Neural circuits subserving the retrieval and maintenance of abstract rules.

Behavior is often governed by abstract rules or instructions for behavior that can be abstracted from one context and applied to another. Prefrontal cortex (PFC) is thought to be important for representing rules, although the contributions of ventrolateral (VLPFC) and dorsolateral (DLPFC) regions remain under-specified. In the present study, event-related fMRI was used to examine abstract rule representation in humans. Prior to scanning, subjects learned to associate unfamiliar shapes and nonwords with particular rules. During each fMRI trial, presentation of one of these cues was followed by a delay and then by sample and probe stimuli. Match and non-match rules required subjects to indicate whether or not the sample and probe matched; go rules required subjects to make a response that was not contingent on the sample/probe relation. Left VLPFC, parietal cortex, and pre-SMA exhibited sensitivity to rule type during the cue and delay periods. Delay-period activation in these regions, but not DLPFC, was greater when subjects had to maintain response contingencies (match, non-match) relative to when the cue signaled a specific response (go). In contrast, left middle temporal cortex exhibited rule sensitivity during the cue but not delay period. These results support the hypothesis that VLPFC interacts with temporal cortex to retrieve semantic information associated with a cue and with parietal cortex to retrieve and maintain relevant response contingencies across delays. Future investigations of cross-regional interactions will enable full assessment of this account. Collectively, these results demonstrate that multiple, neurally separable processes are recruited during abstract rule representation.