Center for Neural Systems of Fear & Anxiety

在阐明动物条件性恐惧的神经通路方面已经取得了相当大的进展。这项工作涉及以杏仁核为中心的回路，以及杏仁核，海马和内侧额叶皮层（mPFC）之间的相互作用，在条件性恐惧的不同方面的获取和/或表达。对人类的研究已经证实了动物工作的重要方面。此外，同样的三个大脑区域（杏仁核，海马，mPFC）也参与了应激激素的调节，并且在恐惧/焦虑症患者中也经常发生变化。恐惧和焦虑神经科学中心（CNFA）的总体研究假设是， 在动物的恐惧回路上，与健康对照组相比，与恐惧相关的疾病患者的大脑中发生的变化相似。为了验证和探索这一假设的含义，我们使用相同的行为范式，恐惧条件反射，来研究大鼠，正常人和恐惧障碍患者。动物实验的目的是研究压力对恐惧回路的行为功能、生理学和形态学的影响。对正常人进行研究的目的是使用行为方法和功能磁共振成像来扩展我们对人类大脑恐惧机制的理解，并开发用于测试恐惧障碍患者的新探针。对恐惧症患者进行研究的目的是确定 健康人在恐惧时的功能性大脑激活模式在患有恐惧障碍的患者中发生了改变，以及这些改变是否与动物实验中确定的压力对恐惧回路的影响一致。在追求这些目标的过程中，还将在各个项目中追求几个新的主题，包括强调恐惧中电路相互作用的问题，个体和性别差异的作用以及治疗相关问题。通过这项转化研究，我们希望揭示恐惧/焦虑症患者的大脑机制，并从长远来看，确定有关如何治疗或预防此类疾病的新假设。

Considerable progress has been made in elucidating the neural pathways underlying conditioned fear in animals. This work has implicated circuits centered around the amygdala, and interactions between the amygdala, hippocampus and medial frontal cortex (mPFC), in the acquisition and/or expression of different aspects of conditioned fear. Research in humans has confirmed essential aspects of the animal work. Further, the same trio of brain regions (amygdala, hippocampus, mPFC) are also implicated in the regulation of stress hormones and are also often altered in patients with fear/anxiety disorders. The overall hypothesis guiding research in the Center for the Neuroscience of Fear and Anxiety (CNFA) is that the effects of stress on fear circuits in animals mimics changes that occur in the brains of patients with fear-related disorders relative to healthy controls. To test and explore the implications of this hypothesis, we use the same behavioral paradigm, fear conditioning, to study rats, normal humans, and patients with fear disorders. The aim of the animal work is to examine the effects of stress on the behavioral functions, physiology, and morphology of fear circuits. The aim of the studies of normal humans is to use behavioral methods and fMRI to extend our understanding of fear mechanisms in the human brain and to develop new probes for testing patients with fear disorders. And the aim of the studies of patients with fear disorders is to determine whether the patterns of functional brain activation during fear in healthy humans are altered in patients with fear disorders, and whether these alterations are consistent with the effects of stress on fear circuits, as determined in the animal work. In pursuing these goals, several new themes will also be pursued across the various projects, including an emphasis on questions about circuit interactions in fear, the role of individual and sex differences, and treatment related issues. Through this translational research we hope to reveal brain mechanisms that are altered in patients with fear/anxiety disorders and, in the long run, to identify new hypotheses about how to treat or prevent such disorders.