Neural mechanisms of long-term planning

描述(由申请人提供)：为了做出适应性决定，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指向即时的回报，也指向延迟的回报。对人类来说，几乎每一个决定都需要某种形式的提前计划，时间从相对较短的时间(去商店买冰淇淋)到极长的时间(现在投资，以便几十年后退休)不等。计划能力对于正常的行为至关重要，而这种能力的受损可能会产生毁灭性的后果。两种主要的精神障碍--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域的功能障碍有关。然而，尽管长期规划很重要，但人们对潜在的神经机制知之甚少。在这里，我们使用序贯决策任务结合猴子外侧顶内区(LIP)的单个神经元记录来解决这个问题。这项任务要求猴子在两种不同的策略中进行选择--一种是针对即时奖励的次优策略，另一种是针对最终(延迟)奖励的最优策略。虽然先前的研究集中在顺序动作的排序和计时机制上，但这里我们关注的是潜在的决策-动作评估-计算。大脑如何根据未来(预计的)奖赏为一项行动分配价值，而未来奖赏只有在多个相互干预的感觉和运动事件之后才会到来？大脑如何区分对获得延迟奖励来说是关键的和非关键的行为？最后，大脑如何解决跨时期的冲突，放弃直接的奖励，以保持专注于最终目标？虽然之前的大多数研究都集中在额叶皮质上，但这里我们记录的是顶叶，它与额叶区域一起，可能对提前计划至关重要。因此，拟议的实验扩展了我们在更广泛的大脑皮层网络中进行长期计划所需的决策机制的知识。这些研究对于从机械上理解长期计划及其在精神障碍期间的崩溃是必要的。1 公共卫生相关性：长期规划能力对正常决策至关重要。计划障碍被认为是精神障碍的病因学的一部分，包括注意力缺陷障碍和成瘾。虽然已经在人类受试者身上进行了长期规划的研究，但其潜在的神经机制在很大程度上仍不清楚。本实验探索了在连续的决策任务中，大脑根据延迟的而不是即时的奖励来分配行动价值的机制。目标是提供对正常行为和精神疾病期间的计划机制的详细了解。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