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: 10389973
• 负责人: Samuel Emerson Cooper
• 金额: $ 6.76万
• 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/10389973
• 关键词: Address; Amygdaloid structure; Animals; Anxiety; Automobile Driving; Back; Behavior; Behavioral; Behavioral Mechanisms; Belief; Benign; Categories; Clinical; Clinical Research; Cognitive; Complex; Conditioned Stimulus; Cues; Emotional; Emotions; Episodic memory; Exhibits; Experimental Models; Fright; Functional Magnetic Resonance Imaging; Future; Goals; Gold; Hippocampus (Brain); Human; Impairment; Individual Differences; Intervention; Knowledge; Lead; 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; Research; Research Domain Criteria; Role; Sampling; Sensory; Stimulus; Symptoms; Techniques; Testing; Translations; United States; Work; anxiety treatment; avoidance behavior; base; behavior test; classical conditioning; clinical anxiety; clinically relevant; conditioned fear; design; disorder control; evidence base; experience; fear memory; improved; indexing; innovation; mental representation; neural circuit; neural patterning; neurobehavioral; neuroimaging; neuromechanism; novel; prevent; reduce symptoms; relating to nervous system; social group; standard care; 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 与焦虑相关的精神病理学在美国是一种严重损害心理健康的疾病， 终生患病率高达惊人的31.2%。治疗慢性阻塞性肺疾病最常用临床技术 与焦虑相关的许多形式的精神病理学都是暴露疗法。然而，一些患者并没有受益 从治疗和体验中回归恐惧。一种可能的解释是，曝光技术 设计主要是针对有限的一组刺激和体验。因此，削减 在恐惧中，往往不会概括到更广泛、更模糊的恐惧联系网络，这种联系通常在 病态焦虑症。根据RDoC倡议和NIMH战略目标1，定义 复杂行为的机制，本应用程序的目的是研究神经行为机制 通过抽象或间接关联网络的更高阶概括过程 发展和传播。为了做到这一点，我们借鉴并结合了两个实验文献，联想学习 (例如，巴甫洛夫条件反射)和情节记忆，以精确地模拟和测试 情绪、学习和记忆，导致密集和难以治疗的高级恐惧联想。目标 这项提议的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)和对照组参与者中整合和检索。高级功能磁共振成像 神经成像技术将用于量化整合程度及其与恐惧学习的关系 和泛化。尽管巴甫洛夫的条件反射模型对测试恐惧泛化很有用，但 焦虑相关的精神病理学负担不仅仅是由内心的恐惧和焦虑经历组成的。 行为回避及其对日常生活的干扰也是这些病理的一个关键组成部分，以及 广义的回避形式特别有害，也很难治疗。此外，回避很快就会 基于抽象概念对刺激进行泛化，例如分类相似性(例如，学会避免 特定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普遍存在的 不同程度的概念相似刺激，并识别与焦虑相关的关键个体差异 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轮廓分析，以优化对不适应形式的回避的预测 泛化。这项提案中列出的综合目标将极大地增强目前对 高阶和概念性概括的神经、认知和行为机制及其联系 临床焦虑症的发病机制及相关特征。完成这些目标将促进对 情绪学习和记忆的神经科学，并有助于未来与焦虑相关的治疗 精神变态学。