The Psychophysiology Of Fear And Anxiety

我们的研究项目致力于研究正常和不正常的情绪，特别强调恐惧和焦虑。这项研究使用了心理生理学、精神药理学和脑成像技术。主要的研究领域包括：1)研究外显线索恐惧和情境恐惧分别作为阶段性恐惧和广泛性焦虑的模型；2)研究精神药物对健康个体和临床群体中恐惧和焦虑的影响；3)发展人类恐惧和焦虑的实验模型。实验方法仅限于人类，但这个研究项目受到情感、动机和联想学习的动物类比的理论和方法的强烈影响。因此，这项研究依赖于将动物研究的结果转化为人类实验和精神病理学研究的努力。 1)将近端威胁与远端威胁或情境威胁分别作为阶段性恐惧和广泛性焦虑的模型进行研究。恐惧与明确可识别的迫在眉睫的威胁有关，而焦虑是一种没有对象的广义恐惧，是对未来潜在威胁的担忧预期。我们的工作假设是，恐惧和焦虑可以分别由线索恐惧和背景恐惧来建模。线索恐惧和情境焦虑之间的区别最初是在对动物的恐惧条件作用研究中做出的。暗示恐惧是由预测即将到来的有害刺激(例如，电击)的明确刺激(例如，光)引起的。情境恐惧是由发生厌恶实验的实验情境(即笼子、实验室)引起的。考虑到情境恐惧与我们对焦虑症的理解的潜在相关性，以及人类在这一领域的研究匮乏，我们正在进行几个领域的调查，重点是情境恐惧。第一个研究考察了与背景恐惧的调节有关的因素。我们已经在几项研究中报道，可预测性通过使用指令恐惧和条件反射程序来缓解情景恐惧。只要令人厌恶的事件足够令人不快，背景恐惧就会因不可预测性而增加。我们目前正在三个方面跟进这些调查结果。在一项功能磁共振研究中，一项研究探讨了大脑机制，将线索恐惧中介到信号休克，将情境焦虑中介到不可预测的休克。初步研究结果表明，在不可预测的电击中，内侧前额叶结构的激活减少。第二项调查评估了精神药理药剂的效果。第三个领域通过调查被诊断为焦虑症或被选为低或高特质焦虑的人的背景恐惧来探索这些发现与精神病理学的相关性。初步证据表明，高特质焦虑受试者和患有广泛性焦虑症、恐慌症或创伤后应激障碍的患者表现出更多的背景恐惧。 2.)精神药理学调查。为了验证我们的焦虑实验模型，我们需要证明缓解焦虑症患者焦虑的药物的有效性。与我们的假设一致，我们已经表明苯二氮卓类阿普唑仑减少了背景焦虑，而不影响线索恐惧。另一方面，SSRI西酞普兰增加了这两种类型的厌恶反应。这与SSRI最初会引起焦虑的临床经验是一致的。只有在经过几周的慢性治疗后，它们才会变得缓解焦虑。 3.)人类恐惧和焦虑状态的实验模型的发展。我们研究计划的一个重要方面是开发程序来研究人类的恐惧和焦虑。尽管最近取得了重要进展，但我们对传统的恐惧条件反射方案越来越不满意。主要有两个问题：条件性反应很弱(即，它们很快就消失了)，而且它们没有随着时间的推移而很好地保持。此外，这些研究中使用的刺激有些简单(例如，显示器上呈现的几何形状)。这些问题限制了有意义的恐惧条件作用程序的发展，尤其是对于精神药理学和背景恐惧研究。我们开始了一个使用计算机生成的虚拟现实来研究恐惧条件作用的项目，最近首次记录了虚拟环境中的情境条件作用(Baas等人，2004年)。在一项新的虚拟现实研究中，我们现在报告说，与可预测的环境相比，更多的焦虑和更多的回避受到了无法预测的电击的影响。

Our research program is devoted to the study of normal and abnormal emotions with a strong emphasis on fear and anxiety. This research is conducted using psychophysiological, psychopharmacological, and brain imaging techniques. The major areas of investigation include: 1) Studies of explicit cue fear and contextual fear as models for phasic fear and generalized anxiety, respectively; 2) investigations of the effects of psychotropic medications on fear and anxiety in healthy individuals and in clinical groups; 3) development of experimental models of fear and anxiety in humans. The experimental approach is restricted to humans, but this program of research is strongly influenced by theories and methods from animal analogues of emotion, motivation, and associative learning. Thus, the research relies on efforts to translate findings from animal research into human experimentation and studies of psychopathology. 1.) Studies of proximal versus distal or contextual threat as models for phasic fear and generalized anxiety, respectively. Fear is associated with a clearly identifiable, imminent threat, whereas anxiety is a generalized fear without object, an apprehensive anticipation of future potential threats. Our working hypothesis is that fear and anxiety can be modeled by cued fear and contextual fear, respectively. The distinction between cued fear and contextual anxiety was first made in fear conditioning studies in animals. Cued fear is elicited by an explicit stimulus (e.g., a light) that predicts an imminent noxious stimulus (e.g., a shock). Contextual fear is caused by the experimental context (i.e., the cage, the experimental room) where an aversive experiment took place. Given the potential relevance of contextual fear for our understanding of anxiety disorders and the paucity of human research in this area, we are pursuing several areas of investigations focusing on contextual fear. The first one examines factors that are involved in the modulation of contextual fear. We have reported in several studies that predictability mitigates contextual fear using instructed fear as well as conditioning procedures. Contextual fear is increased by unpredictability as long as the aversive event is sufficiently unpleasant. We are currently following-up on these findings in three areas. One investigates brain mechanisms mediating cued fear to signaled shocks and contextual anxiety to unpredictable shock in an fMRI study. Preliminary findings indicate reduced activation in medial prefrontal structures during unpredictable shocks. A second investigation assesses the effects of psychopharmacological agents. A third area explores the relevance of these findings to psychopathology by investigating contextual fear in individuals diagnosed with an anxiety disorder or selected for low or high trait anxiety. Preliminary evidence shows that high trait anxious subjects and patients with generalized anxiety disorders, panic disorder or PTSD show increased contextual fear.. 2.) Psychopharmacologic investigations. In order to validate our experimental models of anxiety, we need to show the efficacy of drugs that alleviate anxiety in patients with anxiety disorders. Consistent with our hypothesis, we have shown that the benzodiazepine alprazolam reduces contextual anxiety without affecting cued fear. On the other hand, the SSRI citalopram increased both types of aversive responses. This is consistent with the clinical experience that SSRI are initially anxiogenic. They become anxiolytic only after several weeks of chronic treatments. 3.) Development of experimental models of human fear and anxiety states. One important aspect of our program of research is to develop procedures to study fear and anxiety in humans. Despite important recent progress, we have become increasingly dissatisfied with traditional fear conditioning protocols. There are two main issues: conditioned responses are weak (i.e., they extinguished rapidly) and they are not well retained over time. In addition, the stimuli used in these studies are somewhat unsophisticated (e.g., geometric shapes presented on a monitor). These problems limit the development of meaningful fear conditioning procedures, more particularly for psychopharmacology and contextual fear studies. We have embarked on a project that uses computer-generated virtual reality to investigate fear conditioning and have recently documented for the first time context conditioning in virtual environment (Baas et al 2004). In a new virtual reality study, we now report that more anxiety and more avoidance are conditioned to environments where shocks are administered unpredictably, compared to predictably.