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Cognitive flexibility is fundamental to adaptive intelligent behaviour. Prefrontal cortex has long been associated with flexible cognitive function, but the neurophysiological principles that enable prefrontal cells to adapt their response properties according to context-dependent rules remain poorly understood. Here, we use time resolved population-level neural pattern analyses to explore how context is encoded and maintained in primate prefrontal cortex, and used in flexible decision-making. We show that an instruction cue triggers a rapid series of state transitions before settling into a stable low activity state. The post-cue state is differentially tuned according to the current task-relevant rule. During decision-making, the response to a choice stimulus is characterised by an initial stimulus-specific population response, but depending on the current rule, the stimulus specific response evolves to different final states coding the behavioural decision. These results demonstrate how neural tuning profiles in prefrontal cortex adapt to accommodate changes in behavioural context. Highly flexible tuning could be mediated via short-term synaptic plasticity.


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