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The prefrontal cortex (PFC), which plays key roles in many higher cognitive processes, is a hierarchical system consisting of multi-scale organizations. Optimizing the working state at each scale is essential for PFC's information processing. Typical optimal working states at different scales have been separately reported, including the dopamine-mediated inverted-U profile of the working memory (WM) at the system level, critical dynamics at the network level, and detailed balance of excitatory and inhibitory currents (E/I balance) at the cellular level. However, it remains unclear whether these states are scale-specific expressions of the same optimal state and, if so, what is the underlying mechanism for its regulation traversing across scales. Here, by studying a neural network model, we show that the optimal performance of WM co-occurs with the critical dynamics at the network level and the E/I balance at the level of individual neurons, suggesting the existence of a unified, multi-scale optimal state for the PFC. Importantly, such a state could be modulated by dopamine at the synaptic level through a series of U or inverted-U profiles. These results suggest that seemingly different optimal states for specific scales are multi-scale expressions of one condition regulated by dopamine. Our work suggests a cross-scale perspective to understand the PFC function and its modulation.

Multi-Scale Expressions of One Optimal State Regulated by Dopamine in the Prefrontal Cortex