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 情绪障碍是许多精神疾病的核心，流行病学研究指出 美国日益普遍的恐惧、焦虑、创伤后和情绪障碍。整体而言 该项目的目标是描述功能障碍厌恶的神经机制。 焦虑症患者的学习。未能区分威胁和安全环境的问题是 许多精神病学问题的核心，过度泛化被认为是焦虑的定义特征 精神错乱。在这个项目中，我们(1)翻译了一个健壮的基础科学范式，测试了不同的模式 将厌恶性学习引入临床领域，以及(2)建立一种量化方法来测量间期 厌恶性学习的个体差异。这种方法依赖于一个关于厌恶学习的稳健指数-- 稳态视觉诱发电位(SSVEP)--通过在特定位置呈现视觉提示来测量 频率(例如，每秒15次，15赫兹)，然后在相同的驱动频率下引起神经活动。 当提示之后可靠地跟随了厌恶事件(即CS+)时，SSVEP的幅度升高， 与呈现安全提示(即CS-)的频率的幅度相比，提供了精致的 衡量学习的恐惧程度。 目前的项目评估焦虑症患者的泛化学习，通过呈现一个 反常条件化的CS+，以及与CS+相似的“安全”提示。运行状况良好的试点数据 参与者展示了放置在枕骨上方的传感器的神经锐化(即对CS+的良好辨别) 大脑皮层和顶叶的神经泛化(对最类似于CS+的安全提示的增强反应) 这项研究测量了100名参与者(80名焦虑症患者)的厌恶学习 和20名健康对照)。使用SSVEP(以及惊吓和自我报告)、厌恶锐化和 使用范数(欧几里得)计算每个参与者和每个相关度量的概化 距离)的权重建模锐化或泛化函数之间的差异 参与者的z-变换意味着通过与CS+相似的不同的“安全”提示，产生一个单一的 量化指标，表示每一项指标的泛化和锐化程度。该项目 探索了最重要的假设，即厌恶学习泛化的个体间差异-- -使用SSVEP定量阐明-在维度上与精神病理学的关键特征相关 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，它在焦虑症的病因和维持中发挥作用，以及形成 开发在临床评估和治疗后环境中有用的新技术。