Sleep-dependent negative overgeneralization in peri-pubertal anxiety

围青春期焦虑中睡眠依赖性消极过度概括

基本信息

批准号：
10369666
负责人：
DANA L MCMAKIN
金额：
$ 64.19万
依托单位：
FLORIDA INTERNATIONAL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-06-01 至 2024-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10369666
关键词：
Address Adolescence Affect Age Amygdaloid structure Anxiety Arousal Basic Science Behavior Behavioral Behavioral Mechanisms Binding Biological Markers Clinical Cues Depression and Suicide Development Dimensions Emotional Enrollment Etiology Event Exhibits Fire - disasters Functional disorder Future Goals Health Hippocampus (Brain)Hour Individual Intervention Knowledge Lead Learning Magnetic Resonance Imaging Mediating Mediator of activation protein Memory Mental Depression Methods Modeling National Institute of Mental Health Neurosciences Organism Participant Pattern Physiology Play Polysomnography Process Protocols documentation Psychopathology Randomized Risk Role Sampling Shapes Sleep Sleep disturbances Stimulus Strategic Planning Substance abuse problem Symptoms Testing Wakefulness Youth anxiety symptoms anxious classical conditioning design experience high risk improved indexing long term memory memory consolidation memory process memory recall memory trace reactivation neurodevelopment neuroimaging neuromechanism neurophysiology non rapid eye movement novel randomized trial recruit relating to nervous system response sleep abnormalities sound suicidal risk

项目摘要

PROJECT SUMMARY Up to 50% of peripubertal youth with anxiety have unmet clinical needs, leaving these youth at high risk for suicide, depression and substance abuse across adolescence. In accord with the NIMH strategic plan, we aim to deepen mechanistic understanding of anxiety during the sensitive period of peripuberty to inform novel treatments and reduce health risks. This proposal focuses on negative overgeneralization, which is a core dimension of anxiety that is poorly understood, and refers to the tendency to generalize aversive responses from one context (house fire) to other contexts (camp-fire) that share features. Amygdala activity, induced by heightened emotional arousal, enhances plasticity in associative learning mechanisms, facilitating the binding of contextual features in memory that are only loosely related. We posit that sleep plays a critical role in negative overgeneralization. Specifically, we draw from basic neuroscience to propose a model by which heightened amygdala reactivity during wakefulness, induced by increased emotional arousal, facilitates replay of negative memories during sleep. This facilitated replay leads to the stabilization and integration (consolidation) of negative memories into long-term memory networks via slow wave oscillatory events during NREM sleep. We further propose that facilitated replay of negative memories during sleep promotes generalization by influencing underlying neurocomputational mechanisms (i.e., pattern completion – a computational process that makes neural representations similar). Finally, we propose that sleep-dependent consolidation is malleable, such that Targeted Memory Reactivation (TMR) of positive memories during sleep can competitively displace consolidation of negative memories, and reduce negative overgeneralization. The current proposal tests this model using a novel multi-method approach combining neuroimaging, polysomnography, and a memory task that captures behavioral generalization and its underlying neural mechanisms (i.e. pattern completion). Aim 1 examines 200 peripubertal youth (ages 10-13 years) across a full continuum of anxious symptoms in a randomized sleep (n=140) versus wake (n=60) design to demonstrate sleep-dependent effects on behavioral and neural mechanisms of negative overgeneralization. Aim 2 focuses on the 140 youth in the sleep condition to evaluate amygdala reactivity at encoding and sleep neurophysiology during post-encoding sleep as mediators between anxiety and negative overgeneralization. Aim 3 uses the same design as the sleep condition but recruits a new sample of youth with elevated anxiety (n=60) to enroll in a randomized trial in which positive memories are cued during sleep (TMR, n=30), or sham cues are presented during sleep (n=30), to examine malleability of sleep-dependent mechanisms of negative overgeneralization. This project will set the stage for the long-term goal of developing novel interventions that manipulate sleep (e.g. via TMR) not only to improve existing symptoms, but also to positively shape neurodevelopment and reduce risk in the sensitive period of peripuberty.

项目摘要多达50％自杀，抑郁症和滥用青少年的滥用。为了加深对脑周期中焦虑的机械理解，以告知小说治疗和降低健康风险。焦虑的维度是理解的，是指概括厌恶反应的趋势从一个环境（房屋火）到共享特征的其他环境（营地）。高度的情绪唤醒，增强关联学习机制中的塑料塑料，促进结合在记忆中的上下文特征，我们认为睡眠在负范式过度。在唤醒期间提高杏仁核反应性，引起情绪唤醒，促进重播睡眠期间的负记忆。通过慢波波波波波波波波波波波波波波波波波波波波波波波波波波波波波波波波波波波波波波波波波波波波波波波波波波波波波波波波波波波波波波波波波波波波波波波波波波波波波波波波波波波波波波波波波波波波波（整合） NREM睡眠。通过影响神经计算机制的概括（即模式压缩 - a 使神经表示相似的计算过程）。安慰是可延展的，因此在睡眠期间的积极记忆的靶向记忆重新激活（TMR）可以竞争性的外交巩固负面的记忆，并减少负面的过度当前的提案使用一种新型的多方法方法来测试该模型，该方法结合了神经影像学，多摄影术和记忆任务捕获捕获行为归因，并在神经上为基础机制（即模式压缩）。随机睡眠（n = 140）与唤醒（n = 60）设计中的焦虑症状的连续体睡眠依赖性的影响对范围过度的行为和神经机制在140中，您处于睡眠状态，以评估编码和睡眠神经生理学时的杏仁核反应性在编码后睡眠期间，作为焦虑和负过度的介体。与睡眠状况相同的设计，但招募了焦虑升高（n = 60）的新的青年样本以注册一个随机试验，在睡眠期间表现出积极记忆（TMR，n = 30）或假提示。在睡眠期间（n = 30），以检查负性过高的睡眠内部机制的可锻造性。该项目将为开发新型干预睡眠睡眠的长期目标奠定基础（例如，通过TMR）不是改善现有症状，而是积极地塑造神经发育和在敏感时期降低风险。