Neural basis of temporal decision making

 描述(申请人提供)：包括知觉和运动过程在内的所有认知操作都会及时展开，只有在适当的时间执行行动才能获得成功的结果。然而，在相对较长的时间间隔内控制多个动作并监控它们的结果对大脑来说是一个具有挑战性的计算问题。此外，在各种精神病患者中，利用时间信息的能力也受到损害。 以及神经障碍，包括注意力缺陷/多动障碍(ADHD)、帕金森氏症和药物滥用。尽管有如此广泛的理论和临床意义，但以往关于时间行为和时间决策的神经生物学研究仅局限于与单个时间间隔或单一奖励相关的大脑功能。这项提议的主要目标是对能够同时监测多个时间间隔并评估序列中多个结果的价值的神经机制获得新的见解。首先，我们将使用一项要求动物根据两个同时发生的时间间隔计划不同动作的任务，来研究灵长类前额叶皮质内侧和外侧区域定时信号的解剖学特异性。我们将检验这一假设，即内侧前额叶皮质在从瞬间感觉事件产生内部计时信号并将其转换为运动反应方面发挥特殊作用。其次，我们将研究当动物在两个独立的时间延长的奖励序列中进行选择时，额顶网络中整合多个奖励序列的值的机制。具体地说，我们假设，与奖赏大小相关的信号在后顶叶皮质和前额叶皮质之间的灵活转换是将个体奖赏的价值整合为单一决策变量的过程的基础。这两个实验的结果将促进我们对大脑如何有效地处理关于多个事件的定时信息的了解，并为了解处理时间信息能力受损的临床情况的性质奠定基础。

 DESCRIPTION (provided by applicant): All cognitive operations including perceptual and motor processes unfold in time, and actions lead to successful outcomes only when they are executed at appropriate times. However, controlling multiple actions and monitoring their outcomes over a relatively long temporal interval poses challenging computational problems for the brain. Moreover, the ability to utilize temporal information is impaired in various psychiatric and neurological disorders, including attention-deficit/hyperactivity disorder (ADHD), Parkinson's disease, and substance abuse. Despite such broad theoretical and clinical significance, previous neurobiological studies on timing behavior and temporal decision-making have focused narrowly on the brain functions related to a single temporal interval or a unitary reward. The main goal of this proposal is to gain novel insights into the neural mechanisms capable of concurrently monitoring multiple temporal intervals and evaluating the value of multiple outcomes in a sequence. First, we will investigate the anatomical specificity of timing signals in the medial and lateral areas of the primate prefrontal cortex using a task that requires the animal to plan different actions according to two concurrent temporal intervals. We will test the hypothesis that the medial prefrontal cortex plays a special role in creating the internal timing signals from transient sensory events and transforming them into motor responses. Second, we will study the mechanism in the fronto-parietal network for integrating the values of multiple rewards in a sequence while the animal chooses between two separate temporally extended reward sequences. Specifically, we hypothesize that the flexible transformation of signals related to reward magnitude between the posterior parietal cortex and prefrontal cortex underlies the process of integrating the values of individual rewards into a single decision variable. The results from these two experiments will advance our knowledge about how the brain handles the timing information about multiple events efficiently, and lay the foundation for understanding the nature of clinical conditions with impaired abilities to process temporal information.