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

前额叶皮质(PFC)是人类大脑中最具决定性的结构。它蕴藏着神经元电路，使我们能够在不确定、不断变化和开放的环境中优化我们的行为。在这个项目中，我们将探索人类PFC中的细胞和微电路机制，这些机制构成了上下文相关的短期记忆维持、适应性决策和认知多任务处理，这些都是认知灵活性的标志。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手术的神经外科患者的PFC背侧。与核心假设1一致，我们提出行为相关信息的表征和更新是通过人类PFC中神经元活动的时间协调的任务依赖的变化来实现的。首先，我们将研究在单个神经元的放电活动中编码的工作记忆内容的多层表示和灵活更新。接下来，我们将转向前额叶种群动力学，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合和分离多路信息的贡献。最后，我们将扩展我们的分析，以研究相同的前额神经元及其网络的活动，在基于价值的决策过程中，需要基于变化的回报不断更新选择，以及在涉及传递性、逻辑推理的多步骤演绎推理过程中。因此，这个项目将解决人类在认知任务中和跨认知任务中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前额叶认知功能的物种独立原则提供必要的关键见解。

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.