In previous reports, we described neuronal activity in the polar (PFp), dorsolateral (PFdl), and orbital (PFo) PFC as monkeys performed a cued strategy task with two spatial goals. On each trial, a cue instructed one of two strategies: Stay with the previous goal or shift to the alternative. A delay period followed each cue, and feedback followed each choice, also at a delay. Our initial analysis showed that the mean firing rate of a population of PFp cells encoded the goal chosen on a trial, but only near the time of feedback, not earlier in the trial. In contrast, PFdl cells encoded goals and strategies during the cue and delay periods, and PFo cells encoded strategies in those task periods. Both areas also signaled goals near feedback time. Here we analyzed trial-to-trial variability of neuronal firing, as measured by the Fano factor (FF): the ratio of variance to the mean. Goal-selective PFp neurons had two properties: (1) a lower FF from the beginning of the trial compared with PFp cells that did not encode goals and (2) a weak but significant inverse correlation between FF throughout a trial and the degree of goal selectivity at feedback time. Cells in PFdl and PFo showed neither of these properties. Our findings indicate that goal-selective PFp neurons were engaged in the task throughout a trial, although they only encoded goals near feedback time. Their lower FF could improve the ability of other cortical areas to decode its selected-goal signal.

The concept of the “mnemonic scotoma,” a spatially circumscribed region of working memory impairment produced by unilateral lesions of the PFC, is central to the view that PFC is critical for the short-term retention of information. Presented here, however, are previously unpublished data that offer an alternative, nonmnemonic interpretation of this pattern of deficit. In their study, Wajima and Sawaguchi [Wajima, K., & Sawaguchi, T. The role of GABAergic inhibiton in suppressing perseverative responses in the monkey prefrontal cortex. Neuroscience Research, 50(Suppl. 1), P3–P317, 2004] applied the GABA A antagonist bicuculline methiodide unilaterally to the PFC of two monkeys while they performed an oculomotor delayed-response task. Consistent with previous studies, errors for the initial memory-guided saccade were markedly higher when the cued location fell into the region of the visual field affected by the infusion. These erroneous saccades tended to select an alternative target location (out of a possible 16) that had not been cued on that trial. By extending the analysis window, however, it was observed that the second, “corrective” saccade often acquired the location that had been cued on that trial. Further analysis of the erroneous initial saccades indicated that they tended to be directed to a location that had been relevant on the previous trial. Thus, the deficit was not one of “forgetting” the cued location. Rather, it was one of selecting between currently and previously relevant locations. These findings suggest a need for a reconsideration of the concept of the mnemonic scotoma, which in turn invites a reconsideration of functional interpretations of sustained neuronal activity in PFC.