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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要流行病学研究指出，情绪功能障碍是许多精神疾病的核心在美国，恐惧、焦虑、创伤后和情绪障碍日益普遍。整体拟议项目的目标是描述功能失调厌恶背后的神经机制焦虑症患者的学习。未能区分威胁环境和安全环境的原因在于许多精神问题的核心，过度概括被认为是焦虑的一个决定性特征失调。在这个项目中，我们（1）翻译了一个强大的基础科学范式，测试不同的模式厌恶性学习进入临床领域，以及（2）建立一种定量方法来测量交互厌恶学习的个体差异。该方法依赖于一个强大的厌恶学习指数—— 稳态视觉诱发电位（ssVEP）——通过在特定的位置呈现视觉提示来测量然后以相同的驱动频率引发神经活动。当一个线索可靠地跟随一个令人厌恶的事件（即 CS+）时，ssVEP 的幅度会升高，与呈现安全提示（即 CS-）的频率幅度相比，提供了精致的恐惧学习的衡量标准。当前的项目通过提出一个评估焦虑症患者的泛化学习的方法厌恶性调节的 CS+ 以及与 CS+ 相似性不同的“安全”线索。试点数据健康参与者在枕骨上放置的传感器中表现出神经锐化（即对 CS+ 的良好辨别能力）皮质和顶叶神经泛化（对与 CS+ 最相似的安全线索的增强反应）皮层，拟议的研究测量了 100 名参与者（80 名焦虑症患者）的厌恶学习和 20 个健康对照）。使用 ssVEP（以及惊吓和自我报告）、厌恶锐化和使用范数（欧几里德）计算每个参与者和每个相关测量的泛化距离）的权重建模锐化或泛化函数与每个函数之间的差异参与者的 z 变换意味着跨越与 CS+ 相似性不同的“安全”线索，产生单个表明每项措施的概括和锐化程度的定量指标。项目探讨了总体假设，即厌恶性学习的普遍化存在个体间差异—— - 使用 ssVEP 进行定量阐明——与精神病理学的关键特征在维度上相关跨诊断组。总而言之，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，并构成焦虑的基础开发一种可用于临床评估和治疗后环境的新技术。