How supplementary eye field (SEF) contributes to visual search is unknown. Inputs from cortical and subcortical structures known to represent visual salience suggest that SEF may serve as an additional node in this network. This hypothesis was tested by recording action potentials and local field potentials (LFP) in two monkeys performing an efficient pop-out visual search task. Target selection modulation, tuning width, and response magnitude of spikes and LFP in SEF were compared with those in frontal eye field. Surprisingly, only ~2% of SEF neurons and ~8% of SEF LFP sites selected the location of the search target. The absence of salience in SEF may be due to an absence of appropriate visual afferents, which suggests that these inputs are a necessary anatomical feature of areas representing salience. We also tested whether SEF contributes to overcoming the automatic tendency to respond to a primed color when the target identity switches during priming of pop-out. Very few SEF neurons or LFP sites modulated in association with performance deficits following target switches. However, a subset of SEF neurons and LFP exhibited strong modulation following erroneous saccades to a distractor. Altogether, these results suggest that SEF plays a limited role in controlling ongoing visual search behavior, but may play a larger role in monitoring search performance.

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 is 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.

The role of spike rate versus timing codes in visual target selection is unclear. We simultaneously recorded activity from multiple frontal eye field neurons and asked whether they interacted to select targets from distractors during visual search. When both neurons in a pair selected the target and had overlapping receptive fields (RFs), they cooperated more than when one or neither neuron in the pair selected the target, measured by positive spike timing correlations using joint peristimulus time histogram analysis. The amount of cooperation depended on the location of the search target: it was higher when the target was inside both neurons’ RFs than when it was inside one RF but not the other, or outside both RFs. Elevated spike timing coincidences occurred at the time of attentional selection of the target as measured by average modulation of discharge rates. We observed competition among neurons with spatially non-overlapping RFs, measured by negative spike timing correlations. Thus, we provide evidence for dynamic and task-dependent cooperation and competition among frontal eye field neurons during visual target selection.

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 mathematical 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.

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 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.

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.

We describe a stochastic accumulator model demonstrating that visual search performance can be understood as a gated feedforward cascade from a salience map to multiple competing accumulators. The model quantitatively accounts for behavior and predicts neural dynamics of macaque monkeys performing visual search for a target stimulus among different numbers of distractors. The salience accumulated in the model is equated with the spike trains recorded from visually responsive neurons in the frontal eye field. Accumulated variability in the firing rates of these neurons explains choice probabilities and the distributions of correct and error response times with search arrays of different set sizes if the accumulators are mutually inhibitory. The dynamics of the stochastic accumulators quantitatively predict the activity of presaccadic movement neurons that initiate eye movements if gating inhibition prevents accumulation before the representation of stimulus salience emerges. Adjustments in the level of gating inhibition can control trade-offs in speed and accuracy that optimize visual search performance.

The error-related negativity (ERN) and positivity (Pe) are components of event-related potential (ERP) waveforms recorded from humans that 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.

Background

Cognitive control deficits are pervasive in individuals with schizophrenia 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 schizophrenia and their relationship to symptoms and social and occupational functioning using a behavioral paradigm that provides a translational approach to investigating cognitive control.

Methods

17 patients with schizophrenia and 16 demographically-matched healthy controls 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 the reaction time (RT) adjustments based on 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 following correctly cancelled and erroneously non-cancelled stop signal trials, but patients slowed down more than controls following correctly inhibited saccades.

Conclusion

These results suggest that schizophrenia is associated with a difficulty in inhibiting planned movements and an inflated response adjustment effect after inhibiting a saccade. Further, behavioral results are consistent with potential abnormalities in frontal and supplementary eye fields in patients with schizophrenia.

Stochastic accumulator models account for response time in perceptual decision-making tasks by assuming that perceptual evidence accumulates to a threshold. The present investigation mapped the firing rate of frontal eye field (FEF) visual neurons onto perceptual evidence and the firing rate of FEF movement neurons onto evidence accumulation to test alternative models of how evidence is combined in the accumulation process. The models were evaluated on their ability to predict both response time distributions and movement neuron activity observed in monkeys performing a visual search task. Models that assume gating of perceptual evidence to the accumulating units provide the best account of both behavioral and neural data. These results identify discrete stages of processing with anatomically distinct neural populations and rule out several alternative architectures. The results also illustrate the use of neurophysiological data as a model selection tool and establish a novel framework to bridge computational and neural levels of explanation.

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 (FEF) has been an effective area in which to monitor these processes. Certain neurons in the FEF signal the location of conspicuous or meaningful stimuli that may be the targets for saccades. Other neurons control whether and when the gaze shifts. The existence of distinct neural processes for visual selection and saccade production is necessary to explain the flexibility of visually guided behaviour.

Flexible behavior depends on the brain’s ability to suppress a habitual response or to cancel a planned movement whenever needed. Such inhibitory control has been studied using the countermanding paradigm in which subjects are required to withhold an imminent movement when a stop signal appears infrequently in a fraction of trials. To elucidate the circuit mechanism of inhibitory control of action, we developed a recurrent network model consisting of spiking movement (GO) neurons and fixation (STOP) neurons, based on neurophysiological observations in the frontal eye field and superior colliculus of behaving monkeys. The model places a premium on the network dynamics prior to the onset of a stop signal, especially the experimentally observed high baseline activity of fixation neurons, which is assumed to be modulated by a persistent top-down control, and their synaptic interaction with movement neurons. The model simulated observed neural activity and fit behavioral performance quantitatively. In contrast to a race model in which the stop process is initiated at the onset of a stop signal, in our model whether a movement will eventually be canceled is determined largely by the proactive top-down control and the stochastic network dynamics even before the appearance of the stop signal. A prediction about the correlation between the fixation neural activity and the behavioral outcome was verified in the neurophysiological data recorded from behaving monkeys. The proposed mechanism for adjusting control through tonically active neurons that inhibit movement-producing neurons has significant implications for exploring the basis of impulsivity associated with psychiatric disorders.

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 to 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.

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.

Interest in local field potentials (LFPs) and action potential shape has increased markedly. The present work describes distortions of these signals that occur for two reasons. First, the microelectrode recording circuit operates as a voltage divider producing frequency-dependent attenuation and phase-shifts when electrode impedance is not negligible relative to amplifier input impedance. Because of the much higher electrode impedance at low frequencies, this occurred over frequency ranges of LFPs measured by neurophysiologists for one head-stage tested. Second, frequency-dependent phase shifts are induced by subsequent filters. Thus, we report these effects and the resulting amplitude envelope delays and distortion of waveforms recorded through a commercial data acquisition system and a range of tungsten microelectrodes. These distortions can be corrected, but must be accounted for when interpreting field potential and spike shape data.

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 SC are embedded in different patterns of intracortical circuitry.

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.

Previous research suggests that target templates are stored visual working memory and used to guide attention during visual search. However, observers can search efficiently even if working memory is filled to capacity by a concurrent task. The idea that target templates are stored in working memory receives support primarily from studies of nonhuman primates in which the target varies from trial-to-trial, and it is possible that working memory templates are not necessary when target identity remains constant, as in most studies of visual search in humans. To test this hypothesis, we asked subjects to perform a visual search task during the delay interval of a visual working memory task. The two tasks were found to interfere with each other when the search targets changed from trial-to-trial, but not when target identity remained constant. Thus, a search template is stored in visual working memory only when the target varies from trial-to-trial. These findings suggest that the network of brain areas involved in shifting attention during visual search tasks may be able to operate essentially independently of the anatomical areas that perform visual working memory maintenance of objects, but only if the identity of the visual search target is stable across time.