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.

项目总结/摘要 在美国，与自杀有关的精神病理学是对精神健康的严重损害， 终生患病率高达31.2%。最常用的临床技术在治疗 许多形式的焦虑相关的精神病理学是暴露疗法。然而，有些患者并没有受益。 从治疗和经验返回的恐惧。一个可能的解释是，曝光技术是 它主要是针对一系列有限的刺激和体验。因此，减少 在恐惧中倾向于不概括到更广泛的，更模糊的恐惧联想网络， 病理性焦虑根据RDoC倡议和NIMH战略目标1， 复杂行为的机制，本申请的目的是研究神经行为机制 抽象或间接关联的网络 发展和传播。为此，我们借鉴并联合收割机两个实验文献，联想学习， (e.g.,巴甫洛夫条件反射）和情景记忆，以精确建模和测试复杂的相互作用， 情绪、学习和记忆，导致密集和难以处理的高阶恐惧联想。目的 该提案的第一部分将研究中性和条件性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。高级功能磁共振成像 神经影像技术将被用来量化整合的程度及其与恐惧学习的关系 和概括。虽然巴甫洛夫条件反射模型在测试恐惧泛化方面很有用， 焦虑相关的精神病理学负担不仅仅包括内部恐惧和焦虑体验。 行为回避及其对日常生活的干扰也是这些病理的关键组成部分， 一般形式的回避是特别有害和难以治疗的。此外，回避是迅速， 基于抽象概念，如类别相似性（例如，学会避免 在特定的社会群体中的所有人）。因此，目标2将测试恐惧和回避是如何推广到 不同程度的概念相似性的刺激，并确定关键的焦虑相关的个体差异， 这些过程。在这项行为测试中，心理生理和自我报告指数将提交给 复杂的多层次和潜在的轮廓分析，以优化预测不适应的回避形式 一般化本提案中提出的合并目标将大大加强目前对 神经，认知和行为机制的高阶和概念概括和链接这些 临床焦虑和相关特质的机制。这些目标的完成将促进对 情绪学习和记忆的神经科学，并有助于未来治疗焦虑相关的 精神病理学