Sleep and the Generalization Extinction of Conditioned Fear

睡眠与条件性恐惧的普遍消失

• 批准号: 8045077
• 负责人: Edward F. Pace-Schott
• 金额: $ 22.13万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-02-22 至 2012-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8045077
• 关键词: Address; Affect; Animals; Anxiety Disorders; Behavior Therapy; Clinical; Color; Cues; Data Analyses; Electrocardiogram; Emotional; Event; Extinction (Psychology); Failure; Frequencies; Fright; Galvanic Skin Response; Grant; Hormones; Hour; Human; Hydrocortisone; Learning; Literature; Measures; Memory; Morphologic artifacts; National Institute of Mental Health; Outcome; Patients; Physiological; Physiology; Pilot Projects; Polysomnography; Post-Traumatic Stress Disorders; Process; Publishing; REM Sleep; Rattus; Relative (related person); Research; Role; Saccades; Salivary; Shock; Signal Transduction; Sleep; Sleep Stages; Slow-Wave Sleep; Staging; Stimulus; Stress; Testing; Therapeutic; Time; Training; Trauma; Work; base; clinical practice; conditioned fear; conditioning; density; learning extinction; neurobehavioral; non rapid eye movement; rapid eye movement; research study; response

DESCRIPTION (provided by applicant): The proposed experiments will explore the role of sleep in generalizing memory for the extinction of conditioned fear. We recently discovered this generalization effect in an unfunded but published pilot study. We now wish to further develop this line of research within the R21 grant mechanism. Extinction training represents the neurobehavioral basis of exposure therapy, which is a first-line treatment for post-traumatic stress disorder (PTSD) as well as other anxiety disorders. Generalization extends extinction learning from specifically extinguished cues to other, similar stimuli. Such generalization is essential to successful exposure therapy because the reduction of fearful responding to specific cues, achieved in treatment, must then be extended to the multiplicity of related stimuli encountered outside the therapist's office. Our research has demonstrated that normal overnight sleep promotes generalization of extinction learning. Conditioned responding was established to two previously neutral color stimuli using an electric shock, and skin conductance response (SCR) served as the dependent measure of conditioned responding. One of the CS+'s was then extinguished (CS+E) whereas the other remained unextinguished (CS+U). After a 12-hour delay with intervening sleep, not only did SCR remain reduced following presentations of the CS+E (extinction recall) but it was also reduced following CS+U presentations (extinction generalization). However, such generalization was not seen when the delay contained only waking. The proposed project will first confirm that it is indeed sleep that produces generalization by examining time-of-day factors that potentially confound this previous observation. A 24-hour delay will now follow conditioning and extinction after which the Sleep-first group, trained in the evening, will immediately sleep then spend a normal day's waking whereas the Wake-first group, trained in the morning, will begin their 24 hours with waking. Thus, the Sleep-first group will now be tested at the time-of-day that poorer extinction generalization was previously observed and the Wake-first group at the time-of-day when generalization was best. Sleep physiological correlates of memory consolidation are widely replicated phenomena. We therefore next propose to examine polysomnographic correlates of extinction generalization. Additionally we propose to quantify phasic events in sleep that have been associated with memory phenomena including rapid-eye-movement density in REM sleep and sleep spindle density in Stage 2 non-REM sleep, and examine their association with extinction generalization. PUBLIC HEALTH RELEVANCE: The proposed work will explore relationships between sleep and learning not to fear previously threatening stimuli. Results may have clinical implications for timing of exposure therapy sessions relative to sleep in a manner that maximizes generalization of therapeutic extinction learning in PTSD and other anxiety disorders. Additionally, results may suggest behavioral interventions and pharmacological strategies that can be applied to post-therapy sleep in order to preserve or enhance those aspects of sleep most beneficial for extinction generalization.

描述（由申请人提供）：拟进行的实验将探讨睡眠在消除条件性恐惧的泛化记忆中的作用。我们最近在一项未获资助但已发表的初步研究中发现了这种泛化效应。我们现在希望在R21资助机制下进一步发展这方面的研究。消退训练代表了暴露疗法的神经行为基础，暴露疗法是创伤后应激障碍（PTSD）以及其他焦虑症的一线治疗方法。泛化将灭绝学习从特定的消失线索扩展到其他类似的刺激。这种泛化对于暴露疗法的成功至关重要，因为在治疗中实现的对特定线索的恐惧反应的减少，必须扩展到治疗师办公室外遇到的相关刺激的多样性。我们的研究表明，正常的夜间睡眠促进了灭绝学习的普遍化。条件反应是用电击对两种先前的中性颜色刺激建立的，皮肤电导反应（SCR）作为条件反应的依赖测量。其中一个CS+熄灭（CS+E），而另一个保持未熄灭（CS+U）。经过12小时的睡眠干预后，SCR不仅在CS+E（消失回忆）呈现后仍然降低，而且在CS+U（消失概括）呈现后也有所降低。然而，当延迟只包含唤醒时，这种普遍化并不存在。这个计划中的项目将首先通过检查可能混淆之前观察结果的时间因素来确认确实是睡眠产生了泛化。经过24小时的调节和消失后，在晚上接受训练的睡眠优先组将立即入睡，然后开始正常的一天清醒活动，而在早上接受训练的睡眠优先组将开始他们的24小时清醒活动。因此，睡眠优先组现在将在一天中先前观察到的较差的消退泛化时间进行测试，而清醒优先组将在一天中泛化最好的时间进行测试。与记忆巩固相关的睡眠生理现象被广泛复制。因此，我们下一步建议检查多导睡眠图与消光泛化的相关性。此外，我们建议量化睡眠中与记忆现象相关的相事件，包括快速眼动睡眠中的快速眼动密度和第2阶段非快速眼动睡眠中的睡眠纺锤体密度，并研究它们与消退概化的关系。