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 用于恐惧症和焦虑症患者的临床对比研究。的 情绪的指导理论是从动物的功能研究中衍生出来的， 食欲和防御性动机状态下的大脑活动。工作 戴维斯、勒杜、范斯洛和其他人已经定义了皮层下的恐惧回路， 包括感觉丘脑、杏仁核和导水管周围中央灰质。 惊吓反射和自主神经反应在恐惧时增强， 动物，并且这种效果取决于完整的恐惧回路（例如，病变 杏仁核消除增强作用）。对该项目进行的研究 已经证明了一个平行的惊吓增强和自主变化， 人类在恐惧条件反射，恐惧意象，同时注意到 不愉快的画面和听觉刺激。夸张的惊吓反应 也具有特定的焦虑诊断特征，并且可能随一般性而变化 精神病理学 新的基础研究检查了圆锥和皮层下的反应性 （包括动物模型的脑部位），使用头皮和 硬膜下电生理记录和功能磁共振 成像，以确定是否假设恐惧和厌恶刺激的场合 大脑活动的区域模式标准化图片刺激 和文本诱发的图像，显示可靠地产生情绪相关的ANS， 反射反应，被呈现给磁体中的受试者，以确定是否 在中性，舒适， 和厌恶性刺激，以及这些效应如何被唤醒调节。一 一组平行的实验将利用脑电图检查大脑皮层 对这些相同刺激的反应（ERP和慢波）。随后的EEG和 fMRI研究将检查恐惧症受试者（从 正常人群），而他们看到的图片和/或精神形象，恐怖 和非恐惧症对象。 新的临床研究工作包括主要的焦虑患者评估 研究，使用心理意象和图片范例，和多措施 心理生理记录对焦虑、焦虑、焦虑 紊乱样本包括简单和社交恐惧症，恐慌， 创伤后应激障碍、强迫症和广泛性焦虑 紊乱据计划，新的神经成像技术将在 随着基础研究中程序的发展，添加到本临床方案中。 该项目的目标是加强心理生理的区别， 恐惧（如恐惧症），对特定刺激的阶段性防御反应，以及 焦虑（如在广泛性焦虑症），一个更持久的紧张性防御设置与组件 抑制和抑郁的症状此外，为了评估纪念馆， 认知方式和焦虑症之间的气质差异， 提高鉴别诊断水平，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.