Functional Neuroanatomy of Human Fear Conditioning

人类大脑中存在多个神经系统，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是如何与大脑的结构和回路直接联系起来的。这项研究的长期目标是了解人类受试者的一种特定形式的记忆，即厌恶的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为多种生物体所共有，但对人类这一过程的神经生物学基础知之甚少。我们的一般方法是使用最先进的全脑功能磁共振成像（fMRI）来描述大脑区域和回路，这些区域和回路有助于恐惧条件反射的获得和表现。在差异条件作用范式中，与暴露于CS+或CS-直接相关的脑区域的功能图将被构建。类似的技术将用于描述与自主恐惧反应和程序化刺激之间关系的认知意识最相关的大脑区域。我们将观察这些功能图在条件反应消失期间和成功辨别后的逆转训练期间是如何变化的。我们将用几个刺激间间隔来绘制在痕量条件作用期间的全脑功能活动图，以确定是否有特定的大脑区域在这种范式中活跃，正如从实验动物文献中预测的那样。该项目将重点关注一系列关于杏仁核、海马体、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的现有知识和人类大脑成像中使用的其他记忆范式。在所有情况下，建议对fMRI数据进行广泛的多阶段分析，其中我们将评估与目标刺激和反应相关的事件相关活动模式。研究结果将使我们在理解方面取得非常重大的进展；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脑机制。这些数据在解释因疾病或创伤引起的脑损伤患者的记忆缺陷时将具有很大的价值。

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.