Neural mechanisms underlying simple and complex reinforcement learning

描述(申请人提供)：为了引导有动机的行为，人类和动物需要能够灵活地评估环境中刺激的情感价值-积极或消极-。在精神障碍中，这一过程可能会出错；例如，在创伤后应激障碍(PTSD)中，可能会为与创伤相关的某些刺激分配一个过于消极、僵化的值，即使在它们应该没有威胁性的情况下也是如此。这一建议的重点是如何在大脑中表示刺激值，以及这种表示如何随着环境的变化而变化。为了研究这一点，将同时记录两个大脑区域-杏仁核和眼眶前额叶皮质(OFC)的神经活动，而猴子执行两项任务之一：一项简单的条件任务，在这项任务中，视觉刺激与奖励或惩罚联系在一起；另一项与背景相关的任务，在这项任务中，视觉刺激的意义随着背景线索的变化而变化。更简单的任务将揭示OFC和杏仁核中单个神经元是否以及如何代表刺激值，并将提供关于这些“值信号”的相对时间的信息，这可能会澄清这两个区域如何相互作用。更复杂的任务将揭示这些信号是否能够足够灵活地变化，以反映刺激的价值，而刺激可以根据背景迅速变化。它还可能揭示上下文信息--即解释刺激价值的“规则”--是否以及如何在OFC和/或杏仁核中编码。总而言之，这些实验可能会阐明价值分配是如何形成的，然后被涉及边缘区域(如杏仁核)和可能涉及执行控制情绪反应的区域(如OFC)的神经回路调节。了解这一回路的正常功能是了解它如何在创伤后应激障碍、临床抑郁症和精神分裂症等精神疾病中功能障碍的重要第一步。相关性：为了做出日常决策，人(和动物)需要能够为环境中的物体赋值(如“好的”或“坏的”)，有时还需要根据物体发生的环境改变这些值。这一过程在许多精神障碍中被打断，例如抑郁症和创伤后应激障碍。这项提议的重点是了解情绪和认知大脑区域如何相互作用来学习和修改物体的价值--这些知识可能有助于我们理解并最终治疗精神障碍的原因。

DESCRIPTION (provided by applicant): In order to guide motivated behavior, humans and animals need to be able to flexibly evaluate the affective values - positive or negative - of stimuli in the environment. This process may go awry in psychiatric disorders; for example, in post-traumatic stress disorder (PTSD), an overly negative, inflexible value may be assigned to certain stimuli associated a trauma, even in a context where they should be non- threatening. The focus of this proposal is on how the values of stimuli are represented in the brain, and how this representation changes in response to changing environmental context. To investigate this, neural activity will be recorded simultaneously in two brain areas - the amygdala and orbitofrontal cortex (OFC) - while monkeys perform one of two tasks: a simple conditioning task, in which visual stimuli become linked with reward or punishment, and a context-dependent task, in which the meaning of visual stimuli changes from moment to moment depending upon contextual cues. The simpler task will reveal whether and how stimulus value is represented by individual neurons in OFC and amygdala, and will provide information about the relative timing of these "value signals" that may clarify how these two areas interact. The more complex task will reveal whether these signals can change flexibly enough to reflect the value of a stimulus when it can change rapidly depending on context. It may also reveal whether and how contextual information - i.e., the "rule" for interpreting the value of a stimulus - is encoded in OFC and/or amygdala. Together, these experiments may elucidate how value assignments are formed and then modulated by a neural circuit involving limbic areas (such as the amygdala) and areas that may be involved in the executive control of emotional responses (such as OFC). Learning how this circuit functions normally is an important first step in understanding how it may dysfunction in psychiatric disorders like PTSD, clinical depression, and schizophrenia. Relevance: In order to make everyday decisions, people (and animals) need to be able to assign values (such as "good" or "bad") to objects in the environment, and sometimes to change these values depending on the context in which an object occurs. This process is disrupted in many psychiatric disorders, such as depression and post-traumatic stress disorder. The focus of this proposal is on understanding how emotional and cognitive brain areas interact to learn and modify the values of objects - knowledge that may aid our understanding, and eventually treatment, of the causes of psychiatric disorders.