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

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， 在美国，恐惧、焦虑、创伤后和情绪障碍的患病率不断上升。整体 该项目的目标是描述功能障碍性厌恶的神经机制。 焦虑症患者的学习能力无法区分威胁和安全的环境是在 许多精神病问题的核心，过度概括被认为是焦虑的一个定义特征 紊乱在这个项目中，我们（1）翻译一个强大的基础科学范式，测试不同的模式， 厌恶学习进入临床竞技场，和（2）建立一个定量的方法来衡量间， 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）--通过在特定的时间点提供视觉提示来测量， 频率（例如，每秒15次，15 Hz），然后以相同的驱动频率激发神经活动。 当一个提示被一个厌恶事件（即CS+）可靠地跟随时，ssVEP的幅度被提高， 与呈现安全提示（即CS-）的频率的幅度相比，提供了精确的 学习恐惧的方法 目前的项目评估焦虑症患者的泛化学习，通过提出一个 厌恶条件CS+连同与CS+相似性不同的“安全”线索。健康的试点数据 参与者显示神经锐化（即，在枕部放置的传感器中，CS+的辨别力良好 皮层，和神经泛化（对安全线索的反应增强，最类似于CS+）超过顶叶 皮层，并提出了研究措施厌恶学习的100名参与者（80焦虑症患者 20例健康对照）。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）为每个参与者和每个相关度量计算泛化 距离）的权重建模锐化或泛化函数之间的差异， 参与者的z变换平均值跨越与CS+相似性不同的“安全”线索，产生单个 量化指标，表明每项措施的普遍化和尖锐化程度。项目 探讨了总体假设，即在厌恶学习的泛化中存在个体间差异， - 使用ssVEP定量阐明--在维度上与精神病理学的关键特征相关 在诊断组中。总之，该项目将提供有关功能障碍的关键信息， 厌恶性学习，它在焦虑的病因和维持中起作用，并形成了焦虑的基础。 开发一种在临床评估和治疗后环境中有用的新技术。

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.