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如何与大脑中的结构和电路直接相关。这项研究的长期目标是了解人类受试者中一种特殊形式的记忆--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联想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执行恐惧条件反射的大脑区域和电路。将构建大脑区域的功能图，在这些区域中，活动与CS或CS-在差异条件反射范式中的暴露直接相关。类似的技术将被用来表征大脑中活动与自主恐惧反应最相关的区域，而不是对程序化刺激之间关系的认知意识。我们将观察这些功能图在条件性反应消退和成功辨别后的反转训练过程中如何变化。我们将绘制示踪条件作用期间的整个大脑功能活动图，用几个相互刺激的间隔来确定在这个范例中，独特的大脑区域是否像从实验室动物文献中预测的那样活跃。该项目将专注于一系列关于杏仁核、海马体、前额叶皮质和前扣带回皮质作用的预测，这些预测基于实验室动物研究和其他用于人脑成像的记忆范式。在所有情况下，我们都建议对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。这些结果将使人们在理解方面有很大的进步：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。这些数据在解释因疾病或创伤而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.