Functional Neuroanatomy of Human Fear Conditioning

人类大脑中存在多种神经系统，使我们能够学习和记忆。 目前还不完全清楚人类记忆的许多不同形式如何与大脑中的结构和回路直接相关。 这项研究的长期目标是了解人类受试者中一种特定形式的记忆，厌恶巴甫洛夫条件反射的神经机制。 通过巴甫洛夫条件反射学习关联的能力被各种各样的生物体所共享，但对人类这一过程的神经生物学底物知之甚少。 我们的一般方法是使用最先进的全脑功能磁共振成像（fMRI）来描述有助于获得和表现恐惧条件反射的大脑区域和回路。 将构建大脑区域的功能图，其中活动与在差异条件反射范例中暴露于CS+或CS-直接相关。类似的技术将被用来表征大脑区域的活动是最相关的自主恐惧反应与认知意识之间的关系编程刺激。 我们将观察这些功能图如何在条件反应消退期间和成功辨别后的逆转训练期间发生变化。 我们将绘制整个大脑的功能活动在跟踪条件反射与几个刺激间的间隔，以确定是否独特的大脑区域是活跃的，在这个范例中，将从实验室动物文献预测。 该项目将侧重于一系列关于杏仁核，海马，前额叶皮层和前扣带皮层的作用的预测，这些预测基于实验室动物研究和人类大脑成像中使用的其他记忆范式的现有知识。 在所有情况下，提出了一个广泛的多阶段分析的功能磁共振成像数据，我们将评估与事件相关的活动模式与目标刺激和反应。这些结果将使我们在以下方面的理解取得重大进展：1）陈述性和程序性记忆系统之间的关系，2）意识在学习中的作用，3）记忆的比较神经解剖学，以及4）巴甫洛夫条件反射的大脑机制。 这些数据在解释由于疾病或创伤导致脑损伤的患者的记忆缺陷时将具有重要价值。

Multiple neural systems exist within the human brain that allow us to learn and remember. At the present time it is not entirely clear how the many different forms of human memory relate directly to structures and circuits in the brain. The long-term goals of this study are to understand the neural mechanisms of a specific form of memory, aversive Pavlovian conditioning, in human subjects. The ability to learn associations through Pavlovian conditioning is shared by a wide variety of organisms but very little is known about the neurobiological substrates of this process in humans. Our general approach is to use state of the art whole brain functional magnetic resonance imaging (fMRI) to describe brain regions and circuits that contribute to the acquisition and performance of fear conditioning. Functional maps of brain areas in which activity is directly related to exposure to the CS+ or CS- in a differential conditioning paradigm will be constructed. Similar techniques will be used to characterize brain areas in which activity is best related to autonomic fear responses versus cognitive awareness of the relationship between programmed stimuli. We will observe how these functional maps change during extinction of the conditioned response and during reversal training after successful discrimination. We will map whole brain functional activity during trace conditioning with several inter-stimulus intervals to determine if unique brain areas are active in this paradigm as would be predicted from the laboratory animal literature. The project will focus on a series of predictions regarding the roles of the amygdala, hippocampus, prefrontal cortex, and anterior cingulate cortex based on current knowledge from laboratory animal studies and other memory paradigms used in human brain imaging. In all cases an extensive multi-stage analysis of the fMRI data is proposed in which we will assess event-related patterns of activity related to target stimuli and responses. The results will enable very significant advancement in understanding; 1) the relationship between declarative and procedural memory systems, 2) the role of awareness in learning, 3) the comparative neuroanatomy of memory, and 4) the brain mechanisms of Pavlovian conditioning. These data will be of great value when interpreting memory deficits in patients with brain damage due to disease or trauma.