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The Journal of Neurophysiology Vol. 80 No. 4 October 1998, pp. 2046-2062
Copyright ©1998 by the American Physiological Society
1 Laboratory of Sensorimotor Research, National Eye Institute, Bethesda, Maryland 20892-4435; and 2 Salk Institute for Biological Studies, La Jolla, California 92037
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ABSTRACT |
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 Abstract
 Introduction
Methods
Results
Discussion
References
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Krauzlis, R. J. and F. A. Miles. Role of the oculomotor vermis in generating pursuit and saccades: effects of microstimulation. J. Neurophysiol. 80: 2046-2062, 1998. We studied the eye movements evoked by applying small amounts of current (2-50 µA) within the oculomotor vermis of two monkeys. We first compared the eye movements evoked by microstimulation applied either during maintained pursuit or during fixation. Smooth, pursuitlike changes in eye velocity caused by the microstimulation were directed toward the ipsilateral side and occurred at short latencies (10-20 ms). The amplitudes of these pursuitlike changes were larger during visually guided pursuit toward the contralateral side than during either fixation or visually guided pursuit toward the ipsilateral side. At these same sites, microstimulation also often produced abrupt, saccadelike changes in eye velocity. In contrast to the smooth changes in eye velocity, these saccadelike effects were more prevalent during fixation and during pursuit toward the ipsilateral side. The amplitude and type of evoked eye movements could also be manipulated at single sites by changing the frequency of microstimulation. Increasing the frequency of microstimulation produced increases in the amplitude of pursuitlike changes, but only up to a certain point. Beyond this point, the value of which depended on the site and whether the monkey was fixating or pursuing, further increases in stimulation frequency produced saccadelike changes of increasing amplitude. To quantify these effects, we introduced a novel method for classifying eye movements as pursuitlike or saccadelike. The results of this analysis showed that the eye movements evoked by microstimulation exhibit a distinct transition point between pursuit and saccadelike effects and that the amplitude of eye movement that corresponds to this transition point depends on the eye movement behavior of the monkey. These results are consistent with accumulating evidence that the oculomotor vermis and its associated deep cerebellar nucleus, the caudal fastigial, are involved in the control of both pursuit and saccadic eye movements. We suggest that the oculomotor vermis might accomplish this role by altering the amplitude of a motor error signal that is common to both saccades and pursuit.
The neural coordination of pursuit eye movements involves widespread regions of the cerebral cortex, brain stem, and cerebellum. The best understood pathways involve projections from areas of the cerebral cortex to specific nuclei within the basilar pontine gray, which in turn project to specific portions of the cerebellum. One of these pathways includes cortical areas near the superior temporal sulcus, such as the middle temporal and the medial superior temporal areas (Dürsteler and Wurtz 1988 Data were collected from two adolescent rhesus monkeys (Macaca mulatta), weighing 4-9 kg. All experimental protocols were approved by the Institute Animal Care and Use Committee and complied with Public Health Service Policy on the humane care and use of laboratory animals. Under isoflurane anesthesia and aseptic conditions, the head of each monkey was fitted with a pedestal and secured to the skull with titanium screws and dental acrylic, which allowed the head to be fixed in the standard stereotaxic position during experiments. A scleral search coil was implanted around each eye by using the technique of Judge et al. (1980) Electrical microstimulation
Microstimulation was applied through tungsten microelectrodes (Frederick Haer) with impedances of 0.2-1 M Behavioral paradigms
The monkeys viewed LED stimuli that were projected as 0.1° spots onto a translucent tangent screen located 1 m in front of the animal. The monkeys were trained to maintain fixation of a target spot until it moved or was extinguished. During this fixation period, which had a randomized duration of 1,000-1,500 ms, the monkeys were required to remain within 2° of the central target and to refrain from making saccades, which were detected on-line by the computer as any velocity >48°/s. If these requirements were not met, the target was extinguished and the paradigm reverted to the fixation period after a 2-s delay. If the fixation requirements were met, the target could remain stationary ("fixation trial"), step horizontally to an eccentric location on the tangent screen ("saccade trial"), or step horizontally to a new location and start to move at a constant speed of 15°/s back toward the center of the screen ("pursuit trial"). The amplitude of the step on pursuit trials was adjusted to reduce the need for catch-up saccades (Rashbass 1961 Data collection and analysis
The presentation of stimuli, application of microstimulation, and the acquisition, display, and storage of data were controlled by a personal computer using REX, a real-time experimentation software package (Hays et al. 1982 Histology
After completion of the set of experiments on each monkey, we made small marking lesions (50 µA, 10 s) at several of the sites at which eye movements were evoked with microstimulation. The monkeys were then deeply anesthetized with pentobarbital sodium and perfused through the heart with saline followed by 10% glutaraldehyde. The cerebellum and brain stem were embedded in celloidin and cut into 50 µm parasaggital sections. The sections were stained with cresyl violet and the marking lesions were identified to help reconstruct the electrode penetrations.
We stimulated a total of 112 sites in the "oculomotor vermis" (Fujikado and Noda 1987
Enhancement of pursuitlike effects during ongoing pursuit
Electrical microstimulation could produce pursuitlike smooth changes in eye velocity that were larger when the stimulation was applied during ongoing pursuit than when it was applied during fixation. At some ties, microstimulation during pursuit produced smooth changes in eye velocity directed toward the ipsiversive side (with respect to the site of microstimulation), regardless of whether the pursuit movement was in the ipsiversive or contraversive direction. The results obtained from stimulating at one such site are shown in Fig. 2, A-F. As indicated by the cartoons atop the figure, microstimulation was applied in the left oculomotor vermis (50 µA, 300 Hz) as the monkey maintained fixation of a stationary target (Fig. 2A) or pursued the target as it moved at a constant speed of 15°/s to the right (Fig. 2B) or to the left (Fig. 2C). The microstimulation was applied for the 50-ms interval indicated by the filled bar; data from this period of the trial are shown on an expanded time scale in Fig. 2, D-F. When microstimulation was applied while the monkey was fixating (Fig. 2D), it caused a small leftward (i.e., ipsiversive with respect to the side stimulated) deflection in horizontal eye velocity (thick trace,
Saccadelike effects evoked by microstimulation
during pursuit
In the analysis described previously (Figs. 3 and 4), the segments of eye movements containing saccades were removed to document the effects on pursuit. However, in addition to changes in smooth eye velocity, microstimulation often elicited saccadic eye movements (e.g., Fig. 2, G-I). Thus the observation that the effects of microstimulation were larger during contraversive than ipsiversive pursuit holds true for the smooth eye velocity component but not necessarily for the entire evoked eye movement. We therefore analyzed data from each site again without removing those segments identified as containing saccades. These measurements were taken from the same temporal interval as the measurements of smooth eye velocity (Fig. 3) but were made from individual traces of eye position rather than average traces of smooth eye velocity. The results are summarized by the graph in Fig. 5A, in which each data point represents a single site and indicates the amplitude of the change in eye position evoked during ipsiversive pursuit as a function of the amplitude evoked during contraversive pursuit. The data mostly lie along the line of unity slope, indicating that the net changes in eye position were generally comparable during ipsiversive and contraversive pursuit. In fact, at sites where larger eye movements were evoked, there was a tendency for the effects to be larger during ipsiversive than during contraversive pursuit (arrow).
Classifying evoked eye movements as pursuit- or saccadelike
To document the range of eye movements evoked by microstimulation, it was necessary to develop a novel method for classifying eye movements as either pursuit or saccadelike. The method we devised is a modification of the main sequence used to analyze the metrics of saccadic eye movements (Bahill et al. 1975
Our results demonstrate that microstimulation of the oculomotor vermis can modify smooth pursuit as well as saccadic eye movements. Previous studies have examined the effects of electrical microstimulation within this region but have done so only during either fixation (Fujikado and Noda 1987 Possible mechanisms underlying the microstimulation effects
Because our electrodes were always located in either the cerebellar cortex or the immediately underlying white matter, the effects we observed were caused by either the orthodromic activation of Purkinje cell axons or the antidromic activation of mossy fiber inputs. Two aspects of our data argue that the effects were due predominantly to orthodromic activation of Purkinje cells. First, the direction of the evoked effects is consistent with the activation of Purkinje cells. Injections of muscimol into the caudal fastigial nucleus, the target of vermal Purkinje cells, results in saccadic eye movements that are hypermetric toward the ipsilateral side and hypometric toward the contralateral side (Robinson et al. 1993 Involvement of the oculomotor vermis in saccades and pursuit
The importance of this region for the control of saccades in monkeys was initially established by the observations that ablation of this structure altered the metrics of saccades (Aschoff and Cohen 1971 Possible mechanisms for the vermal contribution to saccades and pursuit
The known anatomy provides multiple sites at which the oculomotor vermis might affect the motor commands for saccades and pursuit. For saccades, the output from the oculomotor vermis could directly change the firing rate of burst neurons responsible for saccades because the caudal fastigial nucleus projects to both the paramedian pontine reticular formation (PPRF) and the rostral interstitial nucleus of the medial longitudinal fasciculus (Noda et al. 1990
INTRODUCTION
Abstract
Introduction
Methods
Results
Discussion
References
; Dürsteler et al. 1987; Newsome et al. 1985), whereas a second pathway includes the frontal eye fields (Keating 1991, 1993; MacAvoy et al. 1991). These different cortical areas tend to project to different portions of the pontine nuclei; the areas near the superior temporal sulcus project primarily to the dorsolateral edge (Glickstein et al. 1980; May and Andersen 1986), whereas the frontal eye fields project more strongly to the dorsomedial portion (Stanton et al. 1988). These regions of the pontine nuclei in turn project to different regions of the cerebellum known to be important for pursuit, including the ventral paraflocculus and so-called oculomotor vermis (Brodal 1979, 1982; Glickstein et al. 1994; Langer et al. 1985; Yamada and Noda 1987). These corticopontocerebellar connections therefore provide alternative descending pathways by which visual information can access the motor pathways for pursuit.
), and microstimulation of the ventral paraflocculus elicits smooth eye movements (Belknap and Noda 1987; Lisberger and Pavelko 1988). The output of the ventral paraflocculus, conveyed by Purkinje cells, exhibits a tonic modulation during maintained pursuit as well as a transient modulation whenever eye speed changes (Krauzlis and Lisberger 1994; Miles et al. 1980; Stone and Lisberger 1990). These two components of Purkinje cell activity have been interpreted as encoding the motor command needed to maintain pursuit eye speed and the visual inputs needed to change pursuit eye speed, respectively. In contrast, the role of the oculomotor vermis in pursuit eye movements is much less clear. Some results are qualitatively similar to those obtained in the ventral paraflocculus; lesions of the oculomotor vermis produce deficits in pursuit eye movements, and Purkinje cells in the oculomotor vermis are modulated during pursuit eye movements (Kase et al. 1979; Keller 1988; Suzuki and Keller 1983, 1988a,b; Takagi et al. 1996). However, unlike Purkinje cells in the ventral paraflocculus, those in the vermis are also modulated during the presentation of moving visual stimuli when no eye movements occur (Sato and Noda 1992a; Suzuki and Keller 1988b; Suzuki et al. 1981). Furthermore, whereas electrical microstimulation within the oculomotor vermis has been shown to elicit saccadic eye movements and to modify the metrics of visually guided saccades (Fujikado and Noda 1987; Keller et al. 1983; McElligott and Keller 1984; Noda and Fujikado 1987a,b), it has not been shown to produce smooth eye movements. Indeed, it has been argued that the oculomotor vermis is involved only in the control of saccadic eye movements and that pursuit-related regions might lie in adjacent folia of the cerebellum (Sato and Noda 1992a).
METHODS
Abstract
Introduction
Methods
Results
Discussion
References
. The coils were used to monitor eye position with the electromagnetic induction technique (Fuchs and Robinson 1966). The AC voltages induced in the search coils were routed to a phase detector circuit that provided separate DC voltage outputs proportional to horizontal and vertical eye position (CNC Engineering). These outputs were low-pass filtered (6-pole Bessel, 
3 dB at 180 Hz) and then sampled at 1 kHz (A/D converter, National Instruments). The coil output voltages were calibrated with respect to eye position by having the animal fixate small light-emitting diode (LED) targets at known eccentricities along the horizontal and vertical meridia.
. Electrodes were advanced through stainless steel guide tubes (23 gauge) with a micromanipulator (Narishige) mounted on top of the recording chamber. The guide tubes were held fixed in the chamber with a grid system (Crist et al. 1988). Microstimulation was applied as biphasic pulses (pulse width 0.2 ms) at frequencies of 50-500 Hz for a duration of 50 ms; currents used for microstimulation ranged from 2 to 50 µA. Sites likely to be concerned with eye movements were identified by recording multiunit activity and by testing the effects of microstimulation at regular intervals (~200 µm) along an electrode track. For each site at which we elicited changes in eye position we determined the minimum current that produced a just noticeable effect on eye velocity. For behavioral paradigms, the current was generally set at twice this minimum value to produce an appreciable effect on smooth eye velocity without always eliciting a saccade. Consistent with previous studies (Fujikado and Noda 1987; Noda and Fujikado 1987a,b), sites that required the lowest currents were also associated with high-frequency multiunit activity characteristic of white matter.
). On fixation trials, the monkey was required to keep its eyes within 2° of the target position. On saccade and pursuit trials, the monkey was required to foveate the target within 450 ms and thereafter keep its eyes within 4.5° of the target position for an additional 500 ms. If eye position strayed outside of these windows, the trial was aborted and followed by a new randomly selected trial. Controlled movements of the target spot were achieved with an X-Y mirror galvanometer system under negative feedback control (General Scanning, CCX101). The monkey was given a liquid reward at the end of each correctly performed trial. The luminances of the target and background were 3.8 and 0.04 cd/m2, respectively.
). Voltage signals encoding the horizontal and vertical components of eye position and the horizontal and vertical mirror position provided by transducers in the galvanometer systems were low-pass filtered (6-pole Bessel, 3 dB at 180 Hz) and then digitized to a resolution of 12 bits, sampling at 1 kHz (A/D converter, National Instruments). All data were stored on disk (Wren Runner II SCSI disk) during the experiment and later transferred to a Unix-based system for subsequent analysis with Silicon Graphics workstations.
3 dB at 54 Hz) to the signals encoding horizontal and vertical eye position, respectively. Most of the measurements reported in this paper were taken directly from these individual traces of eye position and velocity. The interval used for these measurements was based on the observed latency of the evoked eye movements (slightly longer than 10 ms) and the duration of the microstimulation (50 ms). Consequently, we obtained three measurements from the raw traces of eye position and velocity over the interval 10 to 60 ms after the onset of microstimulation: 1) the change in eye position over the 50-ms interval of microstimulation, 2) the peak change in eye velocity over the 50-ms interval of microstimulation, and 3) the change in eye position up to the time of the peak change in eye velocity. For reasons explained in RESULTS, these last two measurements were also obtained from pursuit and saccadic eye movements evoked by movements of the target spot. Statistical significance of differences between the effects of microstimulation obtained under different behavioral conditions was assessed with either a Mann-Whitney test for single comparisons or a Kruskal-Wallis test for multiple comparisons. As described more fully in RESULTS, some of the data were also subjected to a linear discriminant analysis. Statistical tests were performed with commercially available statistical software (BMDP and SigmaStat).
). Average eye velocity was computed by aligning the responses to the same target motion on the onset of the target motion and computing the mean and SD of eye velocity for each millisecond sample of the data. Within each millisecond sample, eye velocity values marked as residing within a saccade were not included in the calculation of mean and SD of smooth eye velocity. However, we documented the occurrence of such marked intervals by computing the frequency with which each millisecond of the trial was included in such an interval; this computation provided the "freq(sacc)" traces shown in RESULTS. To analyze the smooth eye velocity traces, we subtracted the desaccaded eye velocity obtained on trials without microstimulation from the desaccaded eye velocity obtained on trials with microstimulation to generate traces of changes in smooth eye velocity caused by microstimulation. From these traces, we made three measurements: 1) the average change in smooth eye velocity over the 50-ms interval of microstimulation, 2) the average direction associated with this change in smooth eye velocity, and 3) the latency of this change in smooth eye velocity. Latency measurements were obtained with a linear regression algorithm described previously (Krauzlis and Miles 1996). Statistical significance of differences between the effects of microstimulation obtained under different behavioral conditions was again assessed with either a Mann-Whitney test for single comparisons or a Kruskal-Wallis test for multiple comparisons.
RESULTS
Abstract
Introduction
Methods
Results
Discussion
References
; Noda and Fujikado 1987a,b) of two monkeys. The sites were located in lobule VII and the posterior portion of lobule VI, within 2-3 mm of the midline, as indicated by the sample of sites shown for monkey 1 in Fig. 1. A minority of sites was located within the cerebellar cortex; most sites were located in the underlying white matter where the thresholds for evoking eye movements were lower. Microstimulation at these sites produced both pursuitlike smooth changes in eye velocity and saccadelike abrupt changes in eye position. We first describe the pursuitlike effects and show how these were facilitated during pursuit eye movements. We then compare these effects with the saccadelike effects. Finally, we describe a quantitative method for rigorously classifying the effects as pursuit or saccadelike.
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FIG. 1.
Sites in oculomotor vermis at which microstimulation elicited eye movements; sample data from monkey 1. Drawing shows a single parasaggital section, 1 mm from the midline in the left cerebellar hemisphere. 
, individual sites of stimulation; - - -, primary, posterior superior, and prepyramidal fissures, from top left to bottom right. Scale bar indicates 1/2 cm.
HOR), and also increased the likelihood of saccades immediately afterward [freq(sacc)]. In contrast, when the microstimulation was applied while the monkey pursued a target moving toward the right (contraversive) side (Fig. 2E), it caused a more vigorous and abrupt ipsiversive change of horizontal eye velocity (i.e., a deceleration), relative to the eye velocity recorded during this same period of the trial in the absence of microstimulation ("control"). Similarly, when the microstimulation was applied while the monkey pursued toward the left (ipsiversive) side (Fig. 2F), it again caused an ipsiversive change in eye velocity (i.e., an acceleration).
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FIG. 2.
Pursuitlike eye movements evoked by microstimulation at 2 sites (monkey 2). A, D, and G: microstimulation applied during fixation. B, E, and H: microstimulation applied during pursuit toward the contralateral side. C, F, and I: microstimulation applied during pursuit toward the ipsilateral side. Black horizontal bars indicate the 50-ms intervals during which stimulation was applied. Traces in A-C show average horizontal eye position over 26 trials (EHOR) and horizontal target position (dashed line) recorded during microstimulation (50 µA, 300 Hz) at site 1. Eye position traces were not desaccaded. Similar traces (not shown) were recorded during microstimulation (15 µA, 300 Hz) at site 2. Boxes in A-C indicate the peristimulation intervals that are shown on an expanded time scale below. Traces in D-I show average desaccaded horizontal eye velocity ( HOR), average desaccaded vertical eye velocity (VER), and percentage of trials on which a saccade occupied each millisecond of the trial [freq(sacc)]. Thicker eye movement traces show averages on trials with microstimulation; dashed traces indicate either 0 (D and G) or average eye velocity on control trials without microstimulation (E, F, H, and I). For the horizontal eye velocity traces, 0 eye velocity lies below the dashed control traces in E and H but above the dashed control traces in F and I.
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FIG. 3.
Amplitudes of pursuitlike eye movements evoked by microstimulation during pursuit and fixation. Graphs plot the average change in smooth eye velocity evoked during pursuit as a function of the average change evoked during fixation for contraversive (A) and ipsiversive (B) pursuit. Individual symbols represent single sites; different symbol types are used to indicate sites for which the 2 measurements were ( 
) or were not (
) significantly different (P < 0.05, Kruskal-Wallis). - - -, both graphs, unity slope. The amplitude of the evoked movement was measured as the average change in eye speed in the interval 10-60 ms after the onset of the microstimulation minus the change over this same interval on trials without stimulation, using desaccaded traces of eye velocity.
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FIG. 4.
Direction of pursuitlike eye movements evoked by microstimulation during pursuit and fixation in both monkeys. A, C, E, and G: polar plots indicate the size and direction of evoked smooth eye velocity during contraversive pursuit (A), ipsiversive pursuit (E), and during fixation (C and G). Each line summarizes the effects obtained at one site and represents a vector pointing in the direction of the evoked eye movement with a length proportional to the amplitude of the evoked eye movement. B, D, F, and H: histograms summarize the distributions of the directions of evoked smooth eye velocity during contraversive pursuit (solid bars), ipsiversive pursuit (shaded bars), and fixation (open bars). Direction of evoked eye movement was taken as the average direction of desaccaded eye velocity over the interval 10-60 ms after the onset of microstimulation. Two sets of measurements are shown for fixation because for some sites 2 different fixation points were used to provide comparisons with measurements taken from the 2 directions of pursuit.
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FIG. 5.
Combined pursuit- and saccadelike effects evoked by microstimulation during pursuit. A: comparison of the amplitudes of eye movements evoked by microstimulation during contraversive and ipsiversive pursuit. Each datum point shows the net change in eye position over an interval 10-60 ms after the onset of microstimulation during ipsiversive (ordinate) and contraversive (abscissa) pursuit. Measurements were made from individual trials without removing saccades. Different symbol types are used to indicate sites for which the 2 measurements were ( ) or were not () significantly different (P < 0.05, Kruskal-Wallis). Arrow indicates cluster of data points for which evoked movements were larger during ipsiversive pursuit than during contraversive pursuit. B: comparison of the relative numbers of saccades evoked by microstimulation during contraversive and ipsiversive pursuit. The graph plots the percentage of trials on which microstimulation elicited a saccade during ipsiversive pursuit against the corresponding fraction of trials during contraversive pursuit. Each symbol represents measurements from a single site, taken from the interval 10-60 ms after the onset of the microstimulation. Values <0 correspond to sites at which microstimulation decreased the number of saccades compared with control trials. The dashed lines have a slope of one.
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FIG. 6.
Changes in pursuit and saccadelike eye movements caused by changing the frequency of microstimulation. Each panel shows the effect of applying microstimulation (30 µA) during fixation (A and D), contraversive pursuit (B and E), or ipsiversive pursuit (C and F) at either 300 (A-C) or 500 Hz (D-F). Traces in each panel show average horizontal eye position (EHOR, not desaccaded), average desaccaded horizontal eye velocity ( HOR), and percentage of trials on which a saccade occupied each millisecond of the trial [freq(sacc)]. Thicker eye movement traces show averages on trials with microstimulation; dashed traces indicate either 0 (A and D) or average eye position and velocity on control trials without microstimulation (B, C, E, and F). Each average is based on 50 single trials. Black horizontal bars indicate the 50-ms intervals during which stimulation was applied.
; Boghen et al. 1974). The main sequence for saccades is obtained by plotting the peak velocity of each saccade as a function of its amplitude for a set of saccades spanning a range of amplitudes. This type of measurement procedure cannot be applied directly to pursuit because the continuous nature of pursuit eye movements makes measurement of their amplitude arbitrary. Our modification of this procedure is illustrated in Fig. 7. For saccades (Fig. 7A), we measured the peak velocity of the saccade (96.7°/s) but compared this with the displacement of the eye at the time of the peak (0.98°, indicated by the dashed vertical lines) rather than to the total displacement over the entire saccade. The advantage of defining the end of the measurement interval based on the peak velocity is that an analogous procedure can be applied to pursuit. As shown in Fig. 7B, we measured the peak velocity reached during the initiation of pursuit (21.6°/s) and compared this with the displacement of the eye at the time of the peak (1.14°). These measurements document the fact that, for our sample eye movements of similar amplitude (0.98 vs. 1.14°), the saccade moved the eyes much faster (96.7 vs. 21.6°/s).
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FIG. 7.
Method for classifying visually guided eye movements as pursuit or saccadelike. A: example of measurements made from eye position and eye velocity records during a visually guided saccade. B: example of analogous measurements made from records during a single trial of visually guided pursuit. The target motion was a 20°/s step-ramp. C: plot of peak eye velocity against change in eye position for 640 saccadic ( ) and 644 pursuit (
) eye movements. - - -, discriminant function used to demarcate the 2 classes of eye movements. Arrow A indicates location of sample saccade measurements; arrow B indicates location of sample pursuit measurements.
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FIG. 8.
Measuring eye movements evoked by microstimulation on single trials. A-C, top traces, horizontal eye position (EHOR) recorded either on single trials with microstimulation ( 
) or average (not desaccaded) recorded on 54 control trials without microstimulation (- - -); bottom traces, horizontal eye velocity (HOR) either on single trials with microstimulation () or average desaccaded eye velocity on control trials without microstimulation (- - -). All 3 panels are shown with the same vertical scaling. D-F, , differences between the pairs of superimposed traces in A-C; - - -, 0. Vertical scaling is increased in D and E and decreased in F compared with scaling in A-C by factor indicated in parentheses. Vertical bars and numbers in D and E indicate measurements of peak eye velocity and change in eye position derived from these traces.
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FIG. 9.
Classifying eye movements evoked by microstimulation as pursuit or saccadelike. Panels show eye movements evoked by microstimulation (30 µA) at a range of frequencies (100-500 Hz) during fixation (A and B), contraversive pursuit (C and D), and ipsiversive pursuit (E and F) from one site in monkey 2. Each datum point shows measurements taken from a single evoked eye movement and plots the peak change in eye velocity against the change in eye position. The dashed line indicates the same discriminant function shown in Fig. 7. Eye movements whose measurements lie above this line were classified as saccadelike (crosses); those lying below were classified as pursuitlike (circles). Shaded regions in each graph reproduce the individual datum points obtained from the visually guided pursuit and saccades shown in Fig. 7.
those caused by lower microstimulation frequencieswere always classified as pursuitlike. In contrast, as shown by the crosses in the top right regions of the plots in Fig. 9, the largest evoked eye movements were always classified as saccadelike. For evoked eye movements of intermediate amplitudes, there was a transition between pursuit and saccadelike effects. This transition occurred within a much narrower range than the overlap evident in the measurements obtained from visually guided pursuit and saccades (shaded regions). In addition, the location of this transition depended on the eye movement behavior of the animal. When the animal was fixating (Fig. 9, A and B) or pursuing in the ipsilateral direction (Fig. 9, E and F), the transition occurred for smaller eye movements than when the animal was pursuing in the contraversive direction (Fig. 9, C and D). Thus the basis for our observation that the largest smooth eye movements occurred only during contraversive pursuit appears to lie in how the placement of this transition point was affected by the behavioral context.
where P is the probability of a saccade,
![<IT>P</IT> = 1 − δ exp [−(Δ<IT>E</IT>/α)<SUP>β</SUP>]](/content/vol80/issue4/fulltext/2046/img002.gif)
E is the amplitude of the change in eye position, 
is the change in eye position corresponding to a "threshold" probability of 82%, 
is the slope of the function, and 
determines how far less than one the probability can drop. The primary purpose of fitting the data with this function was to provide an objective measure of the transition point, which we defined as the value of for each fitted function (shown within each graph in Fig. 10). These thresholds quantify the point made graphically by the plots of the raw measurements in Fig. 9. For the horizontal component of the eye movement, the transition between pursuit- and saccadelike effects at this site occurred at larger eye movements (Fig. 10C, 0.59°) during contraversive pursuit than during either fixation (Fig. 10A, 0.09°) or ipsiversive pursuit (Fig. 10E, 0.19°).
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FIG. 10.
Estimating the transition points between pursuit and saccadelike evoked eye movements. Panels show frequency plots of eye movements classified as saccadelike during fixation (A and B), contraversive pursuit (C and D), and ipsiversive pursuit (E and F). Each datum point shows the fraction of recorded eye movements at each amplitude that were classified as saccadelike from the data in the corresponding panel in Fig. 9. The numbers in each panel indicate the change in eye position at which the fitted function reached a value of 0.82, defined as the transition point from pursuit- to saccadelike effects.
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FIG. 11.
Summary of transition points from 14 stimulation sites in both monkeys at which multiple frequencies were applied. Panels show distributions of transition points obtained during fixation (A and B), contraversive pursuit (C and D), and ipsiversive pursuit (E and F). Numbers in each panel indicate the means of the distributions.
DISCUSSION
Abstract
Introduction
Methods
Results
Discussion
References
; McElligott and Keller 1984; Noda and Fujikado 1987a,b) or the execution of visually guided saccades (Keller et al. 1983). Consistent with these previous studies, we found that microstimulation applied under these conditions produces predominantly saccadelike effects. However, we also found that, if microstimulation is applied during ongoing pursuit, it can modify smooth eye velocity. These findings support the suggestion that this structure may contribute to both pursuit and saccadic eye movements. We first discuss the possible mechanisms for these effects before considering the functional circuits that include this structure.
) and produces a similar pattern of effects on eye acceleration during pursuit (Robinson et al. 1997). The ipsiversive eye movements we evoked were therefore consistent with a transient inhibition of the caudal fastigial nucleus. Because Purkinje cells in the oculomotor vermis have an inhibitory effect on target neurons in the caudal fastigial nucleus, the effects we observed with microstimulation were likely mediated, at least in part, by activation of Purkinje cell axons. Second, Noda and Fujikado (1987a) showed that the ability to elicit saccadic eye movements with low currents applied in the white matter underlying the vermis was eliminated by injecting kainic acid into the cortex, demonstrating that the evoked eye movements required intact Purkinje cells. Because the location and parameters of microstimulation in our experiments essentially duplicate those of Noda and Fujikado (1987a), it seems likely that the effects we observed also required Purkinje cells. Nonetheless, we cannot rule out the possibility that some of the effects we observed were caused by antidromic activation of inputs to the oculomotor vermis.
; Optican and Robinson 1980; Ritchie 1976) and that electrical microstimulation elicited saccadic eye movements (Ron and Robinson 1973). It was subsequently shown that, although saccades can be evoked or modified by microstimulation within folia V to VII (Keller et al. 1983; McElligott and Keller 1984), saccades can be evoked with low currents (<10 µA) only within a more restricted region referred to as the "oculomotor vermis," consisting of lobule VII and the posterior one-half of lobule VI (Fujikado and Noda 1987; Noda and Fujikado 1987a,b). The mossy fibers and Purkinje cells within these folia both exhibit bursts correlated with the onset and duration of saccadic eye movements (Kase et al. 1980; Sato and Noda 1992a).
; Suzuki and Keller 1988b; Suzuki et al. 1981). Because these cells often also respond to retinal image movement and to head movement, it was suggested that their activity encodes a neural correlate of target velocity that could act as a guide for pursuit eye movements (Kase et al. 1979; Suzuki and Keller 1982, 1988a,b; Suzuki et al. 1981). Some support for a vermal contribution to pursuit was also provided by ablation studies. Lesions of the ventral paraflocculus, the primary cerebellar region involved in pursuit, produce severe but incomplete deficits in smooth eye movements (Zee et al. 1981). In contrast, complete cerebellectomy produces a more nearly complete deficit (Westheimer and Blair 1974), indicating that other cerebellar regions such as the oculomotor vermis also contribute to pursuit. However, only brief reports were made on the effects of vermal lesions on pursuit eye movements (Keller 1988; Suzuki and Keller 1983; Takagi et al. 1996). Furthermore, although previous studies often demonstrated the effects of microstimulation on saccadic eye movements, they have not documented effects on smooth eye movements.
; McElligott and Keller 1984; Ron and Robinson 1973) typically used currents that were much larger (
300 µA) than those used in our current study (2-50 µA). In contrast, using smaller currents (<10 µA) applied during fixation, Noda and Fujikado (1987b) evoked saccadic eye movements with small amplitudes in the same range that we found (<5°). The facilitation of evoked smooth eye movements during ongoing pursuit that we observed in the oculomotor vermis has also been found at other sites in the pathways for pursuit. For example, microstimulation within the foveal portion of the middle temporal area (area MT) or the lateral portion of the medial superior temporal area (area MST) can cause changes in pursuit eye speed during ongoing pursuit, but microstimulation during fixation is ineffective (Komatsu and Wurtz 1989). A similar conditional effect has been observed for microstimulation applied in the dorsolateral pontine nuclei (May et al. 1985), a region to which areas MT and MST both project (Glickstein et al. 1980) and which in turn provides inputs to the oculomotor vermis (Brodal 1979; Yamada and Noda 1987).
). In addition, Purkinje cells sensitive to head rotation are found primarily in lobule VIII but not in the oculomotor vermis (Sato and Noda 1992a). If one defines pursuit-related neurons as those sensitive to both eye and head motion, a combination that holds true in the ventral paraflocculus (Lisberger and Fuchs 1978; Miles et al. 1980), then one can argue that pursuit involves lobule VIII but not the oculomotor vermis (Sato and Noda 1992a). However, if one defines pursuit-related neurons simply as those neurons that are modulated during pursuit eye movements, the majority of both pursuit- and saccade-related neurons lie within the oculomotor vermis. In fact, of the relatively few of these neurons that were tested during both saccades pursuit, approximately one-half are responsive to both types of eye movements (Sato and Noda 1992a; Suzuki and Keller 1988b).
; Stone and Lisberger 1990).
). Disruption of activity in the FOR has been shown to cause both dysmetric saccades (Robinson et al. 1993; Sato and Noda 1992b; Vilis and Hore 1981) and deficits in smooth eye movements (Kurzan et al. 1993; Robinson et al. 1997). Accordingly, the firing rate of neurons in the FOR is modulated during both saccades (Fuchs et al. 1993; Helmchen et al. 1994; Ohtsuka and Noda 1991) and smooth eye movements (Büttner et al. 1991; Fuchs et al. 1994). In the one study that tested both eye movements, 29% of the pursuit-related neurons also exhibited a burst during saccades (Fuchs et al. 1994). This degree of overlap between pursuit- and saccade-related activity is not substantially different from that observed on Purkinje cells in the oculomotor vermis (Sato and Noda 1992a; Suzuki and Keller 1988b).
). Alternatively, the caudal fastigial nucleus could indirectly affect the burst by acting on the pause neurons that are also located in the PPRF. An additional possibility is provided by the projection from the caudal fastigial nucleus to the intermediate layers of the superior colliculus (May et al. 1990). For pursuit, the most direct path might seem to be the projection from the caudal fastigial nucleus to the vestibular nuclei (Noda et al. 1990), but this projection does not include the medial or superior divisions that contain neurons modulated during pursuit. A less direct path could be provided by projections to the nucleus reticularis tegmenti pontis (NRTP), which recent data suggests may also be involved in pursuit (Suzuki et al. 1990; Yamada et al. 1996). Interestingly, the anterograde pattern of termination in the NRTP after caudal fastigial injections (Fig. 2 of Noda et al. 1990) is similar to the retrograde pattern seen after injections of the ventral paraflocculus (Fig. 13 of Langer et al. 1985), suggesting that this nucleus might act as a relay between these two cerebellar regions. The projection to the PPRF is also a possibility because, in addition to burst and pause neurons, this region also contains eye position-related neurons (Keller 1974; Luschei and Fuchs 1972), and microstimulation in the vicinity of these neurons evokes smooth eye movements (Cohen and Komatsuzaki 1972; Keller 1974). Finally, the recent observation that eye movement-related neurons in the rostral superior colliculus are modulated during pursuit eye movements as well as during fixation and small saccades (Krauzlis et al. 1997) suggests that the fastigial projection to the rostral superior colliculus (May et al. 1990) might also affect pursuit.
) and pursuit (Fuchs et al. 1994). Finally, the results we obtained with microstimulation indicate that altering the output of the oculomotor vermis can produce both pursuit and saccadelike eye movements. The abrupt, but orderly, transition between these two types of effects (Fig. 9) suggests the presence of some coordinating influence.
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FIG. 12.
Model that can account for our pattern of results. A: diagram of the model. Numbers in boxes are gains; other boxes contain transfer functions expressed in Laplace notation. Output of box labeled burst is 10 if input is >0; otherwise, output is 0. Changes in value of vermis increment or decrement the output of the fastigial nucleus (FN), which is then multiplied by the value of motor error (ME) in a negative feedback loop. Position error (PE) was set equal to 0.01° in all simulations. Simulations were run on a millisecond timescale, so that the effective time constant of the "plant" was 15 ms. B: simulations of the model that produce primarily pursuitlike effects. Top traces: output of vermis increased from 0 to 6, 7, 8, 8.5, or 9 for 50 ms and then returned to 0. Bias was set to a constant value of 8. Middle traces: Small deflections in eye position (E) result from all but the largest change in vermis. Bottom traces: small pursuitlike evoked eye movements are seen more clearly in traces of simulated eye velocity. High velocities of the largest evoked eye movement are clipped. C: simulations of the model that produced primarily saccadelike effects. Bias was set to a constant value of 5. Other conventions same as in A.
). For example, we do not assign anatomic labels to all parts of the model. In part, this is because little is known about the brain stem pathways for pursuit eye movements. The bias and burst nonlinearity are a simplified version of the omnipause and burst neuron circuit identified in models of saccade generation (e.g., Van Gisbergen et al. 1981), but because of these simplifications we have not identified these parts of the model as specific anatomic structures. However, the bias in the model could be related to omnipause neurons because both increases in the bias of the model and stimulation of the omnipause region prevent the occurrence of saccades (Westheimer and Blair 1973). Because our simulations required changes in the value of the bias signal to reproduce the eye movements evoked during ipsiversive and contraversive pursuit, this predicts that the activity of omnipause neurons should be altered by smooth eye velocity.
), which has the advantage of providing a possible mechanism for the demonstrated plasticity in the pursuit system (Kahlon and Lisberger 1996; Optican et al. 1985). Other studies indicate that this particular model cannot accurately account for several critical features of pursuit (Goldreich et al. 1992), but this does not necessarily invalidate all models containing internal feedback loops (Ringach 1995). An additional consideration is that the signals in the feedback loop of Robinson et al. (1986) are velocities, whereas the signals in the feedback loop for saccades have been traditionally viewed as positions (Robinson 1975; Van Gisbergen et al. 1981). The discrepancy between position and velocity domains could be resolved if the sensory inputs to the premotor circuits were converted into equivalent prospective motor commands rather than handled in their native format as so-called "retinal position" or "visual motion" errors. For example, the conversion of inputs for pursuit and saccades into a common "eye velocity" motor format could explain how a single population of neurons, such as that recorded in the caudal fastigial nucleus (Fuchs et al. 1994), might accelerate or decelerate both saccades and pursuit.
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ACKNOWLEDGEMENTS |
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We thank D. Arends, L. Jensen, N. Nichols, and T. Ruffner for technical assistance, R. Chandra and A. Hays for software support, K. Pettigrew for advice on statistical tests, and J. Steinberg and B. Harvey for secretarial assistance.
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FOOTNOTES |
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Address for reprint requests: R. J. Krauzlis, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037.
Received 4 February 1998; accepted in final form 2 July 1998.
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REFERENCES |
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Abstract
Introduction
Methods
Results
Discussion
References
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