One of the hallmarks of cognitive control is the suppression of prepotent but inappropriate responses. Here we used event-related functional MRI to measure functional brain activation during a stimulus-response incompatibility task. Subjects were instructed before a stimulus appeared either to look at the stimulus (prosaccade) or to look away from the stimulus (antisaccade). Eye movements were recorded so that functional brain activation could be grouped into prosaccades, correct antisaccades, and errors (saccades toward the stimulus on antisaccade trials). Correct antisaccade trials were associated with significantly more activation in frontal and parietal cortical areas compared with prosaccade trials during the late preparatory period before stimulus appearance. Correct antisaccades evoked more activation than errors in the right dorsolateral prefrontal cortex, anterior cingulate cortex (ACC), and presupplementary eye fields during this period. No significant differences were found for any comparisons early in the preparatory period. Our data suggest that the preparation of an antisaccade activates a large frontal and parietal network that may be involved in presetting the oculomotor system for the antisaccade task. These findings indicate that a large network of frontal and posterior areas is modulated during the latter component of the preparatory period on antisaccade compared with prosaccade trials. The results further suggest that the activation level of frontal cortical areas before stimulus presentation is associated with subjects' performance in the antisaccade task. In contrast, we found no areas that were more active for correct antisaccades than prosaccades or for correct antisaccades than error antisaccades during the stimulus-response period. In fact, a number of posterior cortical areas and a few areas in the superior frontal lobe were more active during the stimulus-response period on prosaccade trials than on antisaccade trials. Error antisaccades showed a larger activation in the ACC during the stimulus-response period compared with correct antisaccades.

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Previous functional imaging studies have shown an increased hemodynamic signal in several cortical areas when subjects perform memory-guided saccades than that when they perform visually guided saccades using blocked trial designs. It is unknown, however, whether this difference results from sensory processes associated with stimulus presentation, from processes occurring during the delay period before saccade generation, or from an increased motor signal for memory-guided saccades. We conducted fMRI using an event-related paradigm that separated stimulus-related, delay-related, and saccade-related activity. Subjects initially fixated a central cross, whose color indicated whether the trial was a memory- or a visually guided trial. A peripheral stimulus was then flashed at one of 4 possible locations. On memory-guided trials, subjects had to remember this location for the subsequent saccade, whereas the stimulus was a distractor on visually guided trials. Fixation cross disappearance after a delay period was the signal either to generate a memory-guided saccade or to look at a visual stimulus that was flashed on visually guided trials. We found slightly greater stimulus-related activation for visually guided trials in 3 right prefrontal regions and right rostral intraparietal sulcus (IPS). Memory-guided trials evoked greater delay-related activity in right posterior inferior frontal gyrus, right medial frontal eye field, bilateral supplementary eye field, right rostral IPS, and right ventral IPS but not in middle frontal gyrus. Right precentral gyrus and right rostral IPS exhibited greater saccade-related activation on memory-guided trials. We conclude that activation differences revealed by previous blocked experiments have different sources in different areas and that cortical saccade regions exhibit delay-related activation differences.

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The basal ganglia (BG) play a central role in movement and it has been demonstrated that the discharge rate of neurons in these structures are modulated by the behavioral context of a given task. Here we used the antisaccade task, in which a saccade toward a flashed visual stimulus must be inhibited in favor of a saccade to the opposite location, to investigate the role of the caudate nucleus, a major input structure of the BG, in flexible behavior. In this study, we recorded extracellular neuronal activity while monkeys performed pro- and antisaccade trials. We identified two populations of neurons: those that preferred contralateral saccades (CSNs) and those that preferred ipsilateral saccades (ISNs). CSNs increased their firing rates for prosaccades, but not for antisaccades, and ISNs increased their firing rates for antisaccades, but not for prosaccades. We propose a model in which CSNs project to the direct BG pathway, facilitating saccades, and ISNs project to the indirect pathway, suppressing saccades. This model suggests one possible mechanism by which these neuronal populations could be modulating activity in the superior colliculus.