The abilities of switching between and maintaining task rules are fundamental aspects of goal-oriented behavior. The PFC is thought to implement the cognitive processes underling such rule-based behavior, but the specific contributions of the several cytoarchitecturally distinct subfields of PFC remain poorly understood. Here, we used bilateral cryogenic deactivation to investigate the relative contributions of two regions of the dorsolateral PFC (dlPFC)—the inferior dlPFC (idlPFC) area, consisting of the cortex lining the caudal principal sulcus, and the dorsally adjacent superior dlPFC (sdlPFC)—to different aspects of rule-based behavior. Macaque monkeys performed two variants of a task that required them to alternate unpredictably between eye movements toward (prosaccade) or away from (antisaccade) a visual stimulus. In one version of the task, the current rule was overtly cued. In the second, the task rule was uncued, and successful performance required the animals to detect rule changes on the basis of reward outcome and subsequently maintain the current task rule within working memory. Deactivation of the idlPFC impaired the monkeys' ability to perform pro- and antisaccades in the uncued task only. In contrast, deactivation of the sdlPFC had no effect on performance in either task. Combined deactivation of idlPFC and sdlPFC impaired performance on antisaccade, but not prosaccade, trials in both task variants. These results suggest that the idlPFC is required for mnemonic processes involved in maintenance of task rules, whereas both idlPFC and sdlPFC together are necessary for the deployment of the cognitive control required to perform antisaccades. Together, these data support the concept of a functional specialization of subregions within the dlPFC for rule-guided behavior.

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