Neural basis of temporal decision making

 描述（由申请人提供）：所有认知操作，包括知觉和运动过程，都是及时展开的，只有在适当的时间执行，行动才会产生成功的结果。然而，在相对较长的时间间隔内控制多个动作并监测其结果对大脑构成了具有挑战性的计算问题。此外，利用时间信息的能力在各种精神疾病中受损。 和神经系统疾病，包括注意力缺陷/多动障碍（ADHD）、帕金森病和药物滥用。尽管有如此广泛的理论和临床意义，以前的神经生物学研究的时间行为和时间决策狭隘地集中在一个单一的时间间隔或单一的奖励相关的大脑功能。该提案的主要目标是获得新的见解，能够同时监测多个时间间隔和评估序列中的多个结果的价值的神经机制。首先，我们将研究灵长类动物前额皮质内侧和外侧区域的时序信号的解剖学特异性，该任务要求动物根据两个并发的时间间隔计划不同的行动。我们将检验这样一个假设：内侧前额叶皮层在从短暂的感觉事件中产生内部计时信号并将其转化为运动反应方面起着特殊的作用。其次，我们将研究额顶叶网络中的机制，当动物在两个独立的时间扩展的奖励序列之间选择时，将多个奖励的值整合到一个序列中。具体来说，我们假设，灵活的信号转换相关的奖励幅度之间的后顶叶皮层和前额叶皮层的基础的过程中整合到一个单一的决策变量的价值观的奖励。这两个实验的结果将推进我们关于大脑如何有效处理多个事件的时间信息的知识，并为理解具有处理时间信息能力受损的临床条件的性质奠定基础。

 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.