Discharge patterns of levator palpebrae superioris motoneurons during vertical lid and eye movements in the monkey.

1. We recorded single-unit activity in the caudal central nucleus (CCN) of the oculomotor complex in monkeys trained to make vertical saccadic, smooth-pursuit, and fixation eye movements. We confirmed that our recordings were from motoneurons innervating the upper lid, because small lesions placed at the sites of responsive units were recovered among neurons labeled by horseradish peroxidase (HRP) injections into the levator palpebrae superioris muscle. 2. For fixations above a threshold lid position, levator motoneurons discharged at a steady rate, which increased linearly with upward lid position. The average position sensitivity during fixation was 2.9 spikes/s per deg, and the average lid motoneuron was recruited into steady firing when the eye was looking 10 degrees down. 3. During upward saccades, levator motoneurons discharged a burst of spikes that began, on average, 7.3 ms before the lid movement if the saccade started from a straight-ahead position; the lead time decreased considerably as the initial eye and lid positions shifted downward. The firing rate usually reached its peak (130-280 spikes/s) at the very onset of the burst and declined gradually during the course of the saccade. The steady rate associated with the new fixation position was reached about halfway during the saccade. All units exhibited a pause in firing during the initial half of large downward saccades; during small saccades, the pause was inconspicuous or absent. 4. During vertical sinusoidal smooth pursuit, levator motoneurons exhibited a sinusoidal modulation in firing rate, which led eye position by an average of 23 degrees at 0.3 Hz. The average velocity sensitivity calculated from such data was 0.63 spikes/s per deg/s. 5. Although they exhibit a number of qualitative similarities, the discharge patterns of levator motoneurons and superior rectus motoneurons differ in several respects. First, during a blink, when the lid undergoes a large depression but the eye exhibits only a brief transient displacement, levator motoneurons cease firing completely, whereas superior rectus motoneurons continue to discharge. Second, for all types of coordinated lid and eye movements, levator motoneurons discharge at lower firing rates than do superior rectus motoneurons. Third, during saccades, levator motoneurons have less conspicuous and shorter-lasting bursts and pauses than do motoneurons involved in rotating the eye. 6. During upward gaze, the qualitative similarity of their burst-tonic discharge patterns suggests that levator and superior rectus motoneurons receive input signals that originate from a common source, but that the signals are processed differently to deal with the different loads facing these muscles.(ABSTRACT TRUNCATED AT 400 WORDS)     

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.     

Bilateral lesions of the medial longitudinal fasciculus in monkeys: Effects on the horizontal and vertical components of voluntary and vestibular induced eye movements

Summary Bilateral transections across the brainstem interrupted the medial longitudinal fasciculus (MLF) in three monkeys trained to make eye movements while subjected to horizontal or vertical angular accelerations. Eye movements measured before and after the lesion revealed deficits in both voluntary and vestibular compensatory eye movements; the deficits differed in the horizontal and vertical directions. Vertical saccades in both directions were normal but eccentric positions of fixation could not be maintained; a drift toward the midline followed by a corrective saccade produced vertical fixation nystagmus. Furthermore, the vertical vestibuloocular reflex (VOR) was abolished and vertical smooth pursuit was impaired. Along the horizontal meridian, adduction across the midline could not be achieved during either saccades, smooth pursuit, or the VOR. Temporal saccades were normal whereas nasal saccades were considerably slowed. If the eye was not required to cross the midline, the phase shift during the VOR was within 15 deg of normal in each eye. The gain of the VOR was reduced to about 0.4 immediately after the lesion, but recovered within one month. These findings suggest that the MLF transmits quite different kinds of information to horizontal and vertical oculomotoneurons and that deficits in vertical eye movements may be a sensitive indicator of anterior internuclear ophthalmoplegia.     

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.     

Directional asymmetry in vertical smooth-pursuit and cancellation of the vertical vestibulo-ocular reflex in juvenile monkeys

Young primates exhibit asymmetric eye movements during vertical smooth-pursuit across a textured background such that upward pursuit has low velocity and requires many catch-up saccades. The asymmetric eye movements cannot be explained by the un-suppressed optokinetic reflex resulting from background visual motion across the retina during pursuit, suggesting that the asymmetry reflects most probably, a low gain in upward eye commands (Kasahara et al. in Exp Brain Res 171:306–321, 2006). In this study, we examined (1) whether there are intrinsic differences in the upward and downward pursuit capabilities and (2) how the difficulty in upward pursuit is correlated with the ability of vertical VOR cancellation. Three juvenile macaques that had initially been trained only for horizontal (but not vertical) pursuit were trained for sinusoidal pursuit in the absence of a textured background. In 2 of the 3 macaques, there was a clear asymmetry between upward and downward pursuit gains and in the time course of initial gain increase. In the third macaque, downward pursuit gain was also low. It did not show consistent asymmetry during the initial 2 weeks of training. However, it also exhibited a significant asymmetry after 4 months of training, similar to the other two monkeys. After 6 months of training, these two monkeys (but not the third) still exhibited asymmetry. As target frequency increased in these two monkeys, mean upward eye velocity saturated at ∼15°/s, whereas horizontal and downward eye velocity increased up to ∼40°/s. During cancellation of the VOR induced by upward whole body rotation, downward eye velocity of the residual VOR increased as the stimulus frequency increased. Gain of the residual VOR during upward rotation was significantly higher than that during horizontal and downward rotation. The time course of residual VOR induced by vertical whole body step-rotation during VOR cancellation was predicted by addition of eye velocity during pursuit and VOR x1. These results support our view that the directional asymmetry reflects the difference in the organization of the cerebellar floccular region for upward and downward directions and the preeminent role of pursuit in VOR cancellation.     

Analysis of a naturally occurring asymmetry in vertical smooth pursuit eye movements in a monkey.

1. We have investigated the mechanism of a directional deficit in vertical pursuit eye movements in a monkey that was unable to match upward eye speed to target speed but that had pursuit within the normal range for downward or horizontal target motion. Except for a difference in the axis of deficient pursuit, the symptoms in this monkey were similar to those seen with lesions in the frontal or parietal lobes of the cerebral cortex in humans or monkeys. Our evaluation of vertical pursuit in this monkey suggests a new interpretation for the role of the frontal and parietal lobes in pursuit. 2. The up/down asymmetry was most pronounced for target motion at speeds greater than or equal to 2 degree/s. For target motion at 15 or 30 degree/s, upward step-ramp target motion evoked a brief upward smooth eye acceleration, followed by tracking that consisted largely of saccades. Downward step-ramp target motion evoked a prolonged smooth eye acceleration, followed by smooth, accurate tracking. 3. Varying the amplitude of the target step revealed that the deficit was similar for targets moving across all locations of the visual field. Eye acceleration in the interval 0-20 ms after the onset of pursuit was independent of initial target position and was symmetrical for upward and downward target motion. Eye acceleration in the interval 60-80 ms after the onset of pursuit showed a large asymmetry. For upward target motion, eye acceleration in this interval was small and did not depend on initial target position. For downward target motion, eye acceleration depended strongly on initial target position and was large when the target started close to the position of fixation. 4. We next attempted to understand the mechanism of the up/down asymmetry by evaluating the monkey's vertical motion processing and vertical eye movements under a variety of tracking conditions. For spot targets, the response to upward image motion was similar to that in normal monkeys if the image motion was presented during downward pursuit. In addition, the monkey with deficient upward pursuit was able to use upward image motion to make accurate saccades to moving targets. We conclude that the visual processing of upward image motion was normal in this monkey and that an asymmetry in visual motion processing could not account for the deficit in his upward pursuit. 5. Upward smooth eye acceleration was normal when the spot target was moved together with a large textured pattern.(ABSTRACT TRUNCATED AT 400 WORDS)     

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.     

Characteristics of simian adaptation fields produced by behavioral changes in saccade size and direction.

The gain of saccadic eye movements can be altered gradually by moving targets either forward or backward during targeting saccades. If the gain of saccades to targets of only one size is adapted, the gain change generalizes or transfers only to saccades with similar vectors. In this study, we examined the spatial extent of such saccadic size adaptation, i.e., the gain adaptation field. We also attempted to adapt saccade direction by moving the target orthogonally during the targeting saccade to document the extent of a direction or cross-axis adaptation field. After adaptive gain decreases of horizontal saccades to 15 degrees target steps, >82% of the gain reduction transferred to saccades to 25 degrees horizontal target steps but only approximately 30% transferred to saccades to 5 degrees steps. For the horizontal component of oblique saccades to target steps with 15 degrees horizontal components and 10 degrees upward or downward vertical components, the transfer was similar at 51 and 60%, respectively. Thus the gain decrease adaptation field was quite asymmetric in the horizontal dimension but symmetric in the vertical dimension. Although gain increase adaptation produced a smaller gain change (13% increase for a 30% forward adapting target step) than did gain decrease adaptation (20% decrease for a 30% backward adapting target step), the spatial extent of gain transfer was quite similar. In particular, the gain increase adaptation field displayed asymmetry in the horizontal dimension (58% transfer to 25 degrees saccades but only 32% transfer to 5 degrees saccades) and symmetry in the vertical direction (50% transfer to the horizontal component of 10 degrees upward and 40% transfer to 10 degrees downward oblique saccades). When a 5 degrees vertical target movement was made to occur during a saccade to a horizontal 10 degrees target step, a vertical component gradually appeared in saccades to horizontal targets. More than 88% of the cross-axis change in the vertical component produced in 10 degrees saccades transferred to 20 degrees saccades but only 12% transferred to 4 degrees saccades. The transfer was similar to the vertical component of oblique saccades to target steps with either 10 degrees upward (46%) or 10 degrees downward (46%) vertical components. Therefore both gain and cross-axis adaptation fields have similar spatial profiles. These profiles resemble those of movement fields of neurons in the frontal eye fields and superior colliculus. How those structures might participate in the adaptation process is considered in the DISCUSSION.     

Role of retinal slip in the prediction of target motion during smooth and saccadic pursuit

Visual tracking of moving targets requires the combination of smooth pursuit eye movements with catch-up saccades. In primates, catch-up saccades usually take place only during pursuit initiation because pursuit gain is close to unity. This contrasts with the lower and more variable gain of smooth pursuit in cats, where smooth eye movements are intermingled with catch-up saccades during steady-state pursuit. In this paper, we studied in detail the role of retinal slip in the prediction of target motion during smooth and saccadic pursuit in the cat. We found that the typical pattern of pursuit in the cat was a combination of smooth eye movements with saccades. During smooth pursuit initiation, there was a correlation between peak eye acceleration and target velocity. During pursuit maintenance, eye velocity oscillated at approximately 3 Hz around a steady-state value. The average gain of smooth pursuit was approximately 0.5. Trained cats were able to continue pursuing in the absence of a visible target, suggesting a role of the prediction of future target motion in this species. The analysis of catch-up saccades showed that the smooth-pursuit motor command is added to the saccadic command during catch-up saccades and that both position error and retinal slip are taken into account in their programming. The influence of retinal slip on catch-up saccades showed that prediction about future target motion is used in the programming of catch-up saccades. Altogether, these results suggest that pursuit systems in primates and cats are qualitatively similar, with a lower average gain in the cat and that prediction affects both saccades and smooth eye movements during pursuit.     

Saccadic and smooth pursuit eye movements: computational modeling of a common inhibitory mechanism in brainstem

The oculomotor system coordinates different types of eye movements in order to orient the visual axis, including saccade and smooth pursuit,. It was traditionally thought that the premotor pathways for these different eye movements are largely separate. In particular, a group of midline cells in the pons called omnipause neurons were considered to be part of only the saccadic system. Recent experimental findings have shown activity modulation of these brainstem premotor neurons during both kinds of eye movements. In this study, we propose a new computational model of the brainstem circuitry underlying the generation of saccades and smooth pursuit eye movements. Similar models have been developed earlier, but mainly looking at pure saccades. Here, we integrated recent neurophysiological findings on omnipause neuron activity during smooth pursuit. Our computational model can mimic some new experimental findings as the similarity of "eye velocity profile" with "omnipause neuron pattern of activity" in pursuit movement. We showed that pursuit neuron activity is augmented during catch-up saccades; this increment depends on the initial pursuit velocity in catch-up saccade onset. We conclude that saccadic and pursuit components of catch-up saccades are added to each other nonlinearly.     

Further evidence for selective difficulty of upward eye pursuit in juvenile monkeys: effects of optokinetic stimulation, static roll tilt, and active head movements

The smooth-pursuit system moves the eyes in space accurately to track slowly moving objects of interest despite visual inputs from the moving background and/or vestibular inputs during head movements. Recently, our laboratory has shown that young primates exhibit asymmetric eye movements during vertical pursuit across a textured background; upward eye velocity gain is reduced. To further understand the nature of this asymmetry, we performed three series of experiments in young monkeys. In Experiment 1, we examined whether this asymmetry was due to an un-compensated downward optokinetic reflex induced by the textured background as it moves across the retina in the opposite direction of the pursuit eye movements. For this, we examined the monkeys’ ability to fixate a stationary spot in space during movement of the textured background and compared it with vertical pursuit across the stationary textured background. We also examined gains of optokinetic eye movements induced by downward motion of the textured background during upward pursuit. In both task conditions, gains of downward eye velocity induced by the textured background were too small to explain reduced upward eye velocity gains. In Experiment 2, we examined whether the frame of reference for low-velocity, upward pursuit was orbital or earth vertical. To test this, we first applied static tilt in the roll plane until the animals were nearly positioned on their side in order to dissociate vertical or horizontal eye movements in the orbit from those in space. Deficits were observed for upward pursuit in the orbit but not in space. In Experiment 3, we tested whether asymmetry was observed during head-free pursuit that requires coordination between eye and head movements. Asymmetry in vertical eye velocity gains was still observed during head-free pursuit although it was not observed in vertical head velocity. These results, taken together, suggest that the asymmetric eye movements during vertical pursuit are specific for upward, primarily eye pursuit in the orbit.     

Enhancement of the vestibulo-ocular reflex by prior eye movements.

We investigated the effect of visually mediated eye movements made before velocity-step horizontal head rotations in eleven normal human subjects. When subjects viewed a stationary target before and during head rotation, gaze velocity was initially perturbed by approximately 20% of head velocity; gaze velocity subsequently declined to zero within approximately 300 ms of the stimulus onset. We used a curve-fitting procedure to estimate the dynamic course of the gain throughout the compensatory response to head rotation. This analysis indicated that the median initial gain of compensatory eye movements (mainly because of the vestibulo-ocular reflex, VOR) was 0. 8 and subsequently increased to 1.0 after a median interval of 320 ms. When subjects attempted to fixate the remembered location of the target in darkness, the initial perturbation of gaze was similar to during fixation of a visible target (median initial VOR gain 0.8); however, the period during which the gain increased toward 1.0 was >10 times longer than that during visual fixation. When subjects performed horizontal smooth-pursuit eye movements that ended (i.e., 0 gaze velocity) just before the head rotation, the gaze velocity perturbation at the onset of head rotation was absent or small. The initial gain of the VOR had been significantly increased by the prior pursuit movements for all subjects (P < 0.05; mean increase of 11%). In four subjects, we determined that horizontal saccades and smooth tracking of a head-fixed target (VOR cancellation with eye stationary in the orbit) also increased the initial VOR gain (by a mean of 13%) during subsequent head rotations. However, after vertical saccades or smooth pursuit, the initial gaze perturbation caused by a horizontal head rotation was similar to that which occurred after fixation of a stationary target. We conclude that the initial gain of the VOR during a sudden horizontal head rotation is increased by prior horizontal, but not vertical, visually mediated gaze shifts. We postulate that this "priming" effect of a prior gaze shift on the gain of the VOR occurs at the level of the velocity inputs to the neural integrator subserving horizontal eye movements, where gaze-shifting commands and vestibular signals converge.     

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.     

Directional asymmetry in smooth ocular tracking in the presence of visual background in young and adult primates

The smooth pursuit system moves the eyes in space accurately while compensating for visual inputs from the moving background and/or vestibular inputs during head movements. To understand the mechanisms underlying such interactions, we examined the influence of a stationary textured visual background on smooth pursuit tracking and compared the results in young and adult humans and monkeys. Six humans (three children, three adults) and six macaque monkeys (five young, one adult) were used. Human eye movements were recorded using infrared oculography and evoked by a sinusoidally moving target presented on a computer monitor. Scleral search coils were used for monkeys while they tracked a target presented on a tangent screen. The target moved in a sinusoidal or trapezoidal fashion with or without whole body rotation in the same plane. Two kinds of backgrounds, homogeneous and stationary textured, were used. Eye velocity gains (eye velocity/target velocity) were calculated in each condition to compare the influence of the textured background. Children showed asymmetric eye movements during vertical pursuit across the textured (but not the homogeneous) background; upward pursuit was severely impaired, and consisted mostly of catch-up saccades. In contrast, adults showed no asymmetry during pursuit across the different backgrounds. Monkeys behaved similarly; only slight effects were observed with the textured background in a mature monkey, whereas upward pursuit was severely impaired in young monkeys. In addition, VOR cancellation was severely impaired during upward eye and head movements, resulting in residual downward VOR in young monkeys. From these results, we conclude that the directional asymmetry observed in young primates may reflect a different neural organization of the vertical, particularly upward, pursuit system in the face of conflicting visual and vestibular inputs that can be associated with pursuit eye movements. Apparently, proper compensation matures later. Electronic Publication     

Differential effects of blinks on horizontal saccade and smooth pursuit initiation in humans

Blinks executed during eye movements affect kinetic eye movement parameters, e.g., peak velocity of saccades is decreased, their duration is increased, but their amplitude is not altered. This effect is mainly explained by the decreased activity of premotor neurons in the brainstem: omni-pause neurons (OPN) in the nucleus raphe interpositus. Previous studies examined the immediate effect of blinks directly on eye movements but not their effect when they are elicited several hundred milliseconds before the eye movements. In order to address this question we tested blinks elicited before the target onset of saccades and pursuit and compared the results to the gap effect: if a fixation light is extinguished for several hundred milliseconds, the reaction time (latency) for subsequent saccades or smooth pursuit eye movements is decreased. Monocular eye and lid movements were recorded in nine healthy subjects using the scleral search-coil system. Laser stimuli were front-projected onto a tangent screen in front of the subjects. Horizontal step-ramp smooth pursuit of 20 deg/s was elicited in one session, or 5 deg horizontal visually guided saccades in another experimental session. In one-third of the trials (smooth pursuit or saccades) the fixation light was extinguished for 200 ms before stimulus onset (gap condition), and in another third of the trials reflexive blinks were elicited by a short airpuff before the stimulus onset (blink condition). The last third of the trials served as controls (control condition). Stimulus direction and the three conditions were randomized for saccades and smooth pursuit separately. The latency of the step-ramp smooth pursuit in the blink condition was found to be decreased by 10 ms, which was less than in the gap condition (38 ms). However, the initial acceleration and steady-state velocity of smooth pursuit did not differ in the three conditions. In contrast, the latency of the saccades in the gap condition was decreased by 39 ms, but not in the blink condition. Saccade amplitude, peak velocity, and duration were not different in the three conditions. There was also no difference in blink amplitude and duration of pupil occlusion in the blink condition, neither in saccades nor in smooth pursuit. The latency reduction of smooth pursuit, but not of saccades, may neither be explained by the brief pupil occlusion nor by visual suppression, warning signals, or the startle response. Whether the effects are caused by the influence of blinks on OPNs or other premotor structures remains to be tested.     

Eye movement disorders after frontal eye field lesions in humans

Eye movements were recorded electro-oculographically in three patients with a small ischemic lesion affecting the left frontal eye field (FEF) and in 12 control subjects. Reflexive visually guided saccades (gap and overlap tasks), antisaccades, predictive saccades, memory-guided saccades, smooth pursuit and optokinetic nystagmus (OKN) were studied in the three patients. Staircase saccades and double step saccades were also studied in one of the three patients. For both leftward and rightward saccades, latency in the overlap task (but not in the gap task) and that of correct antisaccades and of memory-guided saccades was significantly increased, compared with the results of controls. There was a significant decrease in the amplitude gain of all rightward saccades programmed using retinotopic coordinates (gap and overlap tasks, predictive and memory-guided saccades), whereas the amplitude gain of corresponding leftward saccades was preserved. Such an asymmetry between leftward and rightward saccades was significant. In the staircase paradigm as well as for the first saccade in the double step paradigm (with the use of retinotopic coordinates in both cases), the amplitude gain of rightward saccades was also significantly lower than that of leftward saccades. Moreover, in the double step paradigm, the amplitude gain of the first rightward saccade was significantly lower than that of the second rightward saccade (programmed using extraretinal signals), which was preserved. The percentage of errors in the antisaccade task did not differ significantly from that of normal subjects. In the predictive saccade paradigm, the percentage of predictive rightward saccades was significantly decreased. The left smooth pursuit gain for all tested velocities, the right smooth pursuit gain for higher velocities, and the left OKN gain were significantly decreased. The results show, for the first time in humans, that the FEF plays an important role in (1) the disengagement from central fixation, (2) the control of contralateral saccades programmed using retinotopic coordinates, (3) saccade prediction and (4) the control of smooth pursuit and OKN, mainly ipsilaterally. In contrast, the left FEF did not appear to be crucial for the control of the only type of saccades programmed using extraretinal signals studied here.     

Effects of reversible inactivation of the primate mesencephalic reticular formation. II. Hypometric vertical saccades

Electrical microstimulation and single-unit recording have suggested that a group of long-lead burst neurons (LLBNs) in the mesencephalic reticular formation (MRF) just lateral to the interstitial nucleus of Cajal (INC) (the peri-INC MRF, piMRF) may play a role in the generation of vertical rapid eye movements. Inactivation of this region with muscimol (a GABA(A) agonist) rapidly produced vertical saccade hypometria (6 injections). In three of six injections, there was a marked reduction in the velocity of vertical saccades out of proportion to saccade amplitude (i.e., saccades fell below the main sequence). This was associated with a moderate increase in saccade duration. Inadvertent inactivation of the INC could not account for these observations because vertical, postsaccadic drift was not observed. Similarly, pure downward saccade hypometria, the hallmark of rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF) inactivation, was always preceded by loss of upward saccades in our experiments. We also found a downward and ipsiversive displacement of initial eye position and evidence of a contraversive head tilt following piMRF injections. Saccade latency was shorter after two of six injections. Simulation of a local feedback model provided three possible explanations for vertical saccade hypometria: 1) a shift in the input to the model to request smaller saccades, 2) a reduction of LLBN input to the vertical saccade medium lead burst neurons (MLBNs), or 3) an increase in the gain of the feedback pathway. However, when the second hypothesis was coupled to a shortened duration of the saccade trigger (i.e., the discharge of the omnipause neurons), the physiological observations of piMRF inactivation could be replicated. This suggested that muscimol had targeted structures that provided both long-lead burst activity to the MLBNs in the riMLF and were critical for reactivation of the omnipause neurons. Evidence of markedly reduced vertical saccade amplitude, curved saccade trajectories, increased saccade duration, and saccades that fall below the amplitude/velocity main sequence in these monkeys closely parallels the oculomotor findings of patients with progressive supranuclear palsy (PSP).     

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.     

A quantitative analysis of the correlations between eye movements and neural activity in the pretectum

The study of the saccadic system has focused mainly on neurons active before the beginning of saccades, in order to determine their contribution in movement planning and execution. However, most oculomotor structures contain also neurons whose activity starts only after the onset of saccades, the maximum of their activity sometimes occurring near saccade end. Their characteristics are still largely unknown. We investigated pretectal neurons with saccade-related activity in the alert cat during eye movements towards a moving target. They emitted a high-frequency burst of action potentials after the onset of saccades, irrespective of their direction, and will be referred to as "pretectal saccade-related neurons". The delay between saccade onset and cell activity varied from 17 to 66 ms on average. We found that burst parameters were correlated with the parameters of saccades; the peak eye velocity was correlated with the peak of the spike density function, the saccade amplitude with the number of spikes in the burst, and burst duration increased with saccade duration. The activity of six pretectal saccade-related neurons was studied during smooth pursuit at different velocities. A correlation was found between smooth pursuit velocity and mean firing rate. A minority of these neurons (2/6) were also visually responsive. Their visual activity was proportional to the difference between eye and target velocity during smooth pursuit (retinal slip). These results indicate that the activity of pretectal saccade-related neurons is correlated with the characteristics of eye movements. This finding is in agreement with the known anatomical projections from premotor regions of the saccadic system to the pretectum.     

Direction of saccadic and smooth eye movements induced by electrical stimulation of the human frontal eye field: effect of orbital position

The present study reports on the direction of saccadic and smooth eye movements, which were induced electrically from the human dorsolateral frontal cortex including the human frontal eye field (FEF). The eye position prior to stimulation was varied in order to examine its effect on induced eye movement direction. The five patients of the study underwent invasive presurgical evaluation for pharmacoresistant epilepsy. The present data show that the direction of electrically induced eye movements was always contralateral and either horizontal or oblique upward if the eye started from the primary position. The elicited direction was changed if the eyes started from an eccentric position. The frequency of oblique eye movements was increased and oblique downward responses were induced, which were not observed if the eye started from the primary position. This was found for saccades and, especially, for smooth eye movements. Head movements, which were almost exclusively induced with saccades, did not depend on initial orbital position. Four conclusions can be drawn. Firstly, saccades and smooth eye movements induced from the human dorsolateral cortex including the human FEF have the same directional bias. Secondly, the frequent upward responses and the absence of downward responses induced from the primary position suggests either a more numerous or a more superficial representation of neurons that code for the former direction. Thirdly, at some sites the direction of saccades and smooth eye movements varies depending on the initial orbital position. Since these directional changes were observed without changes in eye-head coordination, our data suggest that stimulation of the FEF might evoke goal-directed saccades or interferes with a resettable saccade integrator. Fourthly, human studies that investigate eye movements induced from the lateral frontal cortex need to control eye position prior to stimulation. Electronic Publication