The effect of attentive fixation on eye movements evoked by electrical stimulation of the frontal eye fields

Summary Electrical stimulation of the frontal eye fields of the rhesus monkey evokes saccadic eye movements. Both the amplitude of electrically elicited saccades and the threshold current for eliciting them are primarily determined by the location of the stimulating electrode within the frontal eye fields; however, threshold and amplitude also are systematically affected by the monkey's behavioral state when the stimulation is applied. If the monkey is alert, but not performing a task, saccade amplitudes are largest and thresholds are lowest. Conversely, if the monkey actively fixates a visual target, elicited saccades are smaller and threshold currents are higher. Saccades evoked during fixation have slower velocities appropriate for their reduced amplitude. Phase plane plots of eye velocity versus eye position indicate that these saccades are originally programmed to be smaller and slower, and hence are not large saccades voluntarily braked in mid-flight. As opposed to their amplitude and threshold, the direction of electrically evoked saccades is unaffected by the state of fixation. The state of attentive fixation, but not the visual fixation target itself, is the responsible factor for these effects. These results suggest that there is a difference between the state of active fixation and the state of having the eye still in the orbit without active fixation. The oculomotor system in the latter case is relatively more susceptible to signals from the cerebral cortex.     

Spatial attention and eye movements

We previously showed that when attention is allocated to the right or left of the fixation point, saccades directed to targets located above or below the fixation point deviate contralateral to the attention locus. In the present study, we examined how general this phenomenon is and whether the amount of saccade deviation depends on the location of attention with respect to that of the saccade target. Three experiments were carried out. In experiment 1 the location of the imperative stimulus was uncued. Its presentation exogenously directed attention to its location. In experiment 2 the location of the imperative stimulus was cued by a central cognitive cue. In this experiment attention was endogenously directed to the imperative stimulus location before its presentation (expectancy paradigm). In experiment 3 all stimulus boxes contained a possible imperative stimulus at the display presentation. A central cue, presented subsequently, indicated which of them had to be used for the saccade. In this experiment attention was endogenously directed to the imperative stimulus, but after its presentation (no-expectancy paradigm). The results showed that, regardless of how attention was directed to the imperative stimulus, the vertical saccades deviated contralateral to the attention location. The deviation was larger when attention was in the upper field and the saccade was directed upward (same hemifield condition) than when attention was in the upper field and the saccade was directed downward (opposite hemifield condition). The same relationship between the same hemifield condition and opposite hemifield condition was found when attention was in the lower field. Saccadic reaction times (SRTs) were shortest in experiment 2 and longest in experiment 3. In experiment 2, SRTs of the same hemifield condition were significantly longer than those of the opposite hemifield condition. Taken altogether, these results strongly support the notion that attention allocation in space leads to an activation of oculomotor circuits, in spite of eye immobility. The possible mechanisms responsible for saccade deviations and for greater saccade deviations when attention is in the same hemifield as the programmed ocular saccade are discussed.     

Primate frontal eye fields. II. Physiological and anatomical correlates of electrically evoked eye movements

We studied single neurons in the frontal eye fields of awake macaque monkeys and compared their activity with the saccadic eye movements elicited by microstimulation at the sites of these neurons. Saccades could be elicited from electrical stimulation in the cortical gray matter of the frontal eye fields with currents as small as 10 microA. Low thresholds for eliciting saccades were found at the sites of cells with presaccadic activity. Presaccadic neurons classified as visuomovement or movement were most associated with low (less than 50 microA) thresholds. High thresholds (greater than 100 microA) or no elicited saccades were associated with other classes of frontal eye field neurons, including neurons responding only after saccades and presaccadic neurons, classified as purely visual. Throughout the frontal eye fields, the optimal saccade for eliciting presaccadic neural activity at a given recording site predicted both the direction and amplitude of the saccades that were evoked by microstimulation at that site. In contrast, the movement fields of postsaccadic cells were usually different from the saccades evoked by stimulation at the sites of such cells. We defined the low-threshold frontal eye fields as cortex yielding saccades with stimulation currents less than or equal to 50 microA. It lies along the posterior portion of the arcuate sulcus and is largely contained in the anterior bank of that sulcus. It is smaller than Brodmann's area 8 but corresponds with the union of Walker's cytoarchitectonic areas 8A and 45. Saccade amplitude was topographically organized across the frontal eye fields. Amplitudes of elicited saccades ranged from less than 1 degree to greater than 30 degrees. Smaller saccades were evoked from the ventrolateral portion, and larger saccades were evoked from the dorsomedial portion. Within the arcuate sulcus, evoked saccades were usually larger near the lip and smaller near the fundus. Saccade direction had no global organization across the frontal eye fields; however, saccade direction changed in systematic progressions with small advances of the microelectrode, and all contralateral saccadic directions were often represented in a single electrode penetration down the bank of the arcuate sulcus. Furthermore, the direction of change in these progressions periodically reversed, allowing particular saccade directions to be multiply represented in nearby regions of cortex.(ABSTRACT TRUNCATED AT 400 WORDS)     

Orienting of attention and eye movements

According to the premotor theory of attention, the mechanisms responsible for spatial attention and the mechanisms involved in programming ocular saccades are basically the same. The aim of the present experiments was to test this claim. In experiment 1 subjects were presented with a visual display consisting of a fixation point and four boxes arranged horizontally and located above the fixation cross. Two of the boxes were in the left visual hemifield, two in the right. A fifth box was located on the vertical meridian below the fixation cross. Digit cues indicated in which of the upper boxes the imperative stimulus was most likely to appear. Subjects were instructed to direct attention to the cued box and to perform a saccadic eye movement to the lower box on presentation of the imperative stimulus. The trajectory of the saccades deviated contralateral to the hemifield in which the imperative stimulus was presented. This deviation was larger when the hemifield where the imperative stimulus was presented was the cued one. In experiment 2, the visual display consisted of five boxes forming a cross. The central box served as a fixation point. The cue was a small line, linked to the central box, pointing to different directions and indicating where the visual imperative stimulus would appear. In 50% of trials, the imperative stimulus was a visual stimulus presented either in one of the lateral boxes or in the central one. In the remaining 50% of trials, the imperative stimulus was a non-lateralised sound. Half the subjects were instructed to make a saccade to the upper box at the presentation of the visual imperative stimulus and to the lower box at the presentation of the acoustic stimulus. Half the subjects received the opposite instructions. The results confirmed that the saccades deviate contralateral to the hemifield of stimulus presentation in the case of visual imperative stimuli. Most importantly, they showed that the saccades deviate contralateral to the cued hemifield, also in the case of acoustic imperative stimuli. Experiment 3 was similar to experiment 2. It confirmed the results of that experiment and showed that slow ocular drifts, which are observed in the time interval between cue and imperative stimulus presentation, cannot explain the ocular deviations. Taken together, the experiments demonstrate that spatial attention allocation leads to an activation of oculomotor circuits, in spite of eye immobility.     

The effects of frontal eye field and dorsomedial frontal cortex lesions on visually guided eye movements

In the frontal lobe of primates, two areas play a role in visually guided eye movements: the frontal eye fields (FEF) and the medial eye fields (MEF) in dorsomedial frontal cortex. Previously, FEF lesions have revealed only mild deficits in saccadic eye movements that recovered rapidly. Deficits in eye movements after MEF ablation have not been shown. We report the effects of ablating these areas singly or in combination, using tests in which animals were trained to make saccadic eye movements to paired or multiple targets presented at various temporal asynchronies. FEF lesions produced large and long-lasting deficits on both tasks. Sequences of eye movements made to successively presented targets were also impaired. Much smaller deficits were observed after MEF lesions. Our findings indicate a major, long-lasting loss in temporal ordering and processing speed for visually guided saccadic eye movement generation after FEF lesions and a significant but smaller and shorter-lasting loss after MEF lesions.     

Human frontal eye fields and visual search

Recent physiological recording studies in monkeys have suggested that the frontal eye fields (FEFs) are involved in visual scene analysis even when eye movement commands are not required. We examined this proposed function of the human frontal eye fields during performance of visual search tasks in which difficulty was matched and eye movements were neither necessary nor required. Magnetic stimulation over FEF modulated performance on a conjunction search task and a simple feature search task in which the target was unpredictable from trial to trial, primarily by increasing false alarm responses. Simple feature search with a predictable target was not affected. The results establish that human FEFs are critical to visual selection, regardless of the need to generate a saccade command.     

Facilitating visuospatial attention for the contralateral hemifield by repetitive TMS on the posterior parietal cortex

Previous studies have demonstrated that repetitive transcranial magnetic stimulation (rTMS) could modulate the visuospatial functions. In this study, we investigated the effect of off-line high frequency subthreshold rTMS, when applied over the right or left posterior parietal cortex (PPC), on the visuospatial attention of the bilateral hemispaces. The subjects underwent visuospatial tasks before and immediately after receiving 1000 pulses of 10 Hz rTMS for a period of 20 min, and their responses were recorded. Our results demonstrated that the high frequency rTMS applied over the PPC produced facilitative effects on the visuospatial attention to the contralateral hemispace. The inhibitory effect to the ipsilateral hemispace was noticeable only in the left PPC.     

Inhibition of return and the human frontal eye fields

Inhibition of return (IOR) is a bias against reorienting attention to a previously cued location. In this study, using single-pulse transcranial magnetic stimulation (TMS), we show that the human frontal eye fields (FEF) play a crucial role in the generation of IOR. When TMS was applied over the right FEF at a time interval after a visual cue but shortly before the target, IOR was modulated in the hemifield ipsilateral to the TMS such that responses to a previously cued target were no longer slower than responses to uncued targets. Control TMS over the superior parietal lobule, as well as TMS of the FEF shortly after the cue but well before the target, had no influence on IOR. We further show that the FEF is involved with visual selection as responses to targets appearing contralateral to the TMS of the FEF, but not the control site, were delayed. These results suggest that the FEF produces IOR by biasing attention and eye movements away from a previously attended location and facilitating target detection at novel locations. Electronic Publication     

Doing without learning: stimulation of the frontal eye fields and floccular complex does not instruct motor learning in smooth pursuit eye movements

Under natural conditions, motor learning is instructed by sensory feedback. We have asked whether sensory signals that indicate motor errors are necessary to instruct learning or if the motor signals related to movements normally driven by sensory error signals would be sufficient. We measured eye movements in trained rhesus monkeys while employing electrical microstimulation of the floccular complex of the cerebellum and the smooth eye movement region of the frontal eye fields to alter ongoing pursuit eye movements. Repeated electrical stimulation at fixed times after the onset of target motion and pursuit failed to cause any learning that was retained beyond the time period used to instruct learning. Learning was not uncovered when the target was stabilized with respect to the moving eye to prevent competition between instructive signals created by electrical stimulation and visual image motion signals evoked when stimulation drove the eye away from the tracking target. We suggest that signals emanating from motor-related structures in the pursuit circuit do not instruct learning. Instead, instructive sensory error signals seem to be necessary.     

Supplementary eye field: representation of saccades and relationship between neural response fields and elicited eye movements

The functional organization of the low-threshold supplementary eye field (SEF) was studied by analyzing presaccadic activity, electrically elicited saccades, and the relationship between them. Response-field optimal vectors, defined as the visual field coordinates or saccadic eye-movement dimensions evoking the highest neural discharge, were quantitatively estimated for 160 SEF neurons by systematically varying peripheral target location relative to a central fixation point and then fitting the responses to Gaussian functions. Saccades were electrically elicited at 109 SEF sites by microstimulation (70 ms, 10-100 microA) during central fixation. The distribution of response fields and elicited saccades indicated a complete representation of all contralateral saccades in SEF. Elicited saccade polar directions ranged between 97 and 262 degrees (data from left hemispheres were transformed to a right-hemisphere convention), and amplitudes ranged between 1.8 and 26.9 degrees. Response-field optimal vectors (right hemisphere transformed) were nearly all contralateral as well; the directions of 115/119 visual response fields and 80/84 movement response fields ranged between 90 and 279 degrees, and response-field eccentricities ranged between 5 and 50 degrees. Response-field directions for the visual and movement activity of visuomovement neurons were strongly correlated (r = 0.95). When neural activity and elicited saccades obtained at exactly the same sites were compared, response fields were highly predictive of elicited saccade dimensions. Response-field direction was highly correlated with the direction of saccades elicited at the recording site (r = 0.92, n = 77). Similarly, response-field eccentricity predicted the size of subsequent electrically elicited saccades (r = 0.49, n = 60). However, elicited saccades were generally smaller than response-field eccentricities and consistently more horizontal when response fields were nearly vertical. The polar direction of response fields and elicited saccades remained constant perpendicular to the cortical surface, indicating a columnar organization of saccade direction. Saccade direction progressively shifted across SEF; however, these orderly shifts were more indicative of a hypercolumnar organization rather than a single global topography. No systematic organization for saccade amplitude was evident. We conclude that saccades are represented in SEF by congruent visual receptive fields, presaccadic movement fields, and efferent mappings. Thus SEF specifies saccade vectors as bursts of activity by local groups of neurons with appropriate projections to downstream oculomotor structures. In this respect, SEF is organized like the superior colliculus and the frontal eye field even though SEF lacks an overall global saccade topography. We contend that all specialized oculomotor functions of SEF must operate within the context of this fundamental organization.     

Microstimulation of the frontal eye field and its effects on covert spatial attention

Many studies have established that the strength of visual perception and the strength of visual representations within visual cortex vary according to the focus of covert spatial attention. While it is clear that attention can modulate visual signals, the source of this modulation remains unknown. We have examined the possibility that saccade related mechanisms provide a source of spatial attention by studying the effects of electrical microstimulation of the frontal eye fields (FEF) on spatial attention. Monkeys performed a task in which they had to detect luminance changes of a peripheral target while ignoring a flashing distracter. The target luminance change could be preceded by stimulation of the FEF at current levels below that which evoked saccadic eye movements. We found that when the target change was preceded by stimulation of FEF, the monkey could detect smaller changes in target luminance. The increased sensitivity to the target change only occurred when the target was placed in the part of the visual field represented by neurons at the stimulation site. The magnitude of improvement depended on the temporal asynchrony of the stimulation onset and the target event. No significant effect of stimulation was observed when long intervals (>300 ms) between stimulation and the target event were used, and the magnitude of the increased sensitivity decreased systematically with increasing asynchrony. At the shortest asynchrony, FEF stimulation temporally overlapped the target event and the magnitude of the improvement was comparable to that of removing the distracter from the task. These results demonstrate that transient, but potent improvements in the deployment of covert spatial attention can be obtained by microstimulation of FEF sites from which saccadic eye movements are also evoked.     

Electrically evoked saccades from the dorsomedial frontal cortex and frontal eye fields: a parametric evaluation reveals differences between areas

Using electrical stimulation to evoke saccades from the dorsomedial frontal cortex (DMFC) and frontal eye fields (FEF) of rhesus monkeys, parametric tests were conducted to compare the excitability properties of these regions. Pulse frequency and pulse current, pulse frequency and train duration, and pulse current and pulse duration were varied to determine threshold functions for a 50% probability of evoking a saccade. Also a wide range of frequencies were tested to evoke saccades, while holding all other parameters constant. For frequencies beyond 150 Hz, the probability of evoking saccades decreased for the DMFC, whereas for the FEF this probability remained at 100%. To evoke saccades readily from the DMFC, train durations of greater than 200 ms were needed; for the FEF, durations of less than 100 ms were sufficient. Even though the chronaxies of neurons residing in the DMFC and FEF were similar (ranging from 0.1 to 0.24 ms) significantly higher currents were required to evoke saccades from the DMFC than FEF. Thus the stimulation parameters that are optimal for evoking saccades from the DMFC differ from those that are optimal for evoking saccades from the FEF. Although the excitability of neurons in the DMFC and FEF are similar (due to similar chronaxies), we suggest that the density of saccade-relevant neurons is higher in the FEF than in the DMFC. Received: 14 January 1997 / Accepted: 2 June 1997     

Electrical stimulation of the frontal eye field in a monkey produces combined eye and head movements

The frontal eye field (FEF), an area in the primate frontal lobe, has long been considered important for the production of eye movements. Past studies have evoked saccade-like movements from the FEF using electrical stimulation in animals that were not allowed to move their heads. Using electrical stimulation in two monkeys that were free to move their heads, we have found that the FEF produces gaze shifts that are composed of both eye and head movements. Repeated stimulation at a site evoked gaze shifts of roughly constant amplitude. However, that gaze shift could be accomplished with varied amounts of head and eye movements, depending on their (head and eye) respective starting positions. This evidence suggests that the FEF controls visually orienting movements using both eye and head rotations rather than just shifting the eyes as previously thought.     

Discharge of frontal eye field neurons during saccadic and following eye movements in unanesthetized monkeys

Summary The cortical mechanism of eye-movement control was investigated by recording single cell activity from the frontal eye field (FEF) in unanesthetized monkeys seated in a primate chair with head restrained. Two types of cells (I and II) were found. Type I neurons fired during voluntary saccades occurring in a given direction and during the fast phase of nystagmus. Cells of this type were silent during slow pursuit movement. Type II cells showed steady discharge when the eyes were oriented in a specific direction. These cells discharged also during smooth pursuit movements and the slow phase of nystagmus, provided that the eyes were moving across positions which would have been associated with neuronal activity had the eyes come to rest there. All of Type II and a few of Type I neurons were identified by antidromic response to stimulation of the cerebral peduncle. These results indicate that cortical neurons have patterns of discharge distinctly related either to saccadic or to pursuit movements, in line with the view that these two different types of eye movement are generated by distinct neuronal mechanisms.     

Selection and maintenance of saccade goals in the human frontal eye fields

In a delayed-response task, response selection marks an important transition from sensory to motor processing. Using event-related functional magnetic resonance imaging, we imaged the human brain during performance of a novel delayed-saccade task that isolated response selection from visual encoding and motor execution. The frontal eye fields (FEFs) and intraparietal sulcus (IPS) both showed robust contra-lateralized activity time-locked to response selection. Moreover, response selection affected delay-period activity differently in these regions; it persisted throughout the memory delay period following response selection in the FEF but not IPS. Our results indicate that the FEF and IPS both make important but distinct contributions to spatial working memory. The mechanism that the FEF uses to support spatial working memory is tied to the selection and prospective coding of saccade goals, whereas the role of the IPS may be more tied to retrospective coding of sensory representations.