Fear extinction memory in primary insomnia

描述(申请人提供)：睡眠有助于巩固记忆，也在调节情绪方面起着关键作用。消亡是一种情绪记忆，它通过抑制条件性恐惧的表达来促进情绪调节。使用有效的两天人类方案，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，以检验主要假设，即失眠患者的消退记忆将表现出较差的消退记忆。条件性恐惧将被建立为两种颜色的条件刺激(CS)，使用温和的电击作为非条件刺激(US)，皮肤电导反应(SCR)作为条件反应(CR)。第三种颜色永远不会与电击(CS-)配对，这将确认差异条件反射。对一种颜色(CS E)的恐惧将因其在没有美国的情况下反复呈现而消失。24小时后，对这种消亡学习的记忆以及对未熄灭的CS(CS U)的条件性恐惧记忆进行测试。伴随的神经反应将在该方案的每个阶段(恐惧条件作用、消退学习、消退回忆)使用功能磁共振成像(FMRI)进行测量。使用动态多导睡眠图(PSG)在习服之夜、基线之夜以及在学习到条件反射和消退的那一天到24小时后回忆它们之间的夜晚测量睡眠生理学。将在睡眠质量指标(例如，睡眠效率)以及睡眠结构指标(例如，睡眠阶段百分比)和特定于快速眼动(REM)睡眠的指标(例如，REM连续性)之间检查消退记忆性能与睡眠生理学的相关性。据推测，失眠症患者的消退记忆(24小时后对CS-E的SCR仍然受到抑制的程度)会更差。此外，还假设在控制组和失眠组中，消亡回忆的泛化程度(即对CS U和CS E的SCR降低的程度)会更大。还假设，与对照组相比，失眠症患者在消退回忆过程中，其活动与消退学习和记忆相关的神经结构(腹内侧额叶皮质和海马体)将处于低激活状态，而那些与条件性恐惧表达相关的神经结构(杏仁核和背侧扣带回前皮质)将被过度激活。最后，假设在失眠症患者中，消退记忆与睡眠质量以及睡眠结构的完整性呈正相关，尤其是在快速眼动睡眠期间，在消退学习和消退回忆之间的整个夜晚。

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.