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Pontine Omnipause Activity During Conjugate and Disconjugate EyeMovements in Macaques

C. Busettini and L. E. MaysDepartment of Physiological Optics and Vision Science Research Center, University of Alabama at Birmingham,Birmingham, Alabama 35294

Submitted 25 September 2002; accepted in final form 16 August 2003

Busettini, C. and L. E. Mays. Pontine omnipause activity duringconjugate and disconjugate eye movements in macaques. J Neuro-physiol 90: 3838–3853, 2003. First published August 20, 2003;10.1152/jn.00858.2002. Previous reports have shown that saccadesexecuted during vergence eye movements are often slower and longerthan conjugate saccades. Lesions in the nucleus raphe interpositus,where pontine omnipause neurons (OPNs) are located, were alsoshown to result in slower and longer saccades. If vergence transientlysuppresses the activity of the OPNs just before a saccade, thenreduced presaccadic activity might mimic the behavioral effects of alesion. To test this hypothesis, 64 OPNs were recorded from 7 alertrhesus monkeys during smooth vergence and saccades with andwithout vergence. The firing rate of many OPNs was modulated bystatic vergence angle but not by version and showed transient changesduring slow vergence without saccades. This modulation was smooth,and not the abrupt pause seen for saccades, indicating that OPNs donot act as gates for vergence commands. We confirmed that saccadesmade during both convergence and divergence are significantlyslower and longer than conjugate saccades. OPNs paused for allsaccades, and the pause lead (interval between pause onset and sac-cadic onset) was significantly longer for saccades with convergence,in agreement with our hypothesis. Contrary to our hypothesis, pauselead was not longer for saccades with divergence, even though thesesaccades were slowed as much as those occurring during convergence.Furthermore, there was no significant correlation, on a trial-by-trialbasis, between pause lead and saccadic slowing. These results suggestthat it is unlikely that presaccadic slowing of OPNs is responsible forthe slower saccades seen during vergence movements.

I N T R O D U C T I O N

Pontine omnipause neurons (OPNs), located in the nucleusraphe interpositus (Buttner-Ennever et al. 1988) are a criticalcomponent of the primate saccadic eye movement system.These neurons fire tonically in alert animals during fixation andpause just before and during saccades or quick phase eyemovements of any size and direction (Everling et al. 1998;Raybourn and Keller 1977). OPNs must be silent for a saccadeor quick phase to occur or to continue. Electrical microstimu-lation of the raphe interpositus delays the execution of asaccade and interrupts a saccade already started (Becker et al.1981; Keller 1977; Keller et al. 1996; King and Fuchs 1977).OPNs exert this effect on saccades because they stronglyinhibit pontine and midbrain saccadic medium lead burst

(MLB) neurons. These burst neurons provide motoneuronswith the eye velocity signals required for saccades.

The relationship between OPN activity and conjugate (i.e.,without changes in depth) saccades of different sizes anddurations has been investigated in cats (Evinger 1982; Pare andGuitton 1998) and in monkeys (Fuchs 1991). For the monkey,there is general agreement that there is a good correlationbetween saccadic start and pause start. OPNs resume firingaround the saccadic end (Everling et al. 1998; Fuchs 1991),although the timing correlation with the end of the saccade isnot as strong as that between pause onset and saccadic onsetand varies among cells.

The observation that OPNs must pause for saccades tooccur, together with the finding that they receive inputs fromsaccadic-related brain areas, places them in a crucial role inmodels of the saccadic system. Surprisingly, damage to OPNsdoes not cause the devastating effects such as opsoclonus thatmight be expected by the loss of burst neuron inhibition, as anearly model (Zee and Robinson 1979) and some clinical studies(Ashe et al. 1991; Averbuch-Heller and Remler 1996) havesuggested. The most evident effect of experimental damage toOPNs is slower but otherwise normal saccades (Kaneko 1996;Soetedjo et al. 2002). Although the precise mechanism isunknown, this result has been successfully simulated by thereduction of OPN activity within contemporary models of thesaccadic system (Moschovakis 1994; Scudder 1988). In theirmodels, the execution of a saccade is preceded by a gradualcharging of the long lead burst neurons (LLBNs). At saccadiconset the LLBN signal starts to decrease. If a weakened OPNinhibition causes a premature release of the MLB cells duringthe integrating phase and therefore a premature start of thesaccade, the local circuits will start to inhibit the LLBN inte-gration before it reaches its optimal value. Consequently, thepeak firing rate of the MLB cells will be lower. Behaviorally,this translates into a slower and longer saccade.

Several studies (Collewijn et al. 1995; Erkelens et al. 1989;van Leeuwen et al. 1998) have noted that horizontal saccadesare often slowed when combined with vergence eye move-ments. Such mixed saccadic-vergence movements are typicalof refixations in depth. We have noted that some OPNs showsignificant decreases in firing rate during vergence movementsin the absence of saccades (Busettini and Mays 1999). Addi-

Address for reprint requests and other correspondence: C. Busettini, VisionScience Research Center, 402 Worrell Bldg., 924 18th St. So., Birmingham,AL 35294-4390 (E-mail: [email protected]).

The costs of publication of this article were defrayed in part by the paymentof page charges. The article must therefore be hereby marked ‘‘advertisement’’in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

J Neurophysiol 90: 3838–3853, 2003.First published August 20, 2003; 10.1152/jn.00858.2002.

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tional evidence for modification of OPN activity during ver-gence is suggested by the observation of Ramat et al. (1999)that random postsaccadic conjugate ocular oscillations occurduring combined vergence/saccadic eye movements in hu-mans. The authors interpreted these oscillations as evidencethat the postpause resumption of OPN activity was delayed byvergence, allowing irregular firing of the MLBs after the end ofthe saccade proper. The observations that reduced OPN activ-ity attributed to lesions results in slowed saccades and thatvergence reduces OPN activity offer a possible explanation forslowed saccades during vergence. To test this hypothesis, werecorded the activity of OPNs associated with conjugate sac-cades and with saccades during vergence eye movements. OPNactivity related to vergence without saccades was also mea-sured. If reduced OPN activity were responsible for the slowedsaccades seen during vergence, we would expect to see asignificantly lower OPN activity level just before these sac-cades and a positive correlation between presaccadic activityand saccadic slowing.

Brief reports of some of these results were previously pub-lished (Busettini and Mays 1999; Reusser et al. 1995).

M E T H O D S

Pontine omnipause neurons were recorded from 7 juvenile rhesusmonkeys (Macaca mulatta) weighting 6–10 kg. All procedures andexperimental protocols were approved by the Institutional AnimalCare and Use Committee and complied with FDA, AAALAC, andU.S. Public Health Service Policy on the humane care and use oflaboratory animals.

Surgical procedures

Animals were trained to enter a primate chair before a sequence ofaseptic surgical procedures. At the time of the surgery they were givenan intramuscular injection of ketamine (Ketalar), and then intubatedand maintained on isoflurane for the duration of the surgery. Heartrate, respiratory rate, blood pressure, O2 saturation, and body temper-ature were monitored continuously. During the postsurgical period,animals were given analgesics as needed to alleviate any discomfort,and training or experiments were started only after full recovery fromeach surgery.

In the initial surgery, stainless steel plates (Synthes) were attachedto the skull with bone screws. A metal post was affixed to these stripswith dental acrylic cement for head fixation. Following a protocolsimilar to that of Judge et al. (1980), a coil of fine wire (Biomed WireAS633) was implanted under the conjunctiva of the right eye, so thateye position could be monitored using the magnetic search coiltechnique (Fuchs and Robinson 1966). After the animals reached asatisfactory level of training on simple saccadic and tracking trials, a2nd eye coil was implanted on the left eye, allowing the monitoring ofbinocular eye movements. When the monkeys easily performed themore complex in-depth eye movements and preliminary behavioralrecordings were completed, 2 recording cylinders were implantedwith acrylic cement over 15-mm holes trephined into the skull. The 2chambers were stereotaxically positioned bilaterally over the brainstem at a 20° angle to the sagittal plane, 14.5 mm lateral from themidline, and 1 or 2 mm anterior to ear-bar zero.

Behavioral task and visual display

The animal was placed in a primate chair with its head immobilizedand was required to make transfers of fixation in depth and/or direc-tion in response to target motion generated by a mirror haploscopewith a system of lenses that matched the accommodative and vergence

demands (Walton and Mays 2003). A pupillometer (ISCAN) wasaligned with the right eye and functioned as a blink detector. Thevisual subtense for each monitor was �20° (horizontal) and �15°(vertical) and the range of vergence demand, limited by the corre-sponding maximum amount of accommodation demand obtainablewith the system of lenses, was 13°. The monitors generating the visualstimuli had a vertical refresh rate of 90 Hz and the transition from the1st to the 2nd target was completed within 2 video frames (22 ms).The targets were white Maltese crosses 1.2° wide on a black back-ground. A Badal optical system kept the stimulus subtense on theretina constant. Thus changes in apparent depth were not matched bycorresponding changes in stimulus size.

During behavioral training and recording, a brief auditory signalalerted the animal that a new trial was beginning. After 500 ms, aninitial target appeared and the animal had 2,000 ms to look at it. Theanimal was required to maintain its fixation for 1,000–1,500 ms insidea �4° window. Subsequently, the 1st target was turned off and the2nd target was turned on. The animal was required to transfer fixationwithin 1,000 ms and maintain fixation of the new target for 600–1,500ms. The selection of target steps induced the animals to make: 1)purely symmetrical vergence movements (i.e., slow convergence anddivergence) by means of symmetric disparity steps; 2) horizontal andvertical saccades between targets at optical infinity (i.e., conjugatesaccades between 2 far targets); 3) horizontal and vertical saccadeswith convergence (i.e., moving from a far to a near target); 4)horizontal and vertical saccades while converged (i.e., between 2 neartargets); and 5) horizontal and vertical saccades during divergence(i.e., moving from a near to a far target). Although pure disparity stepsenhanced the probability of saccadic-free smooth vergence move-ments, small saccadic intrusions were common and contaminatedtrials were analyzed as combined saccadic/vergence trials. Horizontal,oblique, and vertical versional target steps from 1 to 25° were used,along with vergence demand changes from 0 to 13°, although onlysubsets of these values were employed in a given session. Usually the1st target started at the center of the display, but in some sessions itsposition was randomly offset to allow larger target steps. All trialswere pseudo-randomly intermixed to avoid anticipation by the animal.

Data acquisition and single-unit recording

Presentation of the stimuli, reward administration, and acquisitionof the eye and unit signals were made by a computer. The horizontaland vertical eye positions of both eyes were acquired at either 500 or1,000 Hz. Asynchronous interrupt-driven events with a time resolu-tion of 0.1 ms marked the occurrence of neuronal spikes as detectedby a window discriminator (BAK Electronics). An additional channel,sampled at 20 kHz, was used to store the analog signal from theelectrode. Low-impedance (0.1–0.3 M�) parylene-insulated tungstenmicroelectrodes (MicroProbe) with additional insulation weremounted in 26-gauge steel tubing. These electrodes were advancedthrough a 21-gauge hypodermic needle (used to penetrate the dura andas a guide tube) by a Kopf microdrive. Unit activity was filtered above5 kHz to eliminate the high-frequency (28 kHz) interference producedby the magnetic field coils and was also high-pass filtered at 10 or 100Hz depending on the amount of low frequency noise. The criteria usedto determine that the electrode was located in the omnipause area were1) the presence of neurons that displayed a constant firing rate duringfixation and paused during saccades in all directions and for blinks; 2)the ability of microstimulation (maximum current 40 �A at 250 Hz)to block the occurrence of a saccade or stop an ongoing saccade inmidflight; and 3) by visual observation of small marking lesionsand/or electrode tracks in the omnipause area during histologicalreconstruction.

Data analysisEYE MOVEMENTS. Right and left horizontal and vertical eye posi-tion traces (HR, VR, HL, VL) were linearized with 3rd-order poly-

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nomials and fit with a cubic spline with weight 1 � 108 (0.1 with thetime expressed in ms). Velocity signals were obtained with a 2-pointbackward differentiation. Horizontal version (H) was computed asaverage (HR � HL)/2 of the 2 horizontal eye positions. Horizontalvergence position (VG) was calculated as HL � HR. For the verticaleye movements, the vertical eye positions were used to compute anaverage vertical version signal (VR � VL)/2 and all vertical measureswere made on the vertical version (V) or the vertical version velocity(V). Rightward, upward, and convergence movements are representedby positive values. Pythagorean position (PY) was defined as�H2 � V2 and saccadic identification was performed using thePythagorean velocity (PY). A preliminary analysis indicated minimaldependency of OPN activity on saccadic direction. Therefore wedecided to characterize saccades on the basis of their Pythagoreanamplitude, peak velocity, and duration without regard to saccadicdirection. Saccades were defined as conjugate if the stimulus did notrequire a change in depth. Saccades were defined as divergent if thestimulus required a change in depth from near to far, and convergentif the stimulus required a change in depth from far to near. Using acyclopean peak velocity of 40°/s as the minimum threshold for ourautomatic saccadic detection, all detected conjugate eye movementshad a cyclopean amplitude– peak velocity relationship that followedthe saccadic main sequence (Becker 1989). Saccades during vergenceoften had peak velocities lower than the conjugate main sequence butthe deviations from the conjugate values were never large and werecontinuous with them, strongly suggesting that these movements werealso saccades, albeit more or less slowed. We restricted the analysis tothe primary saccades associated with the stimulus transition from the1st to the 2nd target and to correctives saccades, if any, when the 2ndtarget was still on.

Initially, a velocity threshold of 20°/s applied to the Pythagoreanvelocity was used to mark saccadic onset and offset. This procedureproved unsuitable because the onsets of smaller, slower saccades weredetected too late and their ends were detected too early. This problemwas solved by the use of small timing corrections based on averagedacceleration values. All saccadic onset, end, and duration data arereported using adjusted values.

OPN ACTIVITY. The interval between the last prepause spike andsaccadic onset determined the pause lead (Plead), whereas the intervalbetween saccadic onset and the 1st resuming spike, indicating the endof the pause, was defined as resuming lag (Rlag).

Because a preliminary analysis showed that some OPNs are mod-ulated with eye position, the firing rate of each cell when the animalwas looking straight ahead with the eyes aligned at distance (vergenceangle �2°) was used as a measure of the tonic activity during fixation.For each trial, baseline firing rate was defined as the average firing rateof the cell in the interval 0–40 ms after the visual target stepped fromthe center “far” position. The position of the 2nd target was irrelevant,given that no visual or motor responses to the target step occurredwithin 40 ms of target movement. An average baseline firing rate wascalculated for each cell.

We determined whether the tonic OPN firing rate was sensitive tohorizontal eye position of the left or right eyes, horizontal vergence,horizontal version, or vertical version by measuring the OPN firingrates during periods of fixation at various combinations of vergenceand version values. This was done by displaying each trial so thataverage measures of eye position and firing rate over 100-ms intervalscould be manually selected. Data were accepted if: 1) one of the 2targets were present (i.e., not in a period of darkness); 2) there wereno residual effects attributed to visual responses, eye movements, orblinks; 3) there were no changes associated with impending move-ments; 4) there was steady fixation of the target; and 5) the firing ratewas constant. During long periods of fixation, measures were repeatedevery 200 ms, if possible. Only data sets with �8 trials (i.e., �8measures while fixating the 1st target and �8 measures while fixatingthe 2nd target) are reported. Visual responses were measured on a

subset of the conjugate trials used to measure the baseline firing rate.In addition to the restrictions used earlier for the baseline measures,trials were selected for analysis if: 1) the 2nd target stepped to adifferent location with no change in vergence demand, and 2) thesaccadic-related pause was �130 ms after the stimulus change, so thatOPN activity in the 1st 100 ms after the target step would be unaf-fected by any presaccadic slowdown in activity. In preliminary anal-yses, we noted that visual responses, when present, started about50–60 ms after stimulus onset. To quantify these responses, 2 mea-sures were taken in each of the trials meeting these criteria. The 1stwas the average firing rate in the 0- to 40-ms interval after targetmovement, and the 2nd measure was the average firing rate in theperiod 60–100 ms after target movement. For each neuron with �8valid trials, a paired t-test compared the activity level in the 2nd periodto the 1st. Unless specified otherwise, the statistical level for signif-icance throughout the study is P � 0.01. For each cell, the onset andoffset of the visual response were determined using an objective2-segment linear curve fitting algorithm applied to the average firingrate profile. Before averaging, the individual firing profiles wereinterrupted 30 ms before the 1st saccadic onset. The average profilewas stopped when the average was computed on fewer than 8 remain-ing observations.

The stimuli used to obtain smooth vergence responses were sym-metric steps, inducing an abrupt change in disparity but not in (ver-sional) eccentricity. The goal was to collect, for each cell and each ofthe 2 vergence directions, �8 trials of slow vergence without saccadesor blinks. The mean firing rate of each trial in a 40-ms intervalcentered on the trial’s peak vergence velocity was compared with theestimated baseline firing rate using a paired t-test. Both measures wereadjusted to compensate for positional modulation, using the averageeye positions inside the intervals and the previously determined po-sition sensitivity coefficients. Using a measure centered on the peakvergence velocity, which occurred around 200 ms after stimulusonset, largely eliminated the possibility of contamination from thetransient visual responses elicited by the stimulus onset. Unfortu-nately, some animals had an idiosyncratic tendency to associate anearly, small saccade with all vergence movements in one of the 2vergence directions even for pure symmetric disparity steps, forcingthe elimination of the data set in that direction for that animal.However, trials containing saccades were included if saccadic onset,as defined by a Pythagorean velocity �10°/s, occurred �30 ms afterthe 40-ms measurement interval centered on the peak in horizontalvergence velocity. This was done because a preliminary analysisshowed that OPN activity 30 ms or more before a saccade wasunaffected by the occurrence of a saccade.

ASSESSMENT OF SACCADIC SLOWING. The peak velocity of sac-cades (Svpk) and saccadic duration (Sdur) are known (Becker 1989) tobe monotonic functions of saccadic size (Ssize). To assess the degreeof saccadic slowing associated with vergence, it was necessary to firstcontrol for the effects of saccadic size on peak Pythagorean velocityand duration. This was done by evaluating the following expressionsfor the conjugate trials for each cell

Svpk � A � Ssize � B � Ssize2 (1)

Sdur � A � B � Ssize � C/Ssize (2)

The B � Ssize2 term in Eq. 1 accounts for the saturation seen in thepeak-size main sequence, whereas the C/Ssize term in Eq. 2 accountsfor the duration nonlinearity seen for smaller saccades (Becker 1989).Only cells with �8 conjugate observations were included in thisanalysis. These equations allowed us to assess, for each cell, thedifferences (DIFF) for peak saccadic velocity (DIFFSvpk) and dura-tion (DIFFSdur) between saccades accompanied by either conver-gence or divergence and the conjugate saccades. The dependency ofDIFF on the 2 variables thought likely to influence saccadic dynam-ics, vergence velocity at the start of the saccade (VGONS) and saccadic

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disconjugacy (intrasaccadic vergence change or VG), were evaluatedusing linear regressions

DIFF � A � B � VGONS (3)

DIFF � A � B � VG (4)

We labeled the slopes of these linear regressions as DIFF( ). Forexample, the slope of the linear regression of DIFFSdur with VG isidentified as DIFFSdur(�VG). Measured values and associated av-erages are indicated in italics, whereas estimated parameters andassociated averages are indicated in bold.

The relationship between OPN activity and saccades has usually(Everling 1998; Evinger 1982; Fuchs 1991; Pare and Guitton 1998)been expressed either in terms of pause lead or pause duration versussaccadic duration. We assessed pause lead as a linear function ofsaccadic size, peak velocity, and duration for the conjugate saccadesof each cell. Of the 54 cells for which we had sufficient data, only 8cells showed a significant modulation with one or more saccadicparameters. These relationships were small and in both directions andthere was no significant average change in pause lead for the overallpopulation with any of the 3 parameters. We therefore used a singlevariable to characterize pause lead for conjugate saccades

Plead � A (5)

We then examined the differences in pause lead (DIFFPlead) forsaccades with convergence and divergence (relative to conjugatesaccades) as a function of VGONS and VG using Eqs. 3 and 4. If thereis a correlation between the deviation of pause lead from conjugatesaccades and the perturbation in saccadic dynamics, we expect it to bemirrored by a correlation between DIFFSvpk and DIFFPlead andbetween DIFFSdur and DIFFPlead.

Previous reports in the monkey (Fuchs 1991) have indicated thatthere is a modest positive correlation between saccadic duration andpause duration. However, pause lead is a component of pause dura-tion, given that pause duration is the sum of pause lead and resuminglag. The pause lead values for a given cell should be somewhatvariable because the presaccadic activity of an OPN is likely to berelatively uncorrelated with the occurrence of the saccade and so itsinclusion in pause duration should add a significant amount of uncor-related noise to the relationship between pause duration and saccadicduration. If this is the case, it is more useful to evaluate the relation-ship between saccadic duration and the resuming lag. Accordingly, weevaluated the relationships between pause duration and saccadic du-ration as well as between resuming lag and saccadic duration forconjugate saccades using the following linear regression models

Pdur � A � B � Sdur (6)

Rlag � A � B � Sdur (7)

As anticipated, resuming lag proved to be more highly correlatedwith saccadic duration than did pause duration. Consequently, weexamined the differences in resuming lag (DIFFRlag) for saccadeswith convergence and divergence relative to conjugate saccades ofsimilar duration as a function of VGONS and VG using Eqs. 3 and 4.

R E S U L T S

Overview of OPN characteristics

Sixty-four OPNs were recorded from the nucleus rapheinterpositus of 7 rhesus monkeys. As previously reported (Ev-erling et al. 1998; Raybourn and Keller 1977), these cells hadtonic activity during fixation but paused for saccades in alldirections. Figure 1 shows data for one OPN. This cell showsclear evidence of a transient visual response with a peak around75 ms from stimulus onset. The activity of this cell is clearly

diminished for convergence (Fig. 1A) but not for divergence(Fig. 1C). As a consequence, the presaccadic pause lead can bemuch greater for a saccade with convergence (Fig. 1B) than fora saccade with divergence (Fig. 1D).

Modulation of firing rate with eye position

Overall, the baseline firing rate had a roughly Gaussiandistribution with an average firing rate of 125 spikes/s and SDof 31 spikes/s (n 64). The range was from 50 to 188 spikes/s.These values are very close to those reported by Everling et al.(1998).

We measured the firing rate of the cells when the animal wassteadily fixating at different versional and vergence angles. Twodifferent multiple regression analyses were used to determinewhether the modulation fits either a conjugate � vergence (“Her-ing”) model or a left eye/right eye (“Helmholtz”) model. TheHelmholtz model uses HR, HL, and V as independent variables.The Hering model uses H, VG, and V as independent variables.Using the Hering model, we found a very small and nonsystem-atic positional dependency with horizontal version and vertical

A B

C D

FIG. 1. Examples of single vergence and saccadic-vergence trials from anomnipause neuron (OPN) showing modulation for convergence only. A: slowconvergence from 0.0 to 6.8° without saccadic intrusions. B: convergence from0.2 to 7.3° with a 5.3° rightward 0.8° upward saccade. C: slow divergence from5.9 to 0.0° without saccadic intrusions. D: divergence from 6.2 to 1.1° with a3.2° rightward 1.6° upward saccade. Top traces: horizontal left eye position(HL) in red, horizontal right eye position (HR) in green, vertical versionposition (V) in black, and vergence position (VG) in blue. Bottom traces:corresponding velocity traces with same color coding. In some plots vergencevelocity scale, identified in blue, is different from horizontal and vertical eyevelocity scale, identified in black, attributed to much faster dynamics ofsaccades. Neuronal activity is illustrated by analog output from electrode,corresponding spike events, and firing frequency. Horizontal axis: time. Ver-tical dotted line indicates stimulus onset. Cell 10604.71.



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version, as shown in the “H” and “V” histograms in Fig. 2. Theaverage modulation over the entire population was 0.03 � 0.48spikes/° (�SD if not specified otherwise) for horizontal versionon the 61 cells for which we had data, and 0.13 � 0.65 spikes/°for vertical version on the 48 cells for which we had data. Overall,these averages were not significantly different from zero (P �0.05). In contrast, 35 cells showed a robust, albeit small, modu-lation with vergence angle. This is evident looking at the histo-gram labeled “VG” in Fig. 2. The comparison of this histogram

with the “HR,” “HL” (Helmholtz model), and “H” histogramsalso suggests that this is a true vergence modulation with balancedcontributions by the 2 eyes. We always observed opposite mod-ulations for “HR” and “HL” components, and a much smaller andinconsistent “H” modulation. This would be expected if the mod-ulation were linked to a positional contribution associated withvergence and not to monocular right or monocular left eye signals.Twenty-five cells showed a significant decrease of their activityfor increased convergence, whereas 10 showed a significant in-crease, with a continuous distribution of values ranging from�7.27 spikes/° (SE �0.26 spikes/°) to 2.38 spikes/° (SE �0.08 spikes/°). Overall, the modulation with vergence positionwas �0.50 � 1.51 spikes/°, which was significantly differentfrom zero. Not surprisingly, the modulation with horizontal rightand left eye positions, taken separately, had opposite signs. ForHR the average over the entire population was 0.52 � 1.52spikes/° and significant. For HL the average value was �0.47 �1.55 spikes/° (P � 0.02).

Visual response

Responses of monkey OPNs to visual stimuli were assessedby synchronizing neuronal activity rasters either with the targetstep (Fig. 3A) or with saccadic onset (Fig. 3B). Figure 3 showsthat a presaccadic transient increase in firing rate was associ-ated with the stimulus transition (Fig. 3A) and not with theoccurrence of a saccade (Fig. 3B). For most cells, like the oneshown in Fig. 3, the visual response ended before the onset ofa saccade. Even though vergence movements tended to haveshorter latencies than saccades, some visual responses endedbefore vergence onset as well. This can be seen for 2 of thecells shown in Fig. 4. Trials were synchronized on stimulusonset before averaging. Figure 4A shows averaged vergencevelocity (VG) and firing rate (FR) data for 3 trial types (con-jugate “far” saccade, convergence, divergence). The visualresponse ends before any eye movement. This cell shows adecrease in firing rate related to static convergence (indicatedby the asterisk) and a much more pronounced suppression ofthe firing rate for dynamic convergence than for dynamicdivergence. Figure 4B shows data for 2 levels of convergence,one level of divergence and for conjugate “far” saccades. The

FIG. 2. Positional modulation. For each OPN for which we had sufficientdata, figure shows sensitivity of tonic firing rate of cell for vergence position(VG), horizontal right eye position (HR), horizontal left eye position (HL),horizontal version position (H), and vertical version position (V) in spikes/°.Downward bars indicate decreases in activity. Statistically significant modu-lations are marked with an asterisk and vertical lines are SE of sensitivitycoefficients. Cells are arranged in order of increasing convergence sensitivity(i.e., leftward sets show maximum decrease for increasing convergence andrightward sets show maximum increase for increasing convergence). For somecells we had no vertical data (bar location empty).

FIG. 3. OPN visual response. The two panels show firingrate of an OPN in response to multiple presentations of conju-gate steps of target. A: trials are synchronized with stimulustransition. B: trials are synchronized with start of associatedsaccade. Comparison of single spike trains and of mean firingrates (continuous lines in bottom graphs) between A and Bclearly shows that initial transient occurring about 60 ms afterstimulus transition is time-locked with stimulus change and notwith initiation of associated eye movement. Dotted lines inaverage graphs mark instantaneous SD of firing rate and hori-zontal dashed lines indicate mean baseline firing rate of cell.Vertical dotted line in A shows average time of occurrence ofstimulus transition whereas vertical dotted line in B shows timewhen saccade starts. Eye trace in B is Pythagorean eye positionprofile of one trial of data set.



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visual response is highly stereotyped and identical for all 4conditions, and the firing rate decreases for both convergenceand divergence. The delayed peak in divergence velocity ismatched by a similar delay in the peak of the firing ratesuppression, again suggesting that the main source for thedynamical OPN modulation is a signal related to vergencevelocity. Figure 4C shows data for averaged conjugate “far”saccades and convergence for a cell that had no detectablevisual response. The robust modulation of OPN activity asso-ciated with convergence indicates that this change in activity isunrelated to the presence of visual activation. Finally, data areshown for conjugate “far” saccades, 2 levels of convergenceand one level of divergence for one of only 3 cells that appearto show a continuation of the visual response throughout theconvergence movement (Fig. 4D). It is more likely, on thebasis of the conjugate average profile and the lack of a similarprolonged increase of firing for divergence, that a decayingvisual response was then masked by an actual increase in firingrate associated with the ongoing convergence.

Quantitative measures of the visual responses were per-formed on the conjugate “far” data sets, as described in METH-

ODS. An inspection of average firing data for all cells showedthat no visual response occurred earlier than 45–50 ms aftertarget step, and that the main visual response was seen after 60ms. The average activity in the 60- to 100-ms visual responseperiod was compared with the 40-ms period of baseline activ-ity. Fifty-three of the 64 OPNs tested (83%) showed statisti-cally reliable visual responses in the visual response period. Onaverage, OPNs increased their firing rate 17.6% (�13.3% SD;P � 0.000002) over baseline in the visual response period(range �3.6 to 76.3%). No cell showed a significant decreasein activity during the visual response period. The averagelatency of the visual response, measured on the 53 cells withsignificant visually related activity, was 57 � 5 ms (range 47to 71 ms). On average, the visual response for the same cellsended 140 � 33 ms (range 77 to 240 ms) after target onset.

OPN modulation with slow vergence

Figure 4 indicates that some OPNs transiently decreasedtheir firing rate for convergence, divergence, or both, in theabsence of saccades. Figure 5 shows examples of these re-sponses, together with trial-by-trial activity rasters, synchro-nized on the peak of the vergence velocity. The horizontaldotted lines indicate the baseline firing rate of each cell. It isimportant to note from the raster displays that the decreases infiring rate associated with vergence were always gradual, un-like the abrupt pauses associated with saccades. As Fig. 5shows, small but robust visual responses (elevated dischargebefore vergence onset) were also observed for the symmetricdisparity stimuli used to elicit the smooth vergence responses.For some cells, the visual response was so large as to possiblymask the earliest changes in activity associated with the ver-gence (Fig. 5C), and indeed, the presence of the visual re-sponses on so many OPNs made it impossible to estimate theoverall latency of these vergence-related changes in activity.No OPN showed a significant increase in activity associatedwith smooth divergence and only 4 OPNs showed a significantincrease in activity associated with smooth convergence. Oneof these 4 cases is shown in Fig. 5D. Sufficient data wereavailable for a quantitative analysis of 29 OPNs for conver-gence transients without saccades (Table 1) and 15 cells fordivergence transients without saccades (Table 2). Note thatthere is only partial overlap in the cells shown in these 2 tables.The measures reported are the averages of the single trialaverage measures taken in 40-ms intervals centered on peakvergence velocity. With the vergence velocity peaks occurringaround 200 ms from stimulus onset, it is very unlikely that thevisual responses, with an average offset time of 140 ms fromstimulus onset, influenced the measures. For convergence, 17of the 29 OPNs (59%) showed a significant decrease in firingrate, and 4 (14%) showed a significant increase. For diver-gence, 7 OPNs (47%) showed a significant decrease. Fordivergence, because of the negative sign of the vergence ve-locity, a decrease in firing rate is associated with a positivevalue of the modulation coefficient Dp. The average depth ofOPN activity modulation for convergence was �0.37%/(°/s)[SD �0.64%/(°/s); range �2.51 to 0.70%/(°/s)]. Overall, thismodulation was significantly different from zero. The averagedepth of modulation for divergence was 0.38%/(°/s) [SD�0.36%/(°/s); range �0.12 to 1.27%/(°/s)], which was alsosignificantly different from zero. For both convergence and

A B

C D

FIG. 4. Examples of average temporal course of firing rate for conjugate,convergent, and divergent trials. Conjugate “far” averages (CONJ) are inblack, convergent averages for disparity steps of 6° (CONV [6°]) are in blue,convergent averages for disparity steps between 10 and 12° (CONV [10–12°])are in red, and divergent averages for disparity steps of �6° (DIV [6°]) are ingreen. Traces shown are averages of all trials that met our inclusion criteria forthat cell, synchronized on stimulus onset and discontinued 30 ms before onsetof 1st saccade, if a saccade occurred. Averages are interrupted at point wherenumber of observations, due to reductions in single traces, fell below 8.Divergent trials started with animal converged and asterisks indicate a signif-icant static modulation with vergence position. Top traces: vergence velocityaverages (VG). Bottom traces: firing rate averages (FR). Horizontal axis: time.Visual responses are labeled with an arrow. Vertical dotted line identifiesstimulus onset.



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divergence the average firing rate of the OPN populationdecreased, in agreement with our initial hypothesis of a sup-pressive effect of slow vergence on the OPNs. For our highestvergence velocities, around 70°/s, a slowdown linked to ver-gence velocity of �0.37%/(°/s) translates to a 26% reduction inoverall activity of the OPN population.

There was a significant trend for the cells with the strongestdynamical convergence modulations to also show the strongestpositional vergence modulations. Indeed, for convergence (Table1) the dynamic modulation (Dp) could be estimated as 0.47 �Staticmod with R2 value of 0.64 (t-value 8.5). However, asimilar correlation was not observed for divergence.

Effects of static vergence on pause lead

We determined whether the OPNs show modifications in thepause lead values between conjugate saccades executed atdifferent (static) vergence angles. Forty-six cells had �8 con-jugate saccades executed at static vergence angles covering a

range of values �5°. Of these cells, 43 cells (93%) did notshow any significant change in pause lead with static vergenceangle. Only 2 cells showed significant increases in pause leadwith static vergence angle (0.40 and 0.44 ms/°) and one cellshowed a significant decrease (�0.66 ms/°). The average valuefor the population was 0.07 ms/° (SD �0.35 ms/°; range �0.72to 0.89 ms/°) and was not significantly different from zero(P � 0.05). This result strongly suggests that the changes inbaseline firing rates associated with static vergence are toosmall to modify the average pause lead. A comparison of thesaccadic dynamics for similar saccadic sizes between “near’”and “far” saccades also failed to show any statistical differenceand therefore to compute the conjugate estimates (see follow-ing text), we pooled both “near” and “far” conjugate saccades.

Quantitative analysis of conjugate saccades

The averages of the conjugate estimates for the 54 cells forwhich we had sufficient data are illustrated in Table 3. The

FIG. 5. Subset of OPNs showed sensitivity to slow ver-gence eye movements. Panels show the 4 types of OPN firingbehaviors during slow vergence eye movements found in ourdata sample (excluding case of no change in firing rate). Alltrials are synchronized on peak vergence velocity. In eachpanel, top graph shows mean vergence velocity (continuousline) with its associated instantaneous SD (dotted lines), sin-gle rasters are shown in center, and bottom graph shows meanfiring rate (continuous line) with its associated instantaneousSD (dotted lines). Dashed horizontal line is baseline firing rateof cell. A: example of a cell decreasing its firing rate duringslow convergence. B: a cell decreasing during slow diver-gence. C: a cell with a large visual response that would maskany initial slow vergence modulation. D: a cell increasing itsfiring rate during slow convergence. Initial increase in firingrate attributed to visual response is very evident, as well as,particularly in A and B, change in tonic firing rate resultingfrom positional modulation. Some trials were shortened be-cause of later saccadic intrusions 30 ms before saccadic onset,identified in figure as trials with an abrupt termination ofrasters. Data illustrated here were obtained with symmetricdisparity steps of 10–13°.



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values of the conjugate peak-size main sequence varied onlyslightly among sessions and animals. The quality of the esti-mates, expressed by the R2, was extremely high, with an

average of 0.975 and was always above 0.90. As expected(Becker 1989), the estimates of the conjugate duration-sizemain sequence had lower R2, with an average of 0.84 and a

TABLE 1. Modulation of OPNs with slow vergence: convergence sets

Cell

Convergence

Static mod [%/°]Bp [spikes/s] Mp [spikes/s] Vp [°/s] Dp [%/(°/s)]

10604.71 87.0 �62.8 28.8 �2.51* �4.02*10311.29c 65.9 �39.0 35.7 �1.66* �3.44*30704.x01 152.8 �81.7 55.9 �0.96* �1.21*10908.x01 78.4 �44.3 59.3 �0.95* �1.06*10806.x01 83.2 �39.6 54.3 �0.88* �0.0700317.24d 116.2 �28.4 31.1 �0.78* �2.69*10730.x01 110.6 �37.5 46.7 �0.73* �1.05*20406.35b 118.2 �18.3 23.4 �0.66* �0.1500510.71 134.0 �22.2 28.2 �0.59* �1.86*61108.29c 112.6 �20.6 31.4 �0.58* �0.87*30531.x01 123.1 �21.1 35.3 �0.48* 0.3561026.29c 152.8 �24.5 38.0 �0.42* �0.2100311.35b 113.6 �9.2 26.9 �0.30* �0.98*11127.21 115.3 �15.6 58.0 �0.23* 0.99*01018.21 160.5 �18.1 58.1 �0.19* �0.62*00609.35b 143.6 �6.0 22.5 �0.19 �0.52*10704.21 171.5 �15.9 68.1 �0.14* �0.38*00217.29c 133.7 �5.7 36.3 �0.12* 0.1600702.21 160.6 �7.7 65.6 �0.07 �0.91*00808.x01 117.9 �3.3 67.9 �0.04 �0.0151116.29c 138.5 �1.6 43.3 �0.03 0.0411109.29c 193.4 �1.8 31.5 �0.03 �0.50*10811.x01 112.7 1.1 66.4 0.02 �0.2150702.21 140.1 4.2 64.7 0.05 �1.2110729.x01 109.4 3.4 46.4 0.07 �0.43*01002.x01 120.8 8.6 31.1 0.23* �0.1740804.x01 109.0 26.2 60.4 0.37* 0.75*00804.x01 134.9 35.1 63.1 0.41* 0.51*10904.x01 124.1 32.5 37.4 0.70* 0.50*Mean � SD 125.7 � 28.0 �14.3 � 25.6 45.4 � 15.4 �0.37* � 0.64 �0.66* � 1.15

n 29 cells. For each of the 29 cells for which we had sufficient smooth convergence data, the table shows the means of the following trial-by-trial measures,computed as average values in a 40-ms interval centered on the peak vergence velocity of the trial: Bp is the estimated baseline firing rate of the cell for the eye positionvalues in the measure interval; Mp is the measured change in firing rate during the slow convergence with respect to the estimated baseline; Vp is the vergence velocity.As the average value in the 40-ms interval centered on the peak vergence velocity, Vp is very close to the peak value; Dp is the normalized amplitude of modulation,expressed as % change of the firing rate per °/s of vergence velocity. The Static mod column reports the static modulation values in %/° of the adjusted baseline valueBp for a direct comparison with Dp. The asterisks in the Bp and Static mod columns mark the cells with a significant dynamic and static modulation, respectively. Theamplitude of the disparity steps used for the measure of the vergence velocity sensitivity varied for different data sets from 6 to 12°.

TABLE 2. Modulation of OPNs with slow vergence: divergence sets

Cell

Divergence

Static mod [%/°]Bp [spikes/s] Mp [spikes/s] Vp [°/s] Dp [%/(°/s)]

10730.x01 95.9 �36.0 �29.5 1.27* �1.21*01123.713 156.3 �54.5 �43.3 0.81* 0.1110806.x01 79.9 �15.3 �25.2 0.80* �0.0801023.713 137.7 �61.4 �65.7 0.68* 1.73*10904.x01 127.9 �19.3 �35.7 0.38* 0.49*31021.713 160.5 �32.5 �59.6 0.34* 0.2730531.x01 127.2 �26.4 �68.7 0.32* 0.3461108.29c 105.2 �6.8 �25.1 0.26 �0.94*10604.71 65.7 �5.3 �32.7 0.25 �5.33*10729.x01 103.0 �7.1 �36.7 0.21 �0.46*00317.24d 97.6 �4.7 �21.2 0.19 �3.20*01018.21 150.1 �11.8 �47.6 0.16 �0.66*00804.x01 143.1 �3.9 �28.5 0.11 0.48*11105.29c 163.2 �4.0 �33.9 0.07 �0.42*40804.x01 119.2 3.8 �28.7 �0.12 0.69*Mean � SD 122.2 � 30.2 �19.0 � 19.5 �38.8 � 15.1 0.38* � 0.36 �0.54 � 1.72

n 15 cells. The table shows the same measures used in Table 1 for the 15 cells for which we had sufficient smooth divergence data.



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range from 0.33 to 0.98. Nonetheless, the ranges of the esti-mated parameters were still relatively small.

The pause lead values were, on the contrary, highly variable.As suggested in METHODS, this would be expected if the presac-cadic firing of the cell were largely unaffected by the forth-coming saccade and yet abruptly stopped by a trigger signal.The plots in Fig. 6 show that this is indeed the case. Figure 6Ashows that the average duration of the last prepause interspikeinterval (ISI) was only slightly longer than the average baselineISI after correction for the positional modulation. The averagelengthening was 27% of the corrected baseline ISI. This find-ing is consistent with the one reported by Everling et al. (1998).Functionally, this means that the OPNs are firing near baselineup to the arrival of the trigger signal. Pause lead, which can bethought of as the sum of the trigger lead and of the ISI cut shortby the trigger, is therefore expected to have, for each cell, anaverage and SD value linearly related to the presaccadic firingrate, the best available estimate of which is the average dura-tion of the last prepause ISI of the cell. Figure 6, B and Cconfirm these predictions. Both average pause lead (Fig. 6B)and SD of pause lead (Fig. 6C) are positively correlated withthe duration of the last prepause ISI. The scatter in the conju-gate estimates of pause lead is therefore a secondary effect ofthe variability of the baseline firing rates among the OPN cells.Theoretically, the intercept of the regression line in Fig. 6B(4.1 ms) is the pause lead of a cell with 0-ms duration of theprepause ISI and therefore the value of the trigger lead itself.We expect the actual trigger signal to start a few millisecondsearlier, given that such a signal requires some time to drive theOPNs to a full stop from their presaccadic firing rates.

The inherent random scatter of pause lead is expected tocause a significant reduction in the correlation between pauseduration and saccadic duration. This effect can be eliminatedby using resuming lag instead of pause duration when com-paring neuronal activity to saccadic duration. Figure 7A shows,

FIG. 6. Conjugate presaccadic OPN behavior. A: firing rate of OPNs re-mains elevated up to last interspike interval (ISI) before pause. Duration ofaverage last prepause ISI (y-axis) of each of 54 cells for which we hadsufficient data were, on average, only 27% longer that corresponding averagebaseline ISI after compensation for positional modulation (x-axis). Solid line islinear regression, with equation LASTISI �0.57 � 1.27 � BASELINE.Slope had a t-value of 25.2 and R2 of regression was 0.92. Dotted line istheoretical regression line for no slowdown, with LASTISI BASELINE. B:average pause lead of a cell (y-axis) is directly related to prepause firing rate(x-axis), estimated as average duration of last prepause ISI. This is true for SDof pause lead of a cell as well, as illustrated in C. Solid line in B is linearregression (Plead 4.1 � 1.01 � LASTISI). Slope had a t-value of 8.9 andR2 of regression was 0.61. For regression in C equation was SDEVPlead �0.53 � 0.54 � LASTISI. Slope had a t-value of 10.7 and R2 of regression was0.69. Numbers at end of regression lines are slope values.

TABLE 3. Conjugate estimates

Parameter Mean � SD [Range]

Svpk A � Ssize � B � Ssize2

A [(°/s)/°] 71.8 � 6.0 [55.8 to 85.4]B [(°/s)/°2] �1.90 � 0.50 [�3.22 to �0.76]R2 [—] 0.975 � 0.020 [0.902 to 0.995]

Sdur A � B � Ssize � C/Ssize

A [ms] 30.2 � 2.8 [25.3 to 36.4]B [ms/°] 1.04 � 0.37 [0.00 to 1.75]C [ms � °] �4.3 � 2.6 [�10.9 to �0.1]R2 [—] 0.84 � 0.10 [0.33 to 0.98]

Plead A

A [ms] 14.7 � 4.8 [4.0 to 33.3]SD [ms] 5.1 � 2.4 [1.8 to 13.7]

Pdur A � B � Sdur

A [ms] 16.8 � 17.1 [�29.1 to 57.1]B [—] 0.79 � 0.37 [�0.26 to 1.59]R2 [—] 0.48 � 0.26 [0.00 to 0.96]

Rlag A � B � Sdur

A [ms] 0.3 � 11.6 [�26.0 to 25.3]B [—] 0.85 � 0.28 [0.30 to 1.47]R2 [—] 0.72 � 0.21 [0.06 to 0.97]

n 54 cells. The rows report the average value and SD of the parametersfor the 5 equations described in METHODS and their associated R2 observed vs.predicted estimated with SYSTAT. Because the Plead estimate is a constant,the SD is substituted for R2. Values in square brackets are the observed ranges.The averages are obtained from the 54 data sets (cells) for which we hadconjugate saccadic data.



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for the conjugate saccades from cell 01023.713, the relation-ship between pause duration and saccadic duration, with R2

value of only 0.26. Figure 7B shows the same data set, but nowas the relationship between resuming lag and saccadic dura-tion, with a dramatic increase of the R2 to 0.80. This was aconsistent finding for all cells, as it can be seen comparing theconjugate estimate averages of pause duration and resuminglag in Table 3, where the average R2 increased from 0.48 to0.72. Of the 54 cells of the data set, 43 cells (80%) had R2

values higher than 0.6 between resuming lag and saccadicduration. For pause duration versus saccadic duration, only 21cells (39%) had R2 values higher than 0.6. Even though the useof resuming lag greatly improved the relationship between theactivity of the cell and the behavior, the variability among cellsin both the intercept and slope of the resuming lag versussaccadic duration for conjugate saccades remained high. Thiscan be seen in Fig. 7C, which shows the linear regressions ofthe 54 resuming lag versus saccadic duration comparisons,which have an average slope of 0.85.

Differences between conjugate and disconjugate saccades

The analyses of saccadic peak velocity, duration, pause lead,and resuming lag for conjugate saccades allowed us to estimatetheir variations for saccades executed during vergence move-ments. Table 4 shows the deviations from the conjugate aver-ages for the 54 cells for which we had sufficient data forsaccades with convergence and Table 5 shows the deviationsfrom the conjugate averages for the 19 cells for which we hadsufficient data for saccades with divergence.

For both convergence and divergence, saccades executedduring changes in depth were significantly slower and longerthan conjugate saccades of similar size. The slowing andlengthening were significantly larger for higher VGONS andlarger VG values. For convergence, the average deviation inpeak saccadic velocity (DIFFSvpk), estimated as an average ofthe average deviation from the conjugate peak-size main se-quence model for each cell, was �15.3°/s (�13.3 SD, range�64.9 to 7.6°/s), and was significant for 41 of the 54 data sets(76%). Both the DIFFSvpk(VGONS) and DIFFSvpk(�VG)average slopes were significantly different from zero, indicat-ing that the slowing was related to both of these variables.Although these relationships were robust, being significant forVG in 48 of the 54 data sets (89%), the R2 values wereusually poor, with an average of 0.18 for DIFFSvpk(VGONS)and of 0.39 for DIFFSvpk(�VG), suggesting that other factorsmight play a role in determining the slowdown. Very similarresults were obtained for divergence (Table 5), suggesting thatthe degree of slowing and the robustness of the effects, onaverage, are similar for convergence and divergence.

For a given saccadic size, a slower saccade should takelonger to reach its goal. Therefore we expect that data sets withlarger negative average DIFFSvpk values will also show largerpositive DIFFSdur averages. This is clearly the case, as can beseen by comparing the Svpk-related parameters and Sdur-related parameters in Tables 4 and 5. This consistency waseven more evident when the comparisons were made for eachcell. Figure 8A shows the expected negative relationship (R2 0.57) between the DIFFSdur and DIFFSvpk averages for the54 convergent data sets (in black) and the 19 divergence datasets (in gray). The covariation between the slopes of the

FIG. 7. OPN activity as a function of saccadic duration. Inherent noisinessof pause lead is reflected in a weaker relationship between pause duration andsaccadic duration (A) compared with that for resuming lag and saccadicduration (B) for same data sets. Example illustrated here is conjugate data setfor cell 01023.713. Linear regression in A (continuous line) had an intercept of19.8 ms with a slope of 0.58 ms/ms and a t-value for intercept of 6.9; R2 wasonly 0.26. Linear regression in B (continuous line) had an intercept of 1.6 mswith a slope of 0.69 ms/ms and a t-value for intercept of 23.6; R2 was aremarkable 0.80. Both intercepts and slopes ranges were quite large, resultingin a large between-cell variability of regressions, as illustrated in C, where all54 regression lines are superimposed. Observed range of conjugate saccadicdurations (observed range) is shown to better visually quantify actual scatter ofestimated resuming lags. Overall average regression of 54 conjugate sets isdescribed by equation Rlag 0.25 � 0.85 � Sdur, with a slope significantlydifferent from unity, which would be theoretical slope if overall resuming lagincreased as saccadic duration. Numbers at end of regression lines are slopevalues.



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regression terms DIFFSdur and DIFFSvpk with VG was evenstronger. Figure 8B shows the correlation between theDIFFSdur(�VG) and DIFFSvpk(�VG) slope values (R2 0.83). Similar values were seen for slope parameters related toVGONS. The large range in values for DIFFSvpk and, conse-quently, DIFFSdur, as well as for DIFFSvpk(�VG) and,consequently, for DIFFSdur(�VG), suggests that slowing andlengthening of saccades during vergence varies significantlybetween animals and probably also between sessions for thesame animal. Nonetheless, the covariations in Fig. 8 indicatethat slowing and lengthening are interchangeable in describingthe behavioral effects and that they are both closely related tovergence-related variables VG and VGONS.

A central hypothesis is that the behavioral changes in sac-cadic dynamics are mirrored by modifications in pause lead.For convergence (Table 4) there was a significant lengtheningof pause lead in 22 data sets (41%) and a significant shorteningin 4 data sets (7%), consistent with what was observed for theconvergence smooth vergence data, resulting in an overall

average DIFFPlead of 2.6 ms, an increase that was signifi-cantly different from zero. The modulation of the firing of theOPNs with vergence velocity, DIFFPlead(VGONS), was alsosignificantly positive for 15 cells (24%) and significantly neg-ative for 3 cells (6%), with an overall (significantly positive)average of 0.075 ms/(°/s). Although the results regardingDIFFPlead(�VG) were similar, the overall average was notsignificantly different from zero. For divergence (Table 5),although the pattern of the results was consistent with thedivergence smooth vergence data, the overall averages failed toreach significance, even though the behavioral effects on sac-cadic dynamics were as strong as for convergence. Four cells(21%) showed a significantly longer DIFFPlead for divergenceand 5 cells (26%) showed a significant DIFFPlead(VGONS) buttheir combined effects were not sufficient to generate an over-all significant effect. As with the divergence smooth vergencedata, for divergence no cell showed significantly shorter pauselead values or positive slopes.

If the modifications in pause lead are correlated with the

TABLE 4. Deviations from conjugate estimates: convergent data

Variable Unit Mean � SD t NS �0 �0 [Range] R2(av) � SD

DIFFSvpk [°/s] �15.3* � 13.3 �8.5 13 0 41 [�64.9 to 7.6] —DIFFSvpk(VGONS) [(°/s)/(°/s)] �0.46* � 0.41 �8.3 21 0 33 [�2.01 to 0.18] 0.18 � 0.18DIFFSvpk(�VG) [(°/s)/°] �10.8* � 6.5 �12.2 6 0 48 [�34.4 to �1.5] 0.39 � 0.20DIFFSdur [ms] 3.0* � 2.1 10.1 8 46 0 [�0.5 to 12.0] —DIFFSdur(VGONS) [ms/(°/s)] 0.075* � 0.052 10.6 24 30 0 [0.002 to 0.230] 0.17 � 0.15DIFFSdur(�VG) [ms/°] 1.53* � 0.93 12.2 10 44 0 [0.08 to 4.03] 0.32 � 0.20DIFFPlead [ms] 2.6* � 5.1 3.7 28 22 4 [�4.8 to 22.7] —DIFFPlead(VGONS) [ms/(°/s)] 0.11* � 0.30 2.7 36 15 3 [�0.16 to 1.39] 0.13 � 0.17DIFFPLead(�VG) [ms/°] 1.1 � 3.3 2.5 34 14 6 [�4.4 to 18.6] 0.09 � 0.10DIFFRlag [ms] �0.1 � 6.5 �0.1 14 11 29 [�7.2 to 37.3] —DIFFRlag(VGONS) [ms/(°/s)] 0.08 � 0.32 1.9 31 10 13 [�0.17 to 1.78] 0.15 � 0.18DIFFRlag(�VG) [ms/°] 1.3 � 4.3 2.2 27 13 14 [�2.3 to 21.3] 0.16 � 0.19DIFFSvpk(DIFFPlead) [(°/s)/ms] �0.1 � 1.0 �1.0 47 1 6 [�2.0 to 4.1] 0.05 � 0.09DIFFSdur(DIFFPlead) [ms/ms] 0.05 � 0.22 1.6 39 14 1 [�0.76 to 0.55] 0.08 � 0.12

n 54 cells. The table shows the overall averages computed from the 54 convergent saccadic sets for which we had sufficient data. The 1st rows of the first4 groups of rows show the average deviations of the convergent data from the 4 conjugate estimates (DIFFS). Each of these 4 rows reports the overall meanvalue with an asterisk indicating that the mean was significantly different from zero, the SD, the t-value of the statistical comparison from zero, how many ofthe 54 means were not significantly different from zero (NS), how many were greater than zero (�0), how many were less than zero (�0), and the range of values.For these rows there is no R2. The 2nd rows of the first 4 groups of rows report the overall mean of the slopes with VGONS, whereas the 3rd rows of the first4 groups of rows report the overall mean of the slopes with VG. The 2nd and 3rd rows follow the same layout of the first rows with the exception of the lastcolumn, which shows the average and SD of the R2 of the 54 linear regressions. With the same format, the last 2 rows in the table show the overall mean ofthe slopes of DIFFSvpk and DIFFSdur resulting from the direct comparison with DIFFPlead.

TABLE 5. Deviations from conjugate estimates: divergent data

Variable Unit Mean � SD t NS �0 �0 [Range] R2(av) � SD

DIFFSvpk [°/s] �17.6* � 7.5 �10.3 3 0 16 [�34.8 to �2.3] —DIFFSvpk(VGONS) [(°/s)/(°/s)] 0.63* � 0.47 5.8 8 11 0 [�0.13 to 1.70] 0.14 � 0.12DIFFSvpk(�VG) [(°/s)/°] 9.4* � 5.6 7.4 6 13 0 [0.8 to 19.6] 0.22 � 0.17DIFFSdur [ms] 3.0* � 1.1 11.9 1 18 0 [0.6 to 4.8] —DIFFSdur(VGONS) [ms/(°/s)] �0.14* � 0.14 �4.4 9 0 10 [�0.44 to 0.03] 0.16 � 0.14DIFFSdur(�VG) [ms/°] �1.8* � 1.4 �5.6 8 0 11 [�5.3 to 0.2] 0.26 � 0.19DIFFPlead [ms] 1.6 � 3.4 2.1 15 4 0 [�1.8 to 11.5] —DIFFPlead(VGONS) [ms/(°/s)] �0.15 � 0.41 �1.6 14 0 5 [�1.68 to 0.21] 0.09 � 0.12DIFFPlead(�VG) [ms/°] �1.2 � 4.1 �1.3 15 0 4 [�16.5 to 2.5] 0.09 � 0.12DIFFRlag [ms] �1.4 � 3.2 �1.9 9 1 9 [�9.3 to 5.0] —DIFFRlag(VGONS) [ms/(°/s)] �0.04 � 0.41 �0.4 8 4 7 [�1.55 to 0.28] 0.20 � 0.19DIFFRlag(�VG) [ms/°] 0.0 � 4.8 0.0 9 7 3 [�16.4 to 4.8] 0.24 � 0.22DIFFSvpk(DIFFPlead) [(°/s)/ms] 0.00 � 0.86 0.0 16 0 3 [�1.4 to 2.1] 0.07 � 0.14DIFFSdur(DIFFPlead) [ms/ms] 0.00 � 0.13 0.2 17 2 0 [�0.21 to 0.32] 0.07 � 0.15

n 19 cells. The table shows the overall averages computed from the 19 divergent saccadic sets for which we had sufficient data. The format is identicalto that of Table 4. Because VGONS and VG are negative, the signs of the slopes are reversed.



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changes in saccadic dynamics, we expect to find significantregression slopes DIFFSvpk(DIFFPlead) and DIFFSdur(DIFFPlead). The results, shown on the last 2 lines of Tables4 and 5, suggest, from the average R2 values, very little, if any,trial-by-trial correlation. Furthermore, the overall averageslopes were not significantly different from zero, and indeedfor divergence, only 3 cells (11%) reached significance forDIFFSvpk(DIFFPlead). Nonetheless, 15 cells (28%) reachedsignificance for DIFFSdur(DIFFPlead) for convergence, 14of which had positive values and one was negative. Althoughthe trend was in the right direction for both convergence anddivergence, if the average R2 can be taken as measure of afunctional linkage between DIFFPlead and DIFFSvpk, andconsequently with DIFFSdur, their values in the range 0.05 to0.08 argue against such a linkage.

With regard to the suggestion of Ramat et al. (1999) that thepostsaccadic versional oscillations during vergence in humansare attributed to a delayed resumption of the OPN activity, wedetermined whether there is any significant change in resuminglag (DIFFRlag) for saccades with vergence. If saccadic length-ening is matched by a parallel lengthening of resuming lag, wewould expect to find no significant DIFFRlag, which wouldargue against Ramat’s hypothesis. Interestingly, many cells (29or 54% for convergence and 9 or 47% for divergence) showeda significantly negative DIFFRlag, suggesting that, for thesecells, the saccadic lengthening was greater than the pauseincrease or, in other words, the OPNs resumed their activityearlier with respect to saccadic end for slower and longersaccades, which is the opposite of what was suggested. Only 11cells (20%) in the convergence data set and one cell (5%) in thedivergence data set showed a significant positive DIFFRlag.This is illustrated in Fig. 9A, which shows that these cells werealso the cells with the largest (positive) DIFFPlead values.This is consistent with the vergence effects acting similarly on

both the beginning and end of the OPN pause. Further evidenceof this can be seen in Fig. 9B, where the resuming lag slopevalue [DIFFRlag(�VG)] is plotted as a function of the pauselead slope value [DIFFPlead(�VG)]. The linear regression ofthe combined convergent and divergent data had R2 value of0.71. However, the positive DIFFRlag contribution associatedwith the cells suppressed by the ongoing vergence was can-celled by the negative contribution associated with the cellswith no modulation, with, as a result, no overall significantchange in resuming lag between conjugate and disconjugatesaccades.

D I S C U S S I O N

OPNs and saccadic slowing

Although the effects of saccades on vergence velocity havebeen extensively reported (Enright 1984; Kenyon et al. 1980;Ono and Nakamizo 1978; Zee et al. 1992), the possibility thatvergence might have some effect on saccades has attractedmuch less attention. In studies with humans, horizontal sac-cades during vergence often showed slower velocities andresulted in longer durations than conjugate saccades of com-parable size (Collewijn et al. 1995; Erkelens et al. 1989) but theeffects of vergence on vertical saccades were less clear (vanLeeuwen et al. 1998). In monkeys, superior colliculus (tectal)long lead bursters (TLLBs) show reduced activity for bothhorizontal and vertical saccades during vergence (Walton andMays 2003) and we have preliminary evidence (unpublishedobservations) that this is also seen in medium lead burst neu-rons (MLBs). No precise behavioral quantification of the sac-cadic slowing during an ongoing vergence movement is avail-able for monkeys. Nonetheless, the finding of important ver-gence-related changes in the firing of saccadic-related burstersis a clear indication that vergence affects the saccadic system.Furthermore, those neuronal changes rule out that the saccadicslowing could be attributed to nonlinearities at the level of theoculomotor plant during combined vergence/saccadic eyemovements. The omnidirectionality of this effect and its neu-

FIG. 9. OPN deviations from conjugate estimates. A: cells with largestaverage deviation in DIFFPlead from conjugate average also had largestaverage deviation in DIFFRlag from conjugate estimates. Vergence-relatedinhibition suppressing presaccadic firing also delayed postpause resumption offiring. Linear regression (continuous line) of 73 sets produced an equationDIFFRlag �2.5 � 0.90 � DIFFPlead with a t-value of slope equal to 8.9and R2 value of 0.53. Scatter was greatly reduced (B) when, instead ofaverages, we used slopes of DIFF with VG (or VGONS, not shown). Linearregression (continuous line) of 73 sets had equation DIFFRlag(VG) 0.45 � 1.03 � DIFFPlead(VG) with a t-value of slope equal to 13.3 and R2

value of 0.71. Numbers at end of regression lines are slope values.

FIG. 8. Saccadic deviations from conjugate estimates. A: comparison be-tween average deviation in peak velocity with respect to peak-size conjugatemain sequence (DIFFSvpk) and average deviation in duration with respect toduration-size conjugate main sequence (DIFFSdur) for 54 convergent (inblack) and 19 divergent (in gray) data sets. Data sets with most pronouncedsaccadic slowdown also showed largest saccadic lengthening. Linear regres-sion (continuous line) of 73 sets yielded equation DIFFSdur 1.0 � 0.12 �DIFFSvpk with a t-value of slope equal to �9.7. Relatively modest R2 of 0.57was attributed to a few convergent data sets with a greater lengthening thanpredicted from their DIFFSvpk. B: very strong relationship betweenDIFFSvpk(VG) and DIFFSdur(VG). Linear regression (continuous line) of73 sets had an equation DIFFSdur(VG) �0.17 � 0.15 � DIFFSvpk(VG)with a t-value of slope equal to �18.4 and R2 value of 0.83. Similar re-sults, albeit slightly weaker, were obtained using DIFFSdur(VGONS) andDIFFSvpk(VGONS) (not shown). Numbers at end of regression lines are slopevalues.



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ronal origin suggest an involvement of the OPNs. Furthermore,partial lesions of the nucleus raphe interpositus, where theOPNs are located, result in abnormally long and slow saccades(Kaneko 1996; Soetedjo et al. 2002). Optimal saccadic dynam-ics, as pointed out by Scudder (1988) and Moschovakis (1994)in explaining such OPN lesion-related saccadic slowing, re-quire a precisely timed release of the MLBs by the OPNs.Sparks et al. (1987) found that stimulation in some locations ofthe pons can cause premature saccadic triggering, an indicationof the presence of saccadic-related activity in the pons longbefore the actual execution of the movement. They estimatedthat, for normal visually directed saccades, there is a gradualpresaccadic signal buildup lasting 100 ms or more within thepremotor pontine structures before saccadic initiation. TheOPN inhibition of the MLBs would block any early firing untilthe buildup is completed. A lesion of the OPN area woulddecrease the inhibitory action of the OPNs on the MLBs witha partial, early release of the bursters before the completion ofthe buildup, with abnormal saccadic profiles.

OPN behavior during static version, static vergence, andsaccadic-free slow vergence

The first question addressed was whether OPN firing isaffected by static eye position and vergence angle. With regardto versional eye position, our static data are in agreement withprevious reports (Buttner-Ennever et al. 1988; Luschei andFuchs 1972) stating that OPN firing rates during fixation do notchange with static eye position. These previous studies did notmanipulate viewing distance and therefore the static vergenceangle of the animal was always the same, so that the positionalchanges were restricted to the versional components alone. Themanipulation of the static vergence angle, on the contrary,showed a much stronger modulation for many cells. Thismodulation presented a continuous distribution of valuesacross cells with a bias for a decrease in activity for increasingconvergence angle. The result was an overall small, but sig-nificant, suppression of the average firing rate of the populationsample by �0.50 spikes/°. The almost perfect symmetry of thecontributions to the modulation from the 2 eyes clearly sug-gests that this modulation was from the vergence system,where the contributions from the 2 eyes are presumed to besymmetrically distributed (Hering 1868).

A subset of OPNs also showed a significant transient mod-ulation associated with ongoing saccadic-free slow vergenceafter accounting for positional effects. Its time course followed,to a 1st approximation, the vergence velocity profile. Thismodulation was always smooth, and not the abrupt pause seenfor saccades, indicating that OPNs do not act as gates forvergence commands. Furthermore, no cell showed a modula-tion strong enough to drive the cell to complete inhibitionduring the smooth vergence response. Similarly to the posi-tional modulation, the modulation with slow convergence dy-namics had a continuous distribution of values from a signif-icant decrease in firing rate to a significant increase. Fordivergence, no cell showed a significant increase in firing rate.Unlike the positional data, we did not explicitly test the hy-pothesis that these dynamic effects are related to vergence perse, as opposed to the slow movements of either eye. Indeed,Missal and Keller (2002) recently reported a modulation ofOPNs with smooth pursuit velocity (i.e., with versional veloc-

ity contributions). However, the fact that OPNs were modu-lated for vergence position suggests that the dynamic effectsmay well be related to vergence. Furthermore, a monocularmodulation would be incompatible with the fact that the overallmodulation was a slowdown for both convergence and diver-gence. A hypothetical “left eye” cell would accelerate (decel-erate) its firing rate for convergence and decelerate (accelerate)its firing rate for divergence, whereas the most common be-havior was to have the same sign of the modulation for bothconvergence or divergence or no modulation for one of the 2vergence directions.

Effects of vergence on saccadic dynamics

Because we examined saccades of different sizes, it wasnecessary to first account for the effects of saccadic size onpeak velocity and duration for conjugate movements (Table 3)and then assess the differences seen when saccades were exe-cuted during vergence movements (Tables 4 and 5). The resultwas a small but significant slowing (�15.3°/s) and lengthening(�3.0 ms) of saccades during convergence (Table 4), and asimilar effect (�17.6°/s; �3.0 ms) for divergence (Table 5).Although some data sets did not show significant slowing andlengthening, significant effects were seen in most of the datasets for all animals. The failure to find a significant effect onsome data sets may well have been attributable to a smallernumber of trials for some cells, or to a particular combinationof target steps. We suspect that there may be other variablesthat affect saccadic dynamics in these situations, such as vari-ations in the timing of the saccades relative to the vergencemovements, but these considerations are beyond the scope ofthe present investigation. In any event, the behavioral effectwas quite reliable, albeit relatively small in magnitude.

We examined the effects of 2 vergence-related variables onsaccadic dynamics (VGONS and VG). The former was selectedbecause it provides an index of the magnitude of the vergencevelocity at the onset of the saccade, whereas the latter wasselected because it indicates the overall disconjugacy of thesaccade. Both VGONS and VG were significantly correlatedwith saccadic slowing and lengthening, although VG appearsto be the more potent variable, judging from its consistentlylarger R2 values.

Pause lead

There was no consistent relationship between saccadic pa-rameters such as size, peak velocity or duration, and pause leadfor conjugate saccades. This is in agreement with the report ofa lack of dependency of pause lead with saccadic size (peakvelocity and duration were not tested) in alert head-fixed cats(Pare and Guitton 1998). Pause lead was significantly longerbefore saccades during convergence, but not for divergence.However, even the effect associated with convergence wassmall, and was seen on fewer than one-half of the cells. Notsurprisingly, many of these cells also showed decreases infiring rate for smooth convergence. Indeed, of the 16 cells inTable 1 that decreased their firing rate for smooth convergencefor which we had corresponding data, 11 had a significantlylonger average pause lead for saccades with convergence thanfor saccades without vergence. As expected, VGONS, which isassociated with reduced activity in these cells for smooth



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convergence, was also associated with longer pause leads forsaccades with convergence. There was no consistent effect onpause lead associated with VG for either convergence ordivergence.

Duration of the OPN pause

The strong reciprocal inhibition between OPNs and horizon-tal and vertical medium lead bursters (Moschovakis et al.1996) implies a robust correlation between pause duration andburst duration, and, as a consequence, between pause durationand saccadic duration as well. OPN studies in the monkey(Fuchs et al. 1991) have, contrary to this expectation, yieldedonly modest correlations between the duration of the pause andsaccadic duration. Our results offer an explanation for thisweak correlation. Pause lead is an important component ofpause duration, and because it is uncorrelated with the onset ofthe saccade, it simply adds noise to the relationship betweenpause duration and saccadic duration. As Fig. 6 illustrates, thefiring rate of the OPN just before the saccade is a primarydeterminant of both the pause lead value and its variance. Ifpause lead is removed from the rest of the pause, as can bedone by measuring the interval between saccadic onset and theend of the pause (resuming lag), the correlation between theremainder of the pause and saccadic duration is greatly im-proved (Table 3 and Fig. 7). Therefore we think resuming lag,and not the observed pause duration, more fairly represents themetrics of the OPNs during saccades. However, the averageslope of the relationship between resuming lag and saccadicduration is only 0.85 and not unity (P � 0.01), and thetrial-by-trial variability is still substantial (average R2 0.72).These observations suggest that the linkage between the pauseand saccadic metrics may not be as close as expected from thereciprocal inhibition with the saccadic bursters, with otherfactors, variable from cell to cell, affecting the postsaccadicresumption of the OPN activity.

We found that the resuming lag is not significantly differentfor saccades with vergence than for conjugate saccades, eventhough the saccades with vergence tend to be longer. Thismeans that the average pause duration remains consistent withthe saccadic duration, even for saccades with vergence. Ramatet al. (1999) reported the presence, in humans, of small post-saccadic versional oscillations of the eyes seen only in associ-ation with saccades during vergence. These oscillations neveroccurred after conjugate saccades and their presence was ran-dom, suggesting that humans can adopt more than one strategyto achieve a transfer of gaze in depth. The authors concludedthat the behavior of OPNs during saccades with vergence maynot be the same as that during conjugate saccades: OPNs couldact as combined saccadic/vergence gates with a prolongedpause after a saccade if a saccade is superimposed on anongoing vergence movement. Our data argue against the con-jecture that OPNs might remain off longer after saccades withvergence. However, it should be noted that the Ramat et al.data were for humans. In monkeys, the occurrence of postsac-cadic oscillations associated with vergence was seen on veryfew trials.

Are longer pause leads responsible for slower saccades?

The fundamental questions are whether presaccadic ver-gence slows OPN activity, and if so, is this slowing responsible

for slower saccades seen during vergence? The argument infavor of this idea comes almost entirely from the observationthat, for saccades with convergence, pause leads are signifi-cantly longer, and this effect is at least weakly associated withlarger values of presaccadic vergence velocity (VGONS). How-ever, there is no significant correlation between pause lead andthe degree of disconjugacy of the saccade (VG). Moreover,when we examine, on a trial-by-trial basis, the relationshipbetween saccadic slowing and pause lead [DIFFSvpk(DIFFPlead)], we find the expected result in only 6 of 54 cells(Table 4). The situation is only slightly better when saccadicduration is considered as a function of pause lead [DIFFSdur-(DIFFPlead)], with 14 of 54 cells displaying the expectedrelationship. For saccades with divergence (Table 5) there is nostatistically reliable relationship between pause lead andpresaccadic vergence or between pause lead and the slowing ofsaccades, even if this may be partly attributable to a smallerdivergence data set. This finding, together with the observationthat saccades can be slowed and lengthened as much by diver-gence as by convergence, argues against the idea that a presac-cadic slowing of OPN activity is responsible for the effects ofvergence on saccadic metrics. This assumes, of course, that allof our recorded OPNs contribute equally to the behavioraleffects.

Source of the vergence signal to OPNs

Regardless of the function it might support, there is noquestion that the majority of OPNs are modulated in associa-tion with vergence movements. How might such a signal reachthese cells? OPNs receive direct cortical connections from thefrontal eye field (FEF) (Stanton et al. 1988a,b) and from thesupplementary eye field (Shook et al. 1988). FEF neurons showdisparity sensitivity (Ferraina et al. 2000) and vergence-relatedactivity (Gamlin and Yoon 2000). The lateral intraparietal area,which projects to the FEF (Ferraina et al. 2002) as well as tothe superior colliculus (Gnadt and Beyer 1998), also containsdisparity-sensitive neurons (Gnadt and Mays 1995). Thesecortical areas are believed to be directly involved in program-ming in-depth transfers of gaze. Neurons with vergence posi-tion and velocity signals have been found by Mays (1984),Judge and Cumming (1986), and Mays et al. (1986) in themonkey midbrain. Vergence-related cells were also localizedin the nucleus reticularis tegmenti pontis (Gamlin and Clarke1995) and in the cerebellum (Zhang and Gamlin 1998). Apreliminary report also described vergence-related cells in theposterior brain stem near the MLB and omniburst areas (Gnadtet al. 1988), areas known to project to the OPNs. The functionof these pontine vergence neurons is unknown, as are theirconnections. Nonetheless, there are no conclusive data regard-ing connections of cortical or subcortical neurons with ver-gence-related signals to OPNs.

Visual responses of OPNs

A study of OPNs in the cat (Evinger et al. 1982) demon-strated that activity levels are transiently increased by changesin the visual stimuli. A similar finding has been reported for themacaque (Everling et al. 1998; Fuchs et al. 1991; Missal andKeller 2002), although quantitative data for these animals hasnot been heretofore reported. We found that the vast majority



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of OPNs show small but reliable transient increases in activityassociated with target steps in any direction. In most cases, thevisual response had declined to baseline by the time of theonset of a saccade to the target. Although we were not able toplot receptive fields for this modulation of activity by visualstimuli, it appears that the fields must be large, extendingacross the midline. Pure disparity stimuli with no changes inversional eccentricity elicited consistent visual responses aswell. The significance of this visually evoked activity is notknown. We are confident that the visual responses we havefound are not the same as those reported for “complex” OPNsin the anesthetized cat (Petit et al. 1999). These “complex”OPNs showed a decrease in activity for target motion, whereasall of our cells increased their activity for visual stimuli.Moreover, the decreases in activity of our cells associated withvergence appear to be too early relative to the movement (Figs.1A, 4C) to involve the substantial visual delays in the responseof the cells described by Petit and colleagues.

OPN role in the control of vergence and saccadic eyemovements

Although we found that OPNs show a significant, albeitsmall, modulation with an ongoing vergence eye movement, nocell stopped its firing in association with saccadic-free slowvergence. The modulation was always smooth and the changesin firing rate were always gradual, even when the modulationwas at its strongest. This is in contrast to the abrupt pausesassociated with saccades. Very similar smooth modulations ofOPN activity were observed by Missal and Keller (2002) forsmooth pursuit. Moreover, Missal and Keller reported thatstimulation of the OPNs causes a strong deceleration of thesmooth pursuit response. We have preliminary data showingthat OPN stimulation can also slow convergence. AlthoughMissal and Keller interpreted their results as evidence of acommon inhibitory mechanism for saccades and smooth pur-suit, we offer an alternative suggestion.

The dynamics of conjugate saccades are believed to repre-sent a dynamical upper limit for eye movements. Duringsmooth pursuit, a catch-up saccadic burst must be added toongoing smooth pursuit– related firing in the motoneurons inthe same direction. Similarly, during vergence the eye execut-ing the larger rotation will have the saccadic burst added toongoing (enhanced by the saccade itself) vergence velocitysignals in the same direction. These additions would theoreti-cally drive both eyes (for smooth pursuit) or one of the eyes(for vergence) above their dynamical limits. Thus the (smooth)suppressive modulation of the OPNs by the vergence and thesmooth pursuit subsystems, perhaps including also the vestib-ular system, might have as its function the reduction of thesaccadic dynamics to allow for the subsequent addition of thesesignals. This would avoid strong mechanical nonlinearities atthe plant level that would not be detected by the nonvisualfeedback circuits, which are calibrated for lower dynamicallevels. We therefore expect slower and longer saccades, as wellas the associated bursts in superior colliculus burst neurons,LLBNs, and MLBs to have lower and longer activity patterns,with both vergence and smooth pursuit (and perhaps vestibularresponses as well).

The question as to whether the relatively small changesobserved in OPNs are sufficient to modify saccadic dynamics,

although unlikely, remains as a possibility. We did observe asmall number of OPNs that were very strongly modulated withvergence. Could the action of only a few OPNs influencebehavior? The recent report of strong dynamical effects in theSC bursters observed by Soetedjo et al. (2002) in associationwith small inhibitory injections in the OPNs suggests that theremay be no need for the very large and generalized suppressionof OPN activity, required by earlier models, to modify saccadicdynamics. If so, this mechanism, as also noted by Soetedjo etal. must be substantially different from the one proposed in theearlier models by Scudder (1988) and Moschovakis (1994).

We thank S. Hayley for computer programming, L. Millican, M. Bolding,and A. Yildirim for technical assistance and P. Kontzen for the histologicalreconstruction. Some of the data were collected by T. Reusser, M. Billitz, D.Morrisse, and M. Glaser.

D I S C L O S U R E S

This research was supported by National Eye Institute Grant to L. Mays(R01 EY-03463) and Core Grant P30 EY-03039.

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