FEAR AND THE ANXIETY DISORDERS: BRAIN AND BEHAVIOR

描述(申请人摘要)： 实验计划强调以情绪为框架的基础研究 用于比较恐惧症和焦虑症患者的临床研究。这个 情绪的指导理论源于对功能的动物研究 在食欲和防御动机状态下的大脑活动。工作依据 Davis，LeDoux，Fanselow和其他人定义了皮层下恐惧回路， 包括感觉丘脑、杏仁核和中脑导水管周围中央灰质。 惊吓反射和自主神经反应在恐惧中增强。 动物，而这种影响依赖于完整的恐惧回路(例如， 杏仁核消除增强)。对该项目进行的研究 已经表现出平行的惊吓增强和自主神经变化 处于恐惧条件反射中的人类，恐惧图像，并在关注 令人不快的图片和听觉刺激。夸张的惊吓反应 也以特定的焦虑症诊断为特征，并可能因一般性而异 精神变态的专家。 这项新的基础研究检查了锥体和皮质下的反应性 (包括动物模型的大脑部位)在人类中，使用头皮和 硬膜下电生理记录与功能磁共振 用于确定恐惧和厌恶刺激时机是否假想的成像 大脑活动的区域模式。标准化图像刺激(IAPS) 和文本引发的图像，被显示为可靠地产生与情感相关的ANS和 反射反应，呈现给磁铁中的受试者，以确定 在中性、宜人、 以及厌恶刺激，以及这些效应是如何被唤醒所调制的。一个 一组平行的实验将利用EEG来检查大脑皮质 对相同刺激的反应(事件相关电位和慢波)。随后的脑电和 FMRI研究将检查恐惧症受试者(志愿者从 正常人群)，当他们看到图片和/或精神图像时，恐惧症 和非恐惧性物体。 新的临床研究工作包括对严重焦虑症患者的评估。 研究，使用心理意象和图片范式，并采用多种测量 心理生理记录。对焦虑与焦虑进行了比较分析 精神错乱。样本包括简单和社交恐惧症、恐慌、 创伤后应激、强迫症和广泛性焦虑 精神错乱。据计划，新的神经成像技术将是 随着基础研究中程序的发展，添加到该临床方案中。 该项目的目标是加强男女之间的心理生理差异 恐惧(如恐惧症)，对特定刺激的阶段性防御反应，以及 焦虑(如在GAD中)，一种更持久的补药防御集，包括组件 压抑和抑郁。此外，为了评估纪念碑， 焦虑障碍之间的认知风格和气质差异 提高鉴别诊断，评估抑郁症的意义 共病。

DESCRIPTION (Applicant's Abstract): The plan of experiments emphasizes basic research on emotion as a framework for comparative clinical studies of phobic and anxious patients. The guiding theory of emotion is derived from animal research on functional brain activity in states of appetitive and defensive motivation. Work by Davis, LeDoux, Fanselow and others has defined a subcortical fear circuit, including the sensory thalamus, amygdala, and periaqueductal central gray. The startle reflex, and autonomic reactivity, are augmented in fearful animals, and this effect depends on an intact fear circuit (e.g., lesions of the amygdala eliminate potentiation). Research conducted on this project has demonstrated a parallel startle potentiation and autonomic change in human beings in fear conditioning, fear imagery, and while attending to unpleasant pictures and auditory stimulation. Exaggerated startle reactions also characterized specific anxiety diagnoses, and may vary with generality of psychopathology. The new basic research examines conical and subcortical reactivity (including brain sites of the animal model) in humans, using both scalp and subdural electrophysiological recording and functional magnetic resonance imaging to determine if fearful and aversive stimuli occasion hypothesized regional patterns of brain activity. Standardized picture stimuli (IAPS) and text evoked imagery, shown to reliably produce emotion related ANS and reflex responses, are presented to subjects in the magnet to determine if there are regional blood oxygen level differences between neutral, pleasant, and aversive stimuli, and how these effects are modulated by arousal. A parallel set of experiments will utilize the EEG to examine cortical responses (ERP and slow-wave) to these same stimuli. Subsequent EEG and fMRI studies will examine phobic subjects (volunteers selected from the normal population) while they view pictures of and/or mentally image, phobic and non-phobic objects. The new clinical research effort includes major anxiety patient assessment studies, using mental imagery and picture paradigms, and multi-measure psychophysiological recording. Comparative analyses are made among anxiety disorders. The sample includes simple and social phobia, panic, post-traumatic stress, obsessive- compulsive, and generalized anxiety disorders. It is planned that the new neural imaging techniques will be added to this clinical protocol, as procedures develop in the basic studies. Goals of the project are to sharpen psychophysiological distinctions between fear (as in phobia), a phasic defensive reaction to a specific stimulus, and anxiety (as in GAD), a more persistent tonic defensive set with components of inhibition and depression. and furthermore, to evaluate memorial, cognitive style, and temperament differences among anxiety disorders, to sharpen differential diagnosis and assess the significance of depressive co-morbidity.