The Impact of Anxiety on Neurobehavioral Correlates of Conditioned Fear Generalization

焦虑对条件性恐惧泛化的神经行为相关性的影响

• 批准号: 8969090
• 负责人: Vladimir Miskovic
• 金额: $ 7.09万
• 依托单位: STATE UNIVERSITY OF NY,BINGHAMTON
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-06-17 至 2017-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8969090
• 关键词: Address; Animal Model; Animals; Anterior; Anxiety; Anxiety Disorders; Area; Arousal; Attention; Base of the Brain; Behavior; Behavioral; Benign; Biological Neural Networks; Brain; Brain region; Categories; Chemosensitization; Chronic; Clinical; Cognition; Communities; Complement; Complex; Cues; Diagnosis; Educational workshop; Electroencephalography; Emotions; Ensure; Environment; Event; Experimental Designs; Eye; Feedback; Fostering; Fright; Future; Goals; Health Services; Human; Individual; Intervention; Knowledge; Laboratory Procedures; Learning; Light; Link; Literature; Maintenance; Measures; Mediating; Mental Health; Modeling; Morbidity - disease rate; Motor; Negative Valence; Neurobiology; Neuronal Plasticity; Outcome; Pathologic; Perception; Physiology; Play; Population; Prevention; Procedures; Process; Proliferating; Psychiatric Diagnosis; Psychopathology; Reaction; Reaction Time; Recording of previous events; Reflex action; Reporting; Research; Research Domain Criteria; Research Project Grants; Residual state; Resource Allocation; Rodent; Role; Safety; Sampling; Sensory; Shapes; Shock; Signal Transduction; Stimulus; Symptoms; System; Techniques; Testing; Time; Visual evoked cortical potential; Visual system structure; Work; anxiety states; anxious; anxious individuals; base; clinical anxiety; conditioned fear; emotional stimulus; falls; improved; indexing; innovation; neural circuit; neurobehavioral; neuroregulation; novel; outcome forecast; public health relevance; relating to nervous system; response; selective attention; sensory cortex

 DESCRIPTION (provided by applicant): A poor ability to discriminate between objects that pose a legitimate danger and those that are safe underlies a variety of anxiety disorders. Although a tendency to overgeneralize fear to uncertain or ambiguous stimuli that have minimal resemblance to threat cues has emerged as a reliable pathologic correlate, no studies to date have provided a direct test of how anxiety directly causes such an outcome. The research proposed here represents the first test of how anxiety, induced using a translational procedure that mimics previous animal models, influences fear overgeneralization at neural and behavioral levels. As highlighted by the RDoC Negative Valence Systems Workshop, distinct brain systems underlie fear (i.e., a phasic response to specific cues) and anxiety (i.e., a state of sustained apprehension about unpredictable harm). The overall goal of our research is to reveal the interaction of these two neural systems (i.e., to determine how anxiety enhances fear- based responding to ambiguous stimuli). To reduce the confounding effects of chronic morbidity that have impeded clear conclusions in previous work, we will use a community-based sample that is free of psychiatric illness. We will also use a powerful within-subjects experimental design in which each individual acts as his or her own control. First, we will determine how anxious arousal influences the generalization of cue-specific fears using an innovative brain-based measure (steady state electroencephalography) that indexes fluctuations in attention processing. We will complement this new cortical measure of attention with measures of defensive reflex responding (startle) that are commonly used in animal models of fear and anxiety. In the second aim, we will tap into a specific index of functional brain connectivity to determine how higher brain regions communicate with lower order sensory areas to facilitate the representation of specific stimuli that vary in similarity to a conditioned danger cue. In particulr, we will test the hypothesis that neural connectivity of higher-order and sensory areas plays a pivotal functional role in the threat-related attention abnormalities commonly reported in anxiety. Our findings will shed new light onto the mechanisms that go awry in clinical anxiety disorders, the most common category of psychiatric illnesses.

 描述（由申请人提供）：区分构成合理危险的物体和安全物体的能力差是各种焦虑症的基础。尽管将恐惧过度概括为与威胁线索相似性极小的不确定或模糊刺激的倾向已成为可靠的病理相关性，但迄今为止还没有研究提供了焦虑如何直接导致这种结果的直接测试。这里提出的研究代表了第一次测试焦虑，使用模仿以前动物模型的翻译程序诱导，在神经和行为水平上影响恐惧过度概括。正如RDoC负价系统研讨会所强调的那样，不同的大脑系统是恐惧的基础（即，对特定线索的阶段性反应）和焦虑（即，对不可预测的伤害的持续恐惧状态）。我们研究的总体目标是揭示这两个神经系统的相互作用（即，以确定焦虑如何增强对模糊刺激的基于恐惧的反应）。为了减少慢性病的混淆影响，阻碍了明确的结论，在以前的工作中，我们将使用一个基于社区的样本，是免费的精神疾病。我们还将使用一个强大的受试者内实验设计，其中每个人作为他或她自己的控制。首先，我们将使用一种创新的基于大脑的测量方法（稳态脑电图）来确定焦虑唤醒如何影响特定于线索的恐惧的泛化，该方法将注意力处理中的波动指数化。我们将补充这种新的注意力皮质测量与防御反射反应（惊吓）的措施，通常用于动物模型的恐惧和焦虑。在第二个目标中，我们将利用功能性大脑连接的特定指数来确定高级大脑区域如何与低级感觉区域进行通信，以促进特定刺激的表示，这些刺激与条件危险提示相似。特别是，我们将测试的假设，即高阶和感觉区的神经连接起着关键的功能作用，在威胁相关的注意异常通常报告的焦虑。 我们的发现将为临床焦虑症（最常见的精神疾病类别）的机制提供新的线索。