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

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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.