Rule-dependent anticipatory activity in prefrontal neurons.

The flexibility of the behavior of humans and other primates comes from the cognitive capability to use different behavioral modes depending on the contextual information. To investigate the neural mechanism of such a cognitive function, we trained monkeys to participate in a repeated category-outcome reversal. To perform the task efficiently, they had to explore and remember the relevant rule, i.e., which group of stimuli was associated with which outcome, and apply that rule to the visual cue in order to predict an outcome and select a response correctly. We recorded single-unit activity from the prefrontal cortex, including dorsolateral/ventrolateral prefrontal cortex and orbitofrontal cortex, and found that many neurons in these areas showed rule-dependent changes in activity during the trial and during the inter-trial-interval. The time period when a high proportion of neurons started to show rule-dependent activity was the precue period, and the typical activity pattern at that time was sustained and increasing firing towards the onset of the cue ("anticipatory" precue activity). The results indicate that the prefrontal cortex is involved in maintaining rule information in the short-term memory within and between trials and that the rule information is anticipatorily activated towards the onset of the task-relevant cue.