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Animals likely use a variety of strategies to solve laboratory tasks. Traditionally, combined analysis of behavioral and neural recording data across subjects employing different strategies may obscure important signals and give confusing results. Hence, it is essential to develop techniques that can infer strategy at the single-subject level. We analyzed an experiment in which two male monkeys performed a visually cued rule-based task. The analysis of their performance shows no indication that they used a different strategy. However, when we examined the geometry of stimulus representations in the state space of the neural activities recorded in dorsolateral prefrontal cortex, we found striking differences between the two monkeys. Our purely neural results induced us to reanalyze the behavior. The new analysis showed that the differences in representational geometry are associated with differences in the reaction times, revealing behavioral differences we were unaware of. All these analyses suggest that the monkeys are using different strategies. Finally, using recurrent neural network models trained to perform the same task, we show that these strategies correlate with the amount of training, suggesting a possible explanation for the observed neural and behavioral differences., (© 2024. The Author(s).)

We can adapt flexibly to environment changes and search for the most appropriate rule to a context. The orbital prefrontal cortex (PFo) has been associated with decision making, rule generation and maintenance, and more generally has been considered important for behavioral flexibility. To better understand the neural mechanisms underlying the flexible behavior, we studied the ability to generate a switching signal in monkey PFo when a strategy is changed. In the strategy task, we used a visual cue to instruct two male rhesus monkeys either to repeat their most recent choice (i.e., stay strategy) or to change it (i.e., shift strategy). To identify the strategy switching-related signal, we compared nonswitch and switch trials, which cued the same or a different strategy from the previous trial, respectively. We found that the switching-related signal emerged during the cue presentation and it was combined with the strategy signal in a subpopulation of cells. Moreover, the error analysis showed that the activity of the switch-related cells reflected whether the monkeys erroneously switched or not the strategy, rather than what was required for that trial. The function of the switching signal could be to prompt the use of different strategies when older strategies are no longer appropriate, conferring the ability to adapt flexibly to environmental changes. In our task, the switching signal might contribute to the implementation of the strategy cued, overcoming potential interference effects from the strategy previously cued. Our results support the idea that ascribes to PFo an important role for behavioral flexibility. SIGNIFICANCE STATEMENT We can flexibly adapt our behavior to a changing environment. One of the prefrontal areas traditionally associated with the ability to adapt to new contingencies is the orbital prefrontal cortex (PFo). We analyzed the switching related activity using a strategy task in which two rhesus monkeys were instructed by a visual cue either to repeat or change their most recent choice, respectively using a stay or a shift strategy. We found that PFo neurons were modulated by the strategy switching signal, pointing to the importance of PFo in behavioral flexibility by generating control over the switching of strategies., (Copyright © 2020 the authors.)

Neurons in prefrontal cortex (PF) represent mnemonic information about current goals until the action can be selected and executed. However, the neuronal dynamics underlying the transition from goal into specific actions are poorly understood. Here, we show that the goal-coding PF network is dynamically reconfigured from mnemonic to action selection states and that such reconfiguration is mediated by cell assemblies with heterogeneous excitability. We recorded neuronal activity from PF while monkeys selected their actions on the basis of memorized goals. Many PF neurons encoded the goal, but only a minority of them did so across both memory retention and action selection stages. Interestingly, about half of this minority of neurons switched their goal preference across the goal-action transition. Our computational model led us to propose a PF network composed of heterogeneous cell assemblies with single-state and bistable local dynamics able to produce both dynamical stability and input susceptibility simultaneously., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

In previous work, we studied the activity of neurons in the dorsolateral (PFdl), orbital (PFo), and polar (PFp) prefrontal cortex while monkeys performed a strategy task with 2 spatial goals. A cue instructed 1 of 2 strategies in each trial: stay with the previous goal or shift to the alternative goal. Each trial started with a fixation period, followed by a cue. Subsequently, a delay period was followed by a "go" signal that instructed the monkeys to choose one goal. After each choice, feedback was provided. In this study, we focused on the temporal receptive fields of the neurons, as measured by the decay in autocorrelation (time constant) during the fixation period, and examined the relationship with response and strategy coding. The temporal receptive field in PFdl correlated with the response-related but not with the strategy-related modulation in the delay and the feedback periods: neurons with longer time constants in PFdl tended to show stronger and more prolonged response coding. No such correlation was found in PFp or PFo. These findings demonstrate that the temporal specialization of neurons for temporally extended computations is predictive of response coding, and neurons in PFdl, but not PFp or PFo, develop such predictive properties.

Animals need to learn and to adapt to new and changing environments so that appropriate actions that lead to desirable outcomes are acquired within each context. The prefrontal cortex (PF) is known to underlie such function that directly implies that the outcome of each response must be represented in the brain for behavioral policies update. However, whether such PF signal is context dependent or it is a general representation beyond the specificity of a context is still unclear. Here, we analyzed the activity of neurons in the dorsolateral PF (PFdl) recorded while two monkeys performed two perceptual magnitude discrimination tasks. Both tasks were well known by the monkeys and unexpected changes did not occur but the difficulty of the task varied from trial to trial and thus the monkeys made mistakes in a proportion of trials. We show a context-independent coding of the response outcome with neurons maintaining similar selectivity in both task contexts. Using a classification method of the neural activity, we also show that the trial outcome could be well predicted from the activity of the same neurons in the two contexts. Altogether, our results provide evidence of high degree of outcome generality in PFdl., (Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.)

The estimation of space and time can interfere with each other, and neuroimaging studies have shown overlapping activation in the parietal and prefrontal cortical areas. We used duration and distance discrimination tasks to determine whether space and time share resources in prefrontal cortex (PF) neurons. Monkeys were required to report which of two stimuli, a red circle or blue square, presented sequentially, were longer and farther, respectively, in the duration and distance tasks. In a previous study, we showed that relative duration and distance are coded by different populations of neurons and that the only common representation is related to goal coding. Here, we examined the coding of absolute duration and distance. Our results support a model of independent coding of absolute duration and distance metrics by demonstrating that not only relative magnitude but also absolute magnitude are independently coded in the PF., New & Noteworthy: Human behavioral studies have shown that spatial and duration judgments can interfere with each other. We investigated the neural representation of such magnitudes in the prefrontal cortex. We found that the two magnitudes are independently coded by prefrontal neurons. We suggest that the interference among magnitude judgments might depend on the goal rather than the perceptual resource sharing., (Copyright © 2017 the American Physiological Society.)

The activity of some prefrontal (PF) cortex neurons distinguishes short from long time intervals. Here, we examined whether this property reflected a general timing mechanism or one dependent on behavioral context. In one task, monkeys discriminated the relative duration of 2 stimuli; in the other, they discriminated the relative distance of 2 stimuli from a fixed reference point. Both tasks had a pre-cue period (interval 1) and a delay period (interval 2) with no discriminant stimulus. Interval 1 elapsed before the presentation of the first discriminant stimulus, and interval 2 began after that stimulus. Both intervals had durations of either 400 or 800 ms. Most PF neurons distinguished short from long durations in one task or interval, but not in the others. When neurons did signal something about duration for both intervals, they did so in an uncorrelated or weakly correlated manner. These results demonstrate a high degree of context dependency in PF time processing. The PF, therefore, does not appear to signal durations abstractedly, as would be expected of a general temporal encoder, but instead does so in a highly context-dependent manner, both within and between tasks., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

The prefrontal cortex (PF) is involved in outcome-based flexible adaptation in a dynamically changing environment. The outcome signal dissipates gradually over time, but the temporal dynamics of this dissipation remains unknown. To examine this issue, we analyzed the outcome-related activity of PF neurons in 2 monkeys in a distance discrimination task. The initial prestimulus period of this task varied in duration, allowing us to dissociate the effects of time and event on the decline in previous outcome-related activity -previous correct versus previous error. We observed 2 types of decline in previous outcome representation: PF neurons that ceased to encode the previous outcome as time passed (time-dependent) and neurons that maintained their signal but it decreased rapidly after the occurrence of a new external event (event-dependent). Although the time-dependent dynamics explained the decline in a greater proportion of neurons, the event-dependent decline was also observed in a significant population of neurons.

Rhesus monkeys performed two tasks, both requiring a choice between a red square and a blue circle. In the duration task, the two stimuli appeared sequentially on each trial, for varying durations, and, later, during the choice phase of the task, the monkeys needed to choose the one that had lasted longer. In the matching-to-sample task, one of the two stimuli appeared twice as a sample, with durations matching those in the duration task, and the monkey needed to choose that stimulus during the choice phase. Although stimulus duration was irrelevant in the matching-to-sample task, the monkeys made twice as many errors when the second stimulus was shorter. This across-task interference supports an order-dependent model of the monkeys' choice and reveals something about their strategy in the duration task. The monkeys tended to choose the second stimulus when its duration exceeded the first and to choose the alternative stimulus otherwise. For the duration task, this strategy obviated the need to store stimulus-duration conjunctions for both stimuli, but it generated errors on the matching-to-sample task. We examined duration coding in prefrontal neurons and confirmed that a population of cells encoded relative duration during the matching-to-sample task, as expected from the order-dependent errors., (Copyright © 2015 the American Physiological Society.)

Two rhesus monkeys performed a distance discrimination task in which they reported whether a red square or a blue circle had appeared farther from a fixed reference point. Because a new pair of distances was chosen randomly on each trial, and because the monkeys had no opportunity to correct errors, no information from the previous trial was relevant to a current one. Nevertheless, many prefrontal cortex neurons encoded the outcome of the previous trial on current trials. A smaller, intermingled population of cells encoded the spatial goal on the previous trial or the features of the chosen stimuli, such as color or shape. The coding of previous outcomes and goals began at various times during a current trial, and it was selective in that prefrontal cells did not encode other information from the previous trial. The monitoring of previous goals and outcomes often contributes to problem solving, and it can support exploratory behavior. The present results show that such monitoring occurs autonomously and selectively, even when irrelevant to the task at hand.

Timing is a very abstract representation that shares with other magnitudes, such as numerosity, the peculiarity of being independent from any particular sensory modality. Not only we can time stimuli in different modalities but we can also compare the durations of different visual, auditory and somatosensory stimuli. Furthermore, even though time is not directly associated with space, and we are inclined to consider space and time as two different perceptual dimensions of our existence, an increasing number of studies challenge this idea by showing that timing and spatial processing have some relationship that involves sharing computation resources and that time may have a spatial representation. A more general theory, called theory of magnitude (ATOM), considers both timing and spatial computations, together with other magnitudes, as originating from a general magnitude system [Walsh VA, Trends Cogn Sci 7(11):483-8, 2003]. The neural underpinnings of time and its relationship to the processing of spatial information have started to be investigated only recently, but the field is rapidly growing. It is addressing the representation of time in several cortical and subcortical brain areas. Information processing of time and space are not strictly specialized in neural and cognitive mechanisms and we believe that studying them only separately may restrict our understanding of these processes. In this chapter, we will firstly introduce the role of the prefrontal cortex (PF) in coding relative durations. We will point out that the comparison of durations makes use of intermediate computations based on the order of the events. Secondly, we will describe the comparison mechanisms that are implemented by PF to make perceptual decisions about durations in relation to those involved in making decisions about spatial locations and distances. We will distinguish the decision processes from the goal choices, and we will examine which computational resources are shared between different magnitudes and which are domain-specific. We will summarize our results within the context of a more general PF function in promoting the generation of goals from the current context, consisting of domain- and modality-specific coding of stimuli of different modalities or magnitudes.

This study aimed at investigating the effect of distraction on working memory and its underlying neural mechanisms in children with attention-deficit/hyperactivity disorder (ADHD). To this end, we studied hemodynamic activity in the prefrontal cortex using near-infrared spectroscopy while 16 children with ADHD and 10 typically developing (TD) children performed a working memory task. This task had two conditions: one involved a distraction during the memory delay interval, whereas the other had no systematic distraction. The ADHD patients showed significantly poorer behavioral performance compared with the TD group, particularly under the distraction. The ADHD group exhibited significantly higher level of prefrontal activation than did TD children. The activity level was positively correlated with the severity of ADHD symptoms. These results suggest that the impairment in the inhibition of distraction is responsible for the working memory deficits observed in ADHD children. Inefficient processing in the prefrontal cortex appears to underlie such deficits.

Functional neuroimaging studies show that perceptual judgments about time and space activate similar prefrontal and parietal areas, and it is known that perceptions in these two cognitive domains interfere with each other. These findings have led to the theory that temporal and spatial perceptions, among other metrics, draw on a common representation of magnitude. Our results indicate that an alternative principle applies to the prefrontal cortex. Analysis at the single-cell level shows that separate, domain-specific populations of neurons encode relative magnitude in time and space. These neurons are intermixed with each other in the prefrontal cortex, along with a separate intermixed population that encodes the goal chosen on the basis of these perceptual decisions. As a result, domain-specific neural processing at the single-cell level seems to underlie domain generality as observed at the regional level, with a common representation of prospective goals rather than a common representation of magnitude., (Copyright © 2012 Elsevier Inc. All rights reserved.)

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.

Abstract behavior-guiding rules and strategies allow monkeys to avoid errors in rarely encountered situations. In the present study, we contrasted strategy-related neuronal activity in the dorsolateral prefrontal cortex (PFdl) and the orbital prefrontal cortex (PFo) of rhesus monkeys. On each trial of their behavioral task, the monkeys responded to a foveal visual cue by making a saccade to one of two spatial targets. One response required a leftward saccade, the other required a saccade of equal magnitude to the right. The cues instructed the monkeys to follow one of two response strategies: to stay with their most recent successful response or to shift to the alternative response. Neurons in both areas encoded the stay and shift strategies after the cue appeared, but there were three major differences between the PFo and the PFdl: (1) many strategy-encoding cells in PFdl also encoded the response (left or right), but few, if any, PFo cells did so; (2) strategy selectivity appeared earlier in PFo than in PFdl; and (3) on error trials, PFo neurons encoded the correct strategy-the one that had been cued but not implemented-whereas in PFdl the strategy signals were weak or absent on error trials. These findings indicate that PFo and PFdl both contribute to behaviors guided by abstract response strategies, but do so differently, with PFo encoding a strategy and PFdl encoding a response based on a strategy.

To compare with our previous findings on relative-duration discrimination, we studied prefrontal cortex activity as monkeys performed a relative-distance discrimination task. We wanted to know whether the same parts of the prefrontal cortex compare durations and distances and, if so, whether they use similar mechanisms. Two stimuli appeared sequentially on a video screen, one above a fixed reference point, the other below it by a different distance. After a delay period, the same two stimuli reappeared (as choice stimuli), and the monkeys' task was to choose the one that had appeared farther from the reference point during its initial presentation. We recorded from neurons in the dorsolateral prefrontal cortex (area 46) and the caudal prefrontal cortex (area 8). Although some prefrontal neurons encoded the absolute distance of a stimulus from the reference point, many more encoded relative distance. Categorical representations ("farther") predominated over parametric ones ("how much farther"). Relative-distance coding was most often abstract, coding the farther or closer stimulus to the same degree, independent of its position on the screen. During the delay period before the choice stimuli appeared, feature-based coding supplanted order-based coding, and position-based coding-always rare-decreased to chance levels. The present results closely resembled those for a duration-discrimination task in the same cortical areas. We conclude, therefore, that these areas contribute to decisions based on both spatial and temporal information.

The frontal pole cortex (FPC) expanded markedly during human evolution, but its function remains uncertain in both monkeys and humans. Accordingly, we examined single-cell activity in this area. On every trial, monkeys decided between two response targets on the basis of a 'stay' or 'shift' cue. Feedback followed at a fixed delay. FPC cells did not encode the monkeys' decisions when they were made, but did so later on, as feedback approached. This finding indicates that the FPC is involved in monitoring or evaluating decisions. Using a control task and delayed feedback, we found that decision coding lasted until feedback only when the monkeys combined working memory with sensory cues to 'self-generate' decisions, as opposed to when they simply followed trial-by-trial instructions. A role in monitoring or evaluating self-generated decisions could account for FPC's expansion during human evolution.

We reported previously that as monkeys used abstract response strategies to choose spatial goals, 1 population of prefrontal cortex neurons encoded future goals (F cells), whereas a largely separate population encoded previous goals (P cells). Here, to better understand the mechanisms of goal selection and maintenance, we studied correlated activity among pairs of these neurons. Among the 3 possible types of pairs, F-F and F-P pairs often exhibited significant correlations when and after monkeys selected future goals but P-P pairs rarely did. These correlations were stronger when monkeys shifted from a previous goal than when they stayed with that goal. In addition, members of F-F pairs usually preferred the same goal and thus shared both prospective coding and spatial tuning properties. In contrast, cells composing F-P pairs usually had different spatial preferences and thus shared neither coding nor spatial tuning properties. On the assumption that the neurons composing a pair send convergent outputs to target neurons, their correlated activity could enhance their efficacy in context-dependent goal selection, goal maintenance, and the transformation of goal choices into action.

The prefrontal cortex plays an essential role in various cognitive functions, such as planning and reasoning, yet little is known about how such neural mechanisms develop during childhood, particularly in young children. To better understand this issue, the present article reviews the literature on the development of the prefrontal cortex during early childhood, focusing mainly on the changes in structural architecture, neural activity, and cognitive abilities. Neuroanatomically, the prefrontal cortex undergoes considerable maturation during childhood, including a reduction of synaptic and neuronal density, a growth of dendrites, and an increase in white matter volume, thereby forming distributed neural networks appropriate for complex cognitive processing. Concurrently, behavioral performance of various cognitive tasks improves with age, and intercorrelations among performance on each task become weak through development. Furthermore, the correlation between subcategories of intelligence test decreases as general intellectual efficiency increases. In addition, recent neuroimaging findings suggest that the prefrontal cortex is already functional in 4-year olds and becomes organized into focal, fine-tuned systems through later development. The literature reviewed suggests that fractionation of the functional neural systems plays a key role in the development of prefrontal cortex and such fractionating process has already commenced in preschool children.

The primate prefrontal cortex (PF) plays a central role in choosing goals and strategies. To better understand its mechanisms, we recorded from PF neurons as monkeys used abstract response strategies to select a spatial goal. A visual cue, selected randomly from a set of three cues, appeared on each trial. All three cues were novel when neuronal recording commenced. From trial to trial, the cue could have either been repeated or changed from the previous trial; these were called repeat trials and change trials, respectively. On repeat trials, the monkeys used a Repeat-stay strategy to gain a reward by choosing the same spatial goal as on the previous trial; on change trials, they used a Change-shift strategy to reject the previous goal in favour of an alternative. We reported previously that when monkeys performed the task correctly, many PF neurons had activity encoding one of these two strategies. The monkeys sometimes chose the incorrect strategy, however. Strategy coding was weak or absent during the cue period of error trials which was, for correct trials, the time when the monkeys used a strategy to choose a future goal. By contrast, later in the trial, after the chosen goal had been attained and the monkeys awaited feedback, strategy coding was present and it reflected the strategy used, whether correct or incorrect. The weak cue-period strategy signal could, whatever its cause, have contributed to the errors made, whereas the activity prior to feedback suggests a role in monitoring task performance.

We studied single-neuron activity in the monkey dorsolateral prefrontal cortex during a saccade task, in which correct responses were rewarded after a delay of 0.5 or 1.5 s in one trial-block, and after 1.5 or 3-s delay in the other trial-block. Activity of some neurons depended on the relative length of the delays (longer or shorter) within each block, and activity for the 1.5-s trials was significantly different between the blocks. Activity of another group of neurons reflected the absolute length of delay: hence, the activity in the 1.5-s trials did not differ between the blocks. These results indicate that both relative and absolute time of future reward is represented in subsets of neurons in the dorsolateral prefrontal cortex.

We studied prefrontal cortex activity during a saccade task. On each trial, one of three delay periods elapsed between the onset of a visual stimulus and its offset, which triggered a saccade. After stimulus offset, many neurons showed phasic increases in activity that depended on the duration of the preceding delay period. This delay-dependent activity varied only weakly with reaction time and instead appeared to reflect a more general aspect of elapsed time.

For behaviour to be purposeful, it is important to monitor the preceding behavioural context, particularly for factors regarding stimulus, response and outcome. The dorsolateral prefrontal cortex (DLPFC) appears to play a major role in such a context-dependent, flexible behavioural control system, and this area is likely to have a neuronal mechanism for such retrospective coding, which associates response-outcome with the information and/or neural systems that guided the response. To address this hypothesis, we recorded neuronal activity from the DLPFC of monkeys performing memory- and sensory-guided saccade tasks, each of which had two conditions with reward contingencies. We found that post-response activity of a subset of DLPFC neurons was modulated by three factors relating to earlier events: the direction of the immediately preceding response, its outcome (reward or non-reward) and the information type (memory or sensory) that guided the response. Such neuronal coding should play a role in associating response-outcome with information and/or neural systems used to guide behaviour - that is, 'retrospective monitoring' of behavioural context and/or neural systems used for guiding behaviour - thereby contributing to context-dependent, flexible control of behaviours.

Temporal prediction of future events, especially regarding reward delivery, is critical for controlling/learning purposeful behavior. The dorsolateral prefrontal cortex (DLPFC) has been considered to be involved in behavioral control based on prospective coding for future events, including reward. Thus this area is likely to have a neuronal mechanism responsible for temporal prediction of forthcoming reward. To address this hypothesis, we recorded the neuronal activity from the DLPFC of macaque monkeys while they performed an oculomotor delayed-response task under two conditions regarding the time of reward delivery. In this task, when the subjects made a correct response, the reward was delivered after a reward-delay period of 0.5 or 2 s. At the behavioral level, the onset latency for saccades was significantly faster in the shorter reward-delay trials (0.5 s) than in longer reward-delay trials (2 s), indicating that our subjects actually predicted the time of reward delivery. At the neuronal level, we found that many DLPFC neurons showed differential activity depending on the predicted time of reward delivery during the cue and/or delay periods. These results suggest that a fraction of neurons in the DLPFC represent the temporal prediction of reward and probably a variety of other future events.

It is well known that lateral areas of the prefrontal cortex (LPFC) play a central role in working memory (a critical basis of various cognitive functions), but it remains unknown whether the LPFC of children of preschool age is responsible for working memory. To address this issue, we adopted a recently developed non-invasive imaging technique, optical topography (OT), which can potentially be applied to functional mapping in childhood. We firstly examined changes of activity in the LPFC using OT while adult subjects performed an item-recognition task, which requires working memory, under different memory-load conditions. We observed activation in the bilateral LPFC during performance of this task, the magnitude of which differed depending on memory-load. Then, we applied the same technique on 5- and 6-year-old children and observed the activation associated with working memory in the LPFC. Areas and properties of such activity were similar in adults and preschool children. Thus, for the first time, we demonstrate that the LPFC of preschoolers is active during working memory processes, indicating that in 5- and 6-year-old children, the LPFC has already developed processing of this important cognitive function.

The dorsolateral prefrontal cortex (DLPFC) is involved in visuospatial short-term (or working) memory. Its cellular basis has been widely examined using the delayed-response paradigm in nonhuman primates. Sustained delay-period activity in DLPFC neurons with directional difference (i.e. directional delay-period activity) has been thought to represent visuospatial short-term (or working) memory. However, little is known about the activity of these neurons during a delay period when the sensory input remains. To address this issue, we examined neuronal activity in the DLPFC while macaque monkeys performed a memory-guided saccade (MGS) task and a delayed visually guided saccade (VGS) task. The MGS task required a memory-guided saccade for a remembered target location. The VGS task had the same temporal sequence as the MGS task, but the sensory stimulus remained during the delay period. We found that most of the DLPFC neurons with directional delay-period activity showed sustained activation during the 'delay' period in the VGS task only ('V-neurons', 49%), or in both tasks ('MV-neurons', 46%). Neurons showing directional delay-period activity in the MGS task only ('M-neurons') were only 5% of the DLPFC neurons with directional delay-period activity. These findings indicate that most DLPFC neurons that are active during the delay period are also active when the sensory stimulus remains, suggesting that DLPFC neurons driven by mnemonic information are also driven by sensory input. Such sustained representation of information should have potential utility in flexible cognitive controls of behaviour.

For flexible control of behaviour, it is important to associate preceding behavioural response with its outcome. Since the dorsolateral prefrontal cortex (dlPFC) plays a major role in such control, it is likely that this area has a neuronal mechanism of coding response-outcome, such as reward/non-reward, based on the nature of the behavioural response made immediately before. To test this hypothesis, we examined neuronal activity in the dlPFC while monkeys performed a variant of the oculomotor delayed-response (ODR) task that had two reward conditions. In this task, the correct response was rewarded in half of the trials only and the subject could not expect the outcome (reward/non-reward). The response was followed by a fixation of 2 s (F2-period). We also employed a fixation (FIX) task that required monkeys to fixate on the peripheral target only, with two reward conditions that were similar to those in the ODR task. Post-response activity of a subset of dlPFC neurons was modulated by both the direction of the preceding response and its outcome. None of these neurons showed directional F2-period activity in the FIX task. These results suggest that a subset of dlPFC neurons represent response-outcome (i.e. reward/non-reward associated with directional saccade made immediately before).