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

To understand the neural mechanism of fixation, we investigated effects of electrical stimulation of the frontal eye field (FEF) and its vicinity on visually guided (Vsacs) and memory-guided saccades (Msacs) in trained monkeys and found that there were two types of suppression induced by the electrical stimulation: suppression of ipsilateral saccades and suppression of bilateral saccades. In this report, we characterized the properties of the suppression of bilateral Vsacs and Msacs. Stimulation of the bilateral suppression sites suppressed the initiation of both Vsacs and Msacs in all directions during and approximately 50 ms after stimulation but did not affect the vector of these saccades. The suppression was stronger for ipsiversive larger saccades and contraversive smaller saccades, and saccades with initial eye positions shifted more in the saccadic direction. The most effective stimulation timing for the suppression of ipsilateral and contralateral Vsacs was approximately 40-50 ms before saccade onset, indicating that the suppression occurred most likely in the superior colliculus and/or the paramedian pontine reticular formation. Suppression sites of bilateral saccades were located in the prearcuate gyrus facing the inferior arcuate sulcus where stimulation induced suppression at < or =40 microA but usually did not evoke any saccades at 80 microA and were different from those of ipsilateral saccades where stimulation evoked saccades at < or =50 microA. The bilateral suppression sites contained fixation neurons. The results suggest that fixation neurons in the bilateral suppression area of the FEF may play roles in maintaining fixation by suppressing saccades in all directions.     

Peak velocities of visually and nonvisually guided saccades in smooth-pursuit and saccadic tasks

 Smooth pursuit typically includes corrective catch-up saccades, but may also include such intrusive saccades away from the target as anticipatory or large overshooting saccades. We sought to differentiate catch-up from anticipatory and overshooting saccades by their peak velocities, to see whether the higher velocities of visually rather than nonvisually guided saccades in saccadic tasks may be found also in saccades in pursuit. In experiment 1, 12 subjects showed catch-up, anticipatory, and overshooting saccades to comprise 70.4% of all saccades in pursuit of periodic, 30°/s constant-velocity targets. Catch-up saccades were faster than the others. Saccadic tasks were run as well, on 19 subjects, including the 12 whose pursuit data were analyzed, with target-onset, target-remaining (saccade to the remaining target when the other three extinguish), and antisaccade tasks. For 17 of the 19 subjects, antisaccade velocities were lower than for either target-onset or target-remaining tasks. Velocities for the target-remaining task were near those for target onset, indicating that target presence, not its onset, defines visually guided saccades. Error and reaction-time data suggest greater cognitive difficulty for target remaining than for target onset, so that the cognitive difficulty of typical nonvisually guided saccade tasks is not sufficient to produce their lowered velocity. To produce reliably, in each subject, catch-up and anticipatory saccades with comparable amplitude distributions, nine new subjects were asked in experiment 2 to make intentional catch-up and anticipatory saccades in pursuit, and were presented with embedded target jumps to elicit catch-up saccades, all with periodic target trajectories of 15°/s and 30°/s. Velocities of intentional anticipatory saccades were lower than velocities of intentional catch-up saccades, while velocities of intentional and embedded catch-up saccades were similar. Target-onset and remembered-target saccadic tasks were run, showing the expected higher velocity for the target-onset task in each subject. Both experiments demonstrate higher peak velocities for catch-up saccades than for anticipatory saccades, suggesting that cortical structures preferentially involved in nonvisually guided saccades may initiate the anticipatory and overshooting saccades in pursuit. Received: 1 December 1995 / Accepted: 25 February 1997     

Quantitative analysis of catch-up saccades during sustained pursuit

During visual tracking of a moving stimulus, primates orient their visual axis by combining two very different types of eye movements, smooth pursuit and saccades. The purpose of this paper was to investigate quantitatively the catch-up saccades occurring during sustained pursuit. We used a ramp-step-ramp paradigm to evoke catch-up saccades during sustained pursuit. In general, catch-up saccades followed the unexpected steps in position and velocity of the target. We observed catch-up saccades in the same direction as the smooth eye movement (forward saccades) as well as in the opposite direction (reverse saccades). We made a comparison of the main sequences of forward saccades, reverse saccades, and control saccades made to stationary targets. They were all three significantly different from each other and were fully compatible with the hypothesis that the smooth pursuit component is added to the saccadic component during catch-up saccades. A multiple linear regression analysis was performed on the saccadic component to find the parameters determining the amplitude of catch-up saccades. We found that both position error and retinal slip are taken into account in catch-up saccade programming to predict the future trajectory of the moving target. We also demonstrated that the saccadic system needs a minimum period of approximately 90 ms for taking into account changes in target trajectory. Finally, we reported a saturation (above 15 degrees /s) in the contribution of retinal slip to the amplitude of catch-up saccades.     

Accuracies of saccades to moving targets during pursuit initiation and maintenance

The overall goals of the studies presented here were to compare (1) the accuracies of saccades to moving targets with either a novel or a known target motion, and (2) the relationships between the measures of target motion and saccadic amplitude during pursuit initiation and maintenance. Since resampling of position error just prior to saccade initiation can confound the interpretation of results, the target ramp was masked during the planning and execution of the saccade. The results suggest that saccades to moving targets were significantly more accurate if the target motion was known from the early part of the trial (e.g., during pursuit maintenance) than in the case of novel target motion (e.g., during pursuit initiation); both these types of saccades were more accuate than those when target motion information was not available. Using target velocity in space as a rough estimate of the magnitude of the extra-retinal signal during pursuit maintenance, the saccadic amplitude was significantly associated with the extra-retinal target motion information after accounting for the position error. In most subjects, this association was stronger than the one between retinal slip velocity and saccadic amplitude during pursuit initiation. The results were similar even when the smooth eye motion prior to the saccade was controlled. These results suggest that different sources of target motion information (retinal image velocity vs internal representation of previous target motion in space) are used in planning saccades during different stages of pursuit. The association between retinal slip velocity and saccadic amplitude is weak during initiation, thus explaining poor saccadic accuracy during this stage of pursuit.     

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.     

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.     

Gravity modulates Listing's plane orientation during both pursuit and saccades

Previous studies have shown that the spatial organization of all eye orientations during visually guided saccadic eye movements (Listing's plane) varies systematically as a function of static and dynamic head orientation in space. Here we tested if a similar organization also applies to the spatial orientation of eye positions during smooth pursuit eye movements. Specifically, we characterized the three-dimensional distribution of eye positions during horizontal and vertical pursuit (0.1 Hz, +/-15 degrees and 0.5 Hz, +/-8 degrees) at different eccentricities and elevations while rhesus monkeys were sitting upright or being statically tilted in different roll and pitch positions. We found that the spatial organization of eye positions during smooth pursuit depends on static orientation in space, similarly as during visually guided saccades and fixations. In support of recent modeling studies, these results are consistent with a role of gravity on defining the parameters of Listing's law.     

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.     

The initiation of smooth pursuit eye movements and saccades in normal subjects and in “express-saccade makers”

A vast knowledge exists about saccadic reaction times (RT) and their bi- or multimodal distributions with very fast (express) and regular RT. Recently, there has been some evidence that the smooth pursuit system may show a similar RT behavior. Since moving targets usually evoke a combined pursuit/saccade response, we asked which processes influence the initiation of pursuit and saccadic eye movements. Furthermore, we investigated whether and how the pursuit and saccadic system interact during the initiation of eye movements to moving targets. We measured the RT of the initial smooth pursuit (iSP) response and of the first corrective saccade and compared the RT behavior of both. Furthermore we compared the behavior of the corrective saccades to moving targets to that of saccades to stationary targets, known from the literature. The stimulus consisted of a target that moved suddenly at constant velocity (ramp). In addition, prior to the movement, a temporal gap, a position step or a combination of both could occur (gap-ramp, step-ramp, gap-step-ramp, respectively). Differently from most previous studies, we chose step and ramp with the same direction to provoke competition between the pursuit and saccade system. For the first time we investigated pursuit initiation in "express-saccade makers" (ES makers), a subject group known to produce an abnormally high percentage of short-latency saccades in saccade tasks. We compared their results with subject groups who were either naive or trained with respect to saccade tasks. The iSP started at approximately 100 ms, which corresponds to express saccade latencies. These short iSP-RT occurred reflex-like and almost independent of the experimental task. A bimodal frequency distribution of RT with a second peak of longer iSP-RT occurred exclusively in the ramp paradigm. The RT of the first corrective saccades in a pursuit task were comparable with that in a saccade task and depended on the stimulus. The ability of ES makers to produce a high number of express saccades was transferred to corrective saccades in the pursuit task, but not to pursuit initiation. In summary, short-latency pursuit responses differ from express saccades with respect to their independence of experiment and subject group. Therefore, a simple analogy to express saccades cannot be drawn, although some mechanisms seem to act similarly on both the pursuit and the saccade system (such as disengagement of attention with the gap effect). Furthermore, we found evidence that the initial pursuit response and the first corrective saccade are processed independently of each other. The first corrective saccades to moving targets behave like saccades to stationary targets. Normal pursuit but abnormal saccade RT of ES makers can be explained by recent theories of superior colliculus (SC) function in terms of retinal error handling.     

Neural control of fast-regular saccades and antisaccades: an investigation using positron emission tomography

 Regional cerebral blood flow changes related to the performance of two oculomotor tasks and a central fixation task were compared in ten healthy human subjects. The tasks were: (a) performance of fast-regular saccades; (b) performance of voluntary antisaccades away from a peripheral cue; (c) passive maintenance of central visual fixation in the presence of irrelevant peripheral stimulation. The saccadic task was associated with a relative increase in activity in a number of occipitotemporal areas. Compared with both the fixation and the saccadic task, the performance of antisaccades activated a set of areas including: the superior and inferior parietal lobules, the precentral and prefrontal cortex, the cingulate cortex, and the supplementary motor area. The results of the present study suggest that: (a) compared with self-determined saccadic responses the performance of fast regular, reflexive saccades produces a limited activation of the frontal eye fields; (b) in the antisaccadic task the inferior parietal lobes subserve operations of sensory-motor integration dealing with attentional disengagement from the initial peripheral cue (appearing at an invalid spatial location) and with the recomputation of the antisaccadic vector on the basis of the wrong (e.g., spatially opposite) information provided by the same cue. Received: 20 May 1996 / Accepted: 28 January 1997     

Blink-perturbed saccades in monkey. I. Behavioral analysis

Saccadic eye movements are thought to be influenced by blinking through premotor interactions, but it is still unclear how. The present paper describes the properties of blink-associated eye movements and quantifies the effect of reflex blinks on the latencies, metrics, and kinematics of saccades in the monkey. In particular, it is examined to what extent the saccadic system accounts for blink-related perturbations of the saccade trajectory. Trigeminal reflex blinks were elicited near the onset of visually evoked saccades by means of air puffs directed on the eye. Reflex blinks were also evoked during a straight-ahead fixation task. Eye and eyelid movements were measured with the magnetic-induction technique. The data show that saccade latencies were reduced substantially when reflex blinks were evoked prior to the impending visual saccades as if these saccades were triggered by the blink. The evoked blinks also caused profound spatial-temporal perturbations of the saccades. Deflections of the saccade trajectory, usually upward, extended up to approximately 15 degrees. Saccade peak velocities were reduced, and a two- to threefold increase in saccade duration was typically observed. In general, these perturbations were largely compensated in saccade mid-flight, despite the absence of visual feedback, yielding near-normal endpoint accuracies. Further analysis revealed that blink-perturbed saccades could not be described as a linear superposition of a pure blink-associated eye movement and an unperturbed saccade. When evoked during straight-ahead fixation, blinks were accompanied by initially upward and slightly abducting eye rotations of approximately 2-15 degrees. Back and forth wiggles of the eye were frequently seen; but in many cases the return movement was incomplete. Rather than drifting back to its starting position, the eye then maintained its eccentric orbital position until a downward corrective saccade toward the fixation spot followed. Blink-associated eye movements were quite rapid, albeit slower than saccades, and the velocity-amplitude-duration characteristics of the initial excursions as well as the return movements were approximately linear. These data strongly support the idea that blinks interfere with the saccade premotor circuit, presumably upstream from the neural eye-position integrator. They also indicated that a neural mechanism, rather than passive elastic restoring forces within the oculomotor plant, underlies the compensatory behavior. The tight latency coupling between saccades and blinks is consistent with an inhibition of omnipause neurons by the blink system, suggesting that the observed changes in saccade kinematics arise elsewhere in the saccadic premotor system.     

Discharge dynamics of oculomotor neural integrator neurons during conjugate and disjunctive saccades and fixation

Burst-tonic (BT) neurons in the prepositus hypoglossi and adjacent medial vestibular nuclei are important elements of the neural integrator for horizontal eye movements. While the metrics of their discharges have been studied during conjugate saccades (where the eyes rotate with similar dynamics), their role during disjunctive saccades (where the eyes rotate with markedly different dynamics to account for differences in depths between saccadic targets) remains completely unexplored. In this report, we provide the first detailed quantification of the discharge dynamics of BT neurons during conjugate saccades, disjunctive saccades, and disjunctive fixation. We show that these neurons carry both significant eye position and eye velocity-related signals during conjugate saccades as well as smaller, yet important, "slide" and eye acceleration terms. Further, we demonstrate that a majority of BT neurons, during disjunctive fixation and disjunctive saccades, preferentially encode the position and the velocity of a single eye; only few BT neurons equally encode the movements of both eyes (i.e., have conjugate sensitivities). We argue that BT neurons in the nucleus prepositus hypoglossi/medial vestibular nucleus play an important role in the generation of unequal eye movements during disjunctive saccades, and carry appropriate information to shape the saccadic discharges of the abducens nucleus neurons to which they project.     

Evidence for synergy between saccades and smooth pursuit during transient target disappearance

Visual tracking of moving objects requires prediction to compensate for visual delays and minimize mismatches between eye and target position and velocity. In everyday life, objects often disappear behind an occluder, and prediction is required to align eye and target at reappearance. Earlier studies investigating eye motion during target blanking showed that eye velocity first decayed after disappearance but was sustained or often recovered in a predictive way. Furthermore, saccades were directed toward the unseen target trajectory and therefore appeared to correct for position errors resulting from eye velocity decay. To investigate the synergy between smooth and saccadic eye movements, this study used a target blanking paradigm where both position and velocity of the target at reappearance could vary independently but were presented repeatedly to facilitate prediction. We found that eye velocity at target reappearance was only influenced by expected target velocity, whereas saccades responded to the expected change of target position at reappearance. Moreover, subjects exhibited on-line adaptation, on a trial-by-trial basis, between smooth and saccadic components; i.e., saccades compensated for variability of smooth eye displacement during the blanking period such that gaze at target reappearance was independent of the level of smooth eye displacement. We suggest these results indicate that information arising from efference copies of saccadic and smooth pursuit systems are combined with the goal of adjusting eye position at target reappearance. Based on prior experimental evidence, we hypothesize that this spatial remapping is carried out through interactions between a number of identified neurophysiological structures.     

Interaction between smooth anticipation and saccades during ocular orientation in darkness

A saccade triggered during sustained smooth pursuit is programmed using retinal information about the relative position and velocity of the target with respect to the eye. Thus the smooth pursuit and saccadic systems are coordinated by using common retinal inputs. Yet, in the absence of retinal information about the relative motion of the eye with respect to the target, the question arises whether the smooth and saccadic systems are still able to be coordinated possibly by using extraretinal information to account for the saccadic and smooth eye movements. To address this question, we flashed a target during smooth anticipatory eye movements in darkness, and the subjects were asked to orient their visual axis to the remembered location of the flash. We observed multiple orientation saccades (typically 2-3) toward the memorized location of the flash. The first orienting saccade was programmed using only the position error at the moment of the flash, and the smooth eye movement was ignored. However, subsequent saccades executed in darkness compensated gradually for the smooth eye displacement (mean compensation congruent with 70%). This behavior revealed a 400-ms delay in the time course of orientation for the compensation of the ongoing smooth eye displacement. We conclude that extraretinal information about the smooth motor command is available to the saccadic system in the absence of visual input. There is a 400-ms delay for smooth movement integration, saccade programming and execution.     

Adaptation of catch-up saccades during the initiation of smooth pursuit eye movements

Reduction of retinal speed and alignment of the line of sight are believed to be the respective primary functions of smooth pursuit and saccadic eye movements. As the eye muscles strength can change in the short-term, continuous adjustments of motor signals are required to achieve constant accuracy. While adaptation of saccade amplitude to systematic position errors has been extensively studied, we know less about the adaptive response to position errors during smooth pursuit initiation, when target motion has to be taken into account to program saccades, and when position errors at the saccade endpoint could also be corrected by increasing pursuit velocity. To study short-term adaptation (250 adaptation trials) of tracking eye movements, we introduced a position error during the first catch-up saccade made during the initiation of smooth pursuit—in a ramp-step-ramp paradigm. The target position was either shifted in the direction of the horizontally moving target (forward step), against it (backward step) or orthogonally to it (vertical step). Results indicate adaptation of catch-up saccade amplitude to back and forward steps. With vertical steps, saccades became oblique, by an inflexion of the early or late saccade trajectory. With a similar time course, post-saccadic pursuit velocity was increased in the step direction, adding further evidence that under some conditions pursuit and saccades can act synergistically to reduce position errors.     

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.     

Cortical potentials during the gap prior to express saccades and fast regular saccades

When a temporal gap is introduced between the offset of the central fixation point and the appearance of a new target, saccadic reaction time is reduced (gap effect) and a special population of extremely fast saccades occurs (express saccades). It has been hypothesized that the gap triggers a readiness signal, which is responsible for the reduced saccadic reaction times. Here we recorded event-related potentials during the gap to in vestigate the central processes associated with the gener ation of fast regular saccades and express saccades. Prior to the execution of fast regular saccades, subjects pro duced a slow negative shift, with a maximum at frontal and central channels that started 40 ms after fixation offset. This widespread negativity is similar to a readiness potential. Anticipatory saccades were preceded by an increased frontal and parietal negativity. Prior to express saccades, a frontal negativity was observed, which started 135 ms after the disappearance of the fixation point. It is assumed that the frontal negativity prior to express saccades corresponds to the fixation-disengagement dis charge described in the frontal eye field of monkeys. Therefore, we hypothesize that fast regular saccades are the result of an increased readiness signal, while express saccades are the result of specific preparatory processes.     

Comparison of memory- and visually guided saccades using event-related fMRI

Previous functional imaging studies have shown an increased hemodynamic signal in several cortical areas when subjects perform memory-guided saccades than that when they perform visually guided saccades using blocked trial designs. It is unknown, however, whether this difference results from sensory processes associated with stimulus presentation, from processes occurring during the delay period before saccade generation, or from an increased motor signal for memory-guided saccades. We conducted fMRI using an event-related paradigm that separated stimulus-related, delay-related, and saccade-related activity. Subjects initially fixated a central cross, whose color indicated whether the trial was a memory- or a visually guided trial. A peripheral stimulus was then flashed at one of 4 possible locations. On memory-guided trials, subjects had to remember this location for the subsequent saccade, whereas the stimulus was a distractor on visually guided trials. Fixation cross disappearance after a delay period was the signal either to generate a memory-guided saccade or to look at a visual stimulus that was flashed on visually guided trials. We found slightly greater stimulus-related activation for visually guided trials in 3 right prefrontal regions and right rostral intraparietal sulcus (IPS). Memory-guided trials evoked greater delay-related activity in right posterior inferior frontal gyrus, right medial frontal eye field, bilateral supplementary eye field, right rostral IPS, and right ventral IPS but not in middle frontal gyrus. Right precentral gyrus and right rostral IPS exhibited greater saccade-related activation on memory-guided trials. We conclude that activation differences revealed by previous blocked experiments have different sources in different areas and that cortical saccade regions exhibit delay-related activation differences.     

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.     

Age-related differences of saccade induced cortical activation

Recent functional MRI (fMRI) studies have described the increased task-related brain activation in older subjects during motor, cognitive and perceptual tasks. Age affects the ability to control saccadic eye movements. To investigate the age-related changes of oculomotor control, we studied the representation of saccades in 11 young (median age 29 years) and 11 older (median age 62 years) healthy individuals using fMRI. Brain activation was measured during a visually guided prosaccade trial. Differences in activation between rest and saccades as well as between younger and older subjects were assessed with statistical parametric mapping (SPM). In both age groups, activation of a frontoparietal network was observed. Older subjects showed increased activation compared to younger subjects with overactivation in bilateral parietal eye fields, the right frontal eye field, as well as in the right extrastriate cortex. We conclude that older adults increase activation in an extended oculomotor and visual network to maintain performance during simple prosaccades. This observation also underlines the importance of using appropriate age-matched control groups in fMRI studies after brain lesions.