使用卧床多聚疗法（PSG）进行测量，该夜晚将在学习调节和灭绝的一天之间进行干预，以及在24小时后召回的。将在睡眠质量度量（例如睡眠效率）以及睡眠建筑措施（例如睡眠阶段百分比）和特定于快速眼部运动（例如REM连续性）中进行睡眠质量度量（例如睡眠效率）（例如睡眠阶段百分比）以及睡眠体系结构指标（例如睡眠阶段百分比）之间的相关性与睡眠生理学的相关性。假设灭绝记忆（在24小时后SCR对CS+E保持抑制的程度）在失眠症中会较差。此外，假设灭绝召回的程度（即SCR对CS+U以及CS+E的SCR的程度降低）在对照组与失眠症中的程度将更大。 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.最后，假设在失眠症中，灭绝记忆将与睡眠质量以及睡眠体系结构的完整性（尤其是在REM睡眠期间）正相关，整夜介于灭绝学习和灭绝召回之间。