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Express saccades are rapid saccadic eye movements that can accurately redirect gaze to behaviorally relevant stimuli in the visual environment. This behavior can be commonly observed when the fixation spot disappears at a consistent, short interval before a target spot appears at a repeated location. While seemingly automatic, whether cognitive control can govern express saccade production has not been investigated. Here we report the production and manipulation of express saccades under unfavorable conditions in a saccade countermanding task necessitating cognitive control. To perform this task, we trained two monkeys to fixate a central spot and, following a variable amount of time, saccade to a target stimulus at one of two fixed locations (no-stop trials) presented simultaneously with the disappearance of the fixation dot. On a minority of trials, the fixation point reappeared instructing the monkeys to cancel their planned saccade to the peripheral target (stop-signal trials). Monkeys earned fluid reward for generating saccades to targets on no-stop trials and for maintaining fixation on stop-signal trials. Monkeys and humans adapt to the stop-signal trials by increasing saccade latencies. However, in two macaque monkeys we observed a significant fraction of trials with saccade latencies < 100 ms, resulting in a bimodal distribution of saccadic latencies. Target timing derived from regularities of the fixation interval (foreperiod) was used by some monkeys in some sessions to adapt regular but not express saccade latencies. Furthermore, simulations revealed by varying express saccade production, monkeys could maximize the opportunity for reward. To determine whether monkeys exploited this opportunity, reward contingencies for express saccade were changed. When unrewarded, significantly fewer express saccades were produced. This was confirmed in two other monkeys. This study highlights an unexpected manifestation of cognitive control through release of very short latency responses.

Medial frontal cortex enables executive control by monitoring relevant information and using it to adapt behavior. In macaques performing a saccade countermanding (stop-signal) task, we recorded EEG over and neural spiking across all layers of the supplementary eye field (SEF). We report the laminar organization of concurrently activated neurons monitoring the conflict between incompatible responses and the timing of events serving goal maintenance and executive control. We also show their relation to coincident event-related potentials (ERP). Neurons signaling response conflict were largely broad-spiking found across all layers. Neurons signaling the interval until specific task events were largely broad-spiking neurons concentrated in L3 and L5. Neurons predicting the duration of control and sustaining the task goal until the release of operant control were a mix of narrow- and broad-spiking neurons confined to L2/3. We complement these results with the first report of a monkey homologue of the N2/P3 ERP complex associated with response inhibition. N2 polarization varied with error likelihood and P3 polarization varied with the duration of expected control. The amplitude of the N2 and P3 were predicted by the spike rate of different classes of neurons located in L2/3 but not L5/6. These findings reveal important, new features of the cortical microcircuitry supporting executive control and producing associated ERP.

We discuss the problem of elucidating mechanisms of visual search. We begin by considering the history, logic, and methods of relating behavioral or cognitive processes with neural processes. We then survey briefly the cognitive neurophysiology of visual search and essential aspects of the neural circuitry supporting this capacity. We introduce conceptually and empirically a powerful but underutilized experimental approach to dissect the cognitive processes supporting performance of a visual search task with factorial manipulations of singleton-distractor identifiability and stimulus-response cue discriminability. We show that systems factorial technology can distinguish processing architectures from the performance of macaque monkeys. This demonstration offers new opportunities to distinguish neural mechanisms through selective manipulation of visual encoding, search selection, rule encoding, and stimulus-response mapping.

Selective attention affords scrutinizing items in our environment. However, attentional selection changes over time and across space. Empirically, repetition of visual search conditions changes attentional processing. Priming of pop-out is a vivid example. Repeatedly searching for the same pop-out search feature is accomplished with faster response times and fewer errors. We will review the psychophysical background of priming of pop-out, focusing on the hypothesis that it arises through changes in visual selective attention. We then describe research done with macaque monkeys to understand the neural mechanisms supporting visual selective attention and priming of pop-out. Next, we will survey research on priming of pop-out using noninvasive brain measures with humans. We will conclude by hypothesizing three alternative neural mechanisms and highlighting open questions.

The neural mechanisms of executive and motor control concern both basic researchers and clinicians. In human studies, preparation and cancellation of movements are accompanied by changes in the β-frequency band (15–29 Hz) of electroencephalogram (EEG). Previous studies with human participants performing stop signal (countermanding) tasks have described reduced frequency of transient β-bursts over sensorimotor cortical areas before movement initiation and increased β-bursting over medial frontal areas with movement cancellation. This modulation has been interpreted as contributing to the trial-by-trial control of behavior. We performed identical analyses of EEG recorded over the frontal lobe of macaque monkeys (one male, one female) performing a saccade countermanding task. While we replicate the occurrence and modulation of β-bursts associated with initiation and cancellation of saccades, we found that β-bursts occur too infrequently to account for the observed stopping behavior. We also found β-bursts were more common after errors, but their incidence was unrelated to response time (RT) adaptation. These results demonstrate the homology of this EEG signature between humans and macaques but raise questions about the current interpretation of β band functional significance.SIGNIFICANCE STATEMENTThe finding of increased β-bursting over medial frontal cortex with movement cancellation in humans is difficult to reconcile with the finding of modulation too late to contribute to movement cancellation in medial frontal cortex of macaque monkeys. To obtain comparable measurement scales, we recorded electroencephalogram (EEG) over medial frontal cortex of macaques performing a stop signal (countermanding) task. We replicated the occurrence and modulation of β-bursts associated with the cancellation of movements, but we found that β-bursts occur too infrequently to account for observed stopping behavior. Unfortunately, this finding raises doubts whether β-bursts can be a causal mechanism of response inhibition, which impacts future applications in devices such as brain-machine interfaces.

Ca2+spikes initiated in the distal trunk of layer 5 pyramidal cells (PCs) underlie nonlinear dynamic changes in the gain of cellular response, critical for top-down control of cortical processing. Detailed models with many compartments and dozens of ionic channels can account for this Ca2+spike-dependent gain and associated critical frequency. However, current models do not account for all known Ca2+-dependent features. Previous attempts to include more features have required increasing complexity, limiting their interpretability and utility for studying large population dynamics. We overcome these limitations in a minimal two-compartment biophysical model. In our model, a basal-dendrites/somatic compartment included fast-inactivating Na+and delayed-rectifier K+conductances, while an apical-dendrites/trunk compartment included persistent Na+, hyperpolarization-activated cation (Ih), slow-inactivating K+, muscarinic K+, and Ca2+L-type. The model replicated the Ca2+spike morphology and its critical frequency plus three other defining features of layer 5 PC synaptic integration: linear frequency-current relationships, back-propagation-activated Ca2+spike firing, and a shift in the critical frequency by blocking Ih. Simulating 1000 synchronized layer 5 PCs, we reproduced the current source density patterns evoked by Ca2+spikes and describe resulting medial-frontal EEG on a male macaque monkey. We reproduced changes in the current source density when Ihwas blocked. Thus, a two-compartment model with five crucial ionic currents in the apical dendrites reproduces all features of these neurons. We discuss the utility of this minimal model to study the microcircuitry of agranular areas of the frontal lobe involved in cognitive control and responsible for event-related potentials, such as the error-related negativity.SIGNIFICANCE STATEMENTA minimal model of layer 5 pyramidal cells replicates all known features crucial for distal synaptic integration in these neurons. By redistributing voltage-gated and returning transmembrane currents in the model, we establish a theoretical framework for the investigation of cortical microcircuit contribution to intracranial local field potentials and EEG. This tractable model will enable biophysical evaluation of multiscale electrophysiological signatures and computational investigation of cortical processing.

SummaryModels of the cerebral cortex propose a canonical columnar architecture preserved across the brain. Evidence for this model primarily stems from observations in primary sensory areas, such as the visual cortex, where neurons in an anatomical column respond preferentially to the same stimulus features. Similar columnar feature selectivity has been described for visual area V2, visual area V3 [9, 10], the middle temporal visual area (area V5), and inferotemporal cortex. The fourth visual area (V4) features color selective neurons, organized in clusters across its surface. However, whether these color-sensitive neurons are organized in a columnar fashion is debated and uncertain due to technical limitations. Here, we utilize laminar multielectrode recordings along V4 columns to resolve rival hypotheses. Linear electrode arrays were introduced orthogonally into area V4, spanning all cortical layers. Monkeys viewed color stimuli presented to the visual receptive field of the column of neurons. We found that preference for a specific color was conserved along depth but varied across columns. Interestingly, while color preference (e.g. red or green) was consistent along depth, color selectivity was significantly greater in upper layers relative to the input layer and was weakest in the lower layers. These findings demonstrate that area V4 is organized in functional columns like other visual areas.

Summary We investigated whether a task requiring concurrent perceptual decision-making and response control can be performed concurrently, whether evidence accumulation and response control are accomplished by the same neurons, and whether perceptual decision-making and countermanding can be unified computationally. Based on neural recordings in a prefrontal area of macaque monkeys, we present behavioral, neural, and computational results demonstrating that perceptual decision-making of varying difficulty can be countermanded efficiently, that single prefrontal neurons instantiate both evidence accumulation and response control, and that an interactive race between stochastic GO evidence accumulators for each alternative and a distinct STOP accumulator fits countermanding choice behavior and replicates neural trajectories. Thus, perceptual decision-making and response control, previously regarded as distinct mechanisms, are actually aspects of a common neuro-computational mechanism supporting flexible behavior., Graphical Abstract, Highlights • Monkeys can perform combined perceptual decision-making and countermanding • Prefrontal neurons accumulate evidence, but this accumulation can be interrupted • Interactive race of response accumulators and a stop accumulator explains findings • Results clarify the circuit logic of brain regions involved in decision-making, Biological Sciences; Neuroscience; Behavioral Neuroscience; Sensory Neuroscience; Cognitive Neuroscience

What are the neural correlates that distinguish goal-directed (G) from non-goal-directed movements (nG)? We investigated this question in the monkey frontal eye field, which is implicated in voluntary control of saccades. We found that only for G-saccades, the variability in spike rate across trials decreased, the regularity of spike timings within trials increased, the neural activity increased earlier from baseline and had a concurrent reduction of LFP beta band power.

SUMMARYThe balance of speed with accuracy requires error detection and performance adaptation. To date, neural concomitants of these processes have been investigated only with noninvasive measures. To provide the first neurophysiological description, macaque monkeys performed visual search under cued speed accuracy tradeoff (SAT). Monkeys changed SAT emphasis immediately after a cued switch while neuron discharges were sampled in medial frontal cortex area supplementary eye field (SEF). A multiplicity of SEF neurons signaled production of choice errors and timing errors. Modulation of SEF activity after choice errors predicted production of un-rewarded corrective saccades. Modulation of activity after timing errors signaled reward prediction error. Adaptation of performance during SAT of visual search was accomplished through pronounced changes in neural state from before search array presentation until after reward delivery. These results contextualize previous findings using noninvasive measures, complement neurophysiological findings in visuomotor structures, endorse the role of medial frontal cortex as a critic relative to the actor instantiated in visuomotor structures, and extend our understanding of the distributed neural mechanisms of SAT.HIGHLIGHTSMedial frontal cortex enables post-error adjustment during SATChoice and timing errors were signaled by partially overlapping neural poolsMedial frontal cortex can proactively modulate visuomotor processesMedial frontal cortex is to visuomotor circuits as critic to actor

Neurons in macaque frontal eye field contribute to spatial but typically not feature selection during visual search. Using an innovative visual search task, we report a serendipitous discovery that some frontal eye field neurons can develop rapid selectivity for stimulus orientation that is used to guide gaze during a visual search task with pro-saccade and anti-saccade responses. This feature selectivity occurs simultaneously at multiple locations for all objects sharing that feature and coincides with when neurons select the singleton of a search array. This feature selectivity also reveals the distinct, subsequent operation of selecting the endpoint of the saccade in pro-saccade as well as anti-saccade trials. These results demonstrate that target selection preceding saccade preparation is composed of multiple operations. We conjecture that singleton selection indexes the allocation of attention, which can be divided, to conspicuous items. Consequently, endpoint selection indexes the focused allocation of attention to the endpoint of the saccade. These results demonstrate that saccade target selection is not a unitary process.SIGNIFICANCE STATEMENTFrontal eye field is well known to contribute to spatial selection for attention and eye movements. We discovered that some frontal eye field neurons can acquire selectivity for stimulus orientation when it guides visual search. The chronometry of neurons with and without feature selectivity reveal distinct operations accomplishing visual search.

The medial frontal cortex enables performance monitoring, indexed by the error-related negativity (ERN) and manifested by performance adaptations. We recorded electroencephalogram over and neural spiking across all layers of the supplementary eye field, an agranular cortical area, in monkeys performing a saccade-countermanding (stop signal) task. Neurons signaling error production, feedback predicting reward gain or loss, and delivery of fluid reward had different spike widths and were concentrated differently across layers. Neurons signaling error or loss of reward were more common in layers 2 and 3 (L2/3), whereas neurons signaling gain of reward were more common in layers 5 and 6 (L5/6). Variation of error- and reinforcement-related spike rates in L2/3 but not L5/6 predicted response time adaptation. Variation in error-related spike rate in L2/3 but not L5/6 predicted ERN magnitude. These findings reveal novel features of cortical microcircuitry supporting performance monitoring and confirm one cortical source of the ERN.

Visual Abstract, Frontal eye field (FEF) in macaque monkeys contributes to visual attention, visual–motor transformations and production of eye movements. Traditionally, neurons in FEF have been classified by the magnitude of increased discharge rates following visual stimulus presentation, during a waiting period, and associated with eye movement production. However, considerable heterogeneity remains within the traditional visual, visuomovement, and movement categories. Cluster analysis is a data-driven method of identifying self-segregating groups within a dataset. Because many cluster analysis techniques exist and outcomes vary with analysis assumptions, consensus clustering aggregates over multiple analyses, identifying robust groups. To describe more comprehensively the neuronal composition of FEF, we applied a consensus clustering technique for unsupervised categorization of patterns of spike rate modulation measured during a memory-guided saccade task. We report 10 functional categories, expanding on the traditional 3 categories. Categories were distinguished by latency, magnitude, and sign of visual response; the presence of sustained activity; and the dynamics, magnitude and sign of saccade-related modulation. Consensus clustering can include other metrics and can be applied to datasets from other brain regions to provide better information guiding microcircuit models of cortical function.

Neocortex is striking in its laminar architecture. Tracer studies have uncovered anatomical connectivity among laminae, but the functional connectivity between laminar compartments is still largely unknown. Such functional connectivity can be discerned through spontaneous neural correlations during rest. Previous work demonstrated a robust pattern of mesoscopic resting-state connectivity in macaque primary visual cortex (V1) through interlaminar cross-frequency coupling. Here we investigated whether this pattern generalizes to other cortical areas by comparing resting-state laminar connectivity between V1 and the supplementary eye field (SEF), a frontal area lacking a granular layer 4 (L4). Local field potentials (LFPs) were recorded with linear microelectrode arrays from all laminae of granular V1 and agranular SEF while monkeys rested in darkness. We found substantial differences in the relationship between the amplitude of gamma-band (>30 Hz) LFP and the phase of alpha-band (7–14 Hz) LFP between these areas. In V1, gamma amplitudes in L2/3 and L5 were coupled with alpha-band LFP phase in L5, as previously described. In contrast, in SEF phase-amplitude coupling was prominent within L3 and much weaker across layers. These results suggest that laminar interactions in agranular SEF are unlike those in granular V1. Thus the intrinsic functional connectivity of the cortical microcircuit does not seem to generalize across cortical areas.

Balancing the speed-accuracy tradeoff (SAT) is necessary for successful behavior. Using a visual search task with interleaved cues emphasizing speed or accuracy, we recently reported diverse contributions of frontal eye field (FEF) neurons instantiating salience evidence and response preparation. Here we report replication of visual search SAT performance in two macaque monkeys, new information about variation of saccade dynamics with SAT, extension of the neurophysiological investigation to describe processes in the superior colliculus, and description of the origin of search errors in this task. Saccade vigor varied idiosyncratically across SAT conditions and monkeys, but tended to decrease with response time. As observed in the FEF, speed-accuracy tradeoff was accomplished through several distinct adjustments in the superior colliculus. Visually-responsive neurons modulated baseline firing rate and the time course of salience evidence. Unlike FEF, the magnitude of visual responses in SC did not vary across SAT conditions, but the time to locate the target was longer in Accurate as compared to Fast trials. Also unlike FEF, the activity of SC movement neurons when saccades were initiated was equivalent in Fast and Accurate trials. Search errors occurred when visual salience neurons in FEF and SC treated distractors as targets, even in the Accurate condition. Saccade-related neural activity in SC but less FEF varied with saccade peak velocity. These results extend our understanding of the cortical and subcortical contributions to SAT.Significance statementNeurophysiological mechanisms of speed-accuracy tradeoff (SAT) have only recently been investigated. This paper reports the first replication of SAT performance in nonhuman primates, the first report of variation of saccade dynamics with SAT, the first description of superior colliculus contributions to SAT, and the first description of the origin of errors during SAT. These results inform and constrain new models of distributed decision-making.

Frontal eye field (FEF) in macaque monkeys contributes to visual attention, visual-motor transformations and production of eye movements. Traditionally, neurons in FEF have been classified by the magnitude of increased discharge rates following visual stimulus presentation, during a waiting period, and associated with eye movement production. However, considerable heterogeneity remains within the traditional visual, visuomovement and movement categories. Cluster analysis is a data-driven method of identifying self-segregating groups within a dataset. Because many cluster analysis techniques exist and cluster outcomes vary with analysis assumptions, consensus clustering aggregates over multiple cluster analyses, identifying robust groups. To describe more comprehensively the neuronal composition of FEF, we applied a consensus clustering technique for unsupervised categorization of patterns of spike rate modulation measured during a memory-guided saccade task. We report ten functional categories, expanding on the traditional three. Categories were distinguished by latency, magnitude, and sign of visual response, presence of sustained activity, and dynamics, magnitude and sign of saccade-related modulation. Consensus clustering can include other metrics and can be applied to datasets from other brain regions to provides better information guiding microcircuit models of cortical function.SIGNIFICANCE STATEMENTThe contribution of a brain region cannot be understood without knowing the diversity, arrangement, and circuitry of constituent neurons. Traditional descriptions of frontal eye field include visual, visuo-saccadic, and saccadic categories. Here, we employ a novel consensus clustering method to identify more reliably functional categories in neural data. While confirming the traditional categories, consensus clustering distinguishes additional, previously unappreciated diversity in neural activity patterns. Such information is necessary to formulate correct microcircuit models of cortical function.

Cortical circuit mechanisms in medial frontal cortex enabling executive control are unknown. Hence, in monkeys performing a saccade countermanding task to earn larger or smaller fluid rewards, we sampled spiking and synaptic activity simultaneously across all layers of the supplementary eye field (SEF), an agranular cortical area contributing to performance monitoring in nonhuman primate and human studies. Laminar-specific synaptic currents with associated spike rate facilitation and suppression represented error production, reward gain or loss feedback, and reward delivery. The latency, polarity and magnitude of current and spike rate modulation were not predicted by the canonical cortical microcircuit. Pronounced synaptic currents in layer 2/3, which are modulated by loss magnitude, will contribute to the error-related negativity (ERN) and feedback-related negativity (FRN). These unprecedented findings reveal critical features of the cortical microcircuitry supporting performance monitoring and demonstrate that SEF can contribute to the error- and feedback-related negativity.

Response inhibition in stop signal tasks has been explained as the outcome of a race between GO and STOP processes (e.g., Logan, 1981). Response choice in two-alternative perceptual categorization tasks has been explained as the outcome of an accumulation of evidence for the alternative responses. To begin unifying these two powerful investigation frameworks, we obtained data from humans and macaque monkeys performing a stop signal task with responses guided by perceptual categorization and variable degrees of difficulty, ranging from low to high accuracy. Comparable results across species reinforced the validity of this animal model. Response times and errors increased with categorization difficulty. The probability of failing to inhibit responses on stop signal trials increased with stop signal delay, and the response times for failed stop signal trials were shorter than those for trials with no stop signal. Thus, the Logan race model could be applied to estimate the duration of the stopping process. We found that the duration of the STOP process did not vary across a wide range of discrimination accuracies. This is consistent with the functional, and possibly mechanistic, independence of choice and inhibition mechanisms.

This chapter compares the location, extent, and boundaries of the frontal eye field (FEF) in prosimians, New World monkeys, Old World monkeys, apes, and humans. We are particularly interested in understanding how the location of FEF in humans relates to that in other primate species. We consider whether FEF should be understood as a collection of distinct areas or as a single area with multiple modules that can be of different sizes (and locations) in different species according to lifestyle and habitat. We also consider how the size and location of FEF is a matter of operational definition with resolution specified by the various techniques applied, making comparison across species, especially humans, challenging. Locating FEF is challenged further by the variation of sulcal morphology across species and individuals. Nevertheless, in all investigated primate species FEF appears to be located at the transition zone between premotor area 6 and prefrontal area 8 in a cortical region with significant sulcal variation where it is bordered caudally (in premotor cortex) and rostrally (in prefrontal cortex) by areas also contributing to visually guided gaze behavior. We highlight current areas of uncertainty. In particular, lacking information about precise boundaries, we do not know whether the size and modularity of FEF scales across species with overall neocortical area, or with the complexity of visual and other sensory systems, or with changes in associated subcortical circuits, or with the complexity of the musculature used for visually guided behaviors, or with the complexity of cognitive control over gaze behavior.

Numerous studies have described different functional cell types in the frontal eye field (FEF), but the reliability of the distinction between these types has been uncertain. Studies in other brain areas have described specific differences in the width of action potentials recorded from different cell types. To substantiate the functionally defined cell types encountered in FEF, we measured the width of spikes of visual, movement, and visuomovement types of FEF neurons in macaque monkeys. We show that visuomovement neurons had the thinnest spikes, consistent with a role in local processing. Movement neurons had the widest spikes, consistent with their role in sending eye movement commands to subcortical structures such as the superior colliculus. Visual neurons had wider spikes than visuomovement neurons, consistent with their role in receiving projections from occipital and parietal cortex. These results show how structure and function of FEF can be linked to guide inferences about neuronal architecture.

Most models assume that response time (RT) comprises the time required for successive processing stages, but they disagree about whether information is transmitted continuously or discretely between stages. We tested these alternative hypotheses by measuring when movement-related activity began in the frontal eye field (FEF) of macaque monkeys performing visual search. Previous work showed that RT was longer when visual neurons in FEF took longer to select the target, a finding consistent with prolonged perceptual processing during less efficient search. We now report that the buildup of saccadic movement-related activity in FEF is delayed in inefficient visual search. Variability in the delay of movement-related activity accounted for the difference in RT between search conditions and for the variability of RT within conditions. These findings provide neurophysiological support for the hypothesis that information is transmitted discretely between perceptual and response stages of processing during visual search.

We describe intracranial local field potentials (LFP) recorded in the anterior cingulate cortex (ACC) of macaque monkeys performing a saccade countermanding task. The most prominent feature at ∼70% of sites was greater negative polarity after errors than after rewarded correct trials. This negative polarity was also evoked in unrewarded correct trials. The LFP evoked by the visual target was much less polarized, and the weak presaccadic modulation was insufficient to control the initiation of saccades. When saccades were cancelled, LFP modulation decreased slightly with the magnitude of response conflict that corresponds to the coactivation of gaze-shifting and -holding neurons estimated from the probability of canceling. However, response time adjustments on subsequent trials were not correlated with LFP polarity on individual trials. The results provide clear evidence that error- and feedback-related, but not conflict-related, signals are carried by the LFP in the macaque ACC. Finding performance monitoring field potentials in the ACC of macaque monkeys establishes a bridge between event-related potential and functional brain-imaging studies in humans and neurophysiology studies in non-human primates.

A half-century's worth of research has established the existence of numerous event-related potential components measuring different cognitive operations in humans including the selection of stimuli by covert attention mechanisms. Surprisingly, it is unknown whether nonhuman primates exhibit homologous electrophysiological signatures of selective visual processing while viewing complex scenes. We used an electrophysiological technique with macaque monkeys analogous to procedures for recording scalp event-related potentials from humans and found that monkeys exhibit short-latency visual components sensitive to sensory processing demands and lateralizations related to shifting of covert attention similar to the human N2pc component. These findings begin to bridge the gap between the disparate literatures by using electrophysiological measurements to study the deployment of visual attention in the brains of humans and nonhuman primates.

We tested the hypothesis that frontal eye field (FEF) visual activity integrates visual information with a template of a target by examining whether a target that is not present in a search display influences the target selection in FEF. Neural activity was recorded in FEF of macaque monkeys performing visual search for a singleton target defined by color or direction of motion. The target remained constant throughout, but not across experimental sessions. Trials with distractors dissimilar to the target were interleaved with trials with distractors similar to the target. The hypothesis was tested by measuring the magnitude of activity in randomly interleaved trials with the target absent and only distractors in the display. We found that the response to the distractors was significantly greater when presented with displays consisting of distractors that resembled the absent target than when presented with displays consisting of distractors most different from the absent target. The influence of target-distractor similarity on FEF activity was also observed when the target was present, as reported previously. These data suggest that a template of the absent target can influence the selection process in FEF. This provides more direct evidence that FEF integrates visual information and knowledge of the target to determine the goal of a saccade.

We investigated the neural basis of visual and saccade selection in the frontal eye field of macaque monkeys using a singleton search task with prosaccade or antisaccade responses. Two types of neurons were distinguished. The first initially selected the singleton even in antisaccade trials, although most subsequently selected the endpoint of the saccade. The time the singleton was located was not affected by stimulus-response compatibility and did not vary with reaction time across trials. The second type of neuron selected only the endpoint of the saccade. The time of endpoint selection by these neurons accounted for most of the effect of stimulus-response compatibility on reaction time. These results indicate that visual selection and saccade selection are different processes.

Item does not contain fulltext The primate corticobasal ganglia circuits are understood to be segregated into parallel anatomically and functionally distinct loops. Anatomical and physiological studies in macaque monkeys are summarized as showing that an oculomotor loop begins with projections from the frontal eye fields (FEF) to the caudate nucleus, and a motor loop begins with projections from the primary motor cortex (M1) to the putamen. However, recent functional and structural neuroimaging studies of the human corticostriatal system report evidence inconsistent with this organization. To obtain conclusive evidence, we directly compared the pattern of connectivity between cortical motor areas and the striatum in humans and macaques in vivo using probabilistic diffusion tractography. In macaques we found that FEF is connected with the head of the caudate and anterior putamen, and M1 is connected with more posterior sections of the caudate and putamen, corroborating neuroanatomical tract tracing findings. However, in humans FEF and M1 are connected to largely overlapping portions of posterior putamen and only a small portion of the caudate. These results demonstrate that the corticobasal connectivity for the oculomotor and primary motor loop is not entirely segregated for primates at a macroscopic level and that the description of the anatomical connectivity of corticostriatal motor systems in humans does not parallel that of macaques, perhaps because of an expansion of prefrontal projections to striatum in humans.

Success requires deciding among alternatives, controlling the initiation of movements, and judging the consequences of actions. When alternatives are difficult to distinguish, habitual responses must be overcome, or consequences are uncertain, deliberation is necessary and a supervisory system exerts control over the processes that produce sensory-guided movements. We have investigated these processes by recording neural activity in the frontal lobe of macaque monkeys performing a countermanding task. Distinct neurons in the frontal eye field respond to visual stimuli or control the production of the movements. In the supplementary eye field and anterior cingulate cortex, neurons appear not to control directly movement initiation but instead signal the production of errors, the anticipation and delivery of reinforcement, and the presence of processing conflict. These signals form the core of current models of supervisory control of sensorimotor processes.

Although many studies have explored the neural correlates of visual attention and selection, few have examined the reliability with which neurons represent relevant information. We monitored activity in the frontal eye field (FEF) of monkeys trained to make a saccade to a target defined by the conjunction of color and shape or to a target defined by color differences. The difficulty of conjunction search was manipulated by varying the number of distractors, and the difficulty of feature search was manipulated by varying the similarity in color between target and distractors. The reliability of individual neurons in signaling the target location in correct trials was determined using a neuron—anti-neuron approach within a winner-take-all architecture. On average, approximately seven trials of the activity of single neurons were sufficient to match near-perfect behavioral performance in the easiest search, and ∼14 trials were sufficient in the most difficult search. We also determined how many neurons recorded separately need to be evaluated within a trial to match behavioral performance. Results were quantitatively similar to those of the single neuron analysis. We also found that signal reliability in the FEF did not change with task demands, and overall, behavioral accuracy across the search tasks was approximated when only six trials or neurons were combined. Furthermore, whether combining trials or neurons, the increase in time of target discrimination corresponded to the increase in mean saccade latency across visual search difficulty levels. Finally, the variance of spike counts in the FEF increased as a function of the mean spike count, and the parameters of this relationship did not change with attentional selection.

A central issue in mental chronometry is whether information is transferred between processing stages such as stimulus evaluation and response preparation in a continuous or discrete manner. We tested whether partial information about a stimulus influences the response stage by recording the activity of movement-related neurons in the frontal eye field of macaque monkeys performing a conjunction visual search and a feature visual search with a singleton distractor. While movement-related neurons were activated maximally when the target of the search array was in their movement field, they were also activated for distractors even though a saccade was successfully made to the target outside the movement field. Most importantly, the level of activation depended on the properties of the distractor, with greater activation for distractors that shared a target feature or were the target during the previous session during conjunction search, and for the singleton distractor during feature search. These results support the model of continuous information processing and argue against a strictly discrete model.

Intelligent behaviour requires self-control based on the consequences of actions. The countermanding task is designed to study self-control; it requires subjects to withhold planned movements in response to an imperative stop signal, which they can do with varying success. In humans, the medial frontal cortex has been implicated in the supervisory control of action1,2,3. In monkeys, the supplementary eye field in the dorsomedial frontal cortex is involved in producing eye movements, but its precise function has not been clarified4. To investigate the role of the supplementary eye field in the control of eye movements, we recorded neural activity in macaque monkeys trained to perform an eye movement countermanding task. Distinct groups of neurons were active after errors, after successful withholding of a partially prepared movement, or in association with reinforcement. These three forms of activation could not be explained by sensory or motor factors. Our results lead us to put forward the hypothesis that the supplementary eye field contributes to monitoring the context and consequences of eye movements.

The neural link between a sensory signal and its behavioral report was investigated in macaques trained to locate an intermittently detectable visual target. Neurons in the frontal eye field, an area involved in converting the outcome of visual processing into motor commands, responded at short latencies to the target stimulus whether or not the monkey reported its presence. Neural activity immediately preceding the visual response to the mask was significantly greater on hits than on misses, and was significantly greater on false alarms than on correct rejections. The results show that visual signals masked by light are not filtered out at early stages of visual processing; furthermore, the magnitude of early visual responses in prefrontal cortex predicts the behavioral report.

To gain insight into how vision guides eye movements, monkeys were trained to make a single saccade to a specified target stimulus during feature and conjunction search with stimuli discriminated by color and shape. Monkeys performed both tasks at levels well above chance. The latencies of saccades to the target in conjunction search exhibited shallow positive slopes as a function of set size, comparable to slopes of reaction time of humans during target present/absent judgments, but significantly different than the slopes in feature search. Properties of the selection process were revealed by the occasional saccades to distractors. During feature search, errant saccades were directed more often to a distractor near the target than to a distractor at any other location. In contrast, during conjunction search, saccades to distractors were guided more by similarity than proximity to the target; monkeys were significantly more likely to shift gaze to a distractor that had one of the target features than to a distractor that had none. Overall, color and shape information were used to similar degrees in the search for the conjunction target. However, in single sessions we observed an increased tendency of saccades to a distractor that had been the target in the previous experimental session. The establishment of this tendency across sessions at least a day apart and its persistence throughout a session distinguish this phenomenon from the short-term (

1. The latency between the appearance of a popout search display and the eye movement to the oddball target of the display varies from trial to trial in both humans and monkeys. The source of the delay and variability of reaction time is unknown but has been attributed to as yet poorly defined decision processes. 2. We recorded neural activity in the frontal eye field (FEF), an area regarded as playing a central role in producing purposeful eye movements, of monkeys (Macaca mulatta) performing a popout visual search task. Eighty-four neurons with visually evoked activity were analyzed. Twelve of these neurons had a phasic response associated with the presentation of the visual stimulus. The remaining neurons had more tonic responses that persisted through the saccade. Many of the neurons with more tonic responses resembled visuomovement cells in that they had activity that increased before a saccade into their response field. 3. The visual response latencies of FEF neurons were determined with the use of a Poisson spike train analysis. The mean visual latency was 67 ms (minimum = 35 ms, maximum = 138 ms). The visual response latencies to the target presented alone, to the target presented with distractors, or to the distractors did not differ significantly. 4. The initial visual activation of FEF neurons does not discriminate the target from the distractors of a popout visual search stimulus array, but the activity evolves to a state that discriminates whether the target of the search display is within the receptive field. We tested the hypothesis that the source of variability of saccade latency is the time taken by neurons involved in saccade programming to select the target for the gaze shift. 5. With the use of an analysis adapted from signal detection theory, we determined when the activity of single FEF neurons can reliably indicate whether the target or distractors are present within their response fields. The time of target discrimination partitions the reaction time into a perceptual stage in which target discrimination takes place, and a motor stage in which saccade programming and generation take place. The time of target discrimination occurred most often between 120 and 150 ms after stimulus presentation. 6. We analyzed the time course of target discrimination in the activity of single cells after separating trials into short, medium, and long saccade latency groups. Saccade latency was not correlated with the duration of the perceptual stage but was correlated with the duration of the motor stage. This result is inconsistent with the hypothesis that the time taken for target discrimination, as indexed by FEF neurons, accounts for the wide variability in the time of movement initiation. 7. We conclude that the variability observed in saccade latencies during a simple visual search task is largely due to postperceptual motor processing following target discrimination. Signatures of both perceptual and postperceptual processing are evident in FEF. Procrastination in the output stage may prevent stereotypical behavior that would be maladaptive in a changing environment.

The primate visual system consists of at least two processing streams, one passing ventrally into temporal cortex that is responsible for object vision, and the other running dorsally into parietal cortex that is responsible for spatial vision. How information from these two streams is combined for perception and action is not understood. Visually guided eye movements require information about both feature identity and location, so we investigated the topographic organization of visual cortex connections with frontal eye field (FEF), the final stage of cortical processing for saccadic eye movements. Multiple anatomical tracers were placed either in parietal and temporal cortex or in different parts of FEF in individual macaque monkeys. Convergence from the dorsal and ventral processing streams occurred in lateral FEF but not in medial FEF. Certain extrastriate areas with retinotopic visual field organizations projected topographically onto FEF. The dorsal bank of the superior temporal sulcus projected to medial FEF; the ventral bank, to lateral FEF, and the fundus, throughout FEF. Thus, lateral FEF, which is responsible for generating short saccades, receives visual afferents from the foveal representation in retinotopically organized areas, from areas that represent central vision in inferotemporal cortex and from other areas having no retinotopic order. In contrast, medial FEF, which is responsible for generating longer saccades, is innervated by the peripheral representation of retinotopically organized areas, from areas that emphasize peripheral vision or are multimodal and from other areas that have no retinotopic order or are auditory.

Event-related potentials (ERPs) have provided crucial data concerning the time course of psychological processes, but the neural mechanisms producing ERP components remain poorly understood. This study continues a program of research in which we investigated the neural basis of attention-related ERP components by simultaneously recording intracranially and extracranially from macaque monkeys. Here, we compare the timing of attentional selection by the macaque homologue of the human N2pc component (m-N2pc) with the timing of selection in the frontal eye field (FEF), an attentional-control structure believed to influence posterior visual areas thought to generate the N2pc. We recorded FEF single-unit spiking and local field potentials (LFPs) simultaneously with the m-N2pc in monkeys performing an efficient pop-out search task. We assessed how the timing of attentional selection depends on task demands by direct comparison with a previous study of inefficient search in the same monkeys (e.g., finding a T among Ls). Target selection by FEF spikes, LFPs, and the m-N2pc was earlier during efficient pop-out search rather than during inefficient search. The timing and magnitude of selection in all three signals varied with set size during inefficient but not efficient search. During pop-out search, attentional selection was evident in FEF spiking and LFP before the m-N2pc, following the same sequence observed during inefficient search. These observations are consistent with the hypothesis that feedback from FEF modulates neural activity in posterior regions that appear to generate the m-N2pc even when competition for attention among items in a visual scene is minimal.

Although areas of frontal cortex are thought to be critical for maintaining information in visuospatial working memory, the event-related potential (ERP) index of maintenance is found over posterior cortex in humans. In the present study, we reconcile these seemingly contradictory findings. Here, we show that macaque monkeys and humans exhibit the same posterior ERP signature of working memory maintenance that predicts the precision of the memory-based behavioral responses. In addition, we show that the specific pattern of rhythmic oscillations in the alpha band, recently demonstrated to underlie the human visual working memory ERP component, is also present in monkeys. Next, we concurrently recorded intracranial local field potentials from two prefrontal and another frontal cortical area to determine their contribution to the surface potential indexing maintenance. The local fields in the two prefrontal areas, but not the cortex immediately posterior, exhibited amplitude modulations, timing, and relationships to behavior indicating that they contribute to the generation of the surface ERP component measured from the distal posterior electrodes. Rhythmic neural activity in the theta and gamma bands during maintenance provided converging support for the engagement of the same brain regions. These findings demonstrate that nonhuman primates have homologous electrophysiological signatures of visuospatial working memory to those of humans and that a distributed neural network, including frontal areas, underlies the posterior ERP index of visuospatial working memory maintenance.

The error-related negativity (ERN) and positivity (Pe) are components of event-related potential (ERP) waveforms recorded from humans and are thought to reflect performance monitoring. Error-related signals have also been found in single-neuron responses and local-field potentials recorded in supplementary eye field and anterior cingulate cortex of macaque monkeys. However, the homology of these neural signals across species remains controversial. Here, we show that monkeys exhibit ERN and Pe components when they commit errors during a saccadic stop-signal task. The voltage distributions and current densities of these components were similar to those found in humans performing the same task. Subsequent analyses show that neither stimulus- nor response-related artifacts accounted for the error-ERPs. This demonstration of macaque homologues of the ERN and Pe forms a keystone in the bridge linking human and nonhuman primate studies on the neural basis of performance monitoring.

Humans and macaque monkeys adjust their response time adaptively in stop-signal (countermanding) tasks, responding slower after stop-signal trials than after control trials with no stop signal. We investigated the neural mechanism underlying this adaptive response time adjustment in macaque monkeys performing a saccade countermanding task. Earlier research showed that movements are initiated when the random accumulation of presaccadic movement-related activity reaches a fixed threshold. We found that a systematic delay in response time after stop-signal trials was accomplished not through a change of threshold, baseline, or accumulation rate, but instead through a change in the time when activity first began to accumulate. The neurons underlying movement initiation have been identified with stochastic accumulator models of response time performance. Therefore, this new result provides surprising new insights into the neural instantiation of stochastic accumulator models and the mechanisms through which executive control can be exerted.

A recent review in Trends in Neuroscience by Cole, Yeung, Freiwald and Botvinick identified a potential fundamental difference in functional properties of the anterior cingulate cortex (ACC) of humans and macaque monkeys [Cole et al., 2009]. The key function in question is monitoring of conflict in response preparation. The conflict hypothesis, defended by the senior authors of the review as a general theory of ACC function, states that when a task calls for multiple competing responses, then executive control is required to resolve the conflict. It is supposed to explain the origin and purpose of event-related potential components such as the error-related negativity (ERN) that occurs after response errors [reviewed by Taylor et al., 2007] and a body of functional brain imaging data. The ERN can be generated by a dipole in the ACC; however, uncertainties in the localization of this dipole as well as other neuroimaging and lesion data demonstrate that more dorsal areas of medial frontal cortex including preSMA also contribute to performance monitoring [e.g. Garavan et al., 2003]. The ERN can also be identified with a reward prediction error originating from the dopamine system [Taylor et al., 2007]. An active literature has developed evaluating these and other alternative hypotheses using human subjects. The relative merits of these alternative hypotheses are not the focus of this commentary. Over the last decade this literature derived from human studies has been supplemented by neurophysiological data from macaque monkeys. In monkeys performing an eye movement stop signal task, neurons are found in the supplementary eye field that signal when errors are produced, when reward is delivered and when conflict occurs [Stuphorn et al., 2000]. In contrast, multiple neurophysiological studies of the macaque monkey ACC have reported error and reward signals but an absence of a conflict signal in tasks that should engender such response conflict [Ito et al., 2003; Nakamura et al., 2005; Emeric et al., 2008]. Cole et al. [2009] argue that the lack of a single neuron conflict signal in macaque monkeys in contrast to humans is a manifestation of a fundamental species difference and a greater sensitivity of functional brain imaging methods to weak conflict signals. We will argue that simpler alternative interpretations have not been ruled out. To account for the apparent incommensurability of results in monkeys and humans, Cole et al. [2009] emphasize species differences. We suggest that effector differences should be considered first. The monkey studies that sparked their review were based on data obtained in tasks requiring monkeys to produce or inhibit saccadic eye movements. The human studies used to describe conflict (as well as error and feedback) signals typically employ forelimb movements. Although the motor control of the eyes and of the hands may share common features centrally, they are substantially different peripherally. Eye movements entail fewer degrees of freedom (basically just 2) and need not be concerned about gravity. Natural arm movements entail more degrees of freedom (as many as 7 not counting the fingers) and usually must contend with gravity. Furthermore, and possibly crucially for this review, being an extension of the body, the limbs can get into kinds of trouble that the eyes cannot, e.g. colliding with other objects in the world. Specific neuroanatomical differences should also be highlighted. First, the neurons in the cortex that contribute to eye movement generation do not form synapses on the motor neurons innervating the muscles of the eyes, but the neurons in the cortex that contribute to forelimb movement generation form synapses directly on the motor neurons innervating the muscles of the limbs. Second, parts of cingulate cortex project to motor cortex and the spinal cord [Dum and Strick 2002], and body movements can be evoked by electrical stimulation of these regions, but such connectivity and excitability for saccades is considerably weaker. Indeed, eye movements are evoked only rarely by stimulation of the ACC of most monkeys. Finally, in many of the studies that report conflict signals with manual movements the alternative responses could be generated together, e.g. press buttons with both hands. In contrast, only one saccadic eye movement can be produced at a time. Why are neuronal responses related to error and reward but not response conflict consistently observed in the ACC? We suggest that conflict signals may not be observed because the oculomotor representation of the macaque ACC does not support enough connections to influence gaze. However, the presence of a conflict signal in supplementary eye fields can perform the same function for the eyes that such a signal in the ACC can perform for the limbs. Cole et al. [2009] also suggest that the conflict-sensitive portion of the human ACC has no homologue in macaque monkeys. However, it is not clear that this view is consistent with the most current anatomical descriptions. While the sulcal pattern in humans with the parasplenial lobules is more complex than that in macaques, the cytoarchitecture of the cingulofrontal transitional cortex identified as area 32 is shared by humans and macaques [Vogt et al., 1995, 2005]. In other words, cortex with cytoarchitecture of area 32 is not absent in macaques, just smaller area. In fact, the caudal part of human area 32ac has been identified as a homolog of macaque area 24c, making it part of the cingulate motor areas [Ongur et al., 2003]. The cingulate motor areas in the caudal anterior cingulate are in a unique position to monitor response conflict and exert control on the skeletal motor system through connections with motor cortical areas and the spinal cord [Dum and Strick 2002]. Meta-analyses of cingulate activation have demonstrated that a somatotopic map corresponding to the cingu- late motor areas in monkeys [Picard and Strick, 2001] overlaps with the foci of conflict-related activation across studies within the region labeled area 32′ [e.g. Hester et al., 2004]. Although we heartily endorse distinguishing illusory from actual cross-species differences, drawing categorical conclusions from nuanced and often ambiguous data is premature. Fundamentally, it is not clear why the general conflict model should not apply to macaques who exhibit complex, extended responses to ambiguous stimuli with uncertain payoffs. If macaque monkeys are not equipped to monitor conflict, then specifically what should they not be able to do?

We describe intracranial local field potentials (LFPs) recorded in the supplementary eye field (SEF) of macaque monkeys performing a saccade countermanding task. The most prominent feature at 90% of the sites was a negative-going polarization evoked by a contralateral visual target. At roughly 50% of sites a negative-going polarization was observed preceding saccades, but in stop signal trials this polarization was not modulated in a manner sufficient to control saccade initiation. When saccades were canceled in stop signal trials, LFP modulation increased with the inferred magnitude of response conflict derived from the coactivation of gaze-shifting and gaze-holding neurons. At 30% of sites, a pronounced negative-going polarization occurred after errors. This negative polarity did not appear in unrewarded correct trials. Variations of response time with trial history were not related to any features of the LFP. The results provide new evidence that error-related and conflict-related but not feedback-related signals are conveyed by the LFP in the macaque SEF and are important for identifying the generator of the error-related negativity.

New insight into how the brain makes a decision has come from a study of the effects of the decision-making process on an eye movement evoked by electrical stimulation of the frontal cortex. The accumulation of sensory evidence was found to cause a gradual commitment toward a choice.

The goal of this study was to determine whether the activity of neurons in the supplementary eye field (SEF) is sufficient to control saccade initiation in macaque monkeys performing a saccade countermanding (stop signal) task. As previously observed, many neurons in the SEF increase the discharge rate before saccade initiation. However, when saccades are canceled in response to a stop signal, effectively no neurons with presaccadic activity display discharge rate modulation early enough to contribute to saccade cancellation. Moreover, SEF neurons do not exhibit a specific threshold discharge rate that could trigger saccade initiation. Yet, we observed more subtle relations between SEF activation and saccade production. The activity of numerous SEF neurons was correlated with response time and varied with sequential adjustments in response latency. Trials in which monkeys canceled or produced a saccade in a stop signal trial were distinguished by a modest difference in discharge rate of these SEF neurons before stop signal or target presentation. These findings indicate that neurons in the SEF, in contrast to counterparts in the frontal eye field and superior colliculus, do not contribute directly and immediately to the initiation of visually guided saccades. However the SEF may proactively regulate saccade production by biasing the balance between gaze-holding and gaze-shifting based on prior performance and anticipated task requirements.

Despite nearly a century of electrophysiological studies recording extracranially from humans and intracranially from monkeys, the neural generators of nearly all human event-related potentials (ERPs) have not been definitively localized. We recorded an attention-related ERP component, known as the N2pc, simultaneously with intracranial spikes and local field potentials (LFPs) in macaques to test the hypothesis that an attentional-control structure, the frontal eye field (FEF), contributed to the generation of the macaque homologue of the N2pc (m-N2pc). While macaques performed a difficult visual search task, the search target was selected earliest by spikes from single FEF neurons, later by FEF LFPs, and latest by the m-N2pc. This neurochronometric comparison provides an empirical bridge connecting macaque and human experiments and a step toward localizing the neural generator of this important attention-related ERP component.

The frontal eye field (FEF) contributes to directing visual attention and saccadic eye movement through intrinsic processing, interactions with extrastriate visual cortical areas (e.g. V4), and projections to subcortical structures (e.g. superior colliculus; SC). Several models have been proposed to describe the relationship between the allocation of visual attention and the production of saccades. We obtained anatomical information that might provide useful constraints on these models by evaluating two characteristics of FEF. First, we investigated the laminar distribution of efferent connections from FEF to visual areas V4 + TEO and to SC. Second, we examined the laminar distribution of different populations of GABAergic neurons in FEF. We found that the neurons in FEF that project to V4 + TEO are located predominantly in the supragranular layers, colocalized with the highest density of calbindin- and calretinin-immunoreactive inhibitory interneurons. In contrast, the cell bodies of neurons that project to SC are found only in layer 5 of FEF, colocalized primarily with parvalbumin inhibitory interneurons. None of the neurons in layer 5 that project to V4 + TEO also project to SC. These results provide useful constraints for cognitive models of visual attention and saccade production by indicating that different populations of neurons project to extrastriate visual cortical areas and to SC. This finding also suggests that FEF neurons projecting to visual cortex and superior colliculus are embedded in different patterns of intracortical circuitry.

The dynamics of visual selection and saccade preparation by the frontal eye field was investigated in macaque monkeys performing a search-step task combining the classic double-step saccade task with visual search. Reward was earned for producing a saccade to a color singleton. On random trials the target and one distractor swapped locations before the saccade and monkeys were rewarded for shifting gaze to the new singleton location. A race model accounts for the probabilities and latencies of saccades to the initial and final singleton locations and provides a measure of the duration of a covert compensation process—target-step reaction time. When the target stepped out of a movement field, noncompensated saccades to the original location were produced when movement-related activity grew rapidly to a threshold. Compensated saccades to the final location were produced when the growth of the original movement-related activity was interrupted within target-step reaction time and was replaced by activation of other neurons producing the compensated saccade. When the target stepped into a receptive field, visual neurons selected the new target location regardless of the monkeys’ response. When the target stepped out of a receptive field most visual neurons maintained the representation of the original target location, but a minority of visual neurons showed reduced activity. Chronometric analyses of the neural responses to the target step revealed that the modulation of visually responsive neurons and movement-related neurons occurred early enough to shift attention and saccade preparation from the old to the new target location. These findings indicate that visual activity in the frontal eye field signals the location of targets for orienting, whereas movement-related activity instantiates saccade preparation.

Visual search for a target object among distractors often takes longer when more distractors are present. To understand the neural basis of this capacity limitation, we recorded activity from visually responsive neurons in the frontal eye field (FEF) of macaque monkeys searching for a target among distractors defined by form (randomly oriented T or L). To test the hypothesis that the delay of response time with increasing number of distractors originates in the delay of attention allocation by FEF neurons, we manipulated the number of distractors presented with the search target. When monkeys were presented with more distractors, visual target selection was delayed and neuronal activity was reduced in proportion to longer response time. These findings indicate that the time taken by FEF neurons to select the target contributes to the variation in visual search efficiency.