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The goal of this short review is to call attention to a yawning gap of knowledge that separates two processes essential for saccade production. On the one hand, knowledge about the saccade generation circuitry within the brainstem is detailed and precise – push-pull interactions between gaze-shifting and gaze-holding processes control the time of saccade initiation, which begins when omnipause neurons are inhibited and brainstem burst neurons are excited. On the other hand, knowledge about the cortical and subcortical premotor circuitry accomplishing saccade initiation has crystalized around the concept of stochastic accumulation – the accumulating activity of saccade neurons reaching a fixed value triggers a saccade. Here is the gap: we do not know how the reaching of a threshold by premotor neurons causes the critical pause and burst of brainstem neurons that initiates saccades. Why this problem matters and how it can be addressed will be discussed. Closing the gap would unify two rich but curiously disconnected empirical and theoretical domains.

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.

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.

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 (SC), and a 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. In “Accurate” relative to “Fast” trials, visually responsive neurons in SC as in FEF had lower baseline firing rates and later target selection. The magnitude of these adjustments in SC was indistinguishable from that in FEF. Search errors occurred when visual salience neurons in the FEF and the SC treated distractors as targets, even in the Accurate condition. Unlike FEF, the magnitude of visual responses in the SC did not vary across SAT conditions. Also unlike FEF, the activity of SC movement neurons when saccades were initiated was equivalent in Fast and Accurate trials. Saccade-related neural activity in SC, but not FEF, varied with saccade peak velocity. These results extend our understanding of the cortical and subcortical contributions to SAT. NEW & NOTEWORTHY Neurophysiological mechanisms of speed-accuracy tradeoff (SAT) have only recently been investigated. This article 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.

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.

We investigated the chronometry of neural processes in frontal eye fields of macaques performing double-step saccade visual search in which a conspicuous target changes location in the array on a random fraction of trials. Durations of computational processes producing a saccade to original and final target locations (GO1 and GO2, respectively) are derived from response times (RT) on different types of trials. In these data, GO2 tended to be faster than GO1, demonstrating that inhibition of the initial saccade did not delay production of the compensated saccade. Here, we measured the dynamics of visual, visuomovement, and movement neuron activity in relation to these processes by examining trials when neurons instantiated either process. First, we verified that saccades were initiated when the discharge rate of movement neurons reached a threshold that was invariant across RT and trial type. Second, the time when visual and visuomovement neurons selected the target and when movement neuron activity began to accumulate were not significantly different across trial type. Third, the interval from the beginning of accumulation to threshold of movement-related activity was significantly shorter when instantiating the GO2 relative to the GO1 process. Differences observed between monkeys are discussed. Fourth, random variation of RT was accounted for to some extent by random variation in both the onset and duration of selective activity of each neuron type but mostly by variation of movement neuron accumulation duration. These findings offer new insights into the sources of control of target selection and saccade production in dynamic environments.

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.

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.

Discharge rate modulation of frontal eye field (FEF) neurons has been identified with a representation of visual search salience (physical conspicuity and behavioral relevance) and saccade preparation. We tested whether salience or saccade preparation are evident in the trial-to-trial variability of discharge rate. We quantified response variability via the Fano factor in FEF neurons recorded in monkeys performing efficient and inefficient visual search tasks. Response variability declined following stimulus presentation in most neurons, but despite clear discharge rate modulation, variability did not change with target salience. Instead, we found that response variability was modulated by stimulus luminance and the number of items in the visual field independently of attentional demands. Response variability declined to a minimum before saccade initiation, and presaccadic response variability was directionally tuned. In addition, response variability was correlated with the response time of memory-guided saccades. These results indicate that the trial-by-trial response variability of FEF neurons reflects saccade preparation and the strength of sensory input, but not visual search salience or attentional allocation.

We review a new computational model developed to understand how evidence about stimulus salience in visual search is translated into a saccade command. The model uses the activity of visually responsive neurons in the frontal eye field as evidence for stimulus salience that is accumulated in a network of stochastic accumulators to produce accurate and timely saccades. We discovered that only when the input to the accumulation process was gated could the model account for the variability in search performance and predict the dynamics of movement neuron discharge rates. This union of cognitive modeling and neurophysiology indicates how the visual–motor transformation can occur, and provides a concrete mapping between neuron function and specific cognitive processes.

Background Cognitive control deficits are pervasive in individuals with schizophrenia (SZ) and are reliable predictors of functional outcome, but the specificity of these deficits and their underlying neural mechanisms have not been fully elucidated. The objective of the present study was to determine the nature of response inhibition and response monitoring deficits in SZ and their relationship to symptoms and social and occupational functioning with a behavioral paradigm that provides a translational approach to investigating cognitive control. Methods Seventeen patients with SZ and 16 demographically matched healthy control subjects participated in a saccadic countermanding task. Performance on this task is approximated as a race between movement generation and inhibition processes; this race model provides an estimate of the time needed to cancel a planned movement. Response monitoring can be assessed by reaction time adjustments on the basis of trial history. Results Saccadic reaction time was normal, but patients required more time to inhibit a planned saccade. The latency of the inhibitory process was associated with the severity of negative symptoms and poorer occupational functioning. Both groups slowed down significantly after correctly cancelled and erroneously noncancelled stop signal trials, but patients slowed down more than control subjects after correctly inhibited saccades. Conclusions These results suggest that SZ is associated with a difficulty in inhibiting planned movements and an inflated response adjustment effect after inhibiting a saccade. Furthermore, behavioral results are consistent with potential abnormalities in frontal and supplementary eye fields in patients with SZ.

The goal of this study was to obtain a better understanding of the physiological basis of errors of visual search. Previous research has shown that search errors occur when visual neurons in the frontal eye field (FEF) treat distractors as if they were targets. We replicated this finding during an inefficient form search and extended it by measuring simultaneously a macaque homologue of an event-related potential indexing the allocation of covert attention known as the m-N2pc. Based on recent work, we expected errors of selection in FEF to propagate to areas of extrastriate cortex responsible for allocating attention and implicated in the generation of the m-N2pc. Consistent with this prediction, we discovered that when FEF neurons selected a distractor instead of the search target, the m-N2pc shifted in the same, incorrect direction prior to the erroneous saccade. This suggests that such errors are due to a systematic misorienting of attention from the initial stages of visual processing. Our analyses also revealed distinct neural correlates of false alarms and guesses. These results demonstrate that errant gaze shifts during visual search arise from errant attentional processing.

In the previous studies on the neural control of saccade initiation using the countermanding paradigm, movement and visuomovement neurons in the frontal eye field were grouped as movement-related neurons. The activity of both types of neurons was modulated when a saccade was inhibited in response to a stop signal, and this modulation occurred early enough to contribute to the control of the saccade initiation. We now report a functional difference between these two classes of neurons when saccades are produced. Movement neurons exhibited a progressive accumulation of discharge rate following target presentation that triggered a saccade when it reached a threshold. When saccades were inhibited with lower probability in response to a stop signal appearing at longer delays, this accumulating activity was interrupted at levels progressively closer to the threshold. In contrast, visuomovement neurons exhibited a maintained elevated discharge rate following target presentation that was followed by a further enhancement immediately before the saccade initiation. When saccades were inhibited in response to a stop signal, the late enhancement was absent and the maintained activity decayed regardless of stop-signal delay. These results demonstrate that the activity of movement neurons realizes the progressive commitment to the saccade initiation modeled by the activation of the go unit in computational models of countermanding performance. The lack of correspondence of the activity of visuomovement neurons with any elements of these models indicates that visuomovement neurons perform a function other than the saccade preparation such as a corollary discharge to update visual processing.

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.

Mathematical psychology and systems neuroscience have converged on stochastic accumulator models to explain decision making. We examined saccade decisions in monkeys while neurophysiological recordings were made within their frontal eye field. Accumulator models were tested on how well they fit response probabilities and distributions of response times to make saccades. We connected these models with neurophysiology. To test the hypothesis that visually responsive neurons represented perceptual evidence driving accumulation, we replaced perceptual processing time and drift rate parameters with recorded neurophysiology from those neurons. To test the hypothesis that movement related neurons instantiated the accumulator, we compared measures of neural dynamics with predicted measures of accumulator dynamics. Thus, neurophysiology both provides a constraint on model assumptions and data for model selection. We highlight a gated accumulator model that accounts for saccade behavior during visual search, predicts neurophysiology during search, and provides insights into the locus of cognitive control over decisions.

Disruptions in corollary discharge (CD), motor signals that send information to sensory areas and allow for prediction of sensory states, are argued to underlie the perceived loss of agency in schizophrenia. Behavioral and neurophysiological evidence for CD in primates comes largely from the saccadic double-step task, which requires participants to make two visually triggered saccadic eye movements in brief succession. Healthy individuals use CD to anticipate the change in eye position resulting from the first saccade when preparing the second saccade. In the current study with human participants, schizophrenia patients and healthy controls of both sexes performed a modified double-step task. Most trials required a saccade to a single visual target (T1). On a subset of trials, a second target (T2) was flashed shortly following T1. Subjects were instructed to look directly at T2. Healthy individuals also use CD to make rapid, corrective responses following erroneous saccades to T1. To assess CD in schizophrenia, we examined the following on error trials: (1) frequency and latency of corrective saccades, and (2) mislocalization of the corrective (second) saccade in the direction predicted by a failure to use CD to account for the first eye movement. Consistent with disrupted CD, patients made fewer and slower error corrections. Importantly, the corrective saccade vector angle was biased in a manner consistent with disrupted CD. These results provide novel and clear evidence for dysfunctional CD in the oculomotor system in patients with schizophrenia. Based on neurophysiology work, these disturbances might have their basis in medial thalamus dysfunction. SIGNIFICANCE STATEMENT According to the World Health Organization, acute schizophrenia carries more disability weight than any other disease, but its etiology remains unknown. One promising theory of schizophrenia highlights alterations in a sense of self, in which self-generated thoughts or actions are attributed externally. Disruptions in corollary discharge (CD), motor signals sent to sensory areas that allow for the prediction of impending sensations, are proposed to underlie these symptoms. Direct physiological evidence, however, is limited. In nonhuman primates, inactivation of mediodorsal thalamic neurons disrupts CD associated with eye movements. Using the same task, we show similar impairments in schizophrenia patients, consistent with disrupted CD. These findings allow us to link clinical phenomenology to primate neurophysiology and interpret findings within a biological framework.

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.

Background: Cognitive control impairments are linked to functional outcome in schizophrenia. The goal of the current study was to investigate precise abnormalities in two aspects of cognitive control: reactively changing a prepared response, and monitoring performance and adjusting behavior accordingly. We adapted an oculomotor task from neurophysiological studies of the cellular basis of cognitive control in nonhuman primates. Methods: 16 medicated outpatients with schizophrenia (SZ) and 18 demographically-matched healthy controls performed the modified double-step task. In this task, participants were required to make a saccade to a visual target. Infrequently, the target jumped to a new location and participants were instructed to rapidly inhibit and change their response. A race model provided an estimate of the time needed to cancel a planned movement. Response monitoring was assessed by measuring reaction time (RT) adjustments based on trial history. Results: SZ patients had normal visually-guided saccadic RTs but required more time to switch the response to the new target location. Additionally, the estimated latency of inhibition was longer in patients and related to employment. Finally, although both groups slowed down on trials that required inhibiting and changing a response, patients showed exaggerated performance-based adjustments in RTs, which was correlated with positive symptom severity. Conclusions: SZ patients have impairments in rapidly inhibiting eye movements and show idiosyncratic response monitoring. These results are consistent with functional abnormalities in a network involving cortical oculomotor regions, the superior colliculus, and basal ganglia, as described in neurophysiological studies of non-human primates using an identical paradigm, and provide a translational bridge for understanding cognitive symptoms of SZ.

We obtained behavioral data to evaluate two alternative hypotheses about the neural mechanisms of gaze control. The "fixation" hypothesis states that neurons in rostral superior colliculus (SC) enforce fixation of gaze. The "microsaccade" hypothesis states that neurons in rostral SC encode microsaccades rather than fixation per se. Previously reported neuronal activity in monkey SC during the saccade stop-signal task leads to specific, dissociable behavioral predictions of these two hypotheses. When subjects are required to cancel partially-prepared saccades, imbalanced activity spreads across rostral and caudal SC with a reliable temporal profile. The microsaccade hypothesis predicts that this imbalance will lead to elevated microsaccade production biased toward the target location, while the fixation hypothesis predicts reduced microsaccade production. We tested these predictions by analyzing the microsaccades produced by 4 monkeys while they voluntarily canceled partially prepared eye movements in response to explicit stop signals. Consistent with the fixation hypothesis and contradicting the microsaccade hypothesis, we found that each subject produced significantly fewer microsaccades when normal saccades were successfully canceled. The few microsaccades escaping this inhibition tended to be directed toward the target location. We additionally investigated interactions between initiating microsaccades and inhibiting normal saccades. Reaction times were longer when microsaccades immediately preceded target presentation. However, pre-target microsaccade production did not affect stop-signal reaction time or alter the probability of canceling saccades following stop signals. These findings demonstrate that imbalanced activity within SC does not necessarily produce microsaccades and add to evidence that saccade preparation and cancelation are separate processes.

Previous studies of visually responsive neurons in the frontal eye fields have identified a selection process preceding saccades during visual search. The goal of this experiment was to determine whether the selection process corresponds to the selection of a conspicuous stimulus or to preparation of the next saccade. This was accomplished with the use of a novel task, called search-step, in which the target of a singleton visual search array switches location with a distracter on random trials. The target step trials created a condition in which the same stimulus yielded saccades either toward or away from the target. Visually responsive neurons in frontal eye field selected the current location of the conspicuous target even when gaze shifted to the location of a distractor. This dissociation demonstrates that the selection process manifest in visual neurons in the frontal eye field may be an explicit interpretation of the image and not an obligatory saccade command.

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.

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.

It is known that the prestriate cortical regions that project to area LIP in parietal cortex and to areas TEO and TE in temporal cortex are mostly separated. Two separate streams of information transfer from occipital cortex can thus be distinguished. We wished to determine whether the parietal and temporal streams remain segregated in their projections to frontal cortex. Paired injections of retrograde fluorescent tracers were placed in parietal and temporal cortex, or in the lateral and medial parts of the frontal eye field (FEF). The cortical regions containing retrogradely labeled cells were reconstructed in two-dimensional maps. The results show that temporal cortex mainly projects to lateral FEF (area 45). Parietal cortex sends projections to medial FEF (area 8a) and to lateral FEF, as well as to area 46. Thus, the parietal and temporal streams converge in lateral FEF. Most of the occipital regions projecting to medial FEF are the same as those projecting to parietal cortex, whereas lateral FEF receives afferents from the same occipital regions as those sending projections to temporal cortex. Thus, one can distinguish two interconnected networks. One is associated with the inferotemporal cortex and includes areas of the ventral bank and fundus of the superior temporal sulcus (STS), lateral FEF and ventral prestriate cortex. This network emphasizes central vision, small saccades and form recognition. The other network is linked to cortex of the intraparietal sulcus. It consists of areas of the upper bank and fundus of STS, medial FEF and dorsal prestriate cortex. These areas encode peripheral visual field and are active during large saccades.

Consensus is emerging that the medial frontal lobe of the brain is involved in monitoring performance, but precisely what is monitored remains unclear. A saccade-countermanding task affords an experimental dissociation of neural signals of error, reinforcement, and conflict. Single-unit activity was monitored in the anterior cingulate cortex of monkeys performing this task. Neurons that signaled errors were found, half of which responded to the omission of earned reinforcement. A further diversity of neurons signaled earned or unexpected reinforcement. No neurons signaled the form of conflict engendered by interruption of saccade preparation produced in this task. These results are consistent with the hypothesis that the anterior cingulate cortex monitors the consequences of actions.

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.

The stop signal task is used to investigate motor inhibition. Several groups have reported partial electromyogram (EMG) activation when subjects successfully withhold manual responses and have used this finding to define the nature of response inhibition properties in the spinal motor system. It is unknown whether subthreshold EMG activation from extraocular muscles can be detected in the saccadic response version of the stop signal task. The saccadic spike potential provides a way to examine extraocular EMG activation associated with eye movements in electroencephalogram (EEG) recordings. We used several techniques to isolate extraocular EMG activation from anterior electrode locations of EEG recorded from macaque monkeys. Robust EMG activation was present when eye movements were made, but no activation was detected when saccades were deemed canceled. This work highlights a key difference between the spinal motor system and the saccade system.

Saccade stop signal and target step tasks are used to investigate the mechanisms of cognitive control. Performance of these tasks can be explained as the outcome of a race between stochastic go and stop processes. The race model analyses assume that response times (RTs) measured throughout an experimental session are independent samples from stationary stochastic processes. This article demonstrates that RTs are neither independent nor stationary for humans and monkeys performing saccade stopping and target-step tasks. We investigate the consequences that this has on analyses of these data. Nonindependent and nonstationary RTs artificially flatten inhibition functions and account for some of the systematic differences in RTs following different types of trials. However, nonindependent and nonstationary RTs do not bias the estimation of the stop signal RT. These results demonstrate the robustness of the race model to some aspects of nonindependence and nonstationarity and point to useful extensions of the model.

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.

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.

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.

1. The purpose of this study was to describe the response properties of neurons in the supplementary motor area (SMA), including the supplementary eye fields (SEF) of three rhesus monkeys (Macaca mulatta) performing visually guided eye and forelimb movements. Seven hundred thirty single units were recorded in the dorsomedial agranular cortex while monkeys performed a go/no-go visual tracking task. The unit activity associated with rewarded, task-related movements was compared with that associated with unrewarded, spontaneous movements executed in the intertrial interval or when the task was not running. A number of neuronal response types were identified. 2. Sensory cells were characterized by their response to the visual and/or auditory target stimuli combined with no discharge associated with eye or forelimb movements. New information was provided about the receptive fields of the visual cells; they varied in size and, although many included the ipsilateral hemifield, they tended to emphasize the contralateral. A significant proportion of the visually responsive cells had receptive fields restricted to within 8 degrees of the fovea. The response latency was relatively long (greater than 90 ms) and variable. 3. Preparatory set cells were activated from the appearance of the target until the presentation of the go/no-go cue. This subpopulation ceased firing 50-100 ms before the movement was initiated. These cells tended to respond best in relation to contralateral movements. The response latency was similar to that of the sensory cells, although some of these units began to discharge in anticipation of predictable target presentations. These neurons were not active before unrewarded, spontaneous saccades. 4. Sensory-movement cells comprised the largest population of neurons identified in SMA. They were active from the appearance of the target until after the execution of the saccade. These neurons tended to respond preferentially in association with contraversive saccades. The latency of response to the target was significantly longer than that of the sensory cells. There was a large amount of variability in the time to reach the peak level of activation, and this population of units generally became inactivated shortly after the saccade was initiated. Although there were counterexamples, most sensory-movement cells responded equally in association with visually and auditory guided movements. In addition, these neurons were not active in relation to self-generated eye movements made during the intertrial intervals. 5. Pause-rebound cells were identified by their suppression at the appearance of the target and subsequent discharge associated with the saccade. These units tended to respond preferentially to contralateral targets.(ABSTRACT TRUNCATED AT 400 WORDS)

The countermanding (or stop signal) task probes the control of the initiation of a movement by measuring subjects' ability to withhold a movement in various degrees of preparation in response to an infrequent stop signal. Previous research found that saccades are initiated when the activity of movement-related neurons reaches a threshold, and saccades are withheld if the growth of activity is interrupted. To extend and evaluate this relationship of frontal eye field (FEF) activity to saccade initiation, two new analyses were performed. First, we fit a neurometric function that describes the proportion of trials with a stop signal in which neural activity exceeded a criterion discharge rate as a function of stop signal delay, to the inhibition function that describes the probability of producing a saccade as a function of stop signal delay. The activity of movement-related but not visual neurons provided the best correspondence between neurometric and inhibition functions. Second, we determined the criterion discharge rate that optimally discriminated between the distributions of discharge rates measured on trials when saccades were produced or withheld. Differential activity of movement-related but not visual neurons could distinguish whether a saccade occurred. The threshold discharge rates determined for individual neurons through these two methods agreed. To investigate how reliably movement-related activity predicted movement initiation; the analyses were carried out with samples of activity from increasing numbers of trials from the same or from different neurons. The reliability of both measures of initiation threshold improved with number of trials and neurons to an asymptote of between 10 and 20 movement-related neurons. Combining the activity of visual neurons did not improve the reliability of predicting saccade initiation. These results demonstrate how the activity of a population of movement-related but not visual neurons in the FEF contributes to the control of saccade initiation. The results also validate these analytical procedures for identifying signals that control saccade initiation in other brain structures.

Executive control requires controlling the initiation of movements, judging the consequences of actions, and adjusting performance accordingly. We have investigated the role of different areas in the frontal lobe in executive control expressed by macaque monkeys performing a saccade stop signal task. Certain neurons in the frontal eye field respond to visual stimuli, and others control the production of saccadic eye movements. Neurons in the supplementary eye field do not control directly the initiation of saccades but, instead, signal the production of errors, the anticipation and delivery of reinforcement, and the presence of response conflict. Neurons in the anterior cingulate cortex signal the production of errors and the anticipation and delivery of reinforcement, but not the presence of response conflict. Intracranial local field potentials in the anterior cingulate cortex of monkeys indicate that these medial frontal signals can contribute to event-related potentials related to performance monitoring. Electrical stimulation of the supplementary eye field improves performance in the task by elevating saccade latency. An interactive race model shows how interacting units produce behavior that can be described as the outcome of a race between independent processes and how conflict between gaze-holding and gaze-shifting neurons can be used to adjust performance.

Visually guided movements can be inaccurate, especially if unexpected events occur while the movement is programmed. Often errors of gaze are corrected before external feedback can be processed. Evidence is presented from macaque monkey frontal eye field (FEF), a cortical area that selects visual targets, allocates attention, and programs saccadic eye movements, for a neural mechanism that can correct saccade errors before visual afferent or performance monitoring signals can register the error. Macaques performed visual search for a color singleton that unpredictably changed position in a circular array as in classic double-step experiments. Consequently, some saccades were directed in error to the original target location. These were followed frequently by unrewarded, corrective saccades to the final target location. We previously showed that visually responsive neurons represent the new target location even if gaze shifted errantly to the original target location. Now we show that the latency of corrective saccades is predicted by the timing of movement-related activity in the FEF. Preceding rapid corrective saccades, the movement-related activity of all neurons began before explicit error signals arise in the medial frontal cortex. The movement-related activity of many neurons began before visual feedback of the error was registered and that of a few neurons began before the error saccade was completed. Thus movement-related activity leading to rapid corrective saccades can be guided by an internal representation of the environment updated with a forward model of the error.

The stop-signal or countermanding task probes the ability to control action by requiring subjects to withhold a planned movement in response to an infrequent stop signal which they do with variable success depending on the delay of the stop signal. We investigated whether performance of humans and macaque monkeys in a saccade countermanding task was influenced by stimulus and performance history. In spite of idiosyncrasies across subjects several trends were evident in both humans and monkeys. Response time decreased after successive trials with no stop signal. Response time increased after successive trials with a stop signal. However, post-error slowing was not observed. Increased response time was observed mainly or only after cancelled (signal inhibit) trials and not after noncancelled (signal respond) trials. These global trends were based on rapid adjustments of response time in response to momentary fluctuations in the fraction of stop signal trials. The effects of trial sequence on the probability of responding were weaker and more idiosyncratic across subjects when stop signal fraction was fixed. However, both response time and probability of responding were influenced strongly by variations in the fraction of stop signal trials. These results indicate that the race model of countermanding performance requires extension to account for these sequential dependencies and provide a basis for physiological studies of executive control of countermanding saccade performance.

The supplementary eye field registers the occurrence of conflict, errors and reward in macaque monkeys performing a saccade-countermanding task. Using intracortical microstimulation, we determined whether the supplementary eye field only monitors or can actually influence performance. Weak microstimulation of many sites in the supplementary eye field improved monkeys' performance on a 'stop signal' task by delaying saccade initiation. This effect depended on the context of the task because simple visually guided saccades were not delayed by the same stimulation. These results demonstrate that the supplementary eye field can exert contextual executive control over saccade generation.

There is significant controversy regarding the ability of the primate visual system to construct stable percepts from a never-ending stream of brief fixations and rapid saccadic eye movements. In this study, we examined the timing and occurrence of perisaccadic modulation of LGN single-unit activity in awake-behaving macaque monkeys while they made spontaneous saccades in the dark and made visually guided saccades to discrete stimuli located outside the receptive field. Our hypothesis was that the activity of LGN cells is modulated by efference copies of motor plans to produce saccadic eye movements and that this modulation depends neither on the presence of feedforward visual information nor on a corollary discharge of signals directing saccadic eye movements. On average, 25% of LGN cells demonstrated significant perisaccadic modulation. This modulation consisted of a moderate suppression of activity that began more than 100 ms prior to the initiation of a saccadic eye movement and continued beyond the termination of the saccadic eye movement. This suppression was followed by a large enhancement of activity after the eyes arrived at the next fixation. Although members of all three LGN relay cell classes (magnocellular, parvocellular, and koniocellular) demonstrated significant saccade-related suppression and enhancement of activity, more cells demonstrated postsaccadic enhancement (25%) than perisaccadic suppression (17%). In no case did the timing of the modulation coincide directly with saccade duration. The degree of modulation observed did not vary with LGN cell class, LGN receptive field center location, center sign (ON-center or OFF-center), or saccade latency or velocity. The time course of modulation did, however, vary with saccade size such that suppression was longer for longer saccades. The fact that activity from a percentage of LGN cells from all cell classes was modulated in relationship to saccadic eye movements in the absence of direct visual stimulation suggests that this modulation is a general phenomenon not tied to specific types of visual stimuli. Similarly, because the onset of the modulation preceded eye movements by more than 100 ms, it is likely that this modulation reflects higher order motor-planning rather than a corollary of mechanisms in direct control of eye movements themselves. Finally, the fact that the largest modulation is a postsaccadic enhancement of activity may suggest that perisaccadic modulations are designed more for the facilitation of visual information processing once the eyes land at a new location than for filtering unwanted visual stimuli.

Recent research has provided new insights into the neural processes that select the target for and control the production of a shift of gaze. Being a key node in the network that subserves visual processing and saccade production, the frontal eye field has been an effective area in which to monitor these processes. Certain neurons in the frontal eye field signal the location of conspicuous or meaningful stimuli that may be the targets for saccades. Other neurons control whether and when gaze shifts. The existence of distinct neural processes for visual selection and saccade production is necessary to explain the flexibility of visually guided behavior.

The goal of this experiment was to determine whether the allocation of attention necessarily requires saccade preparation. To dissociate the focus of attention from the endpoint of a saccade, macaque monkeys were trained to perform visual search for a uniquely colored rectangle and shift gaze either toward or opposite this color singleton according to its orientation. A vertical singleton cued a prosaccade, a horizontal singleton, an antisaccade. Saccade preparation was probed by measuring the direction of saccades evoked by intracortical microstimulation of the frontal eye fields at variable times after presentation of the search array. Eye movements evoked on prosaccade trials deviated progressively toward the singleton that was also the endpoint of the correct eye movement. However, eye movements evoked on antisaccade trials never deviated toward the singleton but only progressively toward the location opposite the singleton. This occurred even though previous work showed that on antisaccade trials most neurons in frontal eye fields initially select the singleton while attention is allocated to distinguish its shape. Thus, sensorimotor structures can covertly orient attention without preparing a saccade.