Neural mechanisms of long-term planning

描述（由申请人提供）：为了做出适应性决策，动物需要复杂的机制来跟踪结果的可取性、大小和概率。此外，动物必须在多个时间尺度上整合结果信息，并且必须有能力不仅针对即时奖励，还针对延迟奖励。对于人类来说，几乎每一个决定都需要某种形式的提前计划，时间范围从相对较短（去商店买冰淇淋）到特别长的（现在投资为了几十年后退休）。规划能力对正常行为至关重要，而这种能力的损害可能会造成毁灭性的后果。两种主要的精神疾病——注意力缺陷障碍和成瘾——与计划缺陷以及额叶和顶叶皮质区功能障碍有关。然而，尽管长期规划很重要，但人们对其潜在的神经机制知之甚少。在这里，我们使用序列决策任务结合单神经元记录在猴子侧顶叶内区（LIP）解决这个问题。这项任务要求猴子在两种可选策略中做出选择——一种是面向即时奖励的次优策略，另一种是面向最终（延迟）奖励的最佳策略。先前的研究主要集中在顺序行动的排序和定时机制上，这里我们关注的是潜在的决策-行动评估-计算。大脑是如何根据未来（预计的）奖励来为一个动作分配价值的，而这种奖励只有在多个干预的感觉和运动事件之后才会出现？大脑如何区分对获得延迟奖励至关重要的行为和非至关重要的行为？最后，大脑是如何解决跨时间冲突的，放弃即时奖励以保持对最终目标的关注？虽然大多数先前的研究都集中在额叶皮层上，但在这里，我们从顶叶和额叶区域进行记录，顶叶和额叶区域可能对提前计划至关重要。因此，提出的实验扩展了我们在更广泛的皮层网络中进行长期规划所需的决策机制的知识。这些研究对于从机制上理解精神障碍患者的长期计划及其崩溃是必要的。1

DESCRIPTION (provided by applicant): To make adaptive decisions, animals require sophisticated mechanisms for tracking the desirability, magnitude and probability of an outcome. In addition, animals must integrate outcome information over multiple time scales, and must have the capacity to orient not only toward immediate but also toward delayed rewards. For humans, nearly every decision requires some form of advance planning, on time scales that can range from relatively short (going to the store in order to get an ice cream) to the exceptionally long (investing money now in order to retire in several decades). The capacity for planning is critical for normal behavior, and impairments in this faculty can have devastating consequences. Two major psychiatric disorders - attention deficit disorder and addiction - have been associated with planning deficits and with dysfunction in frontal and parietal cortical areas. However, despite the importance of long-term planning, the underlying neural mechanisms are poorly understood. Here we address this question using a sequential decision making task in conjunction with single- neuron recording in monkey lateral intra-parietal area (LIP). The task requires monkeys to choose between two alternative strategies - a suboptimal strategy oriented toward an immediate reward, and an optimal strategy oriented toward a final (delayed) reward. While prior studies have focused on ordering and timing mechanisms during sequential actions, here we focus on the underlying decisional - action evaluation - computations. How does the brain assign value to an action, based on a future (projected) reward that only arrives after multiple intervening sensory and motor events? How does the brain distinguish between actions that are and those that are not critical for obtaining a delayed reward? And finally, how does the brain resolve inter-temporal conflict, foregoing an immediate reward in order to remain focused on the final goal? While most prior studies have focused on the frontal cortex, here we record from the parietal lobe which, together with frontal areas, is likely to be critical for advance planning. Thus the proposed experiments extend our knowledge of the decision mechanisms required for long-term planning in a broader cortical network. These studies are necessary for a mechanistic understanding of long-term planning and its breakdown during mental disorders. 1 PUBLIC HEALTH RELEVANCE: The capacity for long-term planning is critical for normal decision making. Impairments in planning are thought to be part of the etiology of psychiatric disorders, including attention deficit disorders and addiction. While studies of long-term planning have been carried out in human subjects, the underlying neuronal mechanisms remain largely unknown. The present experiment probes the mechanisms by which the brain assigns action value based on delayed, rather than immediate rewards during a sequential decision making task. The goal is to provide a detailed understanding of planning mechanisms during normal behavior and mental illness. 1