Corticostriatal mechanisms of causal inference and temporal credit assignment.

从经验中学习期望的行动需要通过整合 随着时间的推移分配给每个行动的后果。在真实的世界中，行为和结果发生在复杂的 连续的事件流必须被解析成适当的因果动作对， 这样的结果才能被评估。然而，大脑如何解决这个问题，被称为时间 信用分配（TCA）是未知的。拟议项目的目标是使用一种创新的模式， 测试关于TCA中前额叶皮层记忆的异质动力学作用的新假设。 在我们的背景滞后强盗任务中，猴子会在两个选项中的一个中选择三个选项。 交替的上下文，但在一个上下文中的选择的反馈将被暂时延迟，并在 另一种选择是在另一种情况下作出的。在这个任务中学习最优选择包括两个部分： 推理用于学习任务的因果结构或模型，基于模型的TCA用于学习 每个选择。从延迟结果中学习需要对所选择的行动或资格痕迹（ET）的记忆。 虽然理论假设ET随时间呈指数衰减（即exp-ET），但exp-ET不能解决TCA 当因果行为与结果在时间上被不相关的事件分开时。我们假设 ET的灵活动态可能对因果推理和基于模型的TCA至关重要。 更具体地说，我们假设基于模型的TCA需要动态调制的ET（动态- ET），其在其结果的预测时间被选择性地激活，以使其从 干预事件。对于因果推理，我们假设过去行为的记忆可能会被重新激活， 后见之明寻找新的因果联系（即假设ET，hyp-ET）。我们还假设ET可能是 强烈持续，直到滞后反馈（即持续ET，持续ET），以测试新链接的准确性， 干扰输入的代价。我们将研究如何灵活的动态可能是 支持跨皮质-纹状体网络的不同区域的神经活动的异质动力学。 首先，我们将评估灵长类前额叶皮层（PFC）是否为基于模型的 TCA，而纹状体为基于邻接的TCA提供exp-ET。第二，我们将评估 背内侧和背外侧PFC分别提供hyp-ET和persist-ET。我们将采取高度 综合方法和联合收割机组合多尺度神经记录、扰动和计算建模， 检查是否以及如何复杂的模式和动态的神经活动在前额叶皮层构成 支持基于模型的TCA的充分必要条件。拟议的项目将改变 传统的观点认为记忆是储存，重新铸造记忆作为学习和推理的组成部分， 时间动态是其关键结构。因果推理是患有精神分裂症的人的功能障碍的核心。 精神病症状，我们的工作将有助于了解潜在的前额叶病理生理学。

Learning desired actions from experience requires evaluating alternative actions by integrating the consequences assigned to each action over time. In the real world, actions and outcomes occur in complex sequences, and a continuous stream of events must be parsed into appropriate pairs of causative action and outcome before such pairs can be evaluated. However, how the brain solves this problem, known as temporal credit assignment (TCA) is unknown. The goal of the proposed project is to use an innovative paradigm and test novel hypotheses regarding the role of heterogeneous dynamics of memory in the prefrontal cortex in TCA. In our contextual lagged bandit task, monkeys will choose between three options offered in one of two alternating contexts, but feedback for a choice in one context will be temporally delayed and delivered after another choice is made in the other context. Learning optimal choices in this task consists of two parts: causal inference for learning the causal structure or model of the task, and model-based TCA for learning the value of each choice. Learning from delayed outcome requires memory of a chosen action or eligibility trace (ET). Although theories postulate that ET exponentially decays over time (i.e. exp-ET), exp-ET cannot resolve TCA when causative action is separated from the outcome in time and by irrelevant events. We hypothesize the flexible dynamics of ET might be crucial for causal inference and model-based TCA. More specifically, we hypothesize that model-based TCA requires dynamically-modulated ET (dynamic- ET) which is selectively activated at the predicted time of its outcome to obviate receiving credits from intervening events. For causal inference, we hypothesize that memory of past actions might be re-activated by hindsight in search of a new causal link (i.e. hypothetical ET, hyp-ET). We also hypothesize that ET might be strongly sustained until the lagged feedback (i.e. persistent ET, persist-ET) to test the accuracy of new link at the expense of confounding intervening inputs. We will investigate how flexible dynamics of ETs might be supported by heterogeneous dynamics of neural activity across different regions of cortico-striatal network. First, we will assess whether the primate prefrontal cortex (PFC) provides dynamic-ET for model-based TCA, whereas the striatum provides exp-ET for contiguity-based TCA. Second, we will assess whether dorsomedial and dorsolateral PFC provide hyp-ET and persist-ET, respectively. We will take a highly integrative approach and combine multi-scale neural recordings, perturbations and computational modeling to examine whether and how complex patterns and dynamics of neural activity in the prefrontal cortex constitute necessary and sufficient conditions to support model-based TCA. The proposed project will transform the conventional view of memory as storage, recasting memory as an integral part of learning and reasoning with temporal dynamics being its key structure. Causal inference is central to dysfunction in the individuals with psychotic symptoms and our work will contribute to understanding underlying prefrontal pathophysiology.