Modification of saccadic eye movements by GABA-related substances. I. Effect of muscimol and bicuculline in monkey superior colliculus

Our previous observations led to the hypothesis that cells in the substantia nigra pars reticulata (SNr) tonically inhibit saccade-related cells in the intermediate layers of the superior colliculus (SC). Before saccades to visual or remembered targets, cells in SNr briefly reduce that inhibition, allowing a burst of spikes of SC cells that, in turn, leads to the initiation of a saccadic eye movement. Since this inhibition is likely to be mediated by gamma-aminobutyric acid (GABA), we tested this hypothesis by injecting a GABA agonist (muscimol) or a GABA antagonist (bicuculline) into the superior colliculus and measured the effects on saccadic eye movements made to visual or remembered targets. An injection of muscimol selectively suppressed saccades to the movement field of the cells near the injection site. The affected area expanded over time, thus suggesting the diffusion of muscimol in the SC; the area never included the other hemifield, suggesting that the diffusion was limited to one SC. One of the monkeys became unable to make any saccades to the affected area. Saccades to visual targets following injection of muscimol had longer latency and slightly shorter amplitudes that were corrected by subsequent saccades. The most striking change was a decrease in the peak velocity of the saccade, frequently to less than half the preinjection value. Saccades to remembered targets following injection of muscimol also showed an increase in latency and decrease in velocity, but in addition, showed a striking decrease in the accuracy of the saccades. The trajectories of saccades became distorted as if they were deflected away from the affected area. After muscimol injection, the area over which spontaneous eye movements were made shifted toward the side ipsilateral to the injection. Saccades toward the contralateral side were less frequent and slower. In nystagmus, which developed later, the slow phase was toward the contralateral side. In contrast to muscimol, injection of bicuculline facilitated the initiation of saccades. Injection was followed almost immediately by stereotyped and apparently irrepressible saccades made toward the center of the movement field of the SC cells at the injection site. The monkeys became unable to fixate during the tasks; the fixation was interrupted by saccadic jerks made to the affected area of the visual field and then back to the fixation point.(ABSTRACT TRUNCATED AT 400 WORDS)     

Modification of saccadic eye movements by GABA-related substances. II. Effects of muscimol in monkey substantia nigra pars reticulata

The preceding study (21) showed that a gamma-aminobutyric acid (GABA) agonist or antagonist injected into the superior colliculus (SC) disrupted saccadic eye movements. The purpose of the present experiments was to determine whether this result was due to altering the inhibitory input to the SC from the substantia nigra pars reticulata (SNr). SNr cells are themselves inhibited by GABA. Injection of muscimol, a GABA agonist, into the SNr should increase the inhibition acting on SNr cells and should reduce the inhibition acting on the SC. If the effects of GABA inhibition in the SC results from terminals originating in the SNr, muscimol in the SNr should act like bicuculline in the SC. Muscimol in the SNr has the same general effect as bicuculline in the SC. The monkey made irrepressible saccades toward the contralateral visual field where cells in the SNr at the injection site had their visual or movement field. During visual fixation saccadic jerks occurred, interspersed with spontaneous saccades, instead of saccades to visual targets or to remembered targets. Saccades to remembered targets were more vulnerable to these saccadic intrusions than were saccades to visual targets. Since muscimol in the SNr acts like bicuculline in the SC, we conclude that a substantial fraction of GABA-mediated inhibitory inputs in the SC originates from the SNr. These experiments, in conjunction with previous experiments, show that the SNr exerts a tonic inhibition on saccade-related cells in SC and that this inhibition is mediated by GABA. The role of the SNr in initiation of saccades to remembered targets is particularly important since these saccades are more severely disrupted by muscimol in the SNr as well as in the SC. We suggest that both of these conclusions about eye movement might apply to skeletal movements as well. First, the basal ganglia contribute to the initiation of movement by a release of the target structure from tonic inhibition. Second, this mechanism is particularly critical of the movements based on stored or remembered signals that are not currently available as incoming sensory inputs.     

Activation and inactivation of rostral superior colliculus neurons during smooth-pursuit eye movements in monkeys

Neurons in the intermediate and deep layers of the rostral superior colliculus (SC) of monkeys are active during attentive fixation, small saccades, and smooth-pursuit eye movements. Alterations of SC activity have been shown to alter saccades and fixation, but similar manipulations have not been shown to influence smooth-pursuit eye movements. Therefore we both activated (electrical stimulation) and inactivated (reversible chemical injection) rostral SC neurons to establish a causal role for the activity of these neurons in smooth pursuit. First, we stimulated the rostral SC during pursuit initiation as well as pursuit maintenance. For pursuit initiation, stimulation of the rostral SC suppressed pursuit to ipsiversive moving targets primarily and had modest effects on contraversive pursuit. The effect of stimulation on pursuit varied with the location of the stimulation with the most rostral sites producing the most effective inhibition of ipsiversive pursuit. Stimulation was more effective on higher pursuit speeds than on lower and did not evoke smooth-pursuit eye movements during fixation. As with the effects on pursuit initiation, ipsiversive maintained pursuit was suppressed, whereas contraversive pursuit was less affected. The stimulation effect on smooth pursuit did not result from a generalized inhibition because the suppression of smooth pursuit was greater than the suppression of smooth eye movements evoked by head rotations (vestibular-ocular reflex). Nor was the stimulation effect due to the activation of superficial layer visual neurons rather than the intermediate layers of the SC because stimulation of the superficial layers produced effects opposite to those found with intermediate layer stimulation. Second, we inactivated the rostral SC with muscimol and found that contraversive pursuit initiation was reduced and ipsiversive pursuit was increased slightly, changes that were opposite to those resulting from stimulation. The results of both the stimulation and the muscimol injection experiments on pursuit are consistent with the effects of these activation and inactivation experiments on saccades, and the effects on pursuit are consistent with the hypothesis that the SC provides a position signal that is used by the smooth-pursuit eye-movement system.     

Saccadic eye movements following injection of lidocaine into the superior colliculus

Summary Ablation of the superior colliculus (SC) has generally produced limited deficits in the initiation of saccadic eye movements, usually an increase in the latency of saccades. However, recent studies using muscimol, a GABA agonist, to block afferents to the SC showed deficits in not only latency but in amplitude and velocity of saccades as well. These greater deficits might be dependent upon the testing of saccades shortly after the damage of SC before any compensation for the deficits could develop. The present experiments tested this hypothesis by injecting a local anesthetic into SC. The anesthetic inactivated the cells entirely rather than just deafferenting them, but still allowed testing immediately after the injection. Clear deficits were observed following injection of lidocaine into the SC. The amplitudes of saccades to visual targets were shortened, and the peak velocities of the saccades were reduced even if the reduced amplitude of the saccades was taken into account. Latency of saccades usually increased. The deficits were limited to the area of the visual field that overlapped the movement fields of the cells near the injection site. If the movement fields were in the periphery, saccades to the periphery were shortened following the injection of lidocaine. If the movement fields were near the center of gaze, saccades into the area were shortened, but the monkey was able to make saccades over the visual field related to the affected area to more peripheral targets. These experiments support the view that the SC normally conveys information on the amplitude and velocity of saccadic eye movements, but that gradual compensation can be made over time by other pathways when damage to the structure occurs.     

Effect of reversible inactivation of macaque lateral intraparietal area on visual and memory saccades

Previous studies from our laboratory identified a parietal eye field in the primate lateral intraparietal sulcus, the lateral intraparietal area (area LIP). Here we further explore the role of area LIP in processing saccadic eye movements by observing the effects of reversible inactivation of this area. One to 2 microl of muscimol (8 mg/ml) were injected at locations where saccade-related activities were recorded for each lesion experiment. After the muscimol injection we observed in two macaque monkeys consistent effects on both the metrics and dynamics of saccadic eye movements at many injection sites. These effects usually took place within 10-30 min and disappeared after 5-6 h in most cases and certainly when tested the next day. After muscimol injection memory saccades directed toward the contralesional and upper space became hypometric, and in one monkey those to the ipsilesional space were slightly but significantly hypermetric. In some cases, the scatter of the end points of memory saccades was also increased. On the other hand, the metrics of visual saccades remained relatively intact. Latency for both visual and memory saccades toward the contralesional space was increased and in many cases displayed a higher variance after muscimol lesion. At many injection sites we also observed an increase of latency for visual and memory saccades toward the upper space. The peak velocities for memory saccades toward the contralesional space were decreased after muscimol injection. The peak velocities of visual saccades were not significantly different from those of the controls. The duration of saccadic eye movements either to the ipsilesional or contralesional space remained relatively the same for both visual and memory saccades. Overall these results demonstrated that we were able to selectively inactivate area LIP and observe effects on saccadic eye movements. Together with our previous recording studies these results futher support the view that area LIP plays a direct role in processing incoming sensory information to program saccadic eye movements. The results are consistent with our unit recording data and microstimulation studies, which suggest that area LIP represents contralateral space and also has a bias for the upper visual field.     

Convergence eye movements evoked by microstimulation of the rostral superior colliculus in the cat

Results of our previous studies suggest that the circumscribed area in the rostral superior colliculus (SC) of the cat is involved in the control of accommodation. Accommodation is closely linked with vergence eye movements. In this study, we investigated whether or not vergence eye movements are evoked by microstimulation of the rostral SC in the cat. In addition, we studied the effect of chemical inhibition of the rostral SC on visually guided vergence eye movements. This study was conducted on three cats, weighing 2.5-3.5 kg. The animals were trained to carry out visually guided saccade and convergence tasks. Eye movements were measured using search coils placed on both eyes. We recorded eye movements evoked by microstimulation of the rostral SC in the alert cats. Muscimol was injected into the rostral SC, and the effect of SC inactivation on visually guided vergence eye movements was investigated. Convergence eye movements were evoked by low-current stimulation (< 30 microA) of a circumscribed area in the intermediate layers of the rostral SC on one side. Spontaneous saccades were interrupted by the stimulation of the low-threshold area for evoking convergence. Visually guided convergence eye movements were severely diminished by the injection of muscimol into the low-threshold area for evoking convergence of the SC. The rostral SC is related to the control of vergence eye movements as well as accommodation. The rostral SC may be involved in the functional linkage between accommodation, convergence and visual fixation.     

Extraretinal inputs to neurons in the rostral superior colliculus of the monkey during smooth-pursuit eye movements.

The intermediate and deep layers of the monkey superior colliculus (SC) are known to be important for the generation of saccadic eye movements. Recent studies have also provided evidence that the rostral SC might be involved in the control of pursuit eye movements. However, because rostral SC neurons respond to visual stimuli used to guide pursuit, it is also possible that the pursuit-related activity is simply a visual response. To test this possibility, we recorded the activity of neurons in the rostral SC as monkeys smoothly pursued a target that was briefly extinguished. We found that almost all rostral SC neurons in our sample maintained their pursuit-related activity during a brief visual blink, which was similar to the maintained activity they also exhibited during blinks imposed during fixation. These results indicate that discharge of rostral SC neurons during pursuit is not simply a visual response, but includes extraretinal signals.     

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.     

Discharge patterns of neurons in the rostral superior colliculus of cat: activity related to fixation of visual and auditory targets

Neurons in the rostral superior colliculus (SC) of alert cats exhibit quasi-sustained discharge patterns related to the fixation of visual targets. Because some SC neurons also respond to auditory stimuli, we investigated whether there is a population of neurons in the rostral SC which is active in relation to fixation of both auditory and visual targets. We identified cells which were active with visual fixation and which continued to discharge if the fixation stimulus was briefly extinguished. The population of neurons exhibited similar discharge characteristics when the fixation stimulus was auditory. Few neurons were significantly more active during fixation of visual targets than during fixation of auditory targets. Most fixation neurons showed a diminished discharge rate during spontaneous (self-generated) saccadic eye movements away from a visual fixation stimulus, regardless of the direction of the saccade. this diminished discharge rate (or pause) typically began, on average, 12.2 ms before saccade onset and the duration of the pause was Ionger than the duration of the saccade. These observations are consistent with the hypothesis that increased discharge of these neurons is related to active fixation and that reductions in their activity are important for the generation of saccades. However, the lack of a precise relationship between pause duration and saccade duration implies that these neurons would be unlikely to project directly to the saccadic burst generator. The mean interval from the beginning of the pauses of fixation neurons to be beginning of the saccades away from fixation targets is also shorter than has been found in brainstem omnipause neurons. By analogy with the concept of a receptive field, agaze position error field depicts the range of gaze position error for which a cell is active. Although fixation neurons appear to encode the magnitude and direction of the error between visual targets and the visual axis, visual error fields at the end of fixating eye movements were significantly larger than those at stimulus onset. For auditory stimuli, this difference was not significant. These observations are compatible with a number of recent experiments indicating that neural signals of eye position are damped or delayed with respect to current eye position.     

Correlates of motor planning and postsaccadic fixation in the macaque monkey lateral geniculate nucleus

There is significant controversy regarding the ability of the primate visual system to construct stable percepts from a never-ending stream of brief fixations and rapid saccadic eye movements. In this study, we examined the timing and occurrence of perisaccadic modulation of LGN single-unit activity in awake-behaving macaque monkeys while they made spontaneous saccades in the dark and made visually guided saccades to discrete stimuli located outside the receptive field. Our hypothesis was that the activity of LGN cells is modulated by efference copies of motor plans to produce saccadic eye movements and that this modulation depends neither on the presence of feedforward visual information nor on a corollary discharge of signals directing saccadic eye movements. On average, 25% of LGN cells demonstrated significant perisaccadic modulation. This modulation consisted of a moderate suppression of activity that began more than 100 ms prior to the initiation of a saccadic eye movement and continued beyond the termination of the saccadic eye movement. This suppression was followed by a large enhancement of activity after the eyes arrived at the next fixation. Although members of all three LGN relay cell classes (magnocellular, parvocellular, and koniocellular) demonstrated significant saccade-related suppression and enhancement of activity, more cells demonstrated postsaccadic enhancement (25%) than perisaccadic suppression (17%). In no case did the timing of the modulation coincide directly with saccade duration. The degree of modulation observed did not vary with LGN cell class, LGN receptive field center location, center sign (ON-center or OFF-center), or saccade latency or velocity. The time course of modulation did, however, vary with saccade size such that suppression was longer for longer saccades. The fact that activity from a percentage of LGN cells from all cell classes was modulated in relationship to saccadic eye movements in the absence of direct visual stimulation suggests that this modulation is a general phenomenon not tied to specific types of visual stimuli. Similarly, because the onset of the modulation preceded eye movements by more than 100 ms, it is likely that this modulation reflects higher order motor-planning rather than a corollary of mechanisms in direct control of eye movements themselves. Finally, the fact that the largest modulation is a postsaccadic enhancement of activity may suggest that perisaccadic modulations are designed more for the facilitation of visual information processing once the eyes land at a new location than for filtering unwanted visual stimuli.     

Expression of a re-centering bias in saccade regulation by superior colliculus neurons

In previous studies of saccadic eye movement reaction time, the manipulation of initial eye position revealed a behavioral bias that facilitates the initiation of movements towards the central orbital position. An interesting hypothesis for this re-centering bias suggests that it reflects a visuo-motor optimizing strategy, rather than peripheral muscular constraints. Given that the range of positions that the eyes can take in the orbits delimits the extent of visual exploration by head-fixed subjects, keeping the eyes centered in the orbits may indeed permit flexible orienting responses to engaging stimuli. To investigate the influence of initial eye position on central processes such as saccade selection and initiation, we examined the activity of saccade-related neurons in the primate superior colliculus (SC). Using a simple reaction time paradigm wherein an initially fixated visual stimulus varying in position was extinguished 200 ms before the presentation of a saccadic target, we studied the relationship between initial eye position and neuronal activation in advance of saccade initiation. We found that the magnitude of the early activity of SC neurons, especially during the immediate pre-target period that followed the fixation stimulus disappearance, was correlated with changes in initial eye position. For the great majority of neurons, the pre-target activity increased with changes in initial eye position in the direction opposite to their movement fields, and it was also strongly correlated with the concomitant reduction in reaction time of centripetal saccades directed within their movement fields. Taking into account the correlation with saccadic reaction time, the relationship between neuronal activity and initial eye position remained significant. These results suggest that eye-position-dependent changes in the excitability of SC neurons could represent the neural substrate underlying a re-centering bias in saccade regulation. More generally, the low frequency SC pre-target activity could use eccentric eye position signals to regulate both when and which saccades are produced by promoting the emergence of a high frequency burst of activity that can act as a saccadic command. However, only saccades initiated within ~200 ms of target presentation were associated with SC pre-target activity. This eye-dependent pre-target activation mechanism therefore appears to be restricted to the initiation of saccades with relatively short reaction times, which specifically require the integrity of the SC. Electronic Publication     

Sensorimotor integration in the primate superior colliculus. I. Motor convergence

Orienting movements of the eyes and head are made to both auditory and visual stimuli even though in the primary sensory pathways the locations of auditory and visual stimuli are encoded in different coordinates. This study was designed to differentiate between two possible mechanisms for sensory-to-motor transformation. Auditory and visual signals could be translated into common coordinates in order to share a single motor pathway or they could maintain anatomically separate sensory and motor routes for the initiation and guidance of orienting eye movements. The primary purpose of the study was to determine whether neurons in the superior colliculus (SC) that discharge before saccades to visual targets also discharge before saccades directed toward auditory targets. If they do, this would indicate that auditory and visual signals, originally encoded in different coordinates, have been converted into a single coordinate system and are sharing a motor circuit. Trained monkeys made saccadic eye movements to auditory or visual targets while the activity of visual-motor (V-M) cells and saccade-related burst (SRB) cells was monitored. The pattern of spike activity observed during trials in which saccades were made to visual targets was compared with that observed when comparable saccades were made to auditory targets. For most (57 of 59) V-M cells, sensory responses were observed only on visual trials. Auditory stimuli originating from the same region of space did not activate these cells. Yet, of the 72 V-M and SRB cells studied, 79% showed motor bursts prior to saccades to either auditory or visual targets. This finding indicates that visual and auditory signals, originally encoded in retinal and head-centered coordinates, respectively, have undergone a transformation that allows them to share a common efferent pathway for the generation of saccadic eye movements. Saccades to auditory targets usually have lower velocities than saccades of the same amplitude and direction made to acquire visual targets. Since fewer collicular cells are active prior to saccades to auditory targets, one determinant of saccadic velocity may be the number of collicular neurons discharging before a particular saccade.     

Stimulation in the rostral pole of monkey superior colliculus: effects on vergence eye movements

Recent studies have indicated that the superior colliculus (SC), traditionally considered to be saccade-related, may play a role in the coding of eye movements in both direction and depth. Similarly, it has been suggested that omnidirectional pause neurons are not only involved in the initiation of saccades, but can also modulate vergence eye movements. These new developments provide a challenge for current oculomotor models that attempt to describe saccade-vergence coordination and the neural mechanisms that may be involved. In this paper, we have attempted to study these aspects further by investigating the role of the rostral pole of the SC in the control of vergence eye movements. It is well-known that, by applying long-duration electrical stimulation to rostral sites in the monkey SC, saccadic responses can be prevented and interrupted. We have made use of these properties to extend this paradigm to eye movements that contain a substantial depth component. We found that electrical intervention in the rostral region also has a clear effect on vergence. For an eye movement to a near target, stimulation leads to a significant suppression and change in dynamics of the pure vergence response during the period of stimulation, but the depth component cannot be prevented entirely. When these paradigms are implemented for 3D refixations, the saccade is inactivated, as expected, while the vergence component is often suppressed more than in the case of the pure vergence. The data lead us to conclude that the rostral SC, presumably indirectly via connections with the pause neurons, can affect vergence control for both pure vergence and combined 3D responses. Suppression of the depth component is incomplete, in contrast to the directional movement, and is often different in magnitude for 3D refixations and pure vergence responses. The results are discussed in connection with current models for saccade-vergence interaction.     

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

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

Discharge properties of neurons in the rostral superior colliculus of the monkey during smooth-pursuit eye movements

The intermediate and deep layers of the monkey superior colliculus (SC) comprise a retinotopically organized map for eye movements. The rostral end of this map, corresponding to the representation of the fovea, contains neurons that have been referred to as "fixation cells" because they discharge tonically during active fixation and pause during the generation of most saccades. These neurons also possess movement fields and are most active for targets close to the fixation point. Because the parafoveal locations encoded by these neurons are also important for guiding pursuit eye movements, we studied these neurons in two monkeys as they generated smooth pursuit. We found that fixation cells exhibit the same directional preferences during pursuit as during small saccades-they increase their discharge during movements toward the contralateral side and decrease their discharge during movements toward the ipsilateral side. This pursuit-related activity could be observed during saccade-free pursuit and was not predictive of small saccades that often accompanied pursuit. When we plotted the discharge rate from individual neurons during pursuit as a function of the position error associated with the moving target, we found tuning curves with peaks within a few degrees contralateral of the fovea. We compared these pursuit-related tuning curves from each neuron to the tuning curves for a saccade task from which we separately measured the visual, delay, and peri-saccadic activity. We found the highest and most consistent correlation with the delay activity recorded while the monkey viewed parafoveal stimuli during fixation. The directional preferences exhibited during pursuit can therefore be attributed to the tuning of these neurons for contralateral locations near the fovea. These results support the idea that fixation cells are the rostral extension of the buildup neurons found in the more caudal colliculus and that their activity conveys information about the size of the mismatch between a parafoveal stimulus and the currently foveated location. Because the generation of pursuit requires a break from fixation, the pursuit-related activity indicates that these neurons are not strictly involved with maintaining fixation. Conversely, because activity during the delay period was found for many neurons even when no eye movement was made, these neurons are also not obligatorily related to the generation of a movement. Thus the tonic activity of these rostral neurons provides a potential position-error signal rather than a motor command-a principle that may be applicable to buildup neurons elsewhere in the SC.     

The fixation area of the cat superior colliculus: effects of electrical stimulation and direct connection with brainstem omnipause neurons

The superior colliculus has long been recognized as an important structure in the generation of saccadic displacements of the visual axis. Neurons with presaccadic activity encoding saccade vectors are topographically organized and form a motor map. Recently, neurons with fixation-related activity have been recorded at the collicular rostral pole, at the area centralis representation or fixation area. Another collicular function which deals with the maintenance of fixation behavior by means of active inhibition of orientation commands was then suggested. We tested that hypothesis as it relates to the suppression of gaze saccades (gaze = eye in space = eye in head + head in space) in the head-free cat by increasing the activity of the fixation cells at the rostral pole with electrical microstimulation. Long stimulation trains applied before gaze saccades delayed their initiation. Short stimuli, delivered during the gaze saccades, transiently interrupted both eye and head components. These results provide further support for a role in fixation behavior for collicular fixation neurons. Brainstem omnipause neurons also exhibit fixation-related activity and have been shown to receive a direct excitatory input from the superior colliculus. To determine whether the collicular projection to omnipause neurons arises from the fixation area, the deep layers of the superior colliculus were electrically stimulated either at the rostral pole including the fixation area or in more caudal regions where stimulation evokes orienting responses. Forty-nine neurons were examined in three cats. 61% of the neurons were found to be orthodromically excited by single-pulse stimulation of the rostral pole, whereas only 29% responded to caudal stimulation. In addition, stimuli delivered to the rostral pole activated, on average, omnipause neurons at shorter latencies and with lower currents than those applied in caudal regions. These results suggest that excitatory inputs to omnipause neurons from the superior colliculus are principally provided by the fixation area, via which the superior colliculus could play a role in suppression of gaze shifts.     

Further evidence that a shared efferent collicular pathway drives separate circuits for smooth eye movements and saccades

The aim of the present study was to find out whether smooth eye movements (SEMs) evoked by superior colliculus (SC) stimulation are, as suggested by Breznen et al. (1996), artefactual eye movements resulting from a non-physiological response of the saccadic generator. This question was reinvestigated in head-restrained cats. Long-lasting SC stimulation was found to evoke, in a comparable proportion, either a single saccade followed by an uninterrupted SEM or a staircase of two or three saccades interleaved with SEMs. These two different patterns of eye movements could be elicited at a near-threshold current and at low stimulation frequencies. In most cases, SEM direction clearly differed from that of the preceding saccade. This difference between SEM and saccade directions varied in a systematic way as a function of the initial saccade direction. As demonstrated by computer simulation, this observation can be explained if the neural circuit controlling SEMs reaches a saturation level earlier than the saccadic burst-generator. Our results in cats were reminiscent of those reported by Breznen et al. (1996) in the monkey only in some instances, when high frequency stimulation (400–600 Hz) was applied. Indeed, in the case of near-threshold stimulation-elicited staircase saccades, increasing the stimulation frequency led to a progressive disappearance of the smaller subsequent saccades that were substituted by uninterrupted SEM-like movements. Altogether, the present results confirm the view that SEMs are genuine eye movements. These results rule out the hypothesis that SEMs result from a saturation of the saccadic generator and strengthen the hypothesis that SEMs and saccades are distinct movements. We suggest that the same collicular efferent cells carry out the motor command to saccadic and SEM circuits and that the position error originating from the SC may be distributed amongst separate downstream motor systems. Electronic Publication     

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.     

Multielectrode evidence for spreading activity across the superior colliculus movement map

The monkey superior colliculus (SC) has maps for both visual input and movement output in the superficial and intermediate layers, respectively, and activity on these maps is generally related to visual stimuli only in one part of the visual field and/or to a restricted range of saccadic eye movements to those stimuli. For some neurons within these maps, however, activity has been reported to spread from the caudal SC to the rostral SC during the course of a saccade. This spread of activity was inferred from averages of recordings at different sites on the SC movement map during saccades of different amplitudes and even in different monkeys. In the present experiments, SC activity was recorded simultaneously in pairs of neurons to observe the spread of activity during individual saccades. Two electrodes were positioned along the rostral-caudal axis of the SC with one being more caudal than the other, and 60 neuron pairs whose movement fields were large enough to see a spread of activity were studied. During individual saccades, the relative time of discharge of the two neurons was compared using 1) the time difference between peak discharge of the two neurons, 2) the difference between the "median activation time" of the two neurons, and 3) the shift required to align the two discharge patterns using cross-correlation. All three analysis methods gave comparable results. Many pairs of neurons were activated in sequence during saccade generation, and the order of activation was most frequently caudal to rostral. Such a sequence of activation was not observed in every neuron pair, but over the sample of neuron pairs studied, the spread was statistically significant. When we compared the time of neuronal activity to the time of saccade onset, we found that the caudal neuronal activity was more likely to be before the saccade, whereas the rostral neuronal activity was more likely to be during the saccade. These results demonstrate that when individual pairs of neurons are examined during single saccades there is evidence of a caudal to rostral spread of activity within the monkey SC, and they confirm the previous inferences of a spread of activity drawn from observations on averaged neuronal activity during multiple saccades. The functional contribution of this spread of activity remains to be determined.     

The effect of frontal eye field and superior colliculus lesions on saccadic latencies in the rhesus monkey

Rhesus monkeys were trained to make saccadic eye movements to visual targets using detection and discrimination paradigms in which they were required to make a saccade either to a solitary stimulus (detection) or to that same stimulus when it appeared simultaneously with several other stimuli (discrimination). The detection paradigm yielded a bimodal distribution of saccadic latencies with the faster mode peaking around 100 ms (express saccades); the introduction of a pause between the termination of the fixation spot and the onset of the target (gap) increased the frequency of express saccades. The discrimination paradigm, on the other hand, yielded only a unimodal distribution of latencies even when a gap was introduced, and there was no evidence for short-latency "express" saccades. In three monkeys either the frontal eye field or the superior colliculus was ablated unilaterally. Frontal eye field ablation had no discernible long-term effects on the distribution of saccadic latencies in either the detection or discrimination tasks. After unilateral collicular ablation, on the other hand, express saccades obtained in the detection paradigm were eliminated for eye movements contralateral to the lesion, leaving only a unimodal distribution of latencies. This deficit persisted throughout testing, which in one monkey continued for 9 mo. Express saccades were not observed again for saccades contralateral to the lesion, and the mean latency of the contralateral saccades was longer than the mean latency of the second peak for the ipsiversive saccades. The latency distribution of saccades ipsiversive to the collicular lesion was unaffected except for a few days after surgery, during which time an increase in the proportion of express saccades was evident. Saccades obtained with the discrimination paradigm yielded a small but reliable increase in saccadic latencies following collicular lesions, without altering the shape of the distribution. Unilateral muscimol injections into the superior colliculus produced results similar to those obtained immediately after collicular lesions: saccades contralateral to the injection site were strongly inhibited and showed increased saccadic latencies. This was accompanied by a decrease of ipsilateral saccadic latencies and an increase in the number of saccades falling into the express range. The results suggest that the superior colliculus is essential for the generation of short-latency (express) saccades and that the frontal eye fields do not play a significant role in shaping the distribution of saccadic latencies in the paradigms used in this study.(ABSTRACT TRUNCATED AT 400 WORDS)