INTRODUCTION

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

Natural scenes typically contain a multitude of different objects that could serve as targets for saccadic eye movements. Target selection is thus an important process in the generation of accurate goal-directed saccades. In behavioral studies, it has been found that when there is strong competition between target and distractor saccade goals, the trajectories of saccades to the target may show significant curvature toward the distractor (Findlay and Harris 1984; McPeek and Keller 2001; Minken et al. 1993; Port and Wurtz 2000; Van Gisbergen et al. 1987) in contrast to the relatively straight trajectories seen when only a single saccade goal is present (Bahill and Stark 1977; Keller 1980; King et al. 1986; Quaia et al. 2000; Van Gisbergen et al. 1985; Viviani et al. 1977). This curvature suggests that in some circumstances, execution of a movement may begin before selection of a single saccade goal is finalized.

Specifically, in a visual search task, McPeek and Keller (2000, 2001) hypothesized that ongoing competition between saccade goals in visuo-motor structures such as the superior colliculus (SC) or frontal eye field (FEF) results in saccade curvature due to the presence of simultaneously active, but spatially separated, populations of neurons corresponding to different candidate saccade goals in these topographically organized motor maps. In a double-step task, Port and Wurtz (2000, 2001) similarly hypothesized that the highly curved and averaging saccades that they observed resulted from temporally overlapping bursts of activity at two sites within the SC.

In the present study, we used two different methods to assess the validity of the hypothesis that competition between saccade goals gives rise to curved saccades. First, we recorded from neurons in the SC while monkeys performed a visual search task in which they were rewarded for making a saccade to an odd-colored target presented simultaneously with distractors. In most trials, the monkeys made a single saccade with a rather straight trajectory to the location of the target. However, in some trials, they executed curved saccades (McPeek and Keller 2001). These saccades were initially directed between the target and a distractor but underwent a smooth change in direction during the movement and ended near the location of the target. In the present paper, we show that such curved saccades are associated with increased presaccadic activity in the SC at the site coding the distractor toward which the saccade curved. Near the time of saccade initiation, this activity at the distractor location is rapidly suppressed. In contrast, neurons at the target site show a stereotypical high-frequency burst of activity for saccades to the target, regardless of whether the movements have curved or straight trajectories. These results support the idea that trajectory curvature is produced by temporally overlapping presaccadic activity at two sites in the SC.

To test this hypothesis directly by establishing a causal link between competing activity at two SC sites and saccade curvature, we performed a second experiment in which we used electrical microstimulation of the SC to induce curvature in saccades made to single visual stimuli. Specifically, during the reaction time before a saccade was made to a single visual stimulus, we delivered a train of electrical pulses at a SC site that would have coded a distractor in the search paradigm. We shaped the temporal envelope of the stimulus train so that it closely resembled the activity profile recorded in the SC at distractor sites during curved saccades in search. The stimulation trains were subthreshold for evoking movements, but we found that optimally configured presaccadic trains, delivered to sites in the SC that were not at the location activated by the visual stimulus, produced highly curved saccades. These latter results provide additional support for the hypothesis that competing activity at separate sites in the SC can produce saccadic curvature.

The data presented here have appeared previously in preliminary form (McPeek and Keller 2000).

	METHODS

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

Four male rhesus monkeys (Macaca mulatta) weighing between 4 and 7 kg were used in this study. Monkeys H, G, and M participated in the recording experiments and monkeys G, M, and F participated in the stimulation experiments. All experimental protocols were approved by the Institutional Animal Care and Use Committee at the California Pacific Medical Center and complied with the guidelines of the Public Health Service policy on Humane Care and Use of Laboratory Animals.

A detailed description of the general methods and behavioral tasks has been published recently (McPeek and Keller 2002a). Briefly, a scleral coil (Fuchs and Robinson 1966; Judge et al. 1980) and a head-holder system were implanted under isofluorane anesthesia and aseptic surgical conditions. After training in behavioral tasks (described in the following text), a second surgery was performed to position a stainless steel recording chamber (15 mm ID), tilted 38° posterior from vertical, above a craniotomy centered on the midline. Antibiotics (Cefazolin sodium) and analgesics (Buprenorphine hydrochloride) were administered as needed during the recovery period under the direction of a veterinarian.

Testing was performed in a dimly illuminated room. The monkeys were seated in a primate chair with their heads restrained for the duration of the testing sessions. They executed behavioral tasks for liquid reward and were allowed to work to satiation. Records of each animal's weight and health status were kept, and supplemental water was given as necessary. The animals typically worked for 5 days and were allowed access to water on weekends.

Single-unit recording

We used standard methods to record single neurons in the deeper layers of the SC. Neural activity was recorded using tungsten microelectrodes with impedances ranging from 0.8 to 2.5 M at 1 kHz, advanced by a hydraulic microdrive. Action potentials were identified using a time-amplitude window discriminator. The computer data acquisition system registered the occurrence of spikes and sampled eye position and velocity with a resolution of 1 kHz.

Delayed-saccade paradigm

At the beginning of each trial, a white fixation spot subtending 0.25° in diameter with a luminance of 1.24 cd/m² appeared in the central position against a homogenous dim background of 0.12 cd/m. The monkeys were required to keep their eyes within 1.5-2° of the fixation point during an initial fixation interval of 450-650 ms. At the end of this interval, a target stimulus was presented at a peripheral location while the fixation point remained illuminated. Monkeys were required to maintain central fixation until the disappearance of the fixation point 500-700 ms later. Once the fixation point disappeared, they were rewarded for making a saccade to the peripheral stimulus within 70-400 ms. Early or late responses were not rewarded. Eye position tolerance windows around the target stimuli were made equal to the stimulus eccentricity divided by 5. The target was a red or green disk, with a luminance of 0.90 or 0.92 cd/m², respectively. The size of the target was M-scaled to keep its salience constant across different eccentricities (Rovamo and Virsu 1979). At an eccentricity of 15°, the target subtended 2° of visual angle.

Single-target paradigm

Trials began with a 450- to 650-ms fixation period as for the delayed-saccade task. However, at the end of the fixation period, the fixation point disappeared, and an eccentric target stimulus was presented. The target was randomly selected on each trial to be a red or green disk with luminance and size as described for the delayed-saccade task. In each trial, the target stimulus was randomly presented at one of four possible locations. The four possible target locations were all at the same eccentricity and were separated from each other by angles of 90°. The four locations were adjusted for each neuron so that one of the locations fell near the center of the neuron's response field (RF) as determined in a preliminary on-line analysis using single stimuli. Two of the monkeys were given a liquid reward for bringing their eyes to the location of the target within 70-275 ms of the onset of the stimuli. The third monkey tended to have longer saccade latencies and consequently was allowed 70-300 ms to reach the target.

Search paradigm

The search task was identical to the single-stimulus task described in the preceding text with the difference that three distractor stimuli were presented simultaneously with the target stimulus, at equal eccentricity from fixation, separated by angles of 90° (see Fig. 1, top). The distractors were identical to each other and differed from the target only by virtue of the target's odd color. In each trial, the colors of the target and distractors were randomly chosen.

View larger version (25K): [in this window] [in a new window]   Fig. 1. Schematic representations of the visual search and stimulation paradigms. Left: paradigm events vs. time; right: the spatial arrangement. In the search task, the animal was required to fixate a central fixation point. After a random time interval, the fixation point was extinguished and the stimulus array, consisting of a target and 3 distractors, appeared. The animal was rewarded for making a saccade to the target, which was delineated by its odd color. The array was positioned so that one visual stimulus, either the target or a distractor, always appeared near the center of the response field () of the superior colliculus (SC) neuron being recorded. The stimulus location that neighbors the response field (RF), and is in the same visual hemifield as the RF, is referred to as the ipsi location. The neighboring location in the opposite hemifield is referred to as the contra location. The opposite location is diametrically opposed to the RF location, whereas the into field location coincides with the cell's RF. In the stimulation paradigm, the fixed vector saccade (FVS), an invariant saccade determined primarily by the location of the stimulating electrode in the collicular motor map, was first measured (). After the FVS was determined, a series of trials ensued in which the animal was required to fixate a central fixation point, and after a random interval, the fixation point was extinguished and a single visual target appeared at one of the neighboring locations (ipsi or contra) with respect to the end point of the FVS. The animal was rewarded for saccading to the location of this visual stimulus. On randomly interleaved trials, pulsatile electrical stimulation was delivered through the microelectrode just before the visually evoked saccade began. Stimulation was terminated by saccade onset or after 125 ms, whichever occurred first.

The data were separated into four types of response, illustrated in Fig. 1: into field (the target appeared in the response field of the neuron); ipsi location (the target appeared at the array location separated 90° in direction from the center of the response field and in same visual field as the response field of the neuron); contra location (the target appeared at the array location separated 90° in direction from the center of the response field and in the opposite visual field from the response field of the neuron); and opposite location (the target appeared at the array location that was diametrically opposite in direction to the response field).

Stimulation paradigm

In this paradigm, a microelectrode was lowered into the deeper layers of the SC as determined by monitoring multi-unit activity. The evoked saccade vector for the site was then determined by delivering a short pulse train of high-frequency (400 Hz), biphasic (0.25 ms for each phase) electrical stimulation through the electrode. Current was initially set at the minimum level that would evoke a saccade in every trial. We increased the duration of the stimulation pulse train until the maximal site-specific fixed vector saccade (FVS) was obtained (Stanford et al. 1996).

In the experimental trials, the monkeys performed a simple single-target visually guided saccade paradigm. At the beginning of each trial, the white fixation spot appeared in the central position. The monkeys were required to keep their eyes within 1.5-2° of the fixation point during an initial fixation interval of 450-650 ms. At the end of this interval, the fixation point was turned off, and a single target stimulus appeared at one of two peripheral locations. Monkeys were rewarded for making a saccade to the peripheral stimulus within 70-400 ms. The two possible locations for target appearance were at the same eccentricity as the amplitude of the FVS and at directions 90° displaced from the FVS (ipsi and contra locations; see Fig. 1, bottom). In 50% of trials (randomly selected), we delivered a subthreshold pulse train of electrical stimuli through the microelectrode. The onset of the stimulation occurred a short interval after target appearance (30-80 ms). The frequency of pulses in the stimulation train began at 10 Hz and increased linearly over a period of 125 ms to a maximum frequency of either 200 or 250 Hz. The train was terminated either by saccade onset or after 125 ms, when it had reached its preset maximum frequency. Current was adjusted to produce smoothly curved saccade trajectories that terminated near the visual target and was always less than or equal to the threshold current value required to evoke the FVS using high-frequency (400 Hz) stimulation. We verified that the stimulation parameters were subthreshold for evoking saccades by repeatedly stimulating at the maximum train frequency (200 or 250 Hz) for a duration of 125 ms and observing an absence of evoked movements in every instance. We separately analyzed saccades made with and without stimulation.

Data analysis

Off-line analysis of the eye movement data was performed by algorithms using velocity and acceleration criteria to detect the beginning and end of saccades. The algorithm's identification of saccades was visually inspected for every trial to verify its accuracy. The monkeys performed the search task correctly in 74% of trials, well above chance-level performance (25%) and comparable to human performance in a similar task (McPeek et al. 1999). In a previous report based on different data from those analyzed here, we examined the behavioral characteristics of correct and erroneous saccades in the search task (McPeek and Keller 2001). In this study, erroneous saccades were excluded from analysis as were saccades that were directed toward the correct target but were inaccurate. Inaccurate saccades were defined as those landing outside a circular region centered on the target stimulus with a radius equal to the greater of 2° or 15% of the mean saccade amplitude, where mean saccade amplitude was computed separately for each cell and each stimulus location. As a result of this criterion, we eliminated 229 saccades (~3%) of a total of 7,335 movements directed toward the correct target location. Saccades that were eliminated included hypometric and averaging saccades that landed in between stimulus locations (see McPeek and Keller 2001 for examples of such movements in a similar search task). In the stimulation paradigm, we intentionally adjusted the current level to produce smoothly curved saccades that landed near the visual target. In our analysis of the eye movements in this task, we applied the same accuracy criterion used in the search task. This resulted in the elimination of ~5% of stimulated responses (56 of a total of 1,175) across the 22 stimulation sites.

We calculated the mean curvature of all accurate saccades made to a given stimulus location using a curvature metric described by Smit and Van Gisbergen (1990). In analyses comparing neural discharge for curved and straight saccades (Figs. 2-4), curved saccades were defined as those with curvature values outside a range 0.75 SD from the mean curvature value computed. The mean curvature value was determined using accurate saccades made in the search task and was separately calculated for each of the four stimulus locations used with each neuron.

Measurement of firing rates

We calculated discharge rates by counting spike occurrences during a time-window that began 30 ms before saccade onset and ended with the start of the saccade. The number of spikes in each such presaccadic interval was divided by the duration of the time window. We chose this particular time window because SC movement-related activity typically precedes the onset of the movement (Munoz and Wurtz 1995; Sparks 1978). In the summary analyses comparing discharge for curved and straight saccades, significance tests were performed using the Wilcoxon rank-sum test. Unless otherwise noted, significance was defined as a criterion level of P < 0.05.

Characterization of neurons

We used the delayed-saccade task to characterize each neuron according to the presence or absence of visual, delay-period, and movement-related activity. We analyzed only those cells with movement-related activity, as determined by the presence of a significant (P < 0.05 in the Wilcoxon signed-rank test) increase in firing rate averaged over a period from 25 ms before saccade onset to the end of the saccade, compared with mean activity during the delay period (150-50 ms before the signal to execute the saccade). We measured the presence or absence of delay-period activity in each SC neuron by comparing neural activity during the 100-ms delay-period epoch described in the preceding text with activity during a baseline epoch beginning 75 ms before the visual stimulus was presented and ending 25 ms after stimulus onset (before the beginning of any SC neural response to the visual stimulus). Neurons that showed significantly greater discharge (P < 0.05) during the delay-period epoch than during the baseline epoch were classified as having delay-period activity. These neurons will be referred to as prelude neurons (Glimcher and Sparks 1992) and likely correspond to the build-up neurons described by Munoz and Wurtz (1995). Movement-related cells lacking prelude activity will be called burst neurons (Munoz and Wurtz 1995). All of the neurons included in this report showed visual responses to stimuli in their response fields. Although movement-related neurons lacking visual responses are also found in the SC, we encountered such cells relatively infrequently and, hence, did not include them in the analysis.

Determination of saccade curvature and "corrected curvature"

We defined the curvature of saccades as the maximum deviation from a straight-line trajectory divided by the amplitude of the movement (Smit and Van Gisbergen 1990). Because saccades made to different parts of the visual field by different individual animals can have idiosyncratic natural curvature values, we also computed a "corrected curvature" measure that allowed us to collapse the curvature data across different target positions and different monkeys. To compute corrected curvature, we first converted the curvature measures for each target location in each animal into deviation scores. Specifically, for each cell or stimulation site, we computed the mean curvature for saccades made to each target location in the single-stimulus task. We took these means as the natural curvature values for saccades made to those locations. Because we are interested in deviations from the baseline natural curvature, we subtracted these means from each individual curvature value for saccades made to the same location by the same animal in the search or stimulation paradigms. Finally, we adjusted the sign of curvature so that saccades that curved toward the response field of the cell being recorded (or toward the FVS of the stimulation site) had positive values of curvature and saccades which curved away from the response field (or FVS) had negative curvature values. In the analyses that follow, we call this new curvature measure "corrected curvature," to distinguish it from the raw curvature values.

	RESULTS

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

Neural recordings in the SC

OCCURRENCE OF TRAJECTORY CURVATURE DURING THE SEARCH TASK. Previously, we reported that the trajectories of saccades made in search tend to show greater curvature than those made to single visual stimuli appearing at the same locations in visual space (McPeek and Keller 2001). In the present study, we found that the mean value of unsigned curvature for all saccades made in our search task was 0.052, while the mean unsigned curvature measured when saccades were made to single targets appearing at the same locations was 0.035. Curved and straight saccades did not appear to form two distinct populations of response: for any particular target location in the search task, saccades showed a continuum of curvature values. We also did not find any systematic difference in the distribution of the curvature metric for saccades made to targets located in the cardinal or oblique directions.

DIFFERENCES IN SC NEURAL RESPONSE FOR CURVED VERSUS STRAIGHT SACCADES. Here we report on the activity of 24 burst cells and 39 prelude cells in the deeper layers of the SC during the visual search paradigm. During delay periods, burst and prelude neurons show quite different patterns of activity; but both types of SC neurons produce a saccade-related burst of activity beginning shortly before movement onset. In our analysis of the SC activity associated with curvature, we found that the critical determinant of saccade curvature was SC activity in the period immediately preceding the onset of the saccade. Because we found similar presaccadic modulation of activity associated with curvature in both burst and prelude neurons, we combined the two groups in the analyses that follow.

View larger version (39K): [in this window] [in a new window]   Fig. 2. Activity of a SC neuron during curved or straight saccades in the visual search task. Neural activity is represented by raster plots in which each tick mark signifies the occurrence of a discharge. In the raster plots, the solid horizontal line separates the discharge for straight saccades (trials above the line shown in blue) and curved saccades (trials below the line shown in red). Activity over trials is plotted as average spike density with sigma = 3 ms (Richmond et al. 1987). All data are aligned on saccade onset. The gray bar in the density plots indicates the time interval that was used for quantitative analyses of the difference in discharge for straight and curved saccades. A: saccades made into the response field of the neuron. Top: the saccadic trajectories that accompanied the individual trials shown below. The target location is shown by the open circle and distractor locations by filled circles. The gray regions show the approximate extent of the response field of the neuron when tested using single visual targets. Top left (blue): contains all the straight saccades (n = 14); top right (red): all the curved saccades (n = 6) made when the target was located in the response field of the cell. B: same format as in A except that saccades were made to a target located out of the response field of the neuron. In this case, only saccades made to the target when it was located in the upper-left visual field are shown. Because this field location is in the same hemifield as the response field of the neuron, these sets are labeled the ipsi location. Top left: 16 straight saccades (blue); top right (red): 7 curved saccades.

View larger version (22K): [in this window] [in a new window]   Fig. 3. Comparisons of averaged population discharge for curved and straight saccades. In each temporal plot, - - -, the normalized population mean spike density for straight saccades; , the same for curved saccades. All responses are aligned on saccade onset (time = 0). , the time interval that was used for quantitative analyses of the difference in discharge for straight and curved saccades. Right: schematic representations of the target () and distractor () locations. A: the target appeared in the response field (RF) and saccades with curvature in either direction were included in the computation of mean discharge for curved saccades. B: the target appeared at the ipsi location (in the same visual hemifield as the RF) and discharge for straight saccades was compared with discharge for saccades curved toward the RF. C: the target appeared at the contra location (neighboring location in the opposite hemifield). Again, discharge for straight saccades is compared with discharge for saccades curved toward the RF. D: the target appeared in the Opposite location, and discharge for saccades with curvature in either direction was compared with discharge for straight saccades.

View larger version (22K): [in this window] [in a new window]   Fig. 4. Scatter plots compare, for each neuron, mean presaccadic discharge rates for straight saccades (abscissa) vs. curved saccades (ordinate). Discharge rates for each trial of a particular type were computed for the 30-ms time period just before saccade onset and results from all trials of that type were averaged to determine mean rate. If the rates for curved saccades were the same as straight saccades, the plotted symbols would fall along the diagonal lines. A: result for saccades made to the target when it appeared in the RF of the neuron, comparing straight saccades with saccades curved in either direction. B: result for saccades to the ipsi location, comparing straight saccades with saccades curved toward the cell's RF. C: result for saccades to the contra location, comparing straight saccades with saccades curved toward the cell's RF.

IS THE AMOUNT OF SACCADE CURVATURE RELATED TO SACCADE LATENCY? We observed a great deal of trial-to-trial variability in the magnitude of saccade curvature produced even when data were considered for a single target position in one animal. One possible contributing factor could have been saccade latency. It has been reported that the latency of saccades in the color oddity search task is longer, on average, than the latency of saccades made to the appearance of single visual targets (McPeek and Keller 2001; Schiller et al. 1987). It is possible that the saccades made with the shortest latency in search, when the target direction had less time to be resolved, have the most curvature. We tested this idea by combining the data for all three monkeys included in the recording experiment and computing the correlation of the "corrected curvature" measure (see METHODS) with saccade latency. The correlation explained little of the variance (r² = 0.006, Pearson product moment correlation), but there was a significant trend (P = 0.04) toward greater curvature with shorter latencies.

IS THE AMOUNT OF CURVATURE RELATED TO PRESACCADIC DISCHARGE RATE AT NEIGHBORING SITES? If saccade curvature is caused by competition between neurons coding the target and a distractor, it might be expected that a greater amount of curvature would be accompanied by more intense activity at the distractor site toward which the saccade is curved. We were unable to test this prediction on a neuron-by-neuron basis because of the limited number of saccades curved toward each cell's RF for each neighboring target location. However, pooling the data across neurons allowed us to investigate the relationship between the amount of curvature and the change in firing rate of neurons coding distractor locations.

View larger version (18K): [in this window] [in a new window]   Fig. 5. Relationship between the curvature of saccades to the target and the level of neural discharge at adjacent distractor sites, pooled across neurons. The abscissa indicates the corrected curvature of saccades, with positive values denoting curvature toward the RF and negative values curvature away from the RF. The ordinate represents the difference in presaccadic activity from the mean level seen for straight saccades to the same location. The difference in neural activity is normalized according to the maximal discharge rate for each neuron (see text). Individual responses are binned according to their curvature. The horizontal error bars show the range of each bin and the vertical error bars show the standard error of the mean. Right: increasing curvature toward the RF is accompanied by an increase in presaccadic SC discharge, presumably reflecting greater competition from the distractor goal; left: curvature away from the RF is associated with a slight decrease in activity below the normal baseline level for straight saccades to the same locations.

Presaccadic electrical stimulation in the SC

CURVATURE PRODUCED BY SC STIMULATION. In the neural recording experiments, we found that curved movement trajectories in the search task are correlated with greater than normal discharge, occurring just before saccade onset, at a competing SC site that is not normally associated with the vector of the saccade to be executed. To establish whether this competing SC activity actually causes the observed saccade curvature, we used electrical microstimulation to experimentally induce competing SC activity similar to that observed in the search task.

View larger version (16K): [in this window] [in a new window]   Fig. 6. Saccade curvature produced in visually evoked saccades by subthreshold SC stimulation. A: saccades evoked by conventional high-frequency stimulation at this site in the SC illustrate the site's FVS. B: electrical stimulation at the same site with lower pulse frequency and lower current does not evoke any movement. The dot in the center of the spatial plot shows the position of the eyes as they remain at the fixation point. C: spatial plot shows the saccades made to a single visual target (open circle) that appeared at a location either, left and down, or, up and right. An example movement vs. time is shown on the left. The vertical (top trace) and horizontal (bottom trace) components of one example curved saccade are shown and the stimulus train for that particular trial is plotted at the bottom. The trace in the middle indicates the time of the appearance of the visual target. D: control visually guided saccades made to the same 2 target locations without stimulation.

EFFECT OF DEAD TIME. For each stimulation trial, we measured the time between the final stimulation pulse and the onset of the saccade, which we label "dead time." Figure 7 shows the effects of dead time on saccade curvature for a representative stimulation site in the right SC. The FVS evoked by high-frequency stimulation at this site is shown by the dashed arrow. Movements produced in our subthreshold stimulation paradigm are shown as solid lines. We sorted these trials according to dead time and found that when dead time is greater than ~20 ms (Fig. 7A), saccades show much less curvature than when dead time is <20 ms (Fig. 7B). Indeed, when dead time is long, the saccadic trajectories are not noticeably more curved than in trials in which no stimulation occurred (compare trajectories in Fig. 7, A and C). We conclude that the continuation of stimulation until close to the time of saccade onset is necessary for stimulation-driven activity in the SC to affect the trajectory of the upcoming saccade.

View larger version (17K): [in this window] [in a new window]   Fig. 7. Left: plots show vertical and horizontal eye movement components vs. time for one example movement in each stimulation condition. Right: plots are spatial plots of superimposed saccade trajectories. The particular movement used as an illustration on the left is shown in red in the panels on the right. A: trial in which the stimulus train reached its maximum frequency and was terminated more than 20 ms before saccade onset. Arrow and vertical dashed lines show the time interval between the final stimulation pulse and the onset of the saccade. This interval was called dead time and was >20 ms for the movements shown here. These saccades were not noticeably more curved than unstimulated controls shown in C. B: this saccade occurred before the stimulation train had reached its maximum frequency and dead time was <20 ms (actually near 0 in this case). Saccades with short dead times showed a range of curvatures depending on the frequency of stimulation immediately before saccade onset (see Figs. 9 and 10). C: control saccades to the same target locations without stimulation.

View larger version (20K): [in this window] [in a new window]   Fig. 8. The relationship between saccade curvature and dead time for all stimulation trials pooled across the 22 sites. Close approximation of the end of the stimulus train to the onset of the saccade is necessary for the stimulation to produce saccade curvature. Each data point represents the value of corrected curvature vs. dead time in an individual trial. , the mean corrected curvature of unstimulated trials, with error bars indicating ± SD.

EFFECT OF MEAN FINAL FREQUENCY. In the previous section, we established that saccade curvature in our paradigm depends on stimulation within a temporal window shortly before saccade onset. However, even when only trials with brief dead times are considered, there is still considerable variability in the amount of curvature produced by stimulation (Figs. 7B and 8, oblong cloud of points near 0 dead time). To explain this variance, we examined the relationship between the frequency of stimulation in the immediate presaccadic period and the amount of curvature in the subsequent saccade. In this analysis, we measured the mean frequency of the stimulation train in the 30-ms interval just before saccade onset (Fig. 9A), just as we did in the previously described single-unit analysis, by counting the number of stimulus pulses delivered during the presaccadic time window and calculating the final presaccadic stimulation frequency. In Fig. 9B, we show, for a typical site, the curvature produced in saccades to the ipsi and contra locations for five different mean presaccadic stimulating frequencies. Controls with no stimulation are also shown for comparison.

View larger version (20K): [in this window] [in a new window]   Fig. 9. The relationship between saccade curvature and presaccadic stimulation rate. Same site as in Fig. 6. The FVS is shown by the dashed arrows. A: in each individual trial with stimulation, the mean stimulation rate in the final 30-ms period before saccade onset was computed. In the example shown, the number of stimulus spikes that occurred in this interval was 7 so the mean final stimulation rate was 233 Hz. The vertical (top) and horizontal (bottom) components of the curved saccade associated with that particular stimulus in 1 trial are shown above. B: each plot shows the trajectories of all the saccades made to the ipsilateral (left and down) and contralateral (right and up) target for a range of mean stimulation frequencies in the 30-ms presaccadic interval. The plot at the bottom right shows the trajectories for trials without stimulation. Target locations are shown by the open circles. C: plots show the relationship between corrected saccade curvature and mean stimulus frequency in the 30-ms presaccadic interval at this SC site for movements to the ipsilateral (left) and contralateral (right) target locations. Each symbol represents 1 movement, and the lines represent the mean curvature across stimulation rates. The open circles and vertical error bars at the left edge of the plots show the mean value and SD of curvature obtained in trials in which no stimulation occurred.

View larger version (24K): [in this window] [in a new window]   Fig. 10. Left: summary results across stimulation sites for saccade curvature as a function of stimulation frequency during the 30-ms presaccadic interval. For comparison, analogous results, pooled across neurons, are shown from the recording experiments. Top: results for the ipsi target locations; bottom: the contra target locations. Both sets of graphs plot mean corrected curvature, with error bars indicating the standard error of the mean. In both the stimulation and recording experiments, higher presaccadic stimulation frequency or neural discharge is associated with greater curvature. There is also a tendency, particularly at higher rates, for greater curvature for saccades made to the ipsi target than to the contra target.

EFFECT OF DIRECTIONAL DIFFERENCES IN THE FIXED VECTOR AND VISUALLY GUIDED SACCADE. At a majority of the stimulation sites, we used two visual target locations (both orthogonal to the direction of the FVS). This restricted selection raises the question of whether saccades made to other locations would be similarly affected by our stimulation train. At three sites, we examined the effect of subthreshold presaccadic stimulation when visual targets were presented at other angles with respect to the FVS. These other directions included ±45° from the FVS, in the same direction as the FVS, and in the direction opposite the FVS. Similar curvatures to those produced for orthogonal directions were produced for target locations at ±45°. The amount of curvature observed was greater for comparable stimulus parameters when the visual target was located ipsilateral to the end point of the FVS (i.e., when the visual target was represented in the same colliculus as the stimulation site). Visual targets in the same or directly opposite direction to the FVS did not produce curvature. We believe the mechanism that produces curved saccade trajectories is operable over a broad range of directions, but confirmation of this conjecture requires additional experimental verification.

	DISCUSSION

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

Curved saccade trajectories and target/distractor competition

Curved saccades have been observed in a variety of tasks in which competing saccade targets are present, including double-step tasks (Findlay and Harris 1984; Minken et al. 1993; Van Gisbergen et al. 1987) and visual search tasks (McPeek and Keller 2001). It has been hypothesized that curved saccades are the result of competition between saccade goals in visuo-motor structures such as the SC (McPeek and Keller 2000, 2001; Port and Wurtz 2000, 2001). In the present study, we directly tested this hypothesis by recording the activity of SC neurons at distractor locations during a search task. We found that curvature of the movement trajectory toward a distractor was associated with increased activity at that distractor location. This increased activity, which was absent for straight-trajectory saccades toward the target, occurred immediately before saccade onset and was abruptly curtailed as the movement began. Furthermore, a greater degree of elevated discharge at the distractor site was associated with greater curvature toward the distractor. This suggests that curvature results from an initial competition between two salient saccade goals that is resolved near the time of saccade onset. Due to delays between the time of SC discharge and its effect on eye movement production, this activity immediately preceding the saccade perturbs the initial part of the movement's trajectory.

To establish whether this observed pattern of SC activity actually causes curvature, we used subthreshold electrical microstimulation to experimentally produce competing activity in the SC immediately before saccades to single visual targets. We tailored the stimulus pulse train to resemble the pattern of activity recorded from cells at distractor sites when curved saccades occurred. We found that our stimulation paradigm was highly effective in producing saccades that curved toward the location coded by the stimulation site, indicating that the pattern of SC activity recorded in the search task is causally related to saccade curvature. We did not test other patterns of stimulation to determine whether our particular pattern is uniquely effective in producing curved movements.

The results support our hypothesis that saccade curvature in search arises from competition between the target and a distractor goal that is resolved near the time of saccade onset. We speculate that as a result of this competition, the initial movement vector is directed between the target and the competing distractor, similar to what is seen with averaging movements that result from SC activity at two distinct loci (Edelman and Keller 1998; Robinson 1972; Schiller and Sandell 1983; Schiller et al. 1979; Sparks and Mays 1983). The difference between curved and averaging saccades seems to be that for curved saccades, the competition is quickly resolved near the time of saccade onset. As a result, the initial averaging movement is corrected in-flight and the movement ends near the target. This scenario is illustrated in Fig. 11. When straight saccades are made to the target (illustrated by the dashed trajectory in the visual field schematic on the left), a population of neurons centered at the image of the target in the SC (region T) is activated. For the population of neurons that we recorded (including both prelude and burst neurons), this target-related activity peaks just after saccade onset (Fig. 3A). Neurons located at the SC image of the ipsilateral flanking distractor (region D_ipsi) are almost silent by saccade initiation (Fig. 3B). In contrast, when saccades with curvature toward D_ipsi are made (the solid trajectory shown on the left in Fig. 11), the activity at the ipsilateral flanking distractor site is significantly higher in the immediate presaccadic interval, leading to an initial deviation of the saccade trajectory toward D_ipsi.

View larger version (23K): [in this window] [in a new window]   Fig. 11. Activity in the SC for straight and curved saccade trajectories in a visual search paradigm. Left: schematic shows a typical spatial arrangement of the stimuli in our paradigm superimposed on a map of the visual field. Eccentricity in the field is shown by circles at 2, 5, 10, and 20°. The odd-colored stimulus or target (T) is shown by the green disk. The 3 distractors are shown by red disks. Dipsi is the location of the distractor that neighbors T and is located in the same hemifield. Dcontra is the neighboring distractor in the opposite visual field. Doppos is the distractor located diametrically opposite T. The dashed curve shows the trajectory of a saccade that goes in a straight-line path between the fixation point and T. The solid curve shows a saccade that goes to T after first curving in a direction between Dipsi and T. Right: schematics illustrate the activity that occurs in the left SC in the immediate presaccadic interval, when the movement is straight (middle) or curved (right). The site T in the SC is the image of the target in SC space and Dipsi is the image of the corresponding distractor. The intensity of the population activity in SC is shown with the color-coded intensity scale. The dashed line above shows the location of the midline with respect to the left SC. The gray shaded region indicates the region of the SC that would be expected to become active for the terminal trajectory of the curved saccade, if the SC codes final saccade trajectory.

Port and Wurtz (2000) have reported preliminary results in which they recorded simultaneously from two microelectrodes located at sites that would be roughly equivalent to T and D_ipsi in the schematic shown in Fig. 11, during curved saccades produced in a double-step paradigm. Their curved saccades are initially directed toward one target but then curve away from that target and end near the other target. The initial curvature is accompanied by temporally overlapping activity at the two SC sites, with the site that codes the initial target peaking before the activity at the second site. If we assume that our ipsilateral distractor site corresponds to their initial target site, then our observation of presaccadic activity at this site followed by a peak of activity at the target site slightly after saccade onset is similar to their simultaneously-recorded temporal differences.

Correction of the initial direction error in curved saccades

We found that the SC population activity near T in the SC for curved saccades is virtually the same as that observed for straight movements. This suggests that SC discharge at site T does not reflect the perturbation in saccade trajectory that actually occurs. Near the end of the saccade, the movement vector is in an almost straight upward direction, and this terminal movement vector is not represented by the activity centered at either SC location, T or D_ipsi. This terminal portion of the movement could be explained by two alternative mechanisms. If the colliculus encodes movement trajectory, the final movement vector would be produced by the appearance of activity at the medial edges of both colliculi, which together code upward-directed movement vectors. The field shaded gray in Fig. 11 for curved saccades indicates this latter locus in the ipsilateral SC only. The mechanism responsible for this shift in the locus of SC activity could be similar to the remapping process described by Walker et al. (1995).

Alternatively, if the SC encodes the final goal of the movement but not its trajectory, one would expect the activity at T to remain as the activity at D_ipsi disappeared. Neural structures below the level of the SC (e.g., Quaia et al. 1999) would then be responsible for producing the final curvature to compensate for the initial misdirection of the saccade, allowing the eye to land near the goal (specified by T).

Port and Wurtz (2001) have produced preliminary evidence that collicular neurons recorded in areas that would be equivalent to the gray shaded field in Fig. 11 do not become active during the terminal phase of such curved saccades. These results favor the idea that the SC does not directly control saccade trajectory, at least in the latter portion of curved saccades. This interpretation is consistent with results from the colliding-saccade paradigm (Schlag-Rey et al. 1989) and is also compatible with a study of blink-perturbed saccades to a visual target (Goossens and Van Opstal 2000), which found that activity continues at the site in the SC corresponding to the original, retinotopically coded displacement vector even as the saccade trajectory initially veers away from the target and then curves back to end near it. However, the investigators in this latter experiment did not attempt to record at regions in the SC that could code the direction of the terminal trajectory vector.

Electrical stimulation in the SC and curved saccade trajectories

Although our recording study, as well as the results of Port and Wurtz (2000), demonstrates a neural correlate of curved saccades in the SC, such evidence alone cannot establish whether a given pattern of SC activity actually produces curvature. To verify that this SC activity is causally related to saccade curvature, we used subthreshold electrical stimulation, delivered during the latent period of saccades to single visual targets, to mimic the competitive activity observed at distractor sites during curved saccades in the search task. The stimulation trains increased in frequency up to 200 or 250 Hz and terminated near the time of saccade onset. This frequency (200-250 Hz) was similar to the presaccadic activity level that we recorded from single neurons at ipsilateral distractor sites in the SC for the most highly curved saccades observed in search (compare results shown in Fig. 10).

The stimulation paradigm had an additional advantage: a problem with both the double-step task (Port and Wurtz 2000) and our search task is that highly curved saccades occur only infrequently. Thus it is difficult to obtain enough data from individual neurons to test for subtle changes in the spatiotemporal patterns of activity during these curved movements. Our stimulation experiments allowed us to overcome this limitation to some extent by using electrical stimulation in the SC to substitute for the activity that occurs at distractor sites for curved saccades in search. In this way, the timing, location, and intensity of the competing activity can be easily manipulated across repeated trials.

In the present experiments, we typically placed the stimulating electrode in the SC at sites that would be equivalent to D_ipsi and D_contra as shown in Fig. 11. We found that stimulation produced consistently larger values of curvature when it occurred in the colliculus that was activated by the visual target (ipsi site). However, we did not observe such a clear difference between ipsi and contra activity for curved saccades in our recording experiments (e.g., Fig. 10). Thus it is possible that this ipsi/contra asymmetry is specific to the stimulation paradigm and would not be seen with visual distractors.

Even though we produced a greater proportion of curved saccades in the stimulation paradigm than we observed in search, there was still considerable variability in the amount of curvature, and some relatively straight saccades occurred in the stimulation paradigm (Fig. 6C). We found that the timing of the stimulus with respect to saccade initiation was critical in producing curvature: it was necessary for stimulation to continue until just before saccade onset. Indeed, we found that the mean stimulation frequency (in the stimulation experiments) or mean activity level (in the recording experiments) in the 30-ms period immediately before saccade initiation was well correlated with the curvature of the subsequent saccade.

Directional averaging verses curvature with subthreshold stimulation

While we used subthreshold stimulation to alter the trajectory of saccades to a visual target, subthreshold presaccadic stimulation has also been used to alter the endpoints of subsequent saccades (Glimcher and Sparks 1993). These authors used a delayed, memory saccade paradigm in which two visual targets appeared at separate locations. After the targets disappeared, the animals were cued as to which remembered visual stimulus was to be the target of a delayed saccade. The fixation point was subsequently extinguished, and the animals were rewarded for saccading to the cued location. A stimulating electrode was located in the SC at a site that was the collicular image of one of the visual targets. A low-frequency pulse train was delivered through the stimulating electrode during the delay period, which was several seconds in duration, after the potential targets were extinguished. Low-frequency stimulation biased the distribution of saccade end points but did not initiate saccades. At very low stimulus frequencies (10 Hz), the saccade ended at the location of the cued remembered target. As the stimulation frequency was increased, the end point of the subsequent saccade began to be biased more toward the location in the visual field coded by the stimulated site in the SC. No bias occurred if the termination of the stimulation occurred more than ~40 ms before saccade onset. Thus their experimental conditions produced clear averaging effects, and the resulting saccadic trajectories were straight.

There are several differences in experimental design that may have produced these results, which differ from ours. Our subthreshold presaccadic stimulations were delivered in a reaction-time paradigm in which the visual target remained visible. In our experiments, only one visual target appeared in a particular trial, and the stimulation in the SC played the role of the second visual target. We did not obtain averaging movements, but instead the saccade usually ended very close to the location of the visual target after its initial partial deviation toward the vector coded by the stimulated SC site.

Relationship to behavioral studies

Saccadic eye movements are associated with a mound of activity in the SC, centered on the site coding the movement vector (e.g., Anderson et al. 1998). Our results indicate that the presence of a second locus of SC activity shortly before movement onset