Anxiety and aversive learning: Neural mechanics of generalization and patterns of disorder pathology

焦虑和厌恶学习：泛化的神经机制和疾病病理学模式

• 批准号: 9978957
• 负责人: Andreas Keil
• 金额: $ 19.06万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-16 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9978957
• 关键词: Aftercare; Anxiety; Anxiety Disorders; Arousal; Attention; Automobile Driving; Basic Science; Behavior; Brain; Clinical; Clinical assessments; Complex; Cues; Data; Development; Diagnosis; Diagnostic; Dimensions; Discrimination; Disease; Disease susceptibility; Emotional; Etiology; Event; Face; Failure; Frequencies; Fright; Functional disorder; Goals; Grouping; Human; Impairment; Individual; Individual Differences; Intervention; Learning; Maintenance; Measures; Mechanics; Mediating; Memory; Mental disorders; Methods; Mexican; Modeling; Mood Disorders; National Institute of Mental Health; Occipital lobe; Panic; Parietal; Parietal Lobe; Participant; Pathology; Patient Self-Report; Patients; Pattern; Persons; Phase; Play; Post-Traumatic Stress Disorders; Prevalence; Principal Component Analysis; Procedures; Psychopathology; Psychophysiology; Questionnaires; Reflex action; Research; Research Domain Criteria; Role; Rotation; Safety; Severities; Signal Transduction; Specific Phobia; Standardization; Stimulus; Stimulus Generalization; Stress; Syndrome; Techniques; Testing; Time; Translating; Trauma; United States; Visual; Visual evoked cortical potential; Weight; Work; anxious; base; classical conditioning; cohort; epidemiology study; indexing; negative affect; neuromechanism; neurophysiology; novel; prospective; relating to nervous system; response; sensor; translational study

Project Summary Emotional dysfunction is at the core of many psychiatric disorders, with epidemiological studies noting the growing prevalence of fear, anxiety, post-traumatic, and mood disorders in the United States. The overall goal of the proposed project is to characterize the neural mechanisms that underlie dysfunctional aversive learning in anxiety disorder patients. The failure to discriminate between threatening and safe contexts is at the core of many psychiatric problems, with overgeneralization proposed as a defining feature of anxiety disorders. In this project, we (1) translate a robust basic science paradigm testing different modes of aversive learning into the clinical arena, and (2) establish a quantitative approach for measuring inter- individual differences in aversive learning. The approach relies on a robust index of aversive learning -- the steady state visual evoked potential (ssVEP) -- which is measured by presenting a visual cue at a specific frequency (e.g., 15 times per second, 15 Hz) that then elicits neural activity at the same driving frequency. When a cue is reliably followed by an aversive event (i.e. CS+), the amplitude of the ssVEP is heightened, compared to the amplitude of the frequency at which a safe cue (i.e. CS-) is presented, providing an exquisite measure of fear learning. The current project assesses generalization learning in anxiety disorder patients, by presenting an aversively conditioned CS+ together with "safe" cues that vary in similarity to the CS+. Pilot data with healthy participants shows neural sharpening (i.e., good discrimination of CS+) in sensors placed over occipital cortex, and neural generalization (enhanced responses to safe cues most similar to the CS+) over parietal cortex, and the proposed study measures aversive learning in 100 participants (80 anxiety disorder patients and 20 healthy controls). Using the ssVEP (as well as startle and self-reports), aversive sharpening and generalization are computed for each participant and for each dependent measure using the norm (Euclidian distance) of the difference between weights modeling sharpening or generalization functions and each participant's z-transformed means across "safe" cues that vary in similarity to the CS+, producing a single quantitative index indicating the degree of generalization and sharpening for each measure. The project explores the overarching hypothesis that inter-individual differences in the generalization of aversive learning- - quantitatively elucidated using the ssVEP-- are dimensionally related to key features of psychopathology across diagnostic groups. Taken together, this project will provide key information regarding dysfunction in aversive learning, which plays a role in the etiology and maintenance of anxiety, as well as form the basis for developing a novel technique useful in clinical assessment and post-treatment contexts.

项目摘要 情绪功能障碍是许多精神疾病的核心，流行病学研究指出 美国恐惧，焦虑，创伤后和情绪障碍的越来越流行。总体 拟议项目的目标是表征功能障碍厌恶基础的神经机制 在焦虑症患者中学习。未能区分威胁和安全环境是在 许多精神病问题的核心，提出过度笼统的焦虑特征 疾病。在这个项目中，我们（1）翻译了强大的基础科学范式测试不同的模式 对临床领域的厌恶学习，（2）建立一种定量方法来测量 厌恶学习的个体差异。该方法依赖于厌恶学习的强大索引 - 稳态视觉诱发电位（SSVEP） - 通过在特定的特定方面呈现视觉提示来衡量 频率（例如每秒15次，15 Hz），然后以相同的驱动频率引起神经活动。 当一个可靠地提示之后发生厌恶事件（即CS+）时，SSVEP的幅度会加剧， 与提出安全提示（即CS-）的频率的幅度相比，提供了精美的 度量恐惧学习。 当前的项目通过提出一个 厌恶条件的CS+以及与CS+相似的“安全”提示。健康数据 参与者显示位于枕骨上的传感器中的神经锐化（即CS+的良好歧视） 皮层和神经泛化（对安全性提示的响应增强了，与CS+最相似） 皮层和拟议的研究测量了100名参与者的厌恶性学习（80名焦虑症患者 和20个健康对照）。使用SSVEP（以及惊吓和自我报告），厌恶锐化和 使用规范计算每个参与者的概括和每个因措施（Euclidian） 距离）重量建模锐化或泛化功能与每个差异之间的差异） 参与者的Z转换均意味着与CS+相似的“安全”提示，产生一个 定量指数表示每种度量的概括程度和锐化程度。项目 探讨以下总体假设，即厌恶学习的概括中的个体间差异 - - 使用SSVEP进行定量阐明 - 与精神病理学的关键特征有关 跨诊断组。综上所述，该项目将提供有关功能障碍的关键信息 厌恶学习，在焦虑的病因和维持中发挥作用，并构成 开发一种用于临床评估和治疗后环境中有用的新技术。