Neurobehavioral Mechanisms of Higher-Order and Conceptual Fear and Avoidance Generalization in Anxiety Psychopathology

焦虑精神病理学中高阶和概念恐惧和回避泛化的神经行为机制

• 批准号: 10579833
• 负责人: Samuel Emerson Cooper
• 金额: $ 7.18万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-12-03 至 2023-12-02
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10579833
• 关键词: Address; Amygdaloid structure; Animals; Anxiety; Association Learning; Attention; Automobile Driving; Back; Behavior; Behavioral; Behavioral Mechanisms; Belief; Benign; Categories; Clinical; Clinical Research; Cognitive; Complex; Conditioned Stimulus; Cues; Diagnostic; Emotional; Emotions; Episodic memory; Evidence based treatment; Exhibits; Experimental Models; Fright; Functional Magnetic Resonance Imaging; Future; Goals; Hippocampus; Human; Impairment; Individual Differences; Intervention; Knowledge; Learning; Life; Link; Literature; Maps; Memory; Mental Health; Minority; Modeling; Modification; National Institute of Mental Health; Neurosciences; Outcome; Participant; Pathological anxiety; Pathology; Patient Self-Report; Patients; Pattern; Persons; Phase; Physiological; Population; Post-Traumatic Stress Disorders; Prevalence; Process; Proliferating; Psychology; Psychopathology; Psychophysiology; Reaction; Recovery; Relapse; Research; Research Domain Criteria; Role; Sampling; Sensory; Stimulus; Symptoms; Techniques; Testing; Translations; Trauma; United States; Work; anxiety treatment; avoidance behavior; behavior test; clinical anxiety; clinically relevant; conditioned fear; design; experience; fear memory; improved; indexing; innovation; mental representation; neural; neural circuit; neural patterning; neurobehavioral; neuroimaging; neuromechanism; novel; prevent; reduce symptoms; social group; theories; tool; trait; treatment strategy

PROJECT SUMMARY/ABSTRACT Anxiety-related psychopathology is a serious detriment to mental health in the United States, with total lifetime prevalence a staggering 31.2%. The most commonly used clinical technique in the treatment of many forms of anxiety-related psychopathology is exposure therapy. However, some patients do not benefit from treatment and experience return of fear. One potential explanation is that exposure techniques are designed to primarily address only a circumscribed set of stimuli and experiences. Consequently, reductions in fear tend not to generalize to the broader, more nebulous network of fear associations typically seen in pathological anxiety. In line with the RDoC Initiative and NIMH Strategic Objective 1 to define the mechanism of complex behaviors, the Aims of this application investigate the neurobehavioral mechanisms of higher-order generalization processes through which networks of abstract or indirect associations develop and spread. To do this, we draw on and combine two experimental literatures, associative learning (e.g., Pavlovian conditioning) and episodic memory, to precisely model and test the complex interplay of emotion, learning, and memory that results in dense and difficult to treat higher-order fear associations. Aim 1 of this proposal will investigate the neural mechanisms of how neutral and conditioned fear memories are integrated and retrieved in post-traumatic stress disorder (PTSD) and control participants. Advanced fMRI neuroimaging techniques will be used to quantify the degree of integration and its relation to fear learning and generalization. Although Pavlovian conditioning models are useful for testing fear generalization, the burden of anxiety-related psychopathology is comprised of more than internal fear and anxiety experiences. Behavioral avoidance and its interference in everyday life is also a key component of these pathologies, and generalized forms of avoidance are particularly impairing and difficult to treat. Further, avoidance is quick to generalize across stimuli based on abstract concepts, such as categorical similarity (e.g., learning to avoid all people in a specific social group). Accordingly, Aim 2 will test how fear and avoidance generalize across stimuli of varying degrees of conceptual similarity and identify key anxiety-related individual differences in these processes. In this behavioral test, psychophysiological and self-report indices will be submitted to sophisticated multilevel and latent profile analyses to optimize prediction of maladaptive forms of avoidance generalization. The combined Aims laid out in this proposal will significantly bolster current knowledge of the neural, cognitive, and behavioral mechanisms of higher-order and conceptual generalization and link these mechanisms to clinical anxiety and related traits. Completion of these Aims will advance knowledge of the neuroscience of emotional learning and memory and contribute to future treatments of anxiety-related psychopathology.

项目摘要/摘要 与焦虑有关的心理病理学严重损害了美国的心理健康 终生患病率惊人地31.2％。治疗中最常用的临床技术 许多形式的与焦虑有关的心理病理学是暴露疗法。但是，有些患者没有受益 从恐惧的治疗和经验回报中。一种潜在的解释是曝光技术是 旨在仅处理一套限制的刺激和经验。因此，减少了 在恐惧中，往往不会推广到通常在 病理焦虑。符合RDOC倡议和NIMH战略目标1来定义 复杂行为的机制，该应用的目的研究了神经行为机制 高阶概括过程通过哪些抽象或间接关联网络 发展和传播。为此，我们借鉴并结合了两个实验文献，共同学习 （例如，Pavlovian调节）和情节记忆，以精确模拟和测试复杂的相互作用 情绪，学习和记忆会导致茂密而难以治疗高阶恐惧关联。目的 该提案中的1将调查中性和条件恐惧记忆的神经机制 在创伤后应激障碍（PTSD）和对照参与者中进行整合和检索。高级fMRI 神经影像技术将用于量化整合程度及其与恐惧学习的关系 和概括。尽管Pavlovian调节模型对于测试恐惧概括有用，但 与焦虑有关的心理病理学负担不仅仅包括内部恐惧和焦虑经历。 避免行为及其对日常生活的干扰也是这些病理的关键组成部分， 避免的广义形式特别受损，难以治疗。此外，避免很快 基于抽象概念（例如分类相似性）在刺激上概括（例如，学会避免 特定社会团体中的所有人）。因此，AIM 2将测试恐惧和回避的范围 不同程度的概念相似性的刺激，并确定与焦虑相关的关键个人差异 这些过程。在此行为测试中，心理生理和自我报告指数将提交给 复杂的多级和潜在概况分析，以优化适应不良形式的回避形式的预测 概括。该提案中阐述的合并目标将大大支持当前的知识 高阶和​​概念概括的神经，认知和行为机制，并将其联系起来 临床焦虑和相关特征的机制。这些目标的完成将提高知识 情绪学习和记忆的神经科学，并有助于与焦虑有关的未来治疗 心理病理学。