Through the eye, slowly: delays and localization errors in the visual system.

Reviews on the visual system generally praise its amazing performance. Here we deal with its biggest weakness: sluggishness. Inherent delays lead to mislocalization when things move or, more generally, when things change. Errors in time translate into spatial errors when we pursue a moving object, when we try to localize a target that appears just before a gaze shift, or when we compare the position of a flashed target with the instantaneous position of a continuously moving one (or one that appears to be moving even though no change occurs in the retinal image). Studying such diverse errors might rekindle our thinking about how the brain copes with real-time changes in the world.

Vestibular signals can distort the perceived spatial relationship of retinal stimuli.

The flash-lag phenomenon is an illusion that affects the perceived relationship of a moving object and a briefly visible one: the moving object appears to be ahead of the flashed one. In practically all studies of this phenomenon, the image of the object moves on the retina as the object moves in space. Therefore, explanations of the illusion were sought in terms of purely visual mechanisms. Here we set up a situation in which the object's motion in space is entirely produced by passive rotation of the subject. No motion occurred on the retina. The visual display (a continuously lit stimulus and a flashed one) was mounted on a vestibular chair. While the subjects fixated this display, they were rotated in the dark at a constant speed and suddenly stopped. Perceptual misalignment (flash-lag) was robust and consistent during both the initial phase of rotation and the postrotary period when neither chair, subject, nor stimulus was actually moving. As a vestibular signal can cause an illusory spatial dissociation in the visual domain, we conclude that the mechanism of the flash-lag must be more general than was thought up-to-now.

Reward-predicting and reward-detecting neuronal activity in the primate supplementary eye field.

In addition to cells specifically active with visual stimuli, saccades, or fixation, the supplementary eye field contains cells that fire in precise temporal relationship with the occurrence of reward. We studied reward-related activity in two monkeys performing a prosaccade/antisaccade task and in one monkey trained in memory prosaccades only. Two types of neurons were distinguished by their reciprocal firing pattern: reward-predicting (RP) and reward-detecting (RD). RP neurons linearly increased their firing as early as 150 ms before saccade onset until the occurrence of reward, at which time they abruptly ceased firing. In contrast, RD neurons fired in phase with reward delivery, even when its duration was varied and when it was repeated at different frequencies. RD discharges were little affected or unaffected by the position of a visual cue that briefly anchored the goal at the onset of reward. The complementary firing patterns of the RP and RD neurons could provide a feedback mechanism necessary for learning and performing the task.

Testing quasi-visual neurons in the monkey's frontal eye field with the triple-step paradigm.

To look successively at sites where several spots of light have appeared in the dark, we cannot simply rely on the image left by these targets on our retina. Our brain has to update target coordinates by taking into account each gaze movement that has taken place. A particular type of brain cell--the quasi-visual (QV) neuron--is assumed to play an important role in this updating by combining target coordinates and eye displacement signals. However, what is exactly this role? Is a QV neuron an element of a working memory that encodes the location of a potential target, or is it pointing to the location of the single goal selected for the next saccade? The two roles theoretically correspond to successive stages of processing: the locations of the optional targets would be stored at one stage, whereas the location of the next selected target would be stored at the subsequent stage. With a task that imposes a choice of goals--the triple-step paradigm--we found evidence that several groups of QV neurons can become simultaneously activated in the monkey's frontal eye field (FEF), suggesting that each group represents a different target location. This supports the hypothesis that the FEF itself contains the spatial information about not yet selected targets.

Primate antisaccades. I. Behavioral characteristics.

The antisaccade task requires a subject to make a saccade to an unmarked location opposite to a flashed stimulus. This task was originally designed to study saccades made to a goal specified by instructions. Interest for this paradigm surged after the discovery that frontal lobe lesions specifically and severely affect human performance of antisaccades while prosaccades (i.e., saccades directed to the visual stimulus) are facilitated. Training monkeys to perform antisaccades was rarely attempted in the past, and this study is the first one that describes in detail the properties of such antisaccades compared with randomly intermingled prosaccades of varying amplitude in all directions. Such randomization was found essential to force the monkeys to use the instruction cue (pro- or anti-) and the location cue (peripheral stimulus) provided within a trial rather than to direct their saccades to the location of past rewards. Each trial began with the onset of a central fixation target that conveyed by its shape the instruction to make a pro- or an antisaccade to a subsequent peripheral stimulus. In one version of the task, the monkey was allowed to make an immediate saccade to the goal; in a second version, the saccade had to wait for a go signal. Analyses of the accuracy, velocity, and latency of antisaccades compared with prosaccades were performed on a sample of 7,430 pro-/antisaccades in the "immediate saccade" task (delayed saccades suffering from known distortions). Error rates fluctuated approximately 25%. Results were the same for the two monkeys with respect to accuracy and velocity, but they differed in terms of reaction time. Both monkeys generated antisaccades to stimuli in all directions, at various eccentricities, but antisaccades were significantly less accurate and slower than prosaccades elicited by the same stimuli. Interestingly, saccades to the stimulus could be followed by appropriate antisaccades with no intersaccadic interval. Such instances are here referred to as "turnaround saccades." Because they occurred sometimes with a long latency, turnaround saccades did not simply reflect the cancellation of an early foveation reflex. Consistent with human data, latencies of one monkey were longer for antisaccades than for prosaccades, but the reverse was true for the other monkey who was trained differently. In summary, this study demonstrates the feasibility of providing a subhuman primate model of antisaccade performance, but at the same time it suggests some irreducible differences between human and monkey performance.

Interactions between natural and electrically evoked saccades. III. Is the nonstationarity the result of an integrator not instantaneously reset?

In the monkey, fixed-vector saccades evoked by superior colliculus (SC) stimulation when the animal fixates can be dramatically modified if the stimulation is applied during or immediately after an initial natural saccade. The vector is then deviated in the direction opposite to the displacement just accomplished as if it were compensating for part of the preceding trajectory. Recently, it was suggested that the amplitude of the compensatory deviation is related to the amplitude of the initial saccade linearly, and that the ratio between the two decreases exponentially as stimulation is applied later. These two findings (spatial linearity and temporal nonstationarity) were invoked as evidence for the noninstantaneous resetting of a feedback integrator. Such an integrator is included in most models of saccade generation for the specific purpose of terminating a saccade when it has reached its intended goal. However, the hypothesis of a feedback integrator in the process of being reset implies that the exponential decay of the compensatory deviation is temporally linked to the end of the initial saccade. We analyzed the time course of this decay in stimulation experiments performed at 24 SC sites in two monkeys. The results show that if the start of the exponential decay of compensation is assumed to be linked to the end of the initial saccade, then the relation between the amount of compensatory deviation and the amplitude of the initial saccade is not linear. On the other hand, it is possible to show a linear relation if the measurements of compensatory deviation are made in terms of delay of stimulation from the saccade beginning. We conclude that stimulating the SC just after a visually guided saccade does not seem to test the properties of a feedback integrator. Whether such an integrator is or is not resettable is not likely to be decided by this approach. Conversely, as the nonstationarity of compensation is linked to the beginning of the saccade, the nonstationarity seems to represent a property of an event occurring at saccade onset. We suggest that this event, close to the input of the oculomotor apparatus, is the summation of the visual signal with a damped signal of eye position or displacement.

Interaction of the two frontal eye fields before saccade onset.

A normal environment often contains many objects of interest that compete to attract our gaze. Nevertheless, instead of initiating a flurry of conflicting signals, central populations of oculomotor neurons always seem to agree on the destination of the next saccade. How is such a consensus achieved? In a unit recording and microstimulation study on trained monkeys, we sought to elucidate the mechanism through which saccade-related cells in the frontal eye fields (FEF) avoid issuing competing commands. Presaccadic neuronal activity was recorded in one FEF while stimulating the contralateral FEF with low-intensity currents that evoked saccades. When an eye-movement cell was isolated, we determined: the movement field of the cell, the cell's response to contralateral FEF microstimulation, the cell's response when the evoked saccade was in the preferred direction of the cell (using the collision technique to deviate appropriately the evoked saccade vector), and the cell's response to a stimulation applied during a saccade in the cell's preferred direction, to reveal a possible inhibitory effect. Complete results were obtained for 71 stimulation-recording pairs of FEF sites. The unit responses observed were distributed as follows: 35% of the cells were unaffected, 37% were inhibited, and 20% excited by contralateral stimulation. These response types depended on the site of contralateral stimulation and did not vary when saccades were redirected by collision. This invariant excitation or inhibition of cells, seemingly due to hardwired connections, depended on the angular difference between their preferred vector and the vector represented by the cells stimulated. By contrast, 8% of the cells were either activated or inhibited depending on the vector of the saccade actually evoked by collision. These results suggest that the consensus between cells of oculomotor structures at the time of saccade initiation is implemented by functional connections such that the cells that command similar movements mutually excite each other while silencing those that would produce conflicting movements. Such a rule would be an effective implementation of a winner-take-all mechanism well suited to prevent conflicts.

Antisaccade performance predicted by neuronal activity in the supplementary eye field.

The voluntary control of gaze implies the ability to make saccadic eye movements specified by abstract instructions, as well as the ability to repress unwanted orientating to sudden stimuli. Both of these abilities are challenged in the antisaccade task, because it requires subjects to look at an unmarked location opposite to a flashed stimulus, without glancing at it. Performance on this task depends on the frontal/prefrontal cortex and related structures, but the neuronal operations underlying antisaccades are not understood. It is not known, for example, how excited visual neurons that normally trigger a saccade to a target (a prosaccade) can activate oculomotor neurons directing gaze in the opposite direction. Visual neurons might, perhaps, alter their receptive fields depending on whether they receive a pro- or antisaccade instruction. If the receptive field is not altered, the antisaccade goal must be computed and imposed from the top down to the appropriate oculomotor neurons. Here we show, using recordings from the supplementary eye field (a frontal cortex oculomotor centre) in monkeys, that visual and movement neurons retain the same spatial selectivity across randomly mixed pro- and antisaccade trials. However, these neurons consistently fire more before antisaccades than prosaccades with the same trajectories, suggesting a mechanism through which voluntary antisaccade commands can override reflexive glances.

Perceived geometrical relationships affected by eye-movement signals.

To determine the location of visual objects relative to the observer, the visual system must take account not only of the location of the stimulus on the retina, but also of the direction of gaze. In contrast, the perceived spatial relationship between visual stimuli is normally assumed to depend on retinal information alone, and not to require information about eye position. We now show, however, that the perceived alignment of three dots-tested by a vernier alignment task-is systematically altered in the period immediately preceding a saccade. Thus, information about eye position can modify not only the perceived relationship of the entire retinal image to the observer, but also the relations between elements within the image. The processing of relative position and of egocentric (observer-centred) position may therefore be less distinct than previously believed.

Colliding saccades evoked by frontal eye field stimulation: artifact or evidence for an oculomotor compensatory mechanism underlying double-step saccades?

What happens when the goal is changed before the movement is executed? Both the double-step and colliding saccade paradigms address this issue as they introduce a discrepancy between the retinal images of targets in space and the commands generated by the oculomotor system necessary to attain those targets. To maintain spatial accuracy under such conditions, transformations must update "retinal error' as eye position changes, and must also accommodate neural transmission delays in the system so that retinal and eye position information are temporally aligned. Different hypotheses have been suggested to account for these phenomena, based on observations of dissociable cortical and subcortical compensatory mechanisms. We now demonstrate how a single compensatory mechanism can be invoked to explain both double-step and colliding saccade paradigm results, based on the use of a damped signal of change in position that is used in both cases to update retinal error and, thereby, account for intervening movements. We conclude that the collision effect is not an artifact, but instead reveals a compensatory mechanism for saccades whose targets appear near the onset of a preceding saccade.

Illusory localization of stimuli flashed in the dark before saccades.

A photic stimulus flashed just before a saccade in the dark tends to be mislocalized in the direction of the saccade. This mislocalization is not only perceptual; it is also expressed by errors of ocular targeting. A particular situation arises if the point of light is flashed twice at the same place, the second time, just before a saccade. The point of light may appear at two different places even though neither the site of its retinal image nor the direction of gaze change between the flashes. Experiments were run on five human subjects, head fixed in the dark, with flashes repeated at the site of the saccade goal or at the initial point of fixation. In both cases, the test stimulus was mislocalized. However, its apparent displacement never produced the perception of a streak. Streaks were reported only when there was an actual stimulus movement on the retina (e.g. by flashing the stimulus during the saccade). Mislocalization did not occur if the two flashes were not separated by a dark interval. This implies that, as long as a steady stimulus remains continually visible, there is no updating of the internal representation of eye position assumed to be used for stimulus localization.

The use of egocentric and exocentric location cues in saccadic programming.

Theoretically, the location of a visual target can be encoded with respect to the locations of other stimuli in the visual image (exocentric cues), or with respect to the observer (egocentric cues). Egocentric localization in the oculomotor system has been shown to rely on an internal representation of eye position that inaccurately encodes the time-course of saccadic eye movements, resulting in the mislocalization of visual targets presented near the time of a saccade. In the present investigation, subjects were instructed to localize perisaccadic stimuli in the presence or absence of a visual stimulus that could provide exocentric location information. Saccadic localization was more accurate in the presence of the exocentric cue, suggesting that localization is based on a combination of exocentric and egocentric cues. These findings indicate the need to reassess previously reported neurophysiological studies of spatial accuracy and current models of oculomotor control, which have focused almost exclusively on the egocentric localization abilities of the brain.

Oculomotor localization relies on a damped representation of saccadic eye displacement in human and nonhuman primates.

The oculomotor system has long been thought to rely on an accurate representation of eye displacement or position in a successful attempt to reconcile a stationary target's retinal instability (caused by motion of the eyes) with its corresponding spatial invariance. This is in stark contrast to perceptual localization, which has been shown to rely on a sluggish representation of eye displacement, achieving only partial compensation for the retinal displacement caused by saccadic eye movements. Recent studies, however, have begun to case doubt on the belief that the oculomotor system possess a signal of eye displacement superior to that of the perceptual system. To verify this, five humans and one monkey (Macaca nemestrina) served as subjects in this study of oculomotor localization abilities. Subjects were instructed to make eye movements, as accurately as possible, to the locations of three successive visual stimuli. Presentation of the third stimulus (2-ms duration) was timed so that it fell before, during, or after the subject's saccade from the first stimulus to the second. Localization errors in each subject (human and nonhuman) were consistent with the hypothesis that the oculomotor system has access to only a damped representation of eye displacement--a representation similar to that found in perceptual localization studies.

How the frontal eye field can impose a saccade goal on superior colliculus neurons.

Saccades were electrically evoked from the frontal eye field (FEF) of two trained monkeys while saccade-cells were recorded from the intermediate layers of the superior colliculus (SC). We found that FEF microstimulation, eliciting saccades of a given vector, excited SC saccade-cells encoding the same vector and inhibited all others. Such a mechanism can prevent competing commands from arising simultaneously in different structures.

Supplementary eye field: influence of eye position on neural signals of fixation.

Single units were recorded in the supplementary eye field of monkeys performing visual-oculomotor tasks. Two patterns of unit activity were observed while the animals fixated photic stimuli. One consisted of a step in tonic firing frequency (either an increase or a decrease, depending on the cell), lasting as long as fixation. The occurrence of this pattern did not require the continuous presence of a stimulus but the animal had to be provided with an incentive to fixate a given location. The other pattern was a monotonically varying firing rate dependent on the eye orientation along a particular axis, indicative of eye eccentricity in orbit.

The frontal eye field provides the goal of saccadic eye movement.

Microstimulation of oculomotor regions in primate cortex normally evokes saccadic eye movements of stereotypic directions and amplitudes. The fixed-vector nature of the evoked movements is compatible with the creation of either an artificial retinal or motor error signal. However, when microstimulation is applied during an ongoing natural saccade, the starting eye position of the evoked movement differs from the eye position at stimulation onset (due to the latency of the evoked saccade). An analysis of the effect of this eye position discrepancy on the trajectory of the eventual evoked saccade can clarify the oculomotor role of the structure stimulated. The colliding saccade paradigm of microstimulation was used in the present study to investigate the type of signals conveyed by visual, visuomovement, and movement unit activities in the primate frontal eye field. Colliding saccades elicited from all sites were found to compensate for the portion of the initial movement occurring between stimulation and evoked movement onset, plus a portion of the initial movement occurring before stimulation. This finding suggests that activity in the frontal eye field encodes a retinotopic goal that is converted by a downstream structure into the vector of the eventual saccade.

Primate supplementary eye field. II. Comparative aspects of connections with the thalamus, corpus striatum, and related forebrain nuclei.

The supplementary eye field (SEF) was defined electrophysiologically in behaving monkeys to study its connections with the diencephalon and corpus striatum. The specificity of SEF pathways was determined with horseradish peroxidase (HRP) histochemistry to compare its connections with those of the arcuate frontal eye field (FEF), contiguous dorsocaudal area 6 (6DC), and primary motor cortex (M1, arm/hand region). Results indicate that patterns of SEF connectivity were similar to the FEF and markedly different from areas 6DC and M1. Primary reciprocal thalamic pathways of the SEF were with the magnocellular ventral anterior (VA) nucleus, medial parvicellular VA, medial area X, and paralaminar medialis dorsalis (multiformis and parvicellularis). FEF showed similar connections but its most robust pathway was with MD rather than VA. In contrast, area 6DC showed the most extensive reciprocal connections with lateral VApc and lateral area X with only sparse connections with paralaminar MD. Area 6DC also exhibited reciprocal connections with the ventral lateral (VL) complex and the ventral posterior lateral nucleus, pars oralis (VPLo). M1 showed dense bidirectional connections with VPLo, and to a lesser extent, with VL. M1 pathways with the medial dorsal nucleus were negligible. All areas exhibited connections with the paracentral and central lateral nuclei and only M1 lacked connections with the central superior lateral nucleus. SEF and FEF exhibited similar efferent projections to the caudate and putamen. In the caudate, terminal fields were restricted to a central longitudinal core while those from area 6DC were more widely distributed. Eye field efferents were restricted to the putamen's face region while 6DC projections were more exuberant. The arm/hand region of M1 projected to the arm/hand region of the putamen. Pathways are discussed with respect to their significance in oculomotor control.

Primate supplementary eye field: I. Comparative aspects of mesencephalic and pontine connections.

WGA-HRP was used to examine projections to the brainstem from the supplementary eye field (SEF). The SEF was defined electrophysiologically in awake, behaving monkeys and connections were compared to those of the arcuate frontal eye field (FEF), area 6DC, and primary motor cortex. The SEF was found to have either direct or indirect connections with almost every known pre- and paraoculomotor structure of the brainstem. The SEF was found to project bilaterally to layers I and IV of a tangentially widespread region of the superior colliculus. Terminal label was evident in the pretectal olivary nucleus, nucleus of the optic tract, nucleus raphe interpositus (omnipause region), nucleus prepositus hypoglossi, the perioculomotor cap of the central gray, dorsal central gray, nucleus reticularis tegmenti pontis, nucleus reticularis pontis oralis, and to multiple nuclei of the basis pontis (most densely to the dorsomedial nucleus). Bilateral projections were found in the parvicellular red nucleus. Reciprocal connections were present in the nucleus limitans, the mesencephalic reticular formation, locus coeruleus, and the serotonergic nuclei of the raphe complex (dorsalis and central superior). Overall patterns of connectivity were similar to those of the FEF and markedly different from those of the contiguous dorsocaudal area 6 or primary motor cortex. It was concluded that observed patterns of SEF-brainstem connectivity further justifies viewing this region as a distinct eye field that is likely to serve preparatory and trigger functions in the generation of saccadic eye movements.