Nicolas Orlando Dessaints

PhD Laurent Goffart
email: laurent.goffart@cnrs.fr

Tracking a moving visual target in the rhesus monkey: Influence of the occurrence frequency of the target path

Keywords: saccade, pursuit, tracking, predic on, extrapola on

NEW & NOTEWORTHY (70<=75 words

ABSTRACT

Following previous studies documen ng the ability to generate an cipatory responses, we tested whether the repeated mo on of a visual target along the same path affected its oculomotor tracking. In six rhesus monkeys, we evaluated how the frequency of a target path influenced the onset, the accuracy and velocity of eye movements. Three hundred milliseconds aAer its ex nc on, a central target reappeared and immediately moved toward the periphery in four possible (oblique) direc ons and at constant speed (20 or 40°/s). During each daily sessions, the frequency of one mo on direc on was either uncertain (25% of trials) or certain (100% of trials). Our results show no reduc on of saccade latency between the two sessions. No express saccades were observed in either session. A slow eye movement started aAer target onset (pre-saccadic glissade) and its velocity was larger during the "certain" sessions only with the 40°/s target. No an cipatory eye movement was observed. Longer intersaccadic intervals were found during the "certain" sessions but the post-saccadic pursuit velocity exhibited no change. No correla on was found between the accuracy and precision of saccades (intercep ve or catch-up) and the post-saccadic pursuit velocity. Repeatedly tracking a target that moves always along the same path does not favor the genera on of an cipatory eye movements, saccadic or slow. Their occurrence is not spontaneous but seems to require a preliminary training. Finally, for both sessions, the lack of correla on between the saccaderelated and pursuit-related kinema c parameters is consistent with separate control of saccadic and slow eye movements.

INTRODUCTION

When a small target moves across the visual field, its mo on evokes a trace on the re na that ini ates a cascade of parallel and intertwined neural ac va ons, which lead to the produc on of a saccade and brings the target image within the central visual field. Then, a sequence of slow eye movements and small catch-up saccades maintains the visual centra on [START_REF] Dodge | Five types of eye movements in the horizontal meridian plane of the field of regard[END_REF][START_REF] Westheimer | Eye movement responses to a horizontally moving visual stimulus[END_REF][START_REF] Fuchs | Saccadic and smooth pursuit eye movements in the monkey[END_REF]. In some cases, the gaze moves smoothly as if it were locked onto the current physical loca on of the target. Such a spa otemporal accuracy is quite remarkable with regard to the delays for transmiKng the re nal signals to the extraocular motor nuclei. Recent works in the monkey showed that prac ce is required to acquire this ability to track a moving target con nuously and smoothly, i.e., with no catchup saccade [START_REF] Bourrelly | Learning the trajectory of a moving visual target and evolution of its tracking in the monkey[END_REF][START_REF] Botschko | Smooth pursuit eye movement of monkeys naive to laboratory setups with pictures and artificial stimuli[END_REF][START_REF] Goffart | Synchronizing the tracking eye movements with the motion of a visual target: Basic neural processes[END_REF]. Behavioral studies in human subjects also report that gaze direc on can be con nuously maintained toward a moving target when its path is "predictable" [START_REF] Bahill | Smooth pursuit eye movements in response to predictable target motions[END_REF][START_REF] Barnes | Influence of predictability on control of extra-retinal components of smooth pursuit during prolonged 2D tracking[END_REF]. By contrast, the oculomotor tracking is saltatory and composed of catchup saccades when the path is "unpredictable" [START_REF] Bahill | Smooth pursuit eye movements in response to unpredictable target waveforms[END_REF].

From now on, we will avoid using the no on of "predictability" as much as possible because it is not a physical property of the target but a psychological a:ribute, which depends upon the subject's ability to memorize and remember past events. When the set of possible paths taken by a moving target is limited, the so-called "predictability" of one path results from the frequency of its occurrence (physical factor) but also from the ability to remember prior experience (psychological factor). Behavioral experiments with human subjects reported that, when a target always moves along the same path, their eyes can some mes move in the same direc on as the target before its appearance [START_REF] Damasse | Reinforcement effects in anticipatory smooth eye movements[END_REF][START_REF] Santos | Anticipatory smooth pursuit eye movements evoked by probabilistic cues[END_REF][START_REF] Montagnini | Predicting 2D target velocity cannot help 2D motion integration for smooth pursuit initiation[END_REF][START_REF] Kowler | The effect of expectations on slow oculomotor control -I. Periodic target step[END_REF][START_REF] Kowler | The effect of expectations on slow oculomotor control -II. Single target displacements[END_REF]. Such an cipatory slow eye movements are mostly observed when the disappearance of the fixa on target is followed by a display devoid of targets [START_REF] Boman | Stimulus conditions that enhance anticipatory slow eye movements[END_REF]. Small sta c devia ons of gaze direc on have also been reported in human subjects when a blank interval (gap) separates the disappearance of a central fixa on target from the appearance of a second target always at the same loca on in the peripheral visual field [START_REF] Notaro | Predictions as a window into learning: Anticipatory fixation offsets carry more information about environmental statistics than reactive stimulus-responses[END_REF]. Thus, when there is no target leA to fixate, the repeated experience of a visual event causes a devia on of the eyes toward the visual field in which an target is about to appear. The direc on of gaze can either driA or shiA. It is noteworthy that in the experiments cited above, the visual events were brief and constant and the cadence of their occurrence was rela vely constant, raising the possibility that the ocular responses were merely condi oned automa c responses, i.e., akin to those observed during a Pavlovian condi oning procedure. If it is so, then it is not certain that the driA or shiA of eye posi on indicate a process belonging to the domain of "higher" cogni ve func ons.

In 1967, Dr Albert Fuchs, one of the founders of the modern neurophysiology of eye movements studied the performance of human subjects and monkeys while they tracked repe ve and periodic target mo ons [START_REF] Fuchs | Periodic eye tracking in the monkey[END_REF]. He showed that the monkeys did not produce an cipatory eye movements, contrary to human subjects. According to him, the monkeys were not as mo vated as were their human counterparts to perform the task. Later, another founder, Dr Edward Keller, inves gated with colleagues how macaque monkeys tracked a 2D circular moving target with or without a repe ve and periodic mo on [START_REF] Deno | Characterization of prediction in the primate visual smooth pursuit system[END_REF]. They proposed that the reduc on of the pursuit delay while tracking a rhythmically moving target was due to a "predic ve mechanism" compensa ng for the visuomotor delays and bringing gaze direc on nearby to the current physical target loca on. However, the periodic s muli employed were repe ve and the eye movements could s ll be viewed as sequen al condi oned responses that the monkeys learned in order to be rewarded. [START_REF] Freyberg | Anticipatory smooth-pursuit eye movements in man and monkey[END_REF] avoided the problems caused by periodic target mo ons [START_REF] Freyberg | Anticipatory smooth-pursuit eye movements in man and monkey[END_REF].

When aAer variable fixa on interval, a target moves exclusively to the right at a constant speed and when, in 50% of the trials, the early part of its mo on is ini ally invisible during 500 ms, both the human subjects and monkeys make, some mes, an an cipatory slow eye movement during this blank interval. Its velocity was very low but scaled to the target speed. Likewise, de Brouwer et al. (2001) studied head-restrained cats tracking a target moving at various constant speeds [START_REF] De Brouwer | Role of retinal slip in the prediction of target motion during smooth and saccadic pursuit[END_REF]. In some cases (10-50% of trials), the target disappeared aAer a variable me interval. They proposed that the slow eye movements made during the target ex nc on were driven by a so-called "predic on", i.e., by a process es ma ng the future target loca on.

However, these slow movements could as well be driven by residual target-mo on related signals that persisted aAer target disappearance as suggested by results reported by Mitrani and Dimitrov [START_REF] Mitrani | Pursuit eye movements of a disappearing moving target[END_REF]. Using a more sophis cated experimental protocol, De Hemp nne et al. (2006) showed that monkeys made 10-30 % more an cipatory slow eye movements when the target mo on direc on was cued by a colored fixa on target [START_REF] Hemptinne | Influence of cognitive expectation on the initiation of anticipatory and visual pursuit eye movements in the rhesus monkey[END_REF]. By co-varying the dura on of the fixa on and gap intervals and keeping constant the delay between the onsets of the fixa on and moving targets, [START_REF] Badler | Anticipatory movement timing using prediction and external cues[END_REF] showed also that the an cipatory slow eye movements were med to the disappearance of a fixa on target, sugges ng a temporal learning [START_REF] Badler | Anticipatory movement timing using prediction and external cues[END_REF]. Finally, De Hemp nne et al. (2007) found that longer gaps were associated with a larger width of the latency distribu on of an cipatory eye movements [START_REF] De Hemptinne | How do primates anticipate uncertain future events?[END_REF]. In all these experiments, the monkeys' performance required a long preliminary training.

The frequency of a target loca on and its ming also influence the velocity of saccades.

In human subjects, [START_REF] Bronstein | Predictive eye saccades are different from visually triggered saccades[END_REF] showed that when the target appeared at regular me intervals at the same loca on, the peak velocity of short latency saccades (latency < 100 ms) was 16% lower than saccades to targets whose loca on and ming were randomly selected among a set of values [START_REF] Bronstein | Predictive eye saccades are different from visually triggered saccades[END_REF]. A comparable slowing was observed in eye-head gaze shiAs made by cats orien ng toward a food target that was repeatedly presented on either side of a barrier placed in front of the animal [START_REF] Guitton | Gaze control in the cat: studies and modeling of the coupling between orienting eye and head movements in different behavioral tasks[END_REF]. The peak velocity of gaze shiAs was 26 % lower and their dura on 14% higher during the "predic ve target" condi on than during the "visible target" condi on. In the monkey, Schiller et al. (2004a) explored the effect of the frequency of target appearance at one loca on on the genera on of short-latency (express) saccades [START_REF] Schiller | How do target predictability and precueing affect the production of express saccades in monkeys?[END_REF]. Their occurrence increased with the most frequent target loca ons and longer gaps were associated with a greater propor on of express saccades. However, this propor on diminished when the number of possible target loca ons was increased [START_REF] Schiller | An examination of the variables that affect express saccade generation[END_REF] or when the targets were displayed upon a heterogeneous visual background or under natural viewing condi ons [START_REF] Schiller | Are express saccades generated under natural viewing conditions? Are express saccades generated under natural viewing conditions?[END_REF]. Finally, [START_REF] Carpenter | Neural competition of log likelihood in control of saccadic eye movements[END_REF] reported that as the frequency of occurrence of a sta c target increased, the latencies became shorter, their distribu on shallower and the number of express saccades increased, even though the dura on of the fixa on interval was randomized and no gap interval separated the target onset from the ex nc on of the fixa on target [START_REF] Carpenter | Neural competition of log likelihood in control of saccadic eye movements[END_REF].

In this study, we completed these previous studies by tes ng in the monkey whether the repeated presenta on of a target moving along the same path 1) produced an cipatory eye movements before its appearance and/or 2) affected its oculomotor tracking. More specifically, we evaluated how the frequency of the target path influenced the onset, the velocity and the accuracy of eye movements. On the basis of previous studies, we conjectured that repeatedly tracking a target, which aAer a constant gap interval, would move always along the same path would favor the occurrence of an cipatory slow eye movement and express saccades. We also conjectured that reducing the uncertainty about the target path would make the intercep ve saccades and the post-saccadic velocity less variable, and thus more precise. Finally, aAer showing in naive monkeys that saccadic and pursuit eye movements do not share common mo on signals (4), we tested whether this conclusion also holds in monkeys who were overtrained to track a target moving at constant velocity.

MATERIAL AND METHODS

Subjects and surgical procedures

Six adult male rhesus monkeys (Bi, C, D, E, F and G ; age: 5-12 yr old; weights: 8-14 kg) were used in this study. A head restraint fixture was posi oned on the top front center of the skull and secured with bone cement (Palacos) and stainless screws a:ached to the skull, under general anesthesia (with isoflurane or sevoflurane) and asep c condi ons. For four of these monkeys (monkeys Bi, C, F and G), the monitoring of their eye movements was made with the electromagne c induc on technique. A three-turn search coil was sutured with silk to the sclera under the conjunc va of one eye aAer local anesthesia (with oxybuprocaine). Lead wires were passed under the skin to a connector located on the top of the skull and secured with bone cement. The scleral coil and head restrain fixture was implanted during the same surgery for the monkeys Bi, C, D, F and G. In monkey D, a persistent mydriasis aAer the surgery in the implanted eye led us to remove the coil.

The surgical procedure and experiments were performed in accordance with the guidelines from the French Ministry of Agriculture and the European Community, as well as the Regional Ethics Commi:ee (approvals A13/01/13 and 13889-2018030211578026). The health and the maintenance of the monkeys' housing were monitored daily by a dedicated zoo-technical staff supervised by a full-me veterinarian.

Eye movement recording and visual s5mula5on

During the experimental sessions, the monkeys were seated in a chair with the head restrained, facing a LCD video monitor (Samsung SyncMaster, P227f; 1,280 × 1,024 pixels, 100-Hz refresh rate, 39 × 29 cm) located at a viewing distance of 38 cm. The visual target was a Gaussian blurred white disk of 0.4° diameter displayed over a gray background.

For monkey Bi, C, F and G, the eye movements were recorded with a phase-angle detec on system (CNC Engineering, 3-A. coil frame) and voltage signals encoding separately the horizontal and ver cal posi ons of the eye were sampled at 500 Hz. For monkeys D and E, the eye movements were recorded with an IR eye tracking system (Eyelink 1000, SR Research Ltd).

The data acquisi on, the online control of the oculomotor performance and the triggering of s muli were controlled by a PC using the Beethoven soAware package (Ryklin SoAware). Eye posi on signals were calibrated by having the animal fixate sta onary targets located at ±16° along the horizontal or ver cal meridians.

Behavioral tasks

Figure 1 approximately here

In this study, we describe how the frequency of occurrence of a target path influenced the tracking eye movements. The sessions started several weeks aAer the monkeys were trained to make saccades to sta c targets located at various eccentrici es, ranging from 0 to ±16° horizontally at ver cal eccentricity of ±16°. Each experimental session (las ng 1-2 h) was composed of trials whose number depended upon the monkey's mo va on. Water-deprived in its home cage, each monkey received its hydra on needs during daily sessions that ended when it stopped working, i.e., fixa ng the central target for approximately 10 successive trials.

Each trial started with a warning tone (300 ms) that preceded the appearance of a target at the center of visual display (Figure 1). AAer the monkey directed its gaze toward its loca on within a surrounding fixa on window (8° radius centered on the target) and for a variable fixa on interval (750, 1,000, 1,250 or 1,500 ms), the central target disappeared. Then, a gap interval of 300 ms started during which no target was presented on the visual display. The monkeys were no more required to maintain their gaze within the fixa on window during this gap interval. Then, the target re-appeared at the center of the visual display and immediately moved with a constant speed for 800 or 1200 ms (20°/s) or 600 ms (40°/s), along one out of four possible oblique paths. The monkeys spontaneously tracked the moving target and were rewarded with a small volume of water aAer the target disappeared at the end of its path. All of them performed the experiment with the lowest target speed (20°/s), and only four monkeys (Bi, C, D and E) were tested with the highest target speed (40°/s). We divided the visual field into four quadrants: when the target moved rightward and upward, when it moved rightward and downward, when it moved downward and leAward and when it moved leAward and upward. Considering each target path among four possible ones, two frequencies of occurrence were tested during separate sessions, which were recorded during different days: 25% ("uncertain" sessions) or 100% ("certain" sessions). During the "uncertain" sessions, the direc on of the target path was pseudo-randomly selected from one trial to the next. To avoid oculomotor biases resul ng from prior experience, these sessions always preceded the recordings of tracking eye movements during the "certain" sessions. During the la:er, the monotony of the task caused the monkeys to stop tracking the target before obtaining the same volume of water as that obtained during the "uncertain" sessions. In that case, we managed to reach their hydric sa a on by proposing them other visual tracking tasks that were less monotonous.

Data analysis

Figure 2 approximately here

The recordings of eye movements were digi zed on-line and analyzed off-line using a soAware program (Eyemove, designed by Kathy Pearson and Dr David L. Sparks) that detected the onset and offset of the horizontal and ver cal saccade components based on a velocity threshold (30°/s). The results of this automa c detec on were checked by inspec ng each trial individually and adjusted manually when necessary. Several other parameters were calculated to quan fy the evolu on of the oculomotor responses (Figure 2). From the measurement of eye posi on at different mes (onset and end of saccades) rela ve to target mo on onset (dashed ver cal line labeled 1), we calculated the amplitude and velocity of the intercep ve (IS, grey zone delimited by the lines labeled 2 and 3) and the catch-up saccade (CS, grey zone delimited by the lines labeled 4 and 5). The la:er is defined as the first correc on saccade that follows the intercep ve saccade. We also studied the pre-saccadic glissade (PSG, delimited by the lines labeled 1 and 2), which is the slow eye movement that was eventually made before the intercep ve saccade, and the post-saccadic pursuit (PSP), which is the slow eye movement made from the end of the intercep ve saccade (line 3) to the onset of the catch-up saccade (line 4). By conven on, posi ve values correspond to upward and rightward eye posi ons, nega ve values to downward and leAward eye posi ons.

Data analysis was performed with the Sta s ca SoAware (StatsoA) and Python (Python SoAware Founda on, Python Language Reference, version 3.1). We performed nonparametric Wilcoxon Test for the pairwise comparison of median and interquar le range (IQR) values of each variable, except for monkey D. Indeed, because of his permanent monocular mydriasis, we preferred to examine the data collected in this monkey separately from the others. The comparison of IQR values of a given parameter between the "uncertain" and "certain" sessions enabled us to es mate whether the tracking of a target that moved in the same direc on and at the same velocity during the en re session was associated with a reduc on of the variability of that parameter. Sta s cal significance threshold was set to P < 0.05. When the median and interquar le range (IQR) values were nega ve, we mul plied them by -1 in order to facilitate the comparison with the other values.

In some trials, most oAen in the monkeys Bi, D and E, gaze was deviated upward at the me when the moving target appeared because these monkeys made a spontaneous saccade during the gap interval. Therefore, for making valid comparisons between saccades (comparable re nal s mula ons), we focused only on trials in which the star ng eye posi on at target mo on onset ranged from -5 to 5 degrees (horizontally and ver cally). In addi on to this criterion, the saccades had to land in the visual quadrant in which the target moved, within in a fixa on window ranging from -5 to 5 degrees (horizontally and ver cally) with respect to the target loca on at the me of saccade landing. In the following, we firstly report the influence of the target path frequency on the intercep ve saccades. Then we describe the preand post-saccadic slow eye movements and the catch-up saccades. We excluded the catch-up saccades whose onset occurred 100 ms before the end of the trial. We only considered the catch-up saccades that landed within a window ranging from -5 to 5 degrees (horizontally and ver cally) with respect to the target loca on at the me of their landing.

RESULTS

The report of results follows the temporal order of measured parameters during the course of a trial (as illustrated in Fig. 2). AAer examining whether gaze was moving at target appearance during the "certain" sessions, we will study whether the frequency of the target path changed the pre-saccadic glissade (slow eye movement from target onset to saccade onset), the intercep ve saccade (its latency, velocity, accuracy and precision), the postsaccadic pursuit eye movement and the catch-up saccade.

Repeatedly tracking the same target did not lead to an5cipatory slow eye movement

Figure 3 approximately here

As previous studies reported an cipatory movements before the appearance of the target, we examined whether gaze was moving at target onset by calcula ng the horizontal and ver cal veloci es of the eye displacement during a temporal interval of 80 ms centered on target mo on onset. We did not study the radial velocity because its calcula on leads to posi ve value regardless of the direc on of target mo on. Figure 3 plots the sta s cs (median and IQR) for each monkey, each quadrant and each target velocity. With the 20°/s target, the paired comparison of median and IQR values failed to reveal any sta s cally significant difference of eye velocity at target onset between the two sessions for the horizontal (∆Med = 0.07 ± 0.4 °/s, P value = 0.8; ∆IQR = 0.01 ± 0.05 °/s, P value = 1) and ver cal (∆Med = 0.14 ± 0.4, P value = 0.07; ∆IQR = 0.01 ± 0.08 °/s, P value = 0.48) components. With the 40°/s target, no significant difference was found either between the "certain" and "uncertain" sessions, and this, for each component as well (horizontal: ∆Med = 0.1 ± 0.9°/s; ver cal: ∆Med = 0.1 ± 0.7°/s, P value = 0.77). The horizontal velocity was significantly more variable during the "certain" sessions than during the "uncertain" sessions (∆IQR = 0.02 ± 0.03°/s, P<0.05) but not the ver cal velocity (∆IQR = 0.01 ± 0.06°/s, P value = 0.23). In summary, at the me of target onset and in comparison to the "uncertain" sessions, we found no evidence of eye movement an cipa ng the appearance of the target when it always moved along the same path.

Repeatedly tracking the same target did not enhance the pre-saccadic slow eye movement

Figure 4 approximately here

AAer checking whether the eyes were moving at the me of target appearance, we then studied the eye displacement during the me interval elapsed from the target mo on onset to the saccade onset. Figure 4A shows the amplitude of the eye movement that preceded the intercep ve saccade as a func on of the saccade latency when the target moved in the upper right visual quadrant (data collected in monkey Bi). The sca:er of data points shows that later saccades were associated with larger pre-saccadic changes in eye posi on.

We call this change pre-saccadic glissade because its small value radically differs from the postsaccadic smooth pursuit. To es mate its velocity, we calculated the slope of the rela on between its amplitude and the delay from target mo on onset to saccade onset (which is saccade latency). Considering for example the cases during which the 20°/s target moved in the upper right visual field, the slopes were 13 versus 14 °/s (monkey Bi), 7 versus 2 °/s (monkey C), 11 versus 1 °/s (monkey E), 2 versus 5 °/s (monkey F) and 4 versus 4 °/s (monkey G) during the "uncertain" and "certain" sessions, respec vely. Figure 4B plots the slope values calculated for each visual quadrant, each monkey and each target speed. Their paired comparison revealed no sta s cally significant difference between the "certain" and "uncertain" sessions (∆slope = -0.5 ± 3.6°/s, P value = 0.12). A small but significant change was observed during the "certain" sessions when the target moved at 40°/s (∆slope = 4.3 ± 5.1°/s, P<0.05).

In summary, during both "uncertain" and "certain" sessions, a pre-saccadic glissade started aAer the target started its mo on. In comparison to the sessions in which the target path varied across the trials, its radial velocity was increased (135% increase) during the "certain" sessions when the target moved at 40°/s. However, no difference was observed with the 20°/s target.

Repeatedly tracking the same target reduced neither the latency nor the velocity of intercep5ve saccades.

Following the sugges ons that the latency and velocity of saccades could be used as behavioral markers of the mo va on [START_REF] Takikawa | Modulation of saccadic eye movements by predicted reward outcome[END_REF] and alertness [START_REF] Stasi | Saccadic peak velocity as an alternative index of operator attention: A short review[END_REF], we checked whether the monotony of tracking a target that repeatedly moved along the same path for a large number of trials was associated with a decline in either the mo va on or the vigilance of our monkeys.

Figure 5 approximately here

Regarding the velocity, we calculated for each visual quadrant and each monkey, the ra o between the radial amplitude of saccades and their dura on, i.e. their average velocity.

The comparison of median and interquar le range (IQR) values (Figure 5) revealed no consistent difference between the "certain" and "uncertain" sessions (mean ± std of differences of median values ∆Med = 0.3 ± 15 and 2 ± 28°/s for the 20°/s and 40°/s target, respec vely, Wilcoxon non parametric tests, P value = 0.26 and 0.39). The variability of average veloci es was not changed either as the IQR values were not significantly different between the "certain" and "uncertain" sessions (mean ± std of differences of interquar le range values: ∆IQR = 0.3 ± 15.5 and 2 ± 28°/s for the 20°/s and 40°/s target, respec vely, P values = 0.26 and 0.39).

Figure 6 approximately here

Regarding the latency of intercep ve saccades, figure 6 shows the distribu on of its values for each quadrant of the visual field during the "uncertain" (white) and "certain" (grey) sessions (leA column: 20°/s; right column: 40°/s). Although an interval (gap) separated the target mo on onset from the offset of the fixa on target, the distribu ons of latency values do not exhibit a double peak sugges ve of the presence of express saccades. In our study, we found no saccade with a latency smaller than 102 ms. When we consider for example the saccades toward the 20°/s target moving in the upper right quadrant, the sta s cs of latency values were iden cal between the "uncertain" and "certain" sessions in monkey Bi (both medians ± IQRs = 144 ± 14 ms) and in monkey G (172 ± 21 versus 172 ± 38 ms). Very small differences were observed in the other monkeys: 146 ± 18 versus 152 ± 16 ms (monkey C; 6 ms difference), 154 ± 18 versus 166 ± 24 ms (monkey E; 12 ms difference), 175 ± 16 versus 185 ± 10 ms (monkey F; 10 ms difference).

Figure 7 approximately here

To test whether these small differences were reproducible and sta s cally significant, we performed a paired comparison (Wilcoxon non-parametric test) of median values between the "uncertain" and "certain" sessions for all visual quadrants and all monkeys, except monkey D (values plo:ed in Fig. 7). With the 20°/s target, a very small but significant latency increase (4%) was then detected during the "certain" sessions (average difference of median values= 6 ± 6 ms, P<0.05). No sta s cally significant change was observed in the IQR values between the two sessions (average difference = 3 ± 7 ms, P value = 0.33). With the 40°/s target, the paired comparison of median and IQR values failed to reveal any significant difference between the two sessions (average difference of medians = 6 ± 10 ms, P value = 0.77; average difference of IQRs = 3 ± 5 ms; P value = 0.5).

In summary, within our experimental condi ons, the monkeys did not exhibit any sign of reduced mo va on or reduced alertness while they repeatedly performed the same task from one trial to the next. Between the "certain" and "uncertain" sessions, we found no difference in the average velocity of intercep ve saccades. A negligible increase (4%) of latency was observed in the saccades toward the 20°/ target only. These observa ons contrast with the reduced latency and velocity of "predic ve" saccades as reported in previous studies [START_REF] Bronstein | Predictive eye saccades are different from visually triggered saccades[END_REF][START_REF] Carpenter | Neural competition of log likelihood in control of saccadic eye movements[END_REF] Repeatedly tracking the same target changed neither the accuracy nor the precision of intercep5ve saccades.

Figure 8 approximately here

Then, we inves gated the effect of the target path frequency on the accuracy and precision of intercep ve saccades. Figure 8A plots for each target speed (leAmost graphs: 20°/s, rightmost graphs: 40°/s), the landing posi on (radial value) of intercep ve saccades as a func on of their landing me when the target moved in the upper leA visual field (data from monkey Bi). The landing posi ons were sca:ered near the target (dashed line) during both sessions. The frequency of the target path did not seem to influence the accuracy of saccades: the sca:ers of posi on values did not show any no ceable difference between the "uncertain" and "certain" sessions. To quan fy the accuracy and precision of saccades, we calculated the ra o of their landing posi on over their landing me, a parameter that Groh et al. (1997) called "saccadic velocity compensa on" [START_REF] Stasi | Saccadic peak velocity as an alternative index of operator attention: A short review[END_REF] and that Bourrelly et al. (2018a) called "posi on/ me landing ra o" (P/T ra o) [START_REF] Groh | How is a sensory map read out? Effects of microstimulation in visual area MT on saccades and smooth pursuit eye movements[END_REF]. If the intercep ve saccade lands accurately on the loca on of the moving target, its value should be equal to the target velocity. A ra o larger indicates hypermetria (overshoot) and a smaller ra o hypometria (undershoot). When the 20 °/s target always moved in the upper right visual field, the P/T ra os were close to the target velocity: 19 ± 4, 17 ± 3, 20 ± 3, 22 ± 3 and 23 ± 6°/s during the "uncertain" sessions against 20 ± 3, 18 ± 4, 18 ± 5, 21 ± 5 and 23 ± 6°/s during the "uncertain" sessions (values for monkey Bi, C, E, F and G respec vely). Figure 8B plots the median and IQR values of the posi on/ me (P/T) landing ra o for each visual quadrant and each monkey. Their paired comparison revealed no sta s cally significant difference between the two sessions (∆Med = 3 ± 1 °/s, P value = 0.5; ∆IQR= 0.2 ± 0.85 °/s; P value = 0.26). With the 40°/s target, no significant difference was found either between the "certain" and "uncertain" sessions (∆Med =-0. 6 ± 1.3°/s, P value = 0. 15; ∆IQR = 0.07 ± 0.8°/s, P value = 0.39, all quadrants and all monkeys considered, except monkey D).

In summary, the frequency of the target path did not influence the accuracy and precision of intercep ve saccades. The saccades were neither more accurate nor more precise when they were aimed at a target whose path and velocity were the same from one trial to the next.

Repeatedly tracking the same target did not enhance the post-saccadic slow eye movement

Figure 9 approximately here Two types of eye movements are made while a small visual target is being tracked: a slow eye movement and catchup saccades. We conjectured that tracking a target that moves always along the same path would maintain the ac vity conveyed by the visuomotor channels involved in the genera on of slow eye movements. To test this conjecture, we checked whether the me interval elapsed from the end of the intercep ve saccade to the onset of the first catch-up saccade was longer during the "certain" sessions than during the "uncertain" sessions. Figure 9A documents for each monkey, each visual quadrant and each target speed, the dura on of this first intersaccadic interval. The fact that most median values are situated above the diagonal indicates that the first intersaccadic intervals were indeed longer during the "certain" sessions than during the "uncertain" ones, regardless of whether the target moved at 20 or 40°/s. The paired comparison of median values confirmed longer intersaccadic intervals during the "certain" sessions than during the "uncertain" sessions when the target moved at 20°/s (∆Med = 28 ± 27 ms; P<0.05) and when it moved at 40°/s (∆Med = 30 ± 13 ms; P<0.05). The IQR values were also significantly different between the two sessions when the target moved at 40°/s (∆IQR = 20 ± 11 ms; P<0.05) but not when it moved at 20°/s (∆IQR = 16 ± 23 ms; P value = 0.12). In summary, there was a tendency for the catch-up saccades being made later when the target moved always in the same path (15% and 21% longer intersaccadic intervals for 20°/s and 40°/s target respec vely), sugges ng that visual tracking is smoother (more con nuous with less frequent saccades) during the "certain" sessions during the "uncertain" ones. For the 40°/s target, the dura on of intersaccadic intervals was also more variable during the "certain" sessions.

The longer intersaccadic intervals during the "certain" sessions could result from less variable post-saccadic velocity and/or from less variable distances between gaze and target posi ons. To test these possibili es, we examined the rela on between the amplitude of the post-saccadic pursuit eye movement and its dura on (average post-saccadic pursuit velocity). This rela on is documented in Fig. 9B for all the trials during which monkey Bi tracked the target moving in the upper leA visual field. The data points are slightly below or close to the diagonal dashed line, indica ng that the eye moved either slower or as fast as the target when it moved at 20°/s, regardless of whether the session was "certain" or "uncertain". When the target moved at 40°/s, most data points are below the dashed line during both sessions: the eye moved slower than the target.

To test whether the post-saccadic pursuit velocity was changed during the "certain" sessions, we calculated for each monkey and each visual quadrant, the ra o between the amplitude of the post-saccadic eye displacement and its dura on (Figure 9C). In the majority of cases, the median values were smaller than the target speed during both "certain" and "uncertain" sessions. Most of the data points are indeed situated below the dashed lines, which indicate the target velocity. For example, when we consider the session during which the target moved at 20°/s in the upper right visual field, the post-saccadic pursuit velocity (median ± IQR) was 17 ± 2, 16 ± 2, 12 ± 3, 12 ± 3 and 9 ± 3 °/s during the "uncertain" sessions and 18 ± 2, 17 ± 2, 12 ± 3, 12 ± 2, and 8 ± 2 °/s during the "certain" sessions(values for monkey Bi, C, E, F and G, respec vely). The paired comparison of median values calculated for each monkey and each quadrant did not reveal any change between the "uncertain" and "certain" sessions, regardless of whether the target moved at 20°/s (∆Med = -0.3 ± 1.3°/s; P value = 0.26) or 40°/s (∆Med = -3 ± 3°/s; P value = 0.15). Concerning the variability of post-saccadic pursuit velocity, the IQR values were not significantly different between the "uncertain" and "certain" sessions, neither with the 20°/s target (∆IQR = 0.4 ± 0.7°/s, P value = 0.12) nor with the 40°/s target (∆IQR = 2 ± 3°/s; P value = 0.15). In summary, the longer intersaccadic intervals during the "certain" sessions were not associated with a different post-saccadic pursuit velocity.

Repeatedly tracking the same target did not change the accuracy or precision of catch-up saccades Figure 10 approximately here Catchup saccades being the other important component of the visual tracking, we also studied the influence of the occurrence frequency of the target path on their accuracy and precision. Figure 10A plots for each target velocity the radial landing posi ons of the first catchup saccade as a func on of its landing me when the target moved in upper leA visual field (data collected in monkey Bi). The landing posi on values were sca:ered near the target path (dashed line) during both "uncertain" and "certain" sessions. The frequency of the target path did not seem to influence the accuracy of catch-up saccades as there is no no ceable difference in the shape or in the extent of the sca:ers of posi on values between the "uncertain" and "certai"n sessions. As for the intercep ve saccades, we quan fied the accuracy and precision of catch-up saccades by calcula ng the posi on/ me landing ra os.

Figure 10B documents their value during both sessions. Looking at the graph corresponding to the 20°/s target, we see an asymmetry in the sca:er of data points: the majority of values are larger than the target velocity and the majority of data points are situated below the diagonal line, sugges ng an influence of the frequency of the target path. The paired comparison of median values confirmed a slightly smaller values of P/T landing ra o during the "certain" sessions (∆Med = -0.6 ± 0.8°/s, P<0.05). The lower IQR values during the "certain" sessions was also sta s cally significant (∆IQR = -0.4 ± 0.6 °/s, P<0.05). These small differences between the "uncertain" and "certain" sessions were absent when the target moved at 40 °/s. The paired comparisons revealed no significant difference in the median and IQR values of posi on/ me landing ra os (∆Med = 0.8 ± 1.1°/s, P-value= 0.15; ∆IQR = 0.3 ± 1.2°/s, P-value = 0.77).

In summary, when the target moved at 20°/s along the same path, catch-up saccades were slightly more accurate (2.8% decrease) and more precise (20% decrease) than when its path changed across the trials. However, the difference between the "uncertain" and "certain" sessions was absent when the target moved at 40°/s.

Comparing the posi5on/5me landing ra5o of intercep5ve saccades with the post-saccadic pursuit velocity

Figure 11 approximately here Anatomical, neurophysiological and clinical evidence indicate that saccadic and pursuit eye movements are not driven by common command signals [START_REF] Bourrelly | Pursuit disorder and saccade dysmetria after caudal fastigial inactivation in the monkey[END_REF]. Studies with naive and healthy monkeys also show a clear dissocia on between the saccade and pursuit performances when they track for the first me a moving target (4-5). We further inves gated this dissocia on in our over-trained monkeys. More specifically, we compared the radial posi on/ me landing ra o of intercep ve saccades to the radial post-saccadic pursuit velocity.

Figure 11A shows the values calculated from movements made by monkey Bi when the target moved at 20°/s (leAmost two graphs) and 40°/s (rightmost graphs) in the upper right visual field. The values of posi on/ me landing ra o were sca:ered about the target velocity (dashed lines) during both "uncertain" and "certain" sessions, illustra ng the accuracy of intercep ve saccades (as reported above). By contrast, the post-saccadic pursuit (PSP) velocity values were consistently smaller than the target velocity (values are situated on the leA with respect to the ver cal dashed lines) for both sessions. No correla on was no ceable between these two parameters, sugges ng that intercep ve saccades and pursuit eye movements are driven by different mo on signals.

To further test the consistency of this inference, we compared the median and IQR values of radial posi on/ me landing ra os of intercep ve saccades to those of the radial postsaccadic pursuit velocity (Figure 11B). For both "uncertain" and "certain" sessions, the values of radial posi on/ me landing ra o were sca:ered about the target velocity (horizontal dashed lines) whereas the post saccadic pursuit velocity values were consistently smaller than the target velocity (most data points are situated to the leA of the ver cal dashed lines).

Considering the trials recorded during the "uncertain" sessions when the target moved at 20°/s in the upper right visual field, the median values of radial posi on/ me landing ra o were 20 ± 3°/s, 18 ± 4°/s, 18 ± 5°/s, 21 ± 5°/s and 23 ± 6°/s (values for monkey Bi, C, E, F and G, respec vely), much larger than the medial values of post-saccadic pursuit velocity, which were 17 ± 2°/s, 16 ± 2°/s, 12 ± 3°/s, 12 ± 3°/s and 9 ± 3°/s. Likewise, during the "certain" sessions, the radial posi on/ me landing ra os were most oAen larger than the post-saccadic pursuit veloci es: 19 ± 4 versus 18 ± 2 °/s in monkey Bi, 17 ± 3 versus 17 ± 2 °/s (monkey C), 20 ± 3 versus 12 ± 3 °/s (monkey E), 22 ± 3 versus 12 ± 2 °/s (monkey F) and 23 ± 6 versus 8 ± 2 °/s (monkey G).

The paired comparison of median values calculated for all visual quadrants and all monkeys (except D) confirmed posi on/ me landing ra os that were consistently larger than the post-saccadic velocity values, during both sessions (uncertain: ∆Med = 4.4 ± 4.2°/s; certain: ∆Med = 4.4 ± 4.7 °/s, P<0.05). With the 40°/s target, the posi on/ me landing ra os was again significantly larger than the post-saccadic veloci es during both sessions (uncertain: ∆Med = 12.9 ± 5.4°/s; certain: ∆Med = 10.5 ± 7.9°/s, P<0.05). Regarding the variability, the IQR values of posi on/ me landing ra o of intercep ve saccades were larger than the IQR values of postsaccadic pursuit veloci es, only during the "certain" sessions and when the target moved at 20°/s (certain: ∆IQR = 1.1 ± 1.2 °/s, P<0.05; uncertain: ∆IQR = 0.8 ± 1.2 °/s, P-value = 0.12). This difference is another indica on that intercep ve saccades and post-saccadic pursuit are driven by different mo on signals. However, this difference was absent with the 40°/s target (uncertain: ∆IQR = -1.1 ± 2.3 °/s; certain: ∆IQR = 0.4 ± 0.9 °/s, P-value = 0.38). The absence of sta s cally significant difference can result either from the small size of our sample or from the high velocity of the target mo on. In any case, with regard to their ability to match the target velocity, intercep ve saccades were more accurate than the post-saccadic pursuit eye movements. The significant difference between the posi on/ me landing ra os of intercep ve saccades and the post-saccadic pursuit velocity and the absence of correla on is consistent with the thesis that intercep ve saccades and post-saccadic pursuit are driven by different sets of mo on signals.

Comparing the post-saccadic pursuit velocity with the posi5on/5me landing ra5o of catchup saccades

Figure 12 approximately here

One possible cause for the difference between the posi on/ me landing ra o of intercep ve saccades and the post-saccadic pursuit velocity is the different re nal origins of mo on signals, in the visual periphery for the former, in the central visual field for the la:er. Therefore, we also compared the radial post-saccadic pursuit velocity to the radial posi on/ me landing ra o of catch-up saccades. Figure 12A shows values obtained with the monkeys Bi when the target moved in the upper right quadrant of the visual field. During both "uncertain" and "certain" sessions, the radial posi on/ me landing ra os were s ll sca:ered about the target velocity (ver cal dashed lines) with a tendency however of being slightly faster than the target. By contrast, most of the post-saccadic pursuit velocity values were sca:ered below the target velocity (horizontal dashed lines). There is no sign of correla on between these two parameters.

Then, we compared the median and IQR values of the radial posi on/ me landing ra os of catch-up saccades to those of radial post saccadic pursuit velocity (Figure 12B). As for the intercep ve saccades, the posi on/ me landing ra o of catch-up saccades was more accurate than the post saccadic pursuit velocity. For instance, when the target moved at 20 °/s in the upper right quadrant of the visual field, the median values of radial posi on/ me landing ra o of catch-up saccades during the "uncertain" sessions were 21 ± 2, 19 ± 3, 21 ± 2, 22 ± 3 and 23 ± 4°/s whereas the post-saccadic pursuit velocity values were consistently smaller: 17 ± 2, 16 ± 2, 12 ± 3, 12 ± 3 and 9 ± 3°/s (values for the monkeys Bi, C, E, F and G, respec vely).. Likewise, during the "certain" sessions, the radial posi on/ me landing ra os were consistently larger than the post-saccadic pursuit velocity: 20 ± 2 versus 18 ± 2°/s in monkey Bi, 19 ± 2 versus 17 ± 2°/s in monkey C, 20 ± 1 versus 12 ± 3°/s in monkey E, 22 ± 1 versus 12 ± 2°/s in monkey F and 22 ± 4 versus 8 ± 2°/s in monkey G. When the target moved at 40°/s, the radial posi on/ me landing ra o was smaller than the target velocity but s ll larger than the post-saccadic pursuit veloci es.

Figure 12B plots the median and IQR values of radial post saccadic pursuit velocity calculated for each quadrant of the visual field and each monkey as a func on of the posi on/ me landing ra o of catch-up saccades. The paired comparison of median values confirmed a sta s cally significant larger posi on/ me landing ra o than the post-saccadic velocity for both "certain" and "uncertain" sessions, when the target moved at 20°/s (uncertain: ∆Med = 6.4 ± 4.7°/s; certain: ∆Med = 5.5 ± 4.6 °/s, P<0.05) as well as when it moved at 40°/s (uncertain: ∆Med = 15.6 ± 6.6 °/s; certain: ∆Med = 11.9 ± 9.5°/s, P<0.05). Regarding the variability, the IQR values of posi on/ me landing ra o of catch-up saccades were consistently smaller than the IQR values of post-saccadic pursuit velocity for both sessions, regardless of whether the target moved at 20°/s (uncertain: ∆IQR = 0.7 ± 1 °/s, P<0.05; certain: ∆IQR = 0.7 ± 1.1°/s, P<0.05) or 40°/s (uncertain: ∆IQR = 3.7 ± 2.3°/s; certain: ∆IQR = 2.4 ± 1.2°/s, P<0.05).

In summary, with regard to their ability to match target velocity, the catch-up saccades were more accurate and more precise (smaller IQR) than the post-saccadic pursuit eye movements, during both "uncertain" and "certain" sessions and for both target veloci es.

Comparison of P/T landing ra5o of intercep5ve and catch-up saccades

Figure 13 approximately here Finally, the different re nal origins of intercep ve and catchup saccades led us to compare their accuracy and precision (Figure 22). For both "uncertain" (top row) and "certain" With the 40 °/s target, the posi on/ me landing ra o of catch-up saccades were s ll larger during the "uncertain" sessions (∆Med = 2.7 ± 2.7 °/s, P<0.05). However, the difference disappeared during the "certain" sessions (∆Med = 1.4 ± 2.7 °/s, P value = 0.39). Regarding the precision of saccades, the IQR values of posi on/ me landing ra o were larger for the intercep ve saccades than for the catch-up saccades, indica ng that catch-up saccades were more precise than intercep ve saccades. Indeed, when the path moved at 20 °/s, the average differences were 1.5 ± 1 °/s (P<0.05) and 1.8 ± 0.9 °/s (P<0.05) for the "uncertain" and "certain" sessions, respec vely. Likewise, when the path moved at 40 °/s, the average differences were 2.5 ± 1.5 °/s (P<0.05) and 2.8 ± 0.7 °/s (P<0.05).

DISCUSSION

Our study tested whether the repeated presenta on of a target moving always along the same path changed its tracking in comparison with the performance during sessions in which the target could move along four possible paths. More specifically, we inves gated whether a recurrent target mo on was sufficient to produce an cipatory eye movements, prior to target appearance and with no preliminary training. Our results show some sta s cally significant differences between the two target path frequencies, at the level of intercep ve saccades and at the level of post-saccadic pursuit eye movements and catch-up saccades. In par cular, the latency of saccades was slightly longer (4% increase) during the "certain" sessions only when the target moved at 20°/s, not when it moved at 40°/s (Fig. 7). Intriguingly, in spite of the long gap between the ex nc on of the fixa on target and the appearance of the moving target, no express saccades were observed in the two condi ons of target frequency (Fig. 6). No difference was found between the two sessions, neither in the velocity (Fig. 5) nor in the accuracy and precision of intercep ve saccades (Fig. 8). A slow eye movement started aAer target onset and its amplitude was larger during the "certain" sessions than during the "uncertain" ones only when the target moved at 40°/s (Fig. 4). No an cipatory slow eye movement was observed during the "certain" sessions (Fig. 3). The first intersaccadic interval (i.e. the me elapsed from the end of the intercep ve saccade to the onset of the first catch-up saccade) was longer and more variable during the "certain" sessions than during the "uncertain" ones without change in the post-saccadic pursuit velocity (Fig. 9). The accuracy and precision of catch-up saccades were slightly influenced by the frequency of the target path (Fig. 10): they were more accurate and more precise during the "certain" sessions. Finally, comparisons between saccade-related and pursuit-related parameters provide addi onal arguments corrobora ng the thesis that saccadic and pursuit eye movements are driven by dis nct mo on signals.

Influence of repeatedly tracking the same moving target on saccade genera5on.

Previous studies in cats [START_REF] Guitton | Gaze control in the cat: studies and modeling of the coupling between orienting eye and head movements in different behavioral tasks[END_REF] and human subjects [START_REF] Bronstein | Predictive eye saccades are different from visually triggered saccades[END_REF] showed that when a target appeared at an expected loca on, the peak velocity of saccades was lower than that of saccades toward a target whose loca on and ming were variable. In the monkey tested with the head unrestrained and looking at a target that stepped alternately and at regular intervals between two fixed loca ons, [START_REF] Bizzi | Two modes of active eye-head coordination in monkeys[END_REF] also observed an cipatory movements. The head began to move 150 to 200 ms before the onset of the saccade, which was also slower than during trials in which the target loca on was varied [START_REF] Bizzi | Two modes of active eye-head coordination in monkeys[END_REF]. In our study, we found neither a slowing of saccades nor shorter latencies.

In the monkey, several studies showed that the repe ve exposure to a visual s mulus at the same loca on resulted in a bimodal distribu on of saccade latencies [START_REF] Schiller | An examination of the variables that affect express saccade generation[END_REF][START_REF] Rohrer | Express saccades: the effects of spatial and temporal uncertainty[END_REF]. The first mode corresponds to "express" saccades and the second mode to "regular" saccades. In the human subjects, Carpenter and Williams (1995) also reported an increasing number of express saccades as the target frequency increased [START_REF] Carpenter | Neural competition of log likelihood in control of saccadic eye movements[END_REF]. The observa on of saccades with express latencies is not restricted to experimental condi ons in which a target repeatedly appears at the same loca on (27-29, 37, 38). Schiller (2004b) s ll observed express saccades, although less frequent, when the number of possible loca ons was doubled (from 2 to 4). Shorter latencies were also observed when the target was always presented at the same loca on compared to trials in which the target could appear at two [START_REF] Dorris | Saccadic probability influences motor preparation signals and time to saccadic initiation[END_REF] or eight [START_REF] Basso | Modulation of neuronal activity in superior colliculus by changes in target probability[END_REF] possible loca ons.

However, the latency does not seem to depend upon the prior knowledge of target loca on or the dura on of the gap interval because Rohrer and Sparks (1993) did not observe reduced latencies or more express saccades when the performance during sessions with one single target and one single gap interval dura on was compared to sessions in which the possible target loca ons were more numerous (N=10) and the gap dura ons more variable (N=4) [START_REF] Rohrer | Express saccades: the effects of spatial and temporal uncertainty[END_REF].

In in spite of a long gap interval, we did not observe a bimodal distribu on signaling the presence of express saccades. This absence may lead to infer that the neural processes triggering intercep ve saccades differ from those triggering saccades toward a sta c target but this inference would not be compa ble with observa ons made by Krauzlis & Miles (1996).

These authors reported saccades with very short latency during a task in which the monkeys were required to pursue of a centripetal target [START_REF] Krauzlis | Decreases in the latency of smooth pursuit and saccadic eye movements produced by the "gap paradigm" in the monkey[END_REF]. In our study, the target always started its mo on from the central visual field. This centrality might explain the absence of express saccades if a saccade is not triggered as long as the flows of bilateral ac vity propaga ng from the fovea to the bilateral pre-oculomotor networks stay within a mode in which opposing commands counterbalance with each other [START_REF] Goffart | Kinematics and the neurophysiological study of visually-guided eye movements[END_REF][START_REF] Goffart | Neurophysiology of visually guided eye movements: critical review and alternative viewpoint[END_REF][START_REF] Krauzlis | Neuronal control of fixation and fixational eye movements[END_REF]. Prior to genera ng a saccadic or slow eye movement, the maintenance of gaze direc on involves sustained ac vi es within different groups of neurons in the leA and right parts of the re cular forma on, the cerebellum and the deep superior colliculi [START_REF] Goffart | Neurophysiology of gaze orientation: Core neuronal networks[END_REF]. Concerning the la:er, the ac vity is not restricted to their rostral pole: it extends more caudally, even during steady fixa on. [START_REF] Sparks | The role of the superior colliculus in saccade initiation: a study of express saccades and the gap effect[END_REF] showed bilateral ac vity during the gap interval at sites sensi ve to target eccentrici es of 8 degrees (see their Fig. 4) [START_REF] Sparks | The role of the superior colliculus in saccade initiation: a study of express saccades and the gap effect[END_REF]. Dorris and Munoz (1998) also showed that the firing rate before target presenta on increased when the target repeatedly appeared into the neuron's response field and that its level was nega vely correlated with the saccade latency [START_REF] Dorris | Saccadic probability influences motor preparation signals and time to saccadic initiation[END_REF]. The higher the rate, the shorter the latency. Likewise, Basso and Wurtz (1998) showed that increasing the number of possible loca ons was associated with a decrease of firing rate preceding the target presenta on [START_REF] Basso | Modulation of neuronal activity in superior colliculus by changes in target probability[END_REF]. These two observa ons suggest a link between the prelude ac vity and saccade latency. However, the persistence of the prelude ac vity for a long me without saccade ini a on argue against its causal role in triggering saccades (see the panels G and I in Fig. 4 of [START_REF] Sparks | The role of the superior colliculus in saccade initiation: a study of express saccades and the gap effect[END_REF]46). The level of firing rate likely plays a secondary role in comparison with the bilaterality of ac vity and the number of ac ve neurons during fixa on.

Regarding the accuracy and precision of intercep ve saccades, our result showed no influence of the target path frequency. The posi on/ me landing ra o reached values that were close to the target velocity (see Fig. 6). The observa on of some values slightly exceeding the target velocity does not entail that the monkeys programmed a saccade toward a future loca on of the target. As explained by Goffart et al. (2017), the amplitude of intercep ve saccades is variable like the amplitude of saccades toward a sta c target, and the variability of final errors increases more toward values corresponding to past loca ons of the target than toward values corresponding to its future loca ons (see their Figure 3; 47). Furthermore, it is quite remarkable that our monkeys never performed saccades toward future loca ons of the target, neither during the pre-saccadic interval (Fig. 4A) nor during the intersaccadic interval (Fig. 10A), even during the sessions in which the target moved always along the same path.

Consistent with reserva ons expressed elsewhere [START_REF] Goffart | Neurophysiology of visually guided eye movements: critical review and alternative viewpoint[END_REF][START_REF] Goffart | Synchronizing the tracking eye movements with the motion of a visual target: Basic neural processes[END_REF], the absence of "predic ve" saccades during the "certain" sessions contradicts the claim that "in [their] programming [...], target mo on is used to predict the future target posi on so as to assure a spa al lead of the gaze at the saccade end, instead of a:emp ng a precise capture of the target" [START_REF] Klam | Predictive elements in ocular interception and tracking of a moving target by untrained cats[END_REF][START_REF] Berthoz | Simplexity: Simplifying Principles for a Complex World[END_REF].

Influence of repeatedly tracking the same moving target on smooth pursuit.

Several studies reported that human and monkeys can make an cipatory eye movements (references in the introduc on). In the monkey, Freyberg and Ilg (2008) observed eye movements in the absence of a moving target during sessions in which a monkey tracked a target that moved at a constant speed and always to the right in half of the trials. In the other half, the ini al por on of the target mo on was invisible for 500 ms and the monkeys some mes made a slow eye movement followed by a saccade in the same direc on as the target. Their observa ons seemingly contradict the conclusion that macaque monkeys are not capable of predic ve tracking, contrary to human subjects [START_REF] Fuchs | Periodic eye tracking in the monkey[END_REF]. However, their explana on that an inappropriate training was responsible for the absence of predic ve tracking in the study of Dr Fuchs is unfounded because both studies used a small window to control gaze accuracy and comparable dura on of condi oning procedure (10 versus 8 weeks). In fact, the tasks were quite different between the two studies. In Fuchs (1967), the monkeys were trained to follow a target that periodically moved back and forth between two symmetrical loca ons with respect to straight ahead. Contrary to the human performance, which exhibited a phase lead or an cipa on of target mo on, the monkeys lagged more and more behind the target as the frequency increased. In our study, although the disappearance of the fixa on target was a signal of the target onset 300 ms later, none of our six monkeys exhibited any eye movement during the gap interval. One difference between the study of [START_REF] Freyberg | Anticipatory smooth-pursuit eye movements in man and monkey[END_REF] and ours is that our monkeys were not trained to track the same target for several weeks. Only one or two blocks of trials were recorded for each target path during the "certain" sessions. A second difference is the absence of trials in which the mo on was invisible in our sessions. Other studies did not indicate how long their monkeys were trained [START_REF] Hemptinne | Influence of cognitive expectation on the initiation of anticipatory and visual pursuit eye movements in the rhesus monkey[END_REF][START_REF] Badler | Anticipatory movement timing using prediction and external cues[END_REF][START_REF] De Hemptinne | How do primates anticipate uncertain future events?[END_REF]. This is regre:able because overtraining monkeys to direct their gaze within a small window in order to be rewarded can lead to situa ons in which the eye movements do not belong to the natural animal's behavioral repertoire. For instance, monkeys can learn to make an saccades by merely inver ng the electrical polarity of the cables that connect the eye coil to the phase detector (David L. Sparks, personal communica on).

Several differences dis nguish our study from previous studies in the monkey [START_REF] Hemptinne | Influence of cognitive expectation on the initiation of anticipatory and visual pursuit eye movements in the rhesus monkey[END_REF][START_REF] Badler | Anticipatory movement timing using prediction and external cues[END_REF][START_REF] De Hemptinne | How do primates anticipate uncertain future events?[END_REF].

Firstly, we used longer and variable fixa on intervals (from 500 to 1500 ms by increment of 500 ms versus 500 ms) and lower target veloci es (20 or 40°/s versus 65°/s). It is not certain that the fixed dura on of the fixa on interval is the cri cal factor explaining why we did not observe an cipatory responses. Indeed, in other studies, variable fixa on intervals did not prevent the occurrence of an cipatory eye movements [START_REF] Freyberg | Anticipatory smooth-pursuit eye movements in man and monkey[END_REF] or the occurrence of express saccades and the reduc on of saccade latencies [START_REF] Carpenter | Neural competition of log likelihood in control of saccadic eye movements[END_REF]. Secondly, those previous studies used horizontal target mo ons whereas we used oblique target mo ons. Horizontal and ver cal eye movements are under the control of different neuronal popula ons located in different nuclei in the brainstem [START_REF] Goffart | Neurophysiology of gaze orientation: Core neuronal networks[END_REF]. The genera on of oblique movements involves a coordina on of anatomically separate groups of neurons. The absence of an cipatory eye movement may result from to the fact that they involve more than one neural network. Our observa ons of changes in one component (horizontal or ver cal) but not in the other are compa ble with this explana on [START_REF] Orlando-Dessaints | Etude neurophysiologique et comportementale de l'extrapolation visuomotrice chez le macaque[END_REF]. Finally, in previous studies, the an cipatory eye movements were obtained during a specific experimental paradigm, aAer intense training. By contrast, we did not train our monkeys un l they produced an cipatory responses. We merely wanted to know whether these movements could be rapidly observed with almost no training. Our results indicate that the genera on of an cipatory movements requires training and thus, that predic on or an cipa on are merely reproduc on of learned responses instead of the signature of higher cogni ve func ons. As Ashby (1963) explained: "to predict the future is to perform an opera on on the past. The essen al point is that the agent in the act of predic on depends wholly on the actual past and not in the least on the actual future" [START_REF] Ashby | Induction, prediction and decision-making in cybernetic systems[END_REF].

Regarding the post-saccadic pursuit, we found that the catch-up saccades were made later when the target moved always along the same path; the intersaccadic intervals were longer during the "certain" sessions than during the "uncertain" ones (Fig. 9A). The target was maintained longer within the central visual field during the "certain" sessions, an inference that is consistent with previous studies showing a smoothing of tracking eye movements with less frequent catch-up saccades in the monkey aAer 10-12 daily experimental sessions [START_REF] Bourrelly | Learning the trajectory of a moving visual target and evolution of its tracking in the monkey[END_REF][START_REF] Botschko | Smooth pursuit eye movement of monkeys naive to laboratory setups with pictures and artificial stimuli[END_REF].

The longer inter-saccadic intervals during the "certain" sessions indicate that the repeated presenta on of the same moving target transforms its tracking from saltatory to smooth. The primacy of smooth pursuit during visual tracking presumably results from an expansion of the "mass" of neural ac vity linked to the representa on of the central field. Such an expansion involves not only mo on sensi ve neurons in the visual cortex but also pursuit-related neurons in the rostral SC [START_REF] Basso | Activation and inactivation of rostral superior colliculus neurons during smooth-pursuit eye movements in monkeys[END_REF][START_REF] Krauzlis | Discharge properties of neurons in the rostral superior colliculus of the monkey during smooth-pursuit eye movements[END_REF], the caudal fas gial nuclei [START_REF] Bourrelly | Pursuit disorder and saccade dysmetria after caudal fastigial inactivation in the monkey[END_REF][START_REF] Fuchs | Participation of the caudal fastigial nucleus in smooth-pursuit eye movements. I. Neuronal activity[END_REF] and the ventral paraflocculus [START_REF] Belton | Role of the cerebellar flocculus region in the coordination of eye and head movements during gaze pursuit[END_REF][START_REF] Lisberger | Responses during eye movements of brain stem neurons that receive monosynaptic inhibition from the flocculus and ventral paraflocculus in monkeys[END_REF][START_REF] Noda | Discharges of neurons in the dorsal paraflocculus of monkeys during eye movements and visual stimulation[END_REF].

Comparison of intercep5ve saccades, catch-up saccades and post saccadic pursuit.

Several evidence indicate that saccadic and pursuit eye movements are not driven by common mo on signals. Behavioral studies with naive and healthy monkeys show a clear dissocia on between the saccade and pursuit performances when they track for the first me a moving target [START_REF] Bourrelly | Learning the trajectory of a moving visual target and evolution of its tracking in the monkey[END_REF][START_REF] Botschko | Smooth pursuit eye movement of monkeys naive to laboratory setups with pictures and artificial stimuli[END_REF]. The present study provides addi onal arguments corrobora ng this dissocia on. . The rela on between the posi on/ me landing ra o of saccades (intercep ve or catchup) and the post-saccadic pursuit velocity does not reveal any tendency for a correla on (see Figs. 11A and12A) that would suggest common signals. Lesional studies also support the segrega on of processes underlying the genera on of saccadic and pursuit eye movements. Unilateral pharmacological inac va on of the caudal fas gial nucleus leads to uncorrelated impairments of saccadic and pursuit eye movements [START_REF] Bourrelly | Pursuit disorder and saccade dysmetria after caudal fastigial inactivation in the monkey[END_REF]. [START_REF] Helmchen | Bilateral lesion of the cerebellar fastigial nucleus: Effects on smooth pursuit acceleration and non-reflexive visuallyguided saccades[END_REF] reported a pa ent suffering from bilateral fas gial lesion who exhibited a bilateral saccade hypermetria with a lower (although not sta s cally significant) ini al pursuit accelera on [START_REF] Helmchen | Bilateral lesion of the cerebellar fastigial nucleus: Effects on smooth pursuit acceleration and non-reflexive visuallyguided saccades[END_REF].

Several other studies report cases of pa ents suffering from saccade disorders with no pursuit deficit [START_REF] Büttner | Saccadic dysmetria and "intact" smooth pursuit eye movements after bilateral deep cerebellar nuclei lesions[END_REF] or inversely, subjects exhibi ng difficul es in pursuit with no saccade altera on [START_REF] Keating | Frontal eye field lesions impair predictive and visually-guided pursuit eye movements[END_REF][START_REF] Ohtsuka | Cerebellar peduncle lesion without saccadic abnormalities[END_REF][START_REF] Pierrot-Deseilligny | Vermal infarct with pursuit eye movement disorders[END_REF]. The observa ons reported in our study add to the set of arguments suppor ng the thesis that the neural control of saccadic and pursuit eye movements involves separate processes. This separa on does not entail a lack of coordina on, which has been shown to change with prac ce (4-5) and to involve the caudal fas gial nucleus [START_REF] Bourrelly | Pursuit disorder and saccade dysmetria after caudal fastigial inactivation in the monkey[END_REF] and the frontal eye field [START_REF] Keating | Frontal eye field lesions impair predictive and visually-guided pursuit eye movements[END_REF].

General conclusion

In this study, we thoroughly described in the rhesus macaque monkey how the occurrence frequency of a target path influenced the tracking eye movements. When they were present, the effects were very small. In spite of of a gap interval before the target mo on onset, our monkeys did not generate an cipatory eye movements when the target kept moving along the same path. We observed neither premature saccades nor express saccades.

In line with other works performed by our group [START_REF] Fleuriet | Saccadic interception of a moving visual target after a spatiotemporal perturbation[END_REF][START_REF] Quinet | Does the brain extrapolate the position of a transient moving target?[END_REF], our results are compa ble with a short horizon of predictability during oculomotor tracking in the macaque monkey, in accordance with the conclusion that the predic ve abili es are quite limited in the macaque monkey [START_REF] Fuchs | Periodic eye tracking in the monkey[END_REF]. An alterna ve explana on is that our monkeys were not trained to make an cipatory responses, in which case, they should not be considered as a behavioral marker of the primates' ability to extrapolate but the outcome of learning and remembering past experience.

FIGURE CAPTIONS

Figure 1: Experimental protocol. Each trial started with the appearance of a target at the center of the visual display. The monkey was required to direct and maintain gaze toward its location for a fixation interval whose duration varied pseudo-randomly from 750 to 1500 ms (by increments of 250 ms). A gap interval of 300 ms followed the extinction of the fixation target, after which the target reappeared and moved along one out of four possible oblique paths. The monkey was rewarded for tracking the target until it disappeared. Each target path was tested with two frequencies of occurrence during sessions recorded on different days: 25% ("uncertain" sessions) and 100% ("certain" sessions). Two target velocities (20 and 40deg/s) were tested during separate sessions.

(

  bo:om row) condi ons, the posi on/ me landing ra o of catch-up saccades seemed to be more accurate and more precise than intercep ve ones. For instance, during the "uncertain" sessions, when the target moved at 20 °/s in the upper right visual field, the median values of posi on/ me landing ra o of intercep ve saccades were 20 ± 3, 18 ± 4, 18 ± 5, 21 ± 5 and 23 ± 6 °/s versus 21 ± 2, 19 ± 3, 21 ± 2, 22 ± 3 and 22 ± 4 °/s for the catch-up saccades (monkey Bi, C, E, F and G respec vely). During the "certain" sessions, the values were 19 ± 4, 17 ± 3, 20 ± 3, 22 ± 3, 26 ± 6 °/s (intercep ve saccades) versus 20 ± 2, 19 ± 2, 20 ± 1, 22 ± 1 and 22 ± 4 °/s (catch-up saccades). For the sessions in which the target moved at 20°/s, the paired comparison confirmed significantly larger values of posi on/ me landing ra o for the catchup saccades than for the intercep ve saccades, regardless of whether the target path was certain (∆Med = 1.1 ± 1.2 °/s, P<0.05) or uncertain (average difference = 2 ± 1.7 °/s, P<0.05).

Figure 2 :

 2 Figure 2: Definition of parameters. The presaccadic glissade (PSG) is the change of eye position during the time interval elapsed from target motion onset (black vertical dashed line labeled 1) to the onset (vertical line labeled 2) of the interceptive saccade (IS). A post-saccadic pursuit eye movement (PSP, delimited by the lines labeled 3 and 4) follows the interceptive saccade until a catchup saccade (CS) is launched. The grey dashed lines represent the target moving at 40°/s. The black continuous and dashed curves represent respectively the horizontal and vertical components of the visual tracking response. Data collected in monkey Bi.

Figure 3 :

 3 Figure 3: Eye velocity at target motion onset. The eye velocity of each component (top: horizontal, bottom: vertical) during the "certain" sessions is plotted as a function of the velocity during the uncertain (x-axis) sessions. They were calculated during the interval elapsed from 40 ms before target motion onset to 40 ms after. Different symbols correspond to different quadrants of the visual field and different colors to different monkeys. From left to right, the first and third columns correspond to the median and IQR values obtained with the 20 deg/s target, the second and fourth columns to values with the 40 deg/s target.

Figure 4 :

 4 Figure 4: Pre-saccadic glissade. A: The amplitude (radial value) of the pre-saccadic slow eye movement is plotted as a function of saccade latency. The target moved at 20 or 40°/s in the upper right quadrant of the visual field (left: uncertain sessions; right: certain session). Data collected in monkey Bi. B: Slope of the relation between the pre-saccadic displacement amplitude (from target motion onset to saccade onset) and the saccade latency during the "uncertain" (x axis) and "certain" (y axis) sessions. Different symbols correspond to different quadrants of the visual field and different colors to different monkeys.

Figure 5 :

 5 Figure 5: Average velocity of interceptive saccades during the "uncertain" and "certain" sessions. Different symbols correspond to different quadrants of the visual field and different colors to different monkeys. The two leftmost graphs plot the median values for the 20 and 40°/s targets and the other graphs the interquartile range (IQR) values.

Figure 6 :

 6 Figure 6: Latency of interceptive saccades. Violin plots show for each monkey (x axis) and each quadrant of the visual field the median (white dot) and interquartile range (black box) of latency values and an estimation of their distribution (based on a probability density function) for the "uncertain" (white) and "certain" (grey) sessions. The target moved at 20 deg/s (left column) or 40 deg/s (right column).

Figure 7 :

 7 Figure 7: Saccade latency during the "uncertain" and "certain" sessions. Different symbols correspond to different quadrants of the visual field and different colors to different monkeys. Median (left column) and interquartile interval (IQR, right column) values are plotted for the 20°/s (top) and 40°/s target (bottom).

Figure 8 :

 8 Figure 8: Accuracy and precision of interceptive saccades. A: The landing position (radial value) of saccades is plotted as a function of their landing time, when the target moved in the upper left visual field, during the "uncertain" and "certain" sessions. Data collected in monkey Bi. B: Median and interquartile range (IQR) of the position/time (P/T) landing ratio during the "uncertain" (x-axis) and "certain" (y-axis) sessions. Different symbols correspond to different quadrants of the visual field and different colors to different monkeys. The first and third columns correspond to sessions during which the target moved at 20 deg/s, the second and fourth columns to those in which the 40 deg/s target was used. The horizontal and vertical dashed lines show the target velocity.

Figure 9 :

 9 Figure 9: Post-saccadic pursuit eye movement. A: The median and interquartile interval range (IQR) values of the duration of the first intersaccadic interval (ISI) calculated during the "certain" sessions (y-axis) are plotted as a function of values calculated during the "uncertain" sessions (x-axis). Different symbols correspond to different quadrants of the visual field and different colors to different monkeys. B: The amplitude (radial value) of the post-saccadic eye movement is plotted as a function of the duration of the intersaccadic interval (from the end of the interceptive saccade to the onset of the first catch-up saccade). The target moved in the upper left visual field. Data collected in monkey Bi. C: The median and interquartile range (IQR) values of the post-saccadic slow movement velocity are compared between the "uncertain" (x-axis) and "certain" (y-axis) sessions. Different symbols correspond to different quadrants of the visual field and different colors to different monkeys. From left to right, the first and third columns correspond to movements made in response to the 20 deg/s target, the second and fourth to movements made in response to the 40 deg/s target. The horizontal and vertical dashed lines indicate the target velocity.

Figure 10 :

 10 Figure 10: Landing position of catch-up saccades. A: The landing position (radial value) of each catch-up saccade is plotted as a function of its landing time when the target moved in the upper left visual field, at 20 deg/s (left) or 40 deg/s (right) during the "uncertain" (first and third columns) and "certain" (second and fourth columns) sessions. Dashed lines indicate the target position. Data collected in monkey Bi. B: Median and interquartile range (IQR) values of position/time landing ratio are compared between the "uncertain" (x-axis) and "certain" (yaxis) sessions. Different symbols correspond to different quadrants of the visual field and different colors to different monkeys. From left to right, the first and third columns correspond to catch-up saccades made toward the 20 deg/s target, the second and fourth columns to those made toward the 40 deg/s target. Horizontal and vertical dashed line indicate the target velocity.

Figure 11 :

 11 Figure 11: Position/time landing of interceptive saccades and post-saccadic pursuit velocity. A: The position/time (P/T) landing ratio of interceptive saccades (IS) is plotted as a function of the post-saccadic pursuit (PSP) velocity (radial values). The data were collected in monkey Bi when it tracked a target that moved at 20 deg/s (left half) or 40 deg/s (right half) in the upper right quadrant of the visual field. From left to right, the first and third columns correspond to trials recorded during the "uncertain" sessions and the second and fourth columns to trials recorded during the "certain" sessions. Dashed lines correspond to target velocity. B: Median

Figure12:

  Figure12: Post-saccadic pursuit velocity and position/time landing ratio of catch-up saccades. A: The post-saccadic pursuit (PSP) velocity is plotted as a function of the position/time landing ratio (radial values) for the trials in which the monkey Bi tracked the target while it moved in the upper right quadrant of the visual field during the "uncertain" (first and third columns) and "certain" sessions. Dashed lines correspond to target velocity. B: The median and interquartile range (IQR) values of post saccadic pursuit velocity (y axis) are compared to the values of position/time landing ratio of catch-up saccades (x axis) made during the "uncertain" (top row) and "certain" (bottom) sessions. Different symbols correspond to different quadrants of the visual field and different colors to different monkeys. From left to right, the first and third columns correspond to the 20 deg/s target, the second and fourth to the 40 deg/s target. Horizontal and vertical dashed lines indicate the target velocity.

Figure 13 :

 13 Figure 13: Accuracy and precision of interceptive and catch-up saccades. The median and interquartile range (IQR) values of position/time landing ratio of interceptive saccades (IS, yaxis) are compared to those of catch-up saccades (CS, x-axis) made during the "uncertain" (top row) and "certain" (bottom) sessions. Different symbols correspond to different quadrants of the visual field and different colors to different monkeys. From left to right, the first and third columns correspond to the 20 deg/s target, the other columns to the 40 deg/s target. Horizontal and vertical dashed lines indicate the target velocity.

ACKNOWLEDGMENTS

The authors thank Marc Mar n and Laurence Boes for animal care, Emilie Rapha and Luc Renaud for surgical assistance, Xavier Degiovanni for mechanical assistance, Joel Baurberg for electronic assistance and Ivan Balansard for veterinarian care. We are also grateful to Dr Ivo Vanze:a who kindly lent us one monkey (Bi).

GRANTS

This work was supported by the Centre Na onal de la Recherche Scien fique (LG), partly by the Agence Na onale de la Recherche (Grant PREDICTEYE) and the Fonda on pour la Recherche Médicale (PREDICTEYE).

AUTHOR CONTRIBUTIONS