Functional Neuroanatomy of Human Fear Conditioning

描述(申请人提供)：人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一种特定形式的记忆--厌恶巴甫洛夫条件反射--背后的神经机制。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)来识别有助于获得和执行恐惧条件反射的大脑区域和电路。我们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。类似的技术被用来描述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。 该项目的这一阶段将集中在一系列关于杏仁核、海马体、额叶皮质和扣带皮质的作用的预测上，这是基于我们在上一个资助期的进展以及实验室动物研究和其他人类记忆范式的当前知识。我们将进一步评估我们关于额叶局部活动的研究结果，特别是与应变意识和陈述性记忆有关的活动。我们将探索初级感觉皮层中与学习相关的刺激表征的动力学。我们将比较听觉恐惧条件反射程序和视觉刺激条件反射程序，并进行与恐惧消退和长期记忆提取机制相关的研究。 这些结果将使人们在以下方面获得显著的进步：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)恐惧和焦虑的大脑机制。我们的工作在提高将记忆和情绪的实验室动物模型的基本结果直接转化为健康人类和患者群体的能力方面应该特别有用。这里描述的研究对理解人类记忆和焦虑的基本大脑机制有直接影响。这项工作可能会为治疗影响记忆和情绪的疾病和障碍的新疗法提供有价值的见解。我们对这些问题的处理代表着将大量实验动物基础研究应用于人类临床和实验问题的重要一步。

DESCRIPTION (provided by applicant): 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 goal of this study is to understand the neural mechanisms underlying 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 identify 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 are used to characterize brain areas in which activity is best related to autonomic fear responses versus cognitive awareness of the relationship between programmed stimuli. This phase of the project will focus on a series of predictions regarding the roles of the amygdala, hippocampus, frontal cortex, and cingulate cortex based on our progress during the last funding period and current knowledge from laboratory animal studies and other human memory paradigms. We will further evaluate our findings related to localized frontal lobe activity specifically related to contingency awareness and declarative memory. We will explore the dynamics of learning-related stimulus representations in primary sensory cortex. We will compare an auditory fear conditioning procedure with visual stimulus conditioning, and we will conduct studies related the mechanisms of fear extinction and long-term memory retrieval. The results will enable 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 fear and anxiety. Our work should be particularly useful in improving the ability to translate fundamental results from laboratory animal models of memory and emotion directly to healthy humans as well as patient populations. The research described here has direct implications for understanding basic brain mechanisms of memory and anxiety in humans. This work may provide valuable insights into new treatments for diseases and disorders that affect memory and emotion. Our approach to these issues represents an important step toward the application of a large body of basic research in laboratory animals to clinical and experimental questions in people.