Composition and topographic organization of signals sent from the frontal eye field to the superior colliculus

The frontal eye field (FEF) and superior colliculus (SC) contribute to saccadic eye movement generation, and much of the FEF's oculomotor influence may be mediated through the SC. The present study examined the composition and topographic organization of signals flowing from FEF to SC by recording from FEF neurons that were antidromically activated from rostral or caudal SC. The first and most general result was that, in a sample of 88 corticotectal neurons, the types of signals relayed from FEF to SC were highly diverse, reflecting the general population of signals within FEF rather than any specific subset of signals. Second, many neurons projecting from FEF to SC carried signals thought to reflect cognitive operations, namely tonic discharges during the delay period of a delayed-saccade task (delay signals), elevated discharges during the gap period of a gap task (gap increase signals), or both. Third, FEF neurons discharging during fixation were found to project to the SC, although they did not project preferentially to rostral SC, where similar fixation neurons are found. Neurons that did project preferentially to the rostral SC were those with foveal visual responses and those pausing during the gap period of the gap task. Many of the latter neurons also had foveal visual responses, presaccadic pauses in activity, and postsaccadic increases in activity. These two types of rostral-projecting neurons therefore may contribute to the activity of rostral SC fixation neurons. Fourth, conduction velocity was used as an indicator of cell size to correct for sampling bias. The outcome of this correction procedure suggested that among the most prevalent neurons in the FEF corticotectal population are those carrying putative cognitive-related signals, i.e., delay and gap increase signals, and among the least prevalent are those carrying presaccadic burst discharges but lacking peripheral visual responses. Fifth, corticotectal neurons carrying various signals were biased topographically across the FEF. Neurons with peripheral visual responses but lacking presaccadic burst discharges were biased laterally, neurons with presaccadic burst discharges but lacking peripheral visual responses were biased medially, and neurons carrying delay or gap increase signals were biased dorsally. Finally, corticotectal neurons were distributed within the FEF as a function of their visual or movement field eccentricity and projected to the SC such that eccentricity maps in both structures were closely aligned. We conclude that the FEF most likely influences the activity of SC neurons continuously from the start of fixation, through visual analysis and cognitive manipulations, until a saccade is generated and fixation begins anew. Furthermore, the projection from FEF to SC is highly topographically organized in terms of function at both its source and its termination.     

What the brain stem tells the frontal cortex. I. Oculomotor signals sent from superior colliculus to frontal eye field via mediodorsal thalamus

Neuronal processing in cerebral cortex and signal transmission from cortex to brain stem have been studied extensively, but little is known about the numerous feedback pathways that ascend from brain stem to cortex. In this study, we characterized the signals conveyed through an ascending pathway coursing from the superior colliculus (SC) to the frontal eye field (FEF) via mediodorsal thalamus (MD). Using antidromic and orthodromic stimulation, we identified SC source neurons, MD relay neurons, and FEF recipient neurons of the pathway in Macaca mulatta. The monkeys performed oculomotor tasks, including delayed-saccade tasks, that permitted analysis of signals such as visual activity, delay activity, and presaccadic activity. We found that the SC sends all of these signals into the pathway with no output selectivity, i.e., the signals leaving the SC resembled those found generally within the SC. Visual activity arrived in FEF too late to contribute to short-latency visual responses there, and delay activity was largely filtered out in MD. Presaccadic activity, however, seemed critical because it traveled essentially unchanged from SC to FEF. Signal transmission in the pathway was fast ( approximately 2 ms from SC to FEF) and topographically organized (SC neurons drove MD and FEF neurons having similarly eccentric visual and movement fields). Our analysis of identified neurons in one pathway from brain stem to frontal cortex thus demonstrates that multiple signals are sent from SC to FEF with presaccadic activity being prominent. We hypothesize that a major signal conveyed by the pathway is corollary discharge information about the vector of impending saccades.     

Progression in neuronal processing for saccadic eye movements from parietal cortex area lip to superior colliculus

Neurons in both the lateral intraparietal area (LIP) of the monkey parietal cortex and the intermediate layers of the superior colliculus (SC) are activated well in advance of the initiation of saccadic eye movements. To determine whether there is a progression in the covert processing for saccades from area LIP to SC, we systematically compared the discharge properties of LIP output neurons identified by antidromic activation with those of SC neurons collected from the same monkeys. First, we compared activity patterns during a delayed saccade task and found that LIP and SC neurons showed an extensive overlap in their responses to visual stimuli and in their sustained activity during the delay period. The saccade activity of LIP neurons was, however, remarkably weaker than that of SC neurons and never occurred without any preceding delay activity. Second, we assessed the dependence of LIP and SC activity on the presence of a visual stimulus by contrasting their activity in delayed saccade trials in which the presentation of the visual stimulus was either sustained (visual trials) or brief (memory trials). Both the delay and the presaccadic activity levels of the LIP neuronal sample significantly depended on the sustained presence of the visual stimulus, whereas those of the SC neuronal sample did not. Third, we examined how the LIP and SC delay activity relates to the future production of a saccade using a delayed GO/NOGO saccade task, in which a change in color of the fixation stimulus instructed the monkey either to make a saccade to a peripheral visual stimulus or to withhold its response and maintain fixation. The average delay activity of both LIP and SC neuronal samples significantly increased by the advance instruction to make a saccade, but LIP neurons were significantly less dependent on the response instruction than SC neurons, and only a minority of LIP neurons was significantly modulated. Thus despite some overlap in their discharge properties, the neurons in the SC intermediate layers showed a greater independence from sustained visual stimulation and a tighter relationship to the production of an impending saccade than the LIP neurons supplying inputs to the SC. Rather than representing the transmission of one processing stage in parietal cortex area LIP to a subsequent processing stage in SC, the differences in neuronal activity that we observed suggest instead a progressive evolution in the neuronal processing for saccades.     

Frontal eye field sends delay activity related to movement, memory, and vision to the superior colliculus

Many neurons within prefrontal cortex exhibit a tonic discharge between visual stimulation and motor response. This delay activity may contribute to movement, memory, and vision. We studied delay activity sent from the frontal eye field (FEF) in prefrontal cortex to the superior colliculus (SC). We evaluated whether this efferent delay activity was related to movement, memory, or vision, to establish its possible functions. Using antidromic stimulation, we identified 66 FEF neurons projecting to the SC and we recorded from them while monkeys performed a Go/Nogo task. Early in every trial, a monkey was instructed as to whether it would have to make a saccade (Go) or not (Nogo) to a target location, which permitted identification of delay activity related to movement. In half of the trials (memory trials), the target disappeared, which permitted identification of delay activity related to memory. In the remaining trials (visual trials), the target remained visible, which permitted identification of delay activity related to vision. We found that 77% (51/66) of the FEF output neurons had delay activity. In 53% (27/51) of these neurons, delay activity was modulated by Go/Nogo instructions. The modulation preceded saccades made into only part of the visual field, indicating that the modulation was movement-related. In some neurons, delay activity was modulated by Go/Nogo instructions in both memory and visual trials and seemed to represent where to move in general. In other neurons, delay activity was modulated by Go/Nogo instructions only in memory trials, which suggested that it was a correlate of working memory, or only in visual trials, which suggested that it was a correlate of visual attention. In 47% (24/51) of FEF output neurons, delay activity was unaffected by Go/Nogo instructions, which indicated that the activity was related to the visual stimulus. In some of these neurons, delay activity occurred in both memory and visual trials and seemed to represent a coordinate in visual space. In others, delay activity occurred only in memory trials and seemed to represent transient visual memory. In the remainder, delay activity occurred only in visual trials and seemed to be a tonic visual response. In conclusion, the FEF sends diverse delay activity signals related to movement, memory, and vision to the SC, where the signals may be used for saccade generation. Downstream transmission of various delay activity signals may be an important, general way in which the prefrontal cortex contributes to the control of movement.     

Frontal eye field microstimulation induces task-dependent gamma oscillations in the lateral intraparietal area

Macaque frontal eye fields (FEF) and the lateral intraparietal area (LIP) are high-level oculomotor control centers that have been implicated in the allocation of spatial attention. Electrical microstimulation of macaque FEF elicits functional magnetic resonance imaging (fMRI) activations in area LIP, but no study has yet investigated the effect of FEF microstimulation on LIP at the single-cell or local field potential (LFP) level. We recorded spiking and LFP activity in area LIP during weak, subthreshold microstimulation of the FEF in a delayed-saccade task. FEF microstimulation caused a highly time- and frequency-specific, task-dependent increase in gamma power in retinotopically corresponding sites in LIP: FEF microstimulation produced a significant increase in LIP gamma power when a saccade target appeared and remained present in the LIP receptive field (RF), whereas less specific increases in alpha power were evoked by FEF microstimulation for saccades directed away from the RF. Stimulating FEF with weak currents had no effect on LIP spike rates or on the gamma power during memory saccades or passive fixation. These results provide the first evidence for task-dependent modulations of LFPs in LIP caused by top-down stimulation of FEF. Since the allocation and disengagement of spatial attention in visual cortex have been associated with increases in gamma and alpha power, respectively, the effects of FEF microstimulation on LIP are consistent with the known effects of spatial attention.     

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.     

Saccade-related activity in the lateral intraparietal area. I. Temporal properties; comparison with area 7a.

1. The cortex of the inferior parietal lobule (IPL) contains neurons whose activity is related to saccadic eye movements. The exact role of the IPL in relation to saccades remains, however, unclear. In this and the companion paper, we approach this problem by quantifying many of the spatial and temporal parameters of the saccade-related (S) activity. These parameters have hitherto been largely unstudied. 2. The activity of single neurons was recorded from Macaca mulatta monkeys while they were performing a delayed-saccade task. The analysis presented here is based on 161 neurons recorded from the lateral intraparietal area (LIP), a recently defined subdivision of the IPL; and 54 neurons recorded from the neighboring part of the IPL, area 7a. Overall, 409 IPL neurons were isolated in this study. 3. The typical activity of IPL neurons during the delayed-saccade task has three basic phases: light sensitive (LS), memory (M), and S. These basic phases are common to neurons of both areas LIP and 7a. In each phase (LS, M, and S), individual neurons may or may not be active. Most LIP neurons, however, are active in more than one phase. 4. To compare the activity levels of different neurons, the actual firing rate was weighted by each neuron's background level, yielding an "activity index" for each neuron, in each phase of the task. We calculated the activity index for the LS and M phases and for three phases related to the saccade: a presaccadic (Pre-S), a saccade-coincident (S-Co), and a postsaccadic (Post-S) phase. For area LIP neurons the median values of the activity index were high for the LS, M, Pre-S, and S-Co activities, and slightly lower in the Post-S period. In area 7a the median values were low for the LS phase and, in particular, for the M and Pre-S phases, somewhat higher coincident with the saccade, and high post-saccadically. 5. In area LIP, in each phase, 49-63% of the neurons had excitatory activity, and 10-17% had inhibitory responses. 6. In contrast, in area 7a excitatory responses were most frequent in the Post-S phase (56%). Excitation was particularly infrequent during M (28%) and Pre-S (22%). The incidence of inhibitory responses varied too (4-18%). The time course of inhibition was roughly opposite that of excitation; the highest frequency of inhibitory responses occurred during the saccade.(ABSTRACT TRUNCATED AT 400 WORDS)     

Spike-field activity in parietal area LIP during coordinated reach and saccade movements

The posterior parietal cortex is situated between visual and motor areas and supports coordinated visually guided behavior. Area LIP in the intraparietal sulcus contains representations of visual space and has been extensively studied in the context of saccades. However, area LIP has not been studied during coordinated movements, so it is not known whether saccadic representations in area LIP are influenced by coordinated behavior. Here, we studied spiking and local field potential (LFP) activity in area LIP while subjects performed coordinated reaches and saccades or saccades alone to remembered target locations to test whether activity in area LIP is influenced by the presence of a coordinated reach. We find that coordination significantly changes the activity of individual neurons in area LIP, increasing or decreasing the firing rate when a reach is made with a saccade compared with when a saccade is made alone. Analyzing spike-field coherence demonstrates that area LIP neurons whose firing rate is suppressed during the coordinated task have activity temporally correlated with nearby LFP activity, which reflects the synaptic activity of populations of neurons. Area LIP neurons whose firing rate increases during the coordinated task do not show significant spike-field coherence. Furthermore, LFP power in area LIP is suppressed and does not increase when a coordinated reach is made with a saccade. These results demonstrate that area LIP neurons display different responses to coordinated reach and saccade movements, and that different spike rate responses are associated with different patterns of correlated activity. The population of neurons whose firing rate is suppressed is coherently active with local populations of LIP neurons. Overall, these results suggest that area LIP plays a role in coordinating visually guided actions through suppression of coherent patterns of saccade-related activity.     

Collicular involvement in a saccadic colour discrimination task

Summary We have recorded the neural activity of single superior colliculus (SC) neurons in monkeys engaged in a saccadic target/nontarget discrimination task based on a colour cue. Since correct execution of this task probably depends on cortical signal processing, our experiments are of interest for getting a better insight in the problem of how cortical and subcortical signals, relevant for the visual guidance of saccades, are combined. The experiments were designed to distinguish between two extreme possibilities: 1) The crucial cortical signal affects the saccadic system at or above the level of the SC movement-related cells (serial hypothesis); 2) The colour-based target information bypasses the motor colliculus and affects the saccadic system at a level more downstream (bypass hypothesis). Under conditions where the saccadic system had to select a green target stimulus and to ignore the red nontarget spot, the saccade-related activity in SC visuomotor neurons remained as tightly coupled to the metrics of the saccade as it was in a simple spot-detection task. Since the saccade-related activity of these cells appeared to be based on colour information, we conclude that our data corroborate the serial hypothesis. The initial activity after stimulus onset appeared to be colour nonopponent in all neurons. In some cells the neural activity was quantitatively slightly different for the green target and the red nontarget. Since these minor differences were colour rather than motor response dependent, they were probably not part of the target-selection process. These data suggest the possibility that the decision as to which saccade should be made was largely imposed upon the SC visuomotor cells by an external source. We discuss various possibilities for the origin of the putative intervening signal which orders a saccade by causing a burst in the appropriate SC visuomotor neurons.     

Response of neurons in the lateral intraparietal area to a distractor flashed during the delay period of a memory-guided saccade

Recent experiments raised the possibility that the lateral intraparietal area (LIP) might be specialized for saccade planning. If this was true, one would expect a decreased sensitivity to irrelevant visual stimuli appearing late in the delay period of a memory-guided delayed-saccade task to a target outside the neurons' receptive fields. We trained two monkeys to perform a standard memory-guided delayed-saccade task and a distractor task in which a stimulus flashed for 200 ms at a predictable time 300-100 ms before the end of the delay period. We used two locations, one in the most active part of the receptive field and another well outside the receptive field. We used six kinds of trials randomly intermixed: simple delayed-saccade trials into or away from the receptive field and distractor trials with saccade target and distractor both in the receptive field, both out of the receptive field, or one at each location. This enabled us to study the response to the distractor as a function of the monkey's preparation of a memory-guided delayed-saccade task. We had assumed that the preparation of a saccade away from the receptive field would result in an attenuation of the response to the distractor, i.e., a distractor at the location of the saccade goal would evoke a greater response than when it appeared at a location far from the saccade goal. Instead we found that neurons exhibited either a normal or an enhanced visual response to the distractor during the memory period when the target flashed outside the receptive field. When the distractor flashed at the location of the saccade target, the response to the distractor was either unchanged or diminished. The response to a distractor away from the target location of a memory-guided saccade was even greater than the response to the same target when it was the target for the memory-guided saccade task. Immediate presaccadic activity did not distinguish between a saccade to the receptive field when there was no distractor and a distractor in the receptive field when the monkey made a saccade elsewhere. Nonetheless the distractor had no significant effect on the saccade latency, accuracy, or velocity despite the brisk response it evoked immediately before the saccade. We suggest that these results are inconsistent with a role for LIP in the specific generation of saccades, but they are consistent with a role for LIP in the generation of visual attention.     

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.     

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     

Activity of neurons in the lateral intraparietal area of the monkey during an antisaccade task.

The close relationship between saccadic eye movements and vision complicates the identification of neural responses associated with each function. Visual and saccade-related responses are especially closely intertwined in a subdivision of posterior parietal cortex, the lateral parietal area (LIP). We analyzed LIP neurons using an antisaccade task in which monkeys made saccades away from a salient visual cue. The vast majority of neurons reliably signaled the location of the visual cue. In contrast, most neurons had only weak, if any, saccade-related activity independent of visual stimulation. Thus, whereas the great majority of LIP neurons reliably encoded cue location, only a small minority encoded the direction of the upcoming saccade.     

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.     

Direction selectivity of neurons in the macaque lateral intraparietal area

The lateral intraparietal area (LIP) of the macaque is believed to play a role in the allocation of attention and the plan to make saccadic eye movements. Many studies have shown that LIP neurons generally encode the static spatial location demarked by the receptive field (RF). LIP neurons might also provide information about the features of visual stimuli within the RF. For example, LIP receives input from cortical areas in the dorsal visual pathway that contain many direction-selective neurons. Here we examine direction selectivity of LIP neurons. Animals were only required to fixate while motion stimuli appeared in the RF. To avoid spatial confounds, the motion stimuli were patches of randomly arrayed dots that moved with 100% coherence in eight different directions. We found that the majority (61%) of LIP neurons were direction selective. The direction tuning was fairly broad, with a median direction-tuning bandwidth of 136 degrees. The average strength of direction selectivity was weaker in LIP than that of other areas of the dorsal visual stream but that difference may be because of the fact that LIP neurons showed a tonic offset in firing whenever a visual stimulus was in the RF, independent of direction. Direction-selective neurons do not seem to constitute a functionally distinct subdivision within LIP, because those neurons had robust, sustained delay-period activity during a memory delayed saccade task. The direction selectivity could also not be explained by asymmetries in the spatial RF, in the hypothetical case that the animals attended to slightly different locations depending on the direction of motion in the RF. Our results show that direction selectivity is a distinct attribute of LIP neurons in addition to spatial encoding.     

Reversible inactivation of macaque frontal eye field

 The macaque frontal eye field (FEF) is involved in the generation of saccadic eye movements and fixations. To better understand the role of the FEF, we reversibly inactivated a portion of it while a monkey made saccades and fixations in response to visual stimuli. Lidocaine was infused into a FEF and neural inactivation was monitored with a nearby microelectrode. We used two saccadic tasks. In the delay task, a target was presented and then extinguished, but the monkey was not allowed to make a saccade to its location until a cue to move was given. In the step task, the monkey was allowed to look at a target as soon as it appeared. During FEF inactivation, monkeys were severely impaired at making saccades to locations of extinguished contralateral targets in the delay task. They were similarly impaired at making saccades to locations of contralateral targets in the step task if the target was flashed for ≤100 ms, such that it was gone before the saccade was initiated. Deficits included increases in saccadic latency, increases in saccadic error, and increases in the frequency of trials in which a saccade was not made. We varied the initial fixation location and found that the impairment specifically affected contraversive saccades rather than affecting all saccades made into head-centered contralateral space. Monkeys were impaired only slightly at making saccades to contralateral targets in the step task if the target duration was 1000 ms, such that the target was present during the saccade: latency increased, but increases in saccadic error were mild and increases in the frequency of trials in which a saccade was not made were insignificant. During FEF inactivation there usually was a direct correlation between the latency and the error of saccades made in response to contralateral targets. In the delay task, FEF inactivation increased the frequency of making premature saccades to ipsilateral targets. FEF inactivation had inconsistent and mild effects on saccadic peak velocity. FEF inactivation caused impairments in the ability to fixate lights steadily in contralateral space. FEF inactivation always caused an ipsiversive deviation of the eyes in darkness. In summary, our results suggest that the FEF plays major roles in (1) generating contraversive saccades to locations of extinguished or flashed targets, (2) maintaining contralateral fixations, and (3) suppressing inappropriate ipsiversive saccades. Received: 2 February 1996 / Accepted: 26 February 1997     

Eye position and memory saccade related responses in substantia nigra pars reticulata

The substantia nigra pars reticulata (SNr), a major output nucleus of the basal ganglia, has been implicated anatomically, pharmacologically and physiologically in the generation of saccadic eye movements. However, the unique contribution of the SNr to saccade generation remains elusive. We studied the activity of SNr neurons while rhesus monkeys made saccades from different initial orbital positions, to determine what effects, if any, eye position had on SNr neuronal activity. We found that there was no effect of eye position on SNr neuronal responses. We also examined the responses of SNr neurons during memory-guided saccades to determine whether SNr discharges were affected by whether the target of the upcoming saccade was visible. We found that there was no change in response properties during memory saccade trials as compared to otherwise identical visually guided trials. SNr neurons appear to carry no information about either eye position or whether a movement is guided by a visible or remembered target. These results suggest that nigral signals are encoded in the same coordinate frame as those in the SC and FEF, but that unlike neuronal responses in these areas, SNr activity is not influenced by whether the saccade target remains visible until the movement is executed.     

Discharge properties of monkey tectoreticular neurons

The intermediate layers of the superior colliculus (SC) contain neurons that clearly play a major role in regulating the production of saccadic eye movements: a burst of activity from saccade neurons (SNs) is thought to provide a drive signal to set the eyes in motion, whereas the tonic activity of fixation neurons (FNs) is thought to suppress saccades during fixation. The exact contribution of these neurons to saccade control is, however, unclear because the nature of the signals sent by the SC to the brain stem saccade generation circuit has not been studied in detail. Here we tested the hypothesis that the SC output signal is sufficient to control saccades by examining whether antidromically identified tectoreticular neurons (TRNs: 33 SNs and 13 FNs) determine the end of saccades. First, TRNs had discharge properties similar to those of nonidentified SC neurons and a proportion of output SNs had visually evoked responses, which signify that the saccade generator must receive and process visual information. Second, only a minority of TRNs possessed the temporal patterns of activity sufficient to terminate saccades: Output SNs did not cease discharging at the time of saccade end, possibly continuing to drive the brain stem during postsaccadic fixations, and output FNs did not resume their activity before saccade end. These results argue against a role for SC in regulating the timing of saccade termination by a temporal code and suggest that other saccade centers act to thwart the extraneous SC drive signal, unless it controls saccade termination by a spatial code.     

Role of the basal ganglia in the control of purposive saccadic eye movements

In addition to their well-known role in skeletal movements, the basal ganglia control saccadic eye movements (saccades) by means of their connection to the superior colliculus (SC). The SC receives convergent inputs from cerebral cortical areas and the basal ganglia. To make a saccade to an object purposefully, appropriate signals must be selected out of the cortical inputs, in which the basal ganglia play a crucial role. This is done by the sustained inhibitory input from the substantia nigra pars reticulata (SNr) to the SC. This inhibition can be removed by another inhibition from the caudate nucleus (CD) to the SNr, which results in a disinhibition of the SC. The basal ganglia have another mechanism, involving the external segment of the globus pallidus and the subthalamic nucleus, with which the SNr-SC inhibition can further be enhanced. The sensorimotor signals carried by the basal ganglia neurons are strongly modulated depending on the behavioral context, which reflects working memory, expectation, and attention. Expectation of reward is a critical determinant in that the saccade that has been rewarded is facilitated subsequently. The interaction between cortical and dopaminergic inputs to CD neurons may underlie the behavioral adaptation toward purposeful saccades.     

Interaction of the frontal eye field and superior colliculus for saccade generation

Both the frontal eye field (FEF) in the prefrontal cortex and the superior colliculus (SC) on the roof of the midbrain participate in the generation of rapid or saccadic eye movements and both have projections to the premotor circuits of the brain stem where saccades are ultimately generated. In the present experiments, we tested the contributions of the pathway from the FEF to the premotor circuitry in the brain stem that bypasses the SC. We assayed the contribution of the FEF to saccade generation by evoking saccades with direct electrical stimulation of the FEF. To test the role of the SC in conveying information to the brain stem, we inactivated the SC, thereby removing the circuit through the SC to the brain stem, and leaving only the direct FEF-brain stem pathway. If the contributions of the direct pathway were substantial, removal of the SC should have minimal effect on the FEF stimulation, whereas if the FEF stimulation were dependent on the SC, removal of the SC should alter the effect of FEF stimulation. By acutely inactivating the SC, instead of ablating it, we were able to test the efficiency of the direct FEF-brain stem pathway before substantial compensatory mechanisms could mask the effect of removing the SC. We found two striking effects of SC inactivation. In the first, we stimulated the FEF at a site that evoked saccades with vectors that were very close to those evoked at the site of the SC inactivation, and with such optimal alignment, we found that SC inactivation eliminated the saccades evoked by FEF stimulation. The second effect was evident when the FEF evoked saccades were disparate from those evoked in the SC, and in this case we observed a shift in the direction of the evoked saccade that was consistent with the SC inactivation removing a component of a vector average. Together these observations lead to the conclusion that in the nonablated monkey the direct FEF-brain stem pathway is not functionally sufficient to generate accurate saccades in the absence of the indirect pathway that courses from the FEF through the SC to the brain stem circuitry. We suggest that the recovery of function following SC ablation that has been seen in previous studies must result not from the use of an already functioning parallel pathway but from neural plasticity within the saccadic system.