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.

Numerous studies have established a role for the ACC in cognitive control. Current theories are at odds as to whether ACC itself directly engages or alternatively recruits other frontal cortical areas that implement control. The antisaccade task, in which subjects are required to make a saccade to the location opposite a suddenly appearing visual stimulus, is a simple oculomotor paradigm that has been used extensively to investigate flexible oculomotor control. Here, we tested a causal role of the dorsal ACC in cognitive control by applying electrical microstimulation during a preparatory period while monkeys performed alternating blocks of pro- and antisaccade trials. Microstimulation induced significant changes in saccadic RTs (SRTs) in both tasks. On prosaccade trials, SRTs were increased for saccades contralateral to and decreased for saccades ipsilateral to the stimulated hemisphere. In contrast, SRTs were decreased for both ipsi- and contralaterally directed antisaccades. These data show that microstimulation administered during response preparation facilitated the performance of antisaccades and are suggestive of a direct role of ACC in the implementation of cognitive control.

Visuospatial working memory is one of the most extensively investigated functions of the dorsolateral prefrontal cortex (DLPFC). Theories of prefrontal cortical function have suggested that this area exerts cognitive control by modulating the activity of structures to which it is connected. Here, we used the oculomotor system as a model in which to characterize the output signals sent from the DLPFC to a target structure during a classical spatial working memory task. We recorded the activity of identified DLPFC–superior colliculus (SC) projection neurons while monkeys performed a memory-guided saccade task in which they were required to generate saccades toward remembered stimulus locations. DLPFC neurons sent signals related to all aspects of the task to the SC, some of which were spatially tuned. These data provide the first direct evidence that the DLPFC sends task-relevant information to the SC during a spatial working memory task, and further support a role for the DLPFC in the direct modulation of other brain areas.

Complex behavior often requires the formation of associations between environmental stimuli and motor responses appropriate to those stimuli. Moreover, the appropriate response to a given stimulus may vary depending on environmental context. Stimulus-response associations that are adaptive in one situation may not be in another. The prefrontal cortex (PFC) has been shown to be critical for stimulus-response mapping and the implementation of task context. To investigate the neural representation of sensory-motor associations and task context in the PFC, we recorded the activity of prefrontal neurons in two monkeys while they performed two tasks. The first task was a delayed-match-to-sample task in which monkeys were presented with a sample picture and rewarded for making a saccade to the test picture that matched the sample picture following a delay period. The second task was a conditional visuomotor task in which identical sample pictures were presented. In this task, animals were rewarded for performing either prosaccades or antisaccades following the delay period depending on sample picture identity. PFC neurons showed task selectivity, object selectivity, and combinations of task and object selectivity. These modulations of activity took the form of a reduction in stimulus and delay-related activity, and a pro/anti instruction-based grouping of delay activity in the conditional visuomotor task. These data show that activity in PFC neurons is modulated by experimental context, and that this activity represents the formal demands of the task currently being performed.