Suppression of visually and memory-guided saccades induced by electrical stimulation of the monkey frontal eye field. I. Suppression of ipsilateral saccades

When a saccade occurs to an interesting object, visual fixation holds its image on the fovea and suppresses saccades to other objects. Electrical stimulation of the frontal eye field (FEF) has been reported to elicit saccades, and recently also to suppress saccades. This study was performed to characterize properties of the suppression of visually guided (Vsacs) and memory-guided saccades (Msacs) induced by electrical stimulation of the FEF in trained monkeys. For any given stimulation site, we determined the threshold for electrically evoked saccades (Esacs) at < or =50 microA and then examined suppressive effects of stimulation at the same site on Vsacs and Msacs. FEF stimulation suppressed the initiation of both Vsacs and Msacs during and about 50 ms after stimulation at stimulus intensities lower than those for eliciting Esacs, but did not affect the vector of these saccades. Suppression occurred for ipsiversive but not contraversive saccades, and more strongly for saccades with larger amplitudes and those with initial eye positions shifted more in the saccadic direction. The most effective stimulation timing for suppression was about 50 ms before saccade onset, which suggests that suppression occurred in the efferent pathway for generating Vsacs at the premotor rather than the motoneuronal level, most probably in the superior colliculus and/or the paramedian pontine reticular formation. Suppression sites of ipsilateral saccades were distributed over the classical FEF where saccade-related movement neurons were observed. The results suggest that the FEF may play roles in not only generating contraversive saccades but also maintaining visual fixation by suppressing ipsiversive saccades.     

Suppression of smooth pursuit eye movements induced by electrical stimulation of the monkey frontal eye field

This study was performed to characterize the properties of the suppression of smooth pursuit eye movement induced by electrical stimulation of the frontal eye field (FEF) in trained monkeys. At the stimulation sites tested, we first determined the threshold for generating electrically evoked saccades (Esacs). We then examined the suppressive effects of stimulation on smooth pursuit at intensities that were below the threshold for eliciting Esacs. We observed that FEF stimulation induced a clear deceleration of pursuit at pursuit initiation and also during the maintenance of pursuit at subthreshold intensities. The suppression of pursuit occurred even in the absence of catch-up saccades during pursuit, indicating that suppression influenced pursuit per se. We mapped the FEF area that was associated with the suppressive effect of stimulation on pursuit. In a wide area in the FEF, suppressive effects were observed for ipsiversive, but not contraversive, pursuit. In contrast, we observed the bilateral suppression of both ipsiversive and contraversive pursuit in a localized area in the FEF. This area coincided with the area in which we have previously shown that stimulation suppressed the generation of saccades in bilateral directions and also where fixation neurons that discharged during fixation were concentrated. On the basis of these results, we compared the FEF suppression of pursuit with that of saccades with regard to several physiological properties and then discussed the role of the FEF in the suppression of both pursuit and saccades, and particularly in the maintenance of visual fixation.     

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)     

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     

Muscimol-induced inactivation of monkey frontal eye field: effects on visually and memory-guided saccades.

Muscimol-induced inactivation of the monkey frontal eye field: effects on visually and memory-guided saccades. Although neurophysiological, anatomic, and imaging evidence suggest that the frontal eye field (FEF) participates in the generation of eye movements, chronic lesions of the FEF in both humans and monkeys appear to cause only minor deficits in visually guided saccade generation. Stronger effects are observed when subjects are tested in tasks with more cognitive requirements. We tested oculomotor function after acutely inactivating regions of the FEF to minimize the effects of plasticity and reallocation of function after the loss of the FEF and gain more insight into the FEF contribution to the guidance of eye movements in the intact brain. Inactivation was induced by microinjecting muscimol directly into physiologically defined sites in the FEF of three monkeys. FEF inactivation severely impaired the monkeys' performance of both visually guided and memory-guided saccades. The monkeys initiated fewer saccades to the retinotopic representation of the inactivated FEF site than to any other location in the visual field. The saccades that were initiated had longer latencies, slower velocities, and larger targeting errors than controls. These effects were present both for visually guided and for memory-guided saccades, although the memory-guided saccades were more disrupted. Initially, the effects were restricted spatially, concentrating around the retinotopic representation at the center of the inactivated site, but, during the course of several hours, these effects spread to flanking representations. Predictability of target location and motivation of the monkey also affected saccadic performance. For memory-guided saccades, increases in the time during which the monkey had to remember the spatial location of a target resulted in further decreases in the accuracy of the saccades and in smaller peak velocities, suggesting a progressive loss of the capacity to maintain a representation of target location in relation to the fovea after FEF inactivation. In addition, the monkeys frequently made premature saccades to targets in the hemifield ipsilateral to the injection site when performing the memory task, indicating a deficit in the control of fixation that could be a consequence of an imbalance between ipsilateral and contralateral FEF activity after the injection. There was also a progressive loss of fixation accuracy, and the monkeys tended to restrict spontaneous visual scanning to the ipsilateral hemifield. These results emphasize the strong role of the FEF in the intact monkey in the generation of all voluntary saccadic eye movements, as well as in the control of fixation.     

On the gap effect for saccades evoked by electrical microstimulation of frontal eye fields in monkeys

To investigate the mechanisms of fixation disengagement and saccade initiation, we electrically stimulated the macaque frontal eye fields (FEF) while monkeys performed a visual fixation task. We tested the effect of introducing a temporal gap between fixation target offset and the onset of the electrical stimulus. We found that the duration of the gap had a pronounced effect on the probability of producing electrically evoked saccades at a given current level. The highest probability was found for gaps of 200 ms duration. There were also effects of gap duration on saccade latency and amplitude for most of the stimulation sites. The increase in saccade probability may be associated with lower current thresholds for evoking saccades.     

Activity of monkey frontal eye field neurons projecting to oculomotor regions of the pons.

1. This study identified neurons in the rhesus monkey's frontal eye field that projected to oculomotor regions of the pons and characterized the signals sent by these neurons from frontal eye field to pons. 2. In two behaving rhesus monkeys, frontal eye field neurons projecting to the pons were identified via antidromic excitation by a stimulating microelectrode whose tip was centered in or near the omnipause region of the pontine raphe. This stimulation site corresponded to the nucleus raphe interpositus (RIP). In addition, electrical stimulation of the frontal eye field was used to demonstrate the effects of frontal eye field input on neurons in the omnipause region and surrounding paramedian pontine reticular formation (PPRF). 3. Twenty-five corticopontine neurons were identified and characterized. Most frontal eye field neurons projecting to the pons were either movement neurons, firing in association with saccadic eye movements (48%), or foveal neurons responsive to visual stimulation of the fovea combined with activity related to fixation (28%). Corticopontine movement neurons fired before, during, and after saccades made within a restricted movement field. 4. The activity of identified corticopontine neurons was very similar to the activity of neurons antidromically excited from the superior colliculus where 59% had movement related activity, and 22% had foveal and fixation related activity. 5. High-intensity, short-duration electrical stimulation of the frontal eye field caused omnipause neurons to stop firing. The cessation in firing appeared to be immediate, within < or = 5 ms. The time that the omnipause neuron remained quiet depended on the intensity of the cortical stimulus and lasted up to 30 ms after a train of three stimulus pulses lasting a total of 6 ms at an intensity of 1,000 microA. Low-intensity, longer duration electrical stimuli (24 pulses, 75 microA, 70 ms) traditionally used to evoke saccades from the frontal eye field were also followed by a cessation in omnipause neuron firing, but only after a delay of approximately 30 ms. For these stimuli, the omnipause neuron resumed firing when the stimulus was turned off. 6. The same stimuli that caused omnipause neurons to stop firing excited burst neurons in the PPRF. The latency to excitation ranged from 4.2 to 9.8 ms, suggesting that there is at least one additional neuron between frontal eye field neurons and burst neurons in the PPRF. 7. The present study confirms and extends the results of previous work, with the use of retrograde and anterograde tracers, demonstrating direct projections from the frontal eye field to the pons.(ABSTRACT TRUNCATED AT 400 WORDS)     

Interactions between visually and electrically elicited saccades before and after superior colliculus and frontal eye field ablations in the rhesus monkey

Recent work has shown that humans and monkeys utilize both retinal error and eye position signals to compute the direction and amplitude of saccadic eye movements (Hallett and Lightstone 1976a, b; Mays and Sparks 1980b). The aim of this study was to examine the role the frontal eye fields (FEF) and the superior colliculi (SC) play in this computation. Rhesus monkeys were trained to acquire small, briefly flashed spots of light with saccadic eye movements. During the latency period between target extinction and saccade initiation, their eyes were displaced, in total darkness, by electrical stimulation of either the FEF, the SC or the abducens nucleus area. Under such conditions animals compensated for the electrically induced ocular displacement and correctly reached the visual target area, suggesting that both a retinal error and eye position error signal were computed. The amplitude and direction of the electrically induced saccades depended not only on the site stimulated but also on the amplitude and direction of the eye movement initiated by the animal to acquire the target. When the eye movements initiated by the animal coincided with the saccades initiated by electrical stimulation, the resultant saccade was the weighted average of the two, where one weighing factor was the intensity of the electrical stimulus. Animals did not acquire targets correctly when their eyes were displaced, prior to their intended eye movements, by stimulating in the abducens nucleus area. After bilateral ablation of either the FEF or the SC monkeys were still able to acquire visual targets when their eyes were displaced, prior to saccade initiation, by electrical stimulation of the remaining intact structure. These results suggest that neither the FEF nor the SC is uniquely responsible for the combined computation of the retinal error and the eye position error signals.     

Common inhibitory mechanism for saccades and smooth-pursuit eye movements

The premotor pathways subserving saccades and smooth-pursuit eye movements are usually thought to be different. Indeed, saccade and smooth-pursuit eye movements have different dynamics and functions. In particular, a group of midline cells in the pons called omnipause neurons (OPNs) are considered to be part of the saccadic system only. It has been established that OPNs keep premotor neurons for saccades under constant inhibition during fixation periods. Saccades occur only when the activity of OPNs has completely stopped or paused. Accordingly, electrical stimulation in the region of OPNs inhibits premotor neurons and interrupts saccades. The premotor relay for smooth pursuit is thought to be organized differently and omnipause neurons are not supposed to be involved in smooth-pursuit eye movements. To investigate this supposition, OPNs were recorded during saccades and during smooth pursuit in the monkey (Macaca mulatta). Unexpectedly, we found that neuronal activity of OPNs decreased during smooth pursuit. The resulting activity reduction reached statistical significance in approximately 50% of OPNs recorded during pursuit of a target moving at 40 degrees /s. On average, activity was reduced by 34% but never completely stopped or paused. The onset of activity reduction coincided with the onset of smooth pursuit. The duration of activity reduction was correlated with pursuit duration and its intensity was correlated with eye velocity. Activity reduction was observed even in the absence of catch-up saccades that frequently occur during pursuit. Electrical microstimulation in the OPNs' area induced a strong deceleration of the eye during smooth pursuit. These results suggest that OPNs form an inhibitory mechanism that could control the time course of smooth pursuit. This inhibitory mechanism is part of the fixation system and is probably needed to avoid reflexive eye movements toward targets that are not purposefully selected. This study shows that saccades and smooth pursuit, although they are different kinds of eye movements, are controlled by the same inhibitory system.     

Incomplete suppression of distractor-related activity in the frontal eye field results in curved saccades

Saccades in the presence of distractors show significant trajectory curvature. Based on previous work in the superior colliculus (SC), we speculated that curvature arises when a movement is initiated before competition between the target and distractor goals has been fully resolved. To test this hypothesis, we recorded frontal eye field (FEF) activity for curved and straight saccades in search. In contrast to the SC, activity in FEF is normally poorly correlated with saccade dynamics. However, the FEF, like the SC, is involved in target selection. Thus if curvature is caused by incomplete target selection, we expect to see its neural correlates in the FEF. We found that saccades that curve toward a distractor are accompanied by an increase in perisaccadic activity of FEF neurons coding the distractor location, and saccades that curve away are accompanied by a decrease in activity. In contrast, for FEF neurons coding the target location, there is no significant difference in activity between curved and straight saccades. To establish that the distractor-related activity is causally related to saccade curvature, we applied microstimulation to sites in the FEF before saccades to targets presented without distractors. The stimulation was subthreshold for evoking saccades and the temporal structure of the stimulation train resembled the activity recorded for curved saccades. The resulting movements curved toward the location coded by the stimulation site. These results support the idea that saccade curvature results from incomplete suppression of distractor-related activity during target selection.     

Saccadic burst neurons in the oculomotor region of the fastigial nucleus of macaque monkeys

1. The discharge of 255 neurons in the fastigial nuclei of three trained macaque monkeys was investigated during visually guided saccades. Responses of these neurons were examined also during horizontal head rotation and during microstimulation of the oculomotor vermis (lobules VIc and VII). 2. One hundred and two units were characterized by bursts of firing in response to visually guided saccades. Ninety-eight of these (96.1%) were located within the anatomic confines of the fastigial oculomotor region (FOR), on the basis of reconstruction of recording sites. During contralateral saccades, these neurons showed bursts that preceded the onset of saccades (presaccadic burst), whereas, during ipsilateral saccades, they showed bursts associated with the end of saccades (late saccadic burst). They were hence named saccadic burst neurons. Sixty-one saccadic burst neurons (62.2%) were inhibited during microstimulation of the oculomotor vermis with currents less than 10 microA. 3. All saccadic burst neurons were spontaneously active, and the resting firing rate varied considerably among units, ranging from 10 to 50 imp/s. The tonic levels of activity did not correlate significantly with eye position. 4. The presaccadic burst started 18.5 +/- 4.7 (SD) ms (n = 45) before the onset of saccades in the optimal direction (the direction associated with the maximum values of burst lead time, number of spikes per burst, and burst duration). Optimal directions covered the entire contralateral hemifield, although there was a slightly higher incidence in both horizontal and upper-oblique directions in the present sample. The duration of the presaccadic burst was highly correlated with the duration of saccade (0.85 less than or equal to r less than or equal to 0.97). 5. The late saccadic burst was most robust in the direction opposite to the optimal in each unit (the nonoptimal direction). Its onset preceded the completion of ipsilateral saccade by 30.4 +/- 5.9 ms. The lead time to the end of saccade was consistent among different units and was constant also for saccades of various sizes. Thus the late saccadic burst started even before the saccade onset when the saccade duration was less than 30 ms. Unlike the presaccadic burst, its duration was not related to the duration of saccade. 6. Discharge rates of saccadic burst neurons were correlated neither to eye positions during fixation nor to the initial eye positions before saccades. 7. Eye-position units and horizontal head-velocity units were located rostral to the FOR.(ABSTRACT TRUNCATED AT 400 WORDS)     

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.     

Evidence for a supplementary eye field

Electrical microstimulation and unit recording were performed in dorsomedial frontal cortex of four alert monkeys to identify an oculomotor area whose existence had been postulated rostral to the supplementary motor area. Contraversive saccades were evoked from 129 sites by stimulation. Threshold currents were lower than 20 microA in half the tests. Response latencies were usually longer than 50 ms (minimum: 30 ms). Eye movements were occasionally accompanied by blinks, ear, or neck movements. The cortical area yielding these movements was at the superior edge of the frontal lobe just rostral to the region from which limb movements could be elicited. Depending on the site of stimulation, saccades varied between two extremes: from having rather uniform direction and size, to converging toward a goal defined in space. The transition between these extremes was gradual with no evidence that these two types were fundamentally different. From surface to depth of cortex, direction and amplitude of evoked saccades were similar or changed progressively. No clear systematization was found depending on location along rostrocaudal or mediolateral axes of the cortex. The dorsomedial oculomotor area mapped was approximately 7 mm long and 6 mm wide. Combined eye and head movements were elicited from one of ten sites stimulated when the head was unrestrained. In the other nine cases, saccades were not accompanied by head rotation, even when higher currents or longer stimulus trains were applied. Presaccadic unit activity was recorded from 62 cells. Each of these cells had a preferred direction that corresponded to the direction of the movement evoked by local microstimulation. Presaccadic activity occurred with self-initiated as well as visually triggered saccades. It often led self-initiated saccades by more than 300 ms. Recordings made with the head free showed that the firing could not be interpreted as due to attempted head movements. Many dorsomedial cortical neurons responded to photic stimuli, either phasically or tonically. Sustained responses (activation or inhibition) were observed during target fixation. Twenty-one presaccadic units showed tonic changes of activity with fixation. Justification is given for considering the cortical area studied as a supplementary eye field. It shares many common properties with the arcuate frontal eye field. Differences noted in this study include: longer latency of response to electrical stimulation, possibility to evoke saccades converging apparently toward a goal, and long-lead unit activity with spontaneous saccades.     

Dynamics of abducens nucleus neuron discharges during disjunctive saccades

In this report, we provide the first characterization of abducens nucleus neuron (ABN) discharge dynamics during horizontal disjunctive saccades. These movements function to rapidly transfer the visual axes between targets located at different eccentricities and depths. Our primary objective was to determine whether the signals carried by ABNs during these movements are appropriate to drive the motion of the eye to which they project. We also asked whether ABNs encode eye movements similarly during disjunctive saccades and disjunctive fixation. To address the first objective we 1) assessed whether we could predict the discharge dynamics of individual neurons during disjunctive saccades based on their discharge properties during conjugate saccades and 2) directly estimated the sensitivity of individual neurons to either the ipsilateral/contralateral eye or the conjugate/vergence position and velocity using bootstrap statistics. Our main finding was that during disjunctive saccades in the direction ipsilateral to the recording site (ON-direction), the majority of ABNs preferentially encoded the velocity and the position of the ipsilateral eye. The remaining neurons predominantly encoded the conjugate motion of the eyes (i.e., were equally sensitive to the motion of both eyes). Generally, ipsilateral/contralateral eye based models better described neuronal discharges than conjugate/vergence based models, yet both model structures yielded similar conclusions. Moreover, the preferred eye of individual neurons based on their position and velocity sensitivities were generally well matched. We also found that for saccades in the OFF-direction, the pausing behavior of ABNs was similar during conjugate and disjunctive saccades, with the exception that for movements of small amplitudes, more ABNs paused during conjugate saccades. Finally, we found that putative motoneurons and internuclear neurons encoded ON- and OFF-direction disjunctive saccades in a similar manner. To address our second objective, we compared the discharge properties of individual ABNs during disjunctive saccades and disjunctive fixation. Good coherence was observed between the preferred eye of individual ABNs during the two behaviors. Taken together, our results indicate that although individual ABNs can encode the motion of both eyes to various degrees, the population drive of ABNs accounts for most of the movement of the ipsilateral eye during disjunctive saccades and disjunctive fixation.     

Facilitation of smooth pursuit initiation by electrical stimulation in the supplementary eye fields.

The role of the supplementary eye fields (SEF) during smooth pursuit was investigated with electrical microstimulation. We found that stimulation in the SEF increased the acceleration and velocity of the eyes in the direction of target motion during smooth pursuit initiation but not during sustained pursuit. The increase in eye velocity during initiation will be referred to as pursuit facilitation and was observed at sites where saccades could not be evoked with the same stimulation parameters. On average, electrical stimulation increased eye velocity by approximately 20%. At most sites, the threshold for a significant facilitation was 50 microA with a stimulation frequency of 300 Hz. Facilitation of pursuit initiation depended on the timing of stimulation trains. The effect was most pronounced if the stimulation was delivered before smooth pursuit initiation. On average, eye velocity in stimulation trials increased linearly as a function of eye velocity in control trials, and this function had a slope greater than one, suggesting a multiplicative influence of the stimulation. Stimulation during a fixation task did not evoke smooth eye movements. The latency of catch-up saccades was increased during facilitation, but their accuracy was not affected. Saccades toward stationary targets were not affected by the stimulation. The results are further evidence that the SEF plays a role in smooth pursuit in addition to its known role in saccade planning and suggest that this role may be to control the gain of smooth pursuit during initiation. The covariance between pursuit facilitation and the timing of the catch-up saccade as a result of stimulation suggests that these different eye movements systems are coordinated to achieve a common goal.     

The dorsomedial frontal cortex of the rhesus monkey: topographic representation of saccades evoked by electrical stimulation

The dorsomedial frontal cortex (DMFC) of monkeys has been implicated in mediating visually guided saccadic eye movements. The purpose of this study was to determine whether the DMFC has a topographic map coding final eye position, and to ascertain whether this region subserves the maintenance of eye position. The DMFC was stimulated electrically while monkeys fixated a target presented somewhere in visual space. A series of parametric tests was conducted to ascertain the best stimulation parameters to evoke saccades. Electrical stimulation typically produced contraversive saccades that converged onto a region of space, the termination zone. For some stimulation sites, however, stimulation produced ipsiversive saccades. This occurred when the termination zone was located straight ahead of the monkey. Convergence onto an orbital position was never observed during stimulation of the frontal eye fields (FEF), stimulation of which evoked fixed-vector saccades. The latency to evoke a saccade from the DMFC varied with fixation position, such that it increased monotonically the closer the fix spot was to the termination zone. Moreover, the probability of evoking a saccade from the DMFC decreased the closer the fix spot was to the termination zone. The latency for evoking a saccade and the probability of evoking a saccade from the FEF did not vary with fixation position. Horizontal head movements were not evoked from the DMFC while a monkey fixated targets presented in different positions of visual space. Moveover, changing the position of the head with respect to the body did not change the location of a termination zone with respect to the head. The DMFC was found to contain a topographic coding of termination zones, with rostral sites representing zones in extreme contralateral visual space, and caudal sites representing zones straight ahead or ipsilaterally. Furthermore, lateral sites represented zones in upper visual space, whereas medial sites represented zones in lower visual space. Once the eyes were positioned within a termination zone, further stimulation fixed the gaze and inhibited visually evoked saccades. Following release from inhibition, which occurred shortly after the end of stimulation, the saccades reached the visual target accurately. This shows that the stimulation delayed the execution of the saccades without actually aborting their execution. We conclude that the DMFC contains a map representing eye position in craniotopic coordinates, and we argue that this map is utilized to maintain eye position.     

Comparison of saccades perturbed by stimulation of the rostral superior colliculus, the caudal superior colliculus, and the omnipause neuron region

Over the past decade, considerable research efforts have been focused on the role of the rostral superior colliculus (SC) in control of saccades. The most recent theory separates the deeper intermediate layers of the SC into two functional regions: the rostral pole of these layers constitutes a fixation zone and the caudal region comprises the saccade zone. Sustained activity of fixation neurons in the fixation zone is argued to maintain fixation and help prevent saccade generation by exciting the omnipause neurons (OPNs) in the brain stem. This hypothesis is in contrast to the traditional view that the SC contains a topographic representation of the saccade motor map on which the rostral pole of the SC encodes signals for generating small saccades (<2 degrees ) instead of preventing them. There is therefore an unresolved controversy about the specific role on the most rostral region of the SC, and we reexamined its functional contribution by quantifying and comparing spatial and temporal trajectories of 30 degrees saccades perturbed by electrical stimulation of the rostral pole and more caudal regions in the SC and of the OPN region. If the rostral pole serves to preserve fixation, then saccades perturbed by stimulation should closely resemble interrupted saccades produced by stimulation of the OPN region. If it also contributes to saccade generation, then the disrupted movements would better compare with redirected saccades observed after stimulation of the caudal SC. Our experiments revealed two significant findings: 1) the locus of stimulation was the primary factor determining the perturbation effect. If the directions of the target-directed saccade and stimulation-evoked saccade were aligned and if the stimulation was delivered within approximately the rostral 2 mm (<10 degrees amplitude) of SC, the ongoing saccade stopped in midflight but then resumed after stimulation end to reach the original visually specified goal with close to normal accuracy. When stimulation was applied at more caudal sites, the ongoing saccade directly reached the target location without stopping at an intermediate position. If the directions differed considerably, both initial and resumed components were typically observed for all stimulation sites. 2) A quantitative analysis of the saccades perturbed from the fixation zone showed significant deviations from their control spatial trajectories. Thus they resembled redirected saccades induced by caudal SC stimulation and differed significantly from interrupted saccades produced by OPN stimulation. The amplitude of the initial saccade, latency of perturbation, and spatial redirection were greatest for the most caudal sites and decreased gradually for rostral sites. For stimulation sites within the rostral pole of SC, the measures formed a smooth continuation of the trends observed in the saccade zone. As these results argue for the saccade zone concept, we offer reinterpretations of the data used to support the fixation zone model. However, we also discuss scenarios that do not allow an outright rejection of the fixation zone hypothesis.     

Role of the rostral superior colliculus in active visual fixation and execution of express saccades.

1. In the rostral pole of the monkey superior colliculus (SC) a subset of neurons (fixation cells) discharge tonically when a monkey actively fixates a target spot and pause during the execution of saccadic eye movements. 2. To test whether these fixation cells are necessary for the control of visual fixation and saccade suppression, we artificially inhibited them with a local injection of muscimol, an agonist of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). After injection of muscimol into the rostral pole of one SC, the monkey was less able to suppress the initiation of saccades. Many unwanted visually guided saccades were initiated less than 100 ms after onset of a peripheral visual stimulus and therefore fell into the range of express saccades. 3. We propose that fixation cells in the rostral SC form part of a fixation system that facilitates active visual fixation and suppresses the initiation of unwanted saccadic eye movements. Express saccades can only occur when activity in this fixation system is reduced.     

Reversible inactivation of macaque dorsomedial frontal cortex: effects on saccades and fixations

 Neural recording and electrical stimulation results suggest that the dorsomedial frontal cortex (DMFC) of macaque is involved in oculomotor behavior. We reversibly inactivated the DMFC using lidocaine and examined how saccadic eye movements and fixations were affected. The inactivation methods and monkeys were the same as those used in a previous study of the frontal eye field (FEF), another frontal oculomotor region. In the first stage of the present study, monkeys performed tasks that required the generation of single saccades and fixations. During 15 DMFC inactivations, we found only mild, infrequent deficits. This contrasts with our prior finding that FEF inactivation causes severe, reliable deficits in performance of these tasks. In the second stage of the study, we investigated whether DMFC inactivation affected behavior when a monkey was required to make more than one saccade and fixation. We used a double-step task: two targets were flashed in rapid succession and the monkey had to make two saccades to foveate the target locations. In each of five experiments, DMFC inactivation caused a moderate, significant deficit. Both ipsi- and contraversive saccades were disrupted. In two experiments, the first saccades were made to the wrong place and had increased latencies. In one experiment, first saccades were unaffected, but second saccades were made to the wrong place and had increased latencies. In the remaining two experiments, specific reasons for the deficit were not detected. Saline infusions into DMFC had no effect. Inactivation of FEF caused a larger double-step deficit than did inactivation of DMFC. The FEF inactivation impaired contraversive first or second saccades of the sequence. In conclusion, our results suggest that the DMFC makes an important contribution to generating sequential saccades and fixations but not single saccades and fixations. Compared with the FEF, the DMFC has a weaker, less directional, more task-dependent oculomotor influence. Received: 12 January 1998 / Accepted: 17 July 1998     

Activity of mesencephalic vertical burst neurons during saccades and smooth pursuit

The activity of vertical burst neurons (BNs) was recorded in the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF-BNs) and in the interstitial nucleus of Cajal (NIC-BNs) in head-restrained cats while performing saccades or smooth pursuit. BNs emitted a high-frequency burst of action potentials before and during vertical saccades. On average, these bursts led saccade onset by 14 +/- 4 ms (mean +/- SD, n = 23), and this value was in the range of latencies ( approximately 5-15 ms) of medium-lead burst neurons (MLBNs). All NIC-BNs (n = 15) had a downward preferred direction, whereas riMLF-BNs showed either a downward (n = 3) or an upward (n = 5) preferred direction. We found significant correlations between saccade and burst parameters in all BNs: vertical amplitude was correlated with the number of spikes, maximum vertical velocity with maximum of the spike density, and saccade duration with burst duration. A correlation was also found between instantaneous vertical velocity and neuronal activity during saccades. During fixation, all riMLF-BNs and approximately 50% of NIC-BNs (7/15) were silent. Among NIC-BNs active during fixation (8/15), only two cells had an activity correlated with the eye position in the orbit. During smooth pursuit, most riMLF-BNs were silent (7/8), but all NIC-BNs showed an activity that was significantly correlated with the eye velocity. This activity was unaltered during temporary disappearance of the visual target, demonstrating that it was not visual in origin. For a given neuron, its ON-direction during smooth pursuit and saccades remained identical. The activity of NIC-BNs during both saccades and smooth pursuit can be described by a nonlinear exponential function using the velocity of the eye as independent variable. We suggest that riMLF-BNs, which were not active during smooth pursuit, are vertical MLBNs responsible for the generation of vertical saccades. Because NIC-BNs discharged during both saccades and pursuit, they cannot be regarded as MLBNs as usually defined. NIC-BNs could, however, be the site of convergence of both the saccadic and smooth pursuit signals at the premotoneuronal level. Alternatively, NIC-BNs could participate in the integration of eye velocity to eye position signals and represent input neurons to a common integrator.