Neuro-dynamic mechanisms of cognitive flexibility at the cellular and microcircuit-level in human dorsolateral prefrontal cortex

前额叶皮层（PFC）是人类大脑中最具决定性的结构。它拥有神经回路，使我们能够在面对不确定、变化和开放的环境时优化自己的行为。在这个项目中，我们将探索人类PFC中的细胞和微电路机制，这些机制是认知灵活性的标志——上下文依赖的短期记忆维持、适应性决策和认知多任务处理的基础。为此，我们将使用最近开发的密集皮质内微电极记录，这些记录来自于因医疗目的而清醒操作的神经外科患者的背外侧PFC。根据核心假设1，我们提出行为相关信息的表征和更新是通过人类pfc神经元活动时间协调的任务依赖变化来实现的。首先，我们将研究单个神经元尖峰活动编码的工作记忆内容的多层表征和灵活更新。接下来，我们将转向前额叶种群动态，包括同步振荡活动。我们将阐明神经元兴奋性的节律性变化对连接和分解特定内容的细胞组装和分离多路信息的贡献。最后，我们将扩展我们的分析，以研究相同的前额叶神经元及其网络在基于价值的决策过程中的活动，这需要根据变化的回报不断更新选择，以及在涉及传递性逻辑推理的多步演绎推理过程中。因此，该项目将解决人类认知任务内部和跨认知任务的认知灵活性的前额叶神经元基础。与核心假设1一致，它还将为建立共同的、独立于物种的前额叶认知功能原则提供重要的见解。

The prefrontal cortex (PFC) is the most defining structure of the human brain. It harbors the neuronal circuitry that allows us to optimize our behavior in the face of uncertain, changing and open-ended environments. In this project, we will explore the cellular and microcircuit mechanisms in the human PFC that underlie context-dependent short-term memory maintenance, adaptive decision-making and cognitive multitasking, the hallmarks of cognitive flexibility. For this, we will use recently developed dense intracortical microelectrode recordings acquired from the dorsolateral PFC of neurosurgical patients who are operated awake for medical purposes. In line with core hypothesis 1, we propose that the representation and updating of behaviorally relevant information is implemented by task-dependent changes in the temporal coordination of neuronal activity in human PFC. First, we will investigate the multi-layered representation and flexible updating of working memory content encoded in the spiking activity of individual neurons. Next, we will turn to prefrontal population dynamics, including synchronized oscillatory activity. We will elucidate the contribution of rhythmic changes in neuronal excitability to linking and disbanding content-specific cell assemblies and separating multiplexed information. Finally, we will extend our analyses to study the activity of the same prefrontal neurons and their networks during value-based decision-making that requires constant updating of choices based on changing returns and during multi-step deductive reasoning that involves transitive, logical inference. This project will thus address the prefrontal neuronal basis of human cognitive flexibility within and across cognitive tasks. In line with core hypothesis 1, it will also provide crucial insights necessary for establishing shared species-independent principles of prefrontal cognitive functioning.