Neural mechanisms underlying simple and complex reinforcement learning

描述（由申请人提供）：为了引导动机行为，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。这一过程在精神障碍中可能会出错;例如，在创伤后应激障碍（PTSD）中，可能会对与创伤相关的某些刺激赋予过于消极、不灵活的价值，即使在它们应该是无威胁的情况下。这个建议的重点是如何刺激的值在大脑中表示，以及这种表示如何响应不断变化的环境背景而变化。为了研究这一点，我们将同时记录两个大脑区域的神经活动--杏仁核和眶额皮层（OFC）--同时猴子执行两个任务之一：一个是简单的条件反射任务，在这个任务中，视觉刺激与奖励或惩罚联系在一起;另一个是情境依赖任务，在这个任务中，视觉刺激的意义根据情境线索而随时变化。更简单的任务将揭示刺激值是否以及如何由OFC和杏仁核中的单个神经元表示，并将提供有关这些“价值信号”的相对时间的信息，这些信息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可以灵活地改变，以反映刺激的价值，当它可以根据上下文快速变化时。它还可以揭示上下文信息是否以及如何-即，解释刺激值的“规则”编码在眶额皮层和/或杏仁核中。总之，这些实验可以阐明价值分配是如何形成的，然后由涉及边缘区（如杏仁核）和可能参与情绪反应执行控制的区域（如OFC）的神经回路进行调制。了解这个回路如何正常运作是理解它如何在PTSD，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，人们（和动物）需要能够为环境中的对象分配值（例如“好”或“坏”），有时还需要根据对象出现的上下文来改变这些值。这一过程在许多精神疾病中被破坏，如抑郁症和创伤后应激障碍。这项建议的重点是了解情感和认知脑区如何相互作用，以学习和修改对象的价值-知识，可能有助于我们理解，并最终治疗精神疾病的原因。

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.