The effects of prefrontal cortex inactivation on object responses of single neurons in the inferotemporal cortex during visual search.

Inferotemporal cortex (IT) is believed to be directly involved in object processing and necessary for accurate and efficient object recognition. The frontal eye field (FEF) is an area in the primate prefrontal cortex that is involved in visual spatial selection and is thought to guide spatial attention and eye movements. We show that object-selective responses of IT neurons and behavioral performance are affected by changes in frontal eye field activity. This was found in monkeys performing a search classification task by temporarily inactivating subregions of FEF while simultaneously recording the activity from single neurons in IT. The effect on object selectivity and performance was specific, occurring in a predictable spatially dependent manner and was strongest when the IT neuron's preferred target was presented in the presence of distractors. FEF inactivation did not affect IT responses on trials in which the nonpreferred target was presented in the search array.

Paired neuron recordings in the prefrontal and inferotemporal cortices reveal that spatial selection precedes object identification during visual search.

We addressed the question of how we locate and identify objects in complex natural environments by simultaneously recording single neurons from two brain regions that play different roles in this familiar activity--the frontal eye field (FEF), an area in the prefrontal cortex that is involved in visual spatial selection, and the inferotemporal cortex (IT), which is involved in object recognition--in monkeys performing a covert visual search task. Although the monkeys reported object identity, not location, neural activity specifying target location was evident in FEF before neural activity specifying target identity in IT. These two distinct processes were temporally correlated implying a functional linkage between the end stages of "where" and "what" visual processing and indicating that spatial selection is necessary for the formation of complex object representations associated with visual perception.

Cooperation and competition among frontal eye field neurons during visual target selection.

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.

Frontal eye field activity enhances object identification during covert visual search.

We investigated the link between neuronal activity in the frontal eye field (FEF) and the enhancement of visual processing associated with covert spatial attention in the absence of eye movements. We correlated activity recorded in the FEF of monkeys manually reporting the identity of a visual search target to performance accuracy and reaction time. Monkeys were cued to the most probable target location with a cue array containing a popout color singleton. Neurons exhibited spatially selective responses for the popout cue stimulus and for the target of the search array. The magnitude of activity related to the location of the cue prior to the presentation of the search array was correlated with trends in behavioral performance across valid, invalid, and neutral cue trial conditions. However, the speed and accuracy of the behavioral report on individual trials were predicted by the magnitude of spatial selectivity related to the target to be identified, not for the spatial cue. A minimum level of selectivity was necessary for target detection and a higher level for target identification. Muscimol inactivation of FEF produced spatially selective perceptual deficits in the covert search task that were correlated with the effectiveness of the inactivation and were strongest on invalid cue trials that require an endogenous attention shift. These results demonstrate a strong functional link between FEF activity and covert spatial attention and suggest that spatial signals from FEF directly influence visual processing during the time that a stimulus to be identified is being processed by the visual system.

Neural control of visual search by frontal eye field: effects of unexpected target displacement on visual selection and saccade preparation.

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.

Cognitively directed spatial selection in the frontal eye field in anticipation of visual stimuli to be discriminated.

Single neuron activity was recorded in the frontal eye field (FEF) of monkeys trained to perform a difficult luminance discrimination task. The appearance of a cue stimulus informed the monkeys of the locations of two gray luminance stimuli that would appear within 500-1500ms. The monkeys were rewarded for making a saccade to the brighter of the two luminance stimuli, or if they were the same luminance, for making a saccade to the cue stimulus. Sixty percent (51/85) of FEF neurons exhibited elevated activity when the cue informed the monkeys that one of the luminance stimuli would appear in their response field (RF). This spatially selective anticipatory activity occurred without any visual stimulus appearing in their RF and was not related to saccade choice or latency. The responses of 27 of the anticipatory neurons (32% of the total sample) were also incompatible with the hypothesis that the activity represents saccade probability because they did not exhibit elevated activity for the cue stimulus which was the most probable saccade target. Behaviorally, monkeys exhibited improved perception at locations informed by cue than at unpredictable locations. These results provide physiological evidence that FEF serves an important role in endogenous spatial attention in addition to its well-known role in saccade production.

A perceptual representation in the frontal eye field during covert visual search that is more reliable than the behavioral report.

Neuronal activity in the frontal eye field (FEF) identifies locations of behaviorally important objects for guiding attention and eye movements. We recorded neural activity in the FEF of monkeys trained to manually turn a lever towards the location of a pop-out target of a visual search array without shifting gaze. We examined whether the reliability of the neural representation of the salient target location predicted the monkeys' accuracy of reporting target location. We found that FEF neurons reliably encoded the location of the target stimulus not only on correct trials but also on error trials. The representation of target location in FEF persisted until the manual behavioral report but did not increase in magnitude. This result suggests that, in the absence of an eye movement report, FEF encodes the perceptual information necessary to perform the task but does not accumulate this sensory evidence towards a perceptual decision threshold. These results provide physiological evidence that, under certain circumstances, accurate perceptual representations do not always lead to accurate behavioral reports and that variability in processes outside of perception must be considered to account for the variability in perceptual choice behavior.

Measurements of simultaneously recorded spiking activity and local field potentials suggest that spatial selection emerges in the frontal eye field.

The frontal eye field (FEF) participates in selecting the location of behaviorally relevant stimuli for guiding attention and eye movements. We simultaneously recorded local field potentials (LFPs) and spiking activity in the FEF of monkeys performing memory-guided saccade and covert visual search tasks. We compared visual latencies and the time course of spatially selective responses in LFPs and spiking activity. Consistent with the view that LFPs represent synaptic input, visual responses appeared first in the LFPs followed by visual responses in the spiking activity. However, spatially selective activity identifying the location of the target in the visual search array appeared in the spikes about 30 ms before it appeared in the LFPs. Because LFPs reflect dendritic input and spikes measure neuronal output in a local brain region, this temporal relationship suggests that spatial selection necessary for attention and eye movements is computed locally in FEF from spatially nonselective inputs.

Frontal eye field contributions to rapid corrective saccades.

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.

Neuronal basis of covert spatial attention in the frontal eye field.

The influential "premotor theory of attention" proposes that developing oculomotor commands mediate covert visual spatial attention. A likely source of this attentional bias is the frontal eye field (FEF), an area of the frontal cortex involved in converting visual information into saccade commands. We investigated the link between FEF activity and covert spatial attention by recording from FEF visual and saccade-related neurons in monkeys performing covert visual search tasks without eye movements. Here we show that the source of attention signals in the FEF is enhanced activity of visually responsive neurons. At the time attention is allocated to the visual search target, nonvisually responsive saccade-related movement neurons are inhibited. Therefore, in the FEF, spatial attention signals are independent of explicit saccade command signals. We propose that spatially selective activity in FEF visually responsive neurons corresponds to the mental spotlight of attention via modulation of ongoing visual processing.

Frontal eye field activity before visual search errors reveals the integration of bottom-up and top-down salience.

We investigated the saccade decision process by examining activity recorded in the frontal eye field (FEF) of monkeys performing 2 separate visual search experiments in which there were errors in saccade target choice. In the first experiment, the difficulty of a singleton search task was manipulated by varying the similarity between the target and distractors; errors were made more often when the distractors were similar to the target. On catch trials in which the target was absent the monkeys occasionally made false alarm errors by shifting gaze to one of the distractors. The second experiment was a popout color visual search task in which the target and distractor colors switched unpredictably across trials. Errors occurred most frequently on the first trial after the switch and less often on subsequent trials. In both experiments, FEF neurons selected the saccade goal on error trials, not the singleton target of the search array. Although saccades were made to the same stimulus locations, presaccadic activation and the magnitude of selection differed across trial conditions. The variation in presaccadic selective activity was accounted for by the variation in saccade probability across the stimulus-response conditions, but not by variations in saccade metrics. These results suggest that FEF serves as a saccade probability map derived from the combination of bottom-up and top-down influences. Peaks on this map represent the behavioral relevance of each item in the visual field rather than just reflecting saccade preparation. This map in FEF may correspond to the theoretical salience map of many models of attention and saccade target selection.

A visual salience map in the primate frontal eye field.

Models of attention and saccade target selection propose that within the brain there is a topographic map of visual salience that combines bottom-up and top-down influences to identify locations for further processing. The results of a series of experiments with monkeys performing visual search tasks have identified a population of frontal eye field (FEF) visually responsive neurons that exhibit all of the characteristics of a visual salience map. The activity of these FEF neurons is not sensitive to specific features of visual stimuli; but instead, their activity evolves over time to select the target of the search array. This selective activation reflects both the bottom-up intrinsic conspicuousness of the stimuli and the top-down knowledge and goals of the viewer. The peak response within FEF specifies the target for the overt gaze shift. However, the selective activity in FEF is not in itself a motor command because the magnitude of activation reflects the relative behavioral significance of the different stimuli in the visual scene and occurs even when no saccade is made. Identifying a visual salience map in FEF validates the theoretical concept of a salience map in many models of attention. In addition, it strengthens the emerging view that FEF is not only involved in producing overt gaze shifts, but is also important for directing covert spatial attention.

Effects of search efficiency on surround suppression during visual selection in frontal eye field.

Previous research has shown that visually responsive neurons in the frontal eye field of macaque monkeys select the target for a saccade during efficient, pop-out visual search through suppression of the representation of the nontarget distractors. For a fraction of these neurons, the magnitude of this distractor suppression varied with the proximity of the target to the receptive field, exhibiting more suppression of the distractor representation when the target was nearby than when the target was distant. The purpose of this study was to determine whether the variation of distractor suppression related to target proximity varied with target-distractor feature similarity. The effect of target proximity on distractor suppression did not vary with target-distractor similarity and therefore may be an endogenous property of the selection process.

Effect of target-distractor similarity on FEF visual selection in the absence of the target.

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.