Laboratory of Sensorimotor Research, National Eye Institute, Bethesda, Maryland 20892
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ABSTRACT |
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Basso, Michele A., Richard J. Krauzlis, and Robert H. Wurtz. Activation and Inactivation of Rostral Superior Colliculus Neurons During Smooth-Pursuit Eye Movements in Monkeys. J. Neurophysiol. 84: 892-908, 2000. Neurons in the intermediate and deep layers of the rostral superior colliculus (SC) of monkeys are active during attentive fixation, small saccades, and smooth-pursuit eye movements. Alterations of SC activity have been shown to alter saccades and fixation, but similar manipulations have not been shown to influence smooth-pursuit eye movements. Therefore we both activated (electrical stimulation) and inactivated (reversible chemical injection) rostral SC neurons to establish a causal role for the activity of these neurons in smooth pursuit. First, we stimulated the rostral SC during pursuit initiation as well as pursuit maintenance. For pursuit initiation, stimulation of the rostral SC suppressed pursuit to ipsiversive moving targets primarily and had modest effects on contraversive pursuit. The effect of stimulation on pursuit varied with the location of the stimulation with the most rostral sites producing the most effective inhibition of ipsiversive pursuit. Stimulation was more effective on higher pursuit speeds than on lower and did not evoke smooth-pursuit eye movements during fixation. As with the effects on pursuit initiation, ipsiversive maintained pursuit was suppressed, whereas contraversive pursuit was less affected. The stimulation effect on smooth pursuit did not result from a generalized inhibition because the suppression of smooth pursuit was greater than the suppression of smooth eye movements evoked by head rotations (vestibular-ocular reflex). Nor was the stimulation effect due to the activation of superficial layer visual neurons rather than the intermediate layers of the SC because stimulation of the superficial layers produced effects opposite to those found with intermediate layer stimulation. Second, we inactivated the rostral SC with muscimol and found that contraversive pursuit initiation was reduced and ipsiversive pursuit was increased slightly, changes that were opposite to those resulting from stimulation. The results of both the stimulation and the muscimol injection experiments on pursuit are consistent with the effects of these activation and inactivation experiments on saccades, and the effects on pursuit are consistent with the hypothesis that the SC provides a position signal that is used by the smooth-pursuit eye-movement system.
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INTRODUCTION |
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In the previous paper, we described how rostral
superior colliculus (SC) neurons change their activity as the position
of a parafoveal target changes. By stepping a visual target to
locations around the fovea out to an eccentricity of 5°, we showed
that rostral SC neurons increase their activity with target locations in the contralateral hemifield. Like neurons further caudal in the SC,
rostral neurons are tuned for particular locationsshowing peaks of
activity between 0.2 and 3° eccentricity. Moreover these neurons
cease to discharge if the target steps into the ipsilateral hemifield.
Rostral neurons have two additional properties. First, they behave
similarly whether monkeys remain fixating after the target steps or if
they make a saccade to the eccentric target. Second, rostral SC neurons
are active in a similar manner during smooth-pursuit eye movements. For
example, if a visual target moves smoothly into the contralateral
hemifield and monkeys are required to pursue the target, these neurons
increase their discharge rates. Moving a target slightly into the
ipsilateral hemifield results in decreased discharge rates of these
neurons. Thus rather than representing a static command to keep the
eyes still, we suggest that these neurons reflect a position-error
signal for movements of the eyes close to the fovea, including pursuit
(Krauzlis et al. 1997
, 2000
). According to this
hypothesis, a signal reflecting the difference between eye and target
position
an error signal
would be shared by these oculomotor
subsystems, saccades, fixation, and pursuit.
These single neuron experiments, however, only correlate the neuronal activity to smooth-pursuit behavior and do not show that the activity contributes to the production of pursuit. For example, one way in which the neuronal activity might change with pursuit without contributing to pursuit generation would be for it to change in relation to preparation of a saccade that is ultimately not produced. Since the direction of the impending pursuit and the impending saccade would both be related to the activity of the same SC neurons, it would not be possible to separate activity into that related to the impending pursuit and that related to the impending saccade. Therefore to test directly the contribution of these rostral SC neurons to pursuit, we altered their activity and measured the effects on smooth-pursuit eye movements independent of saccades.
We performed two sets of experiments. First, we used electrical stimulation of the rostral SC during pursuit initiation and maintenance to determine if activation of these neurons influences smooth-pursuit eye movements. Second, we inactivated the neurons using the GABA agonist muscimol to determine whether a reduction of the activity of these neurons also influences pursuit eye movements. The results of these experiments show that changing the activity of rostral SC neurons influences smooth-pursuit eye movements. Additionally, the results of our experiments are consistent with the hypothesis that the SC may provide a position signal for the smooth-pursuit system.
Brief reports of some of these experiments have been made previously
(Basso et al. 1997, 1998
; Krauzlis et al.
1997b
).
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METHODS |
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Two monkeys were prepared for chronic
electrophysiological recording of single neurons, electrical
stimulation, and reversible lesions of the SC and recording of eye
movements. The surgical procedures were described in previous reports
on experiments in which the same monkeys were used (Basso and
Wurtz 1998; Krauzlis et al. 1997a
-c
). All
protocols were approved by the Institute Animal Care and Use Committee
and complied with the Public Health Service Policy on the humane care
and use of laboratory animals.
Behavioral paradigms
The general behavioral paradigms and storage of data
were identical to that described in the preceding paper
(Krauzlis et al. 2000).
Monkeys performed visually guided saccade and pursuit tasks. For the
saccade tasks, monkeys fixated a centrally located light-emitting diode
(LED) for a duration of 500 ms, after which time the fixation point
stepped to a peripheral location of 15° in either hemifield on the
horizontal meridian. Monkeys were required to make a saccadic eye
movement to the target quickly and accurately. Trials were aborted if
the monkeys failed to acquire the target within 500 ms or were not
accurate within 2° as measured by an electronic window. For pursuit
trials, monkeys fixated a centrally located LED for a variable duration
of 1,000-1,500 ms and with an accuracy of at least 2°. After this
time, the target either started to move away from the fovea at a
constant velocity (ramp trials) or stepped horizontally to a slightly
eccentric position and then moved back toward the fovea (step-ramp
trials). The amplitude of the step was adjusted to minimize the
occurrence of catch-up saccades (Rashbass 1961). Monkeys
were required to track the target with an accuracy of 3°. If the
monkeys failed to track the target, the trial was aborted by
extinguishing the target and delaying the onset of the next trial by
2 s.
During correct performance of trials in all experiments, monkeys were rewarded with a drop of fruit juice or water. Monkeys worked daily until satiated and were given supplemental fluid as required. The monkeys' weight was monitored daily and they remained under the supervision of the Institute veterinarian.
Electrical stimulation
Electrical stimulation was applied through tungsten
microelectrodes (Frederick Haer) with impedances between 0.3 and 1.0 M measured at 1 kHz. Electrodes were aimed toward the SC through stainless steel guide tubes held in place by a plastic grid that was
secured to the recording chamber (Crist et al. 1988
).
Electrical stimulation was applied as biphasic pulses. The parameters
of stimulation were adjusted on-line to produce the maximum effects on
saccades following the parameters used by Munoz and Wurtz
(1993b)
and Paré and Guitton
(1994)
for the fixation zone. The minimum pulse width was 100 µs and did not exceed 250 µs. The minimum frequency was 100 Hz and
did not exceed 250 Hz. These parameters are also consistent with
producing a sustained activity similar to that seen in buildup neurons
rather than the high-frequency bursting (>600 spikes/s) of the saccade
related burst neurons. Current intensity ranged between 9 and 35 µA.
The duration of stimulus train differed depending on the behavioral
paradigm as described in the following text.
During stimulation trials, saccades frequently were suppressed for the
duration of the presentation of the electrical stimulation train.
During these trials, the size of the windows was adjusted to avoid
deterring task performance. The electrical stimulation parameters were
adjusted at this time to maximize the effects on saccades. We also
interleaved trials in which electrical stimulation occurred while
monkeys attentively fixated at primary position without a visual
stimulus present to determine the amplitude of any evoked saccades,
thereby identifying the location of the stimulating electrode on the SC
map (Robinson 1972).
After the stimulation parameters were set for a given site, tests of the effects of stimulation on pursuit commenced. Two basic experimental manipulations were used, namely, stimulation during pursuit initiation and stimulation during maintained pursuit (Fig. 1). We applied stimulation during pursuit initiation simultaneously with the onset of the target motion (15°/s) in the ramp trials and continued for 400 ms (Fig. 1, initiation). For a number of sites, we varied the relative timing of the stimulus train and the onset of the target motion in ramp trials. In these experiments, two conditions were used. First, the stimulation occurred simultaneously with the onset of the target motion (0 ms). In the second condition, stimulation occurred 100 ms before the onset of target motion (100 ms). In both conditions, the speed of target motion was 15°/s. In another set of experiments, we varied the speed of the target motion in step-ramp trials. The speeds tested were 2, 5, 10, and 15°/s. For these experiments, we started the stimulation simultaneously with the onset of target motion. Finally, for the experiments testing the effects of SC stimulation on maintained pursuit (Fig. 1, maintained), a stimulus train of 300 ms occurred during maintained pursuit in step-ramp trials, defined as 600 ms after the onset of target motion. This period was typically well after any catch-up saccades if they occurred and after pursuit had maintained a constant speed approximating that of the target (either 5 or 15°/s).
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We also tested the effects of SC stimulation on smooth eye movements evoked by vestibular stimulation and compared these effects to those obtained during visually driven smooth eye movements. To evoke vestibular eye movements, monkeys experienced whole body passive rotation achieved by mounting the primate chair on a rotating platform. The monkeys were rotated sinusoidally at 0.4 Hz and a peak-to-peak amplitude of 20° about a vertical axis that intersected the interaural line, producing movement along the horizontal meridian. Monkeys were required to maintain eye position at a central location while they were rotated in complete darkness with no visible fixation stimulus present. In one monkey, we were unable to control completely for eye position, but the effects of the stimulation did not differ dramatically between the two monkeys. SC stimulation began during the phase of the sinusoidal motion in which eye velocity was maximal for each direction, ipsiversive or contraversive, and was maintained for 400 ms. For a direct comparison with visually driven smooth eye movements, the monkeys remained stationary and a visual target moved along the horizontal meridian sinusoidally with a frequency of 0.4 Hz and a peak to peak amplitude of 20°. Identical to the vestibular condition, SC stimulation began during the phase of the sinusoid in which the eye velocity was maximal for each direction and was maintained for 400 ms. For all experimental conditions, the stimulation and no-stimulation trials were presented in an interleaved fashion except for the vestibular and sinusoidal pursuit trials, which were presented in separate, interleaved blocks.
Muscimol injections
We injected muscimol (Sigma) dissolved in saline in the
SC of two monkeys. The injection technique we used was originally described by Dias and Segraves (1997). Briefly,
a closed pressure system was used to inject small volumes of muscimol
into the SC. This system allows for precise control and measurement of
the injected volumes. The micropipette system was adapted for use with
the grid and guide-tube system described by Crist et al. (1988)
. Moreover, a fine wire inserted within the pipette
allowed us to electrically stimulate or record the neuronal activity
prior to making the injection. Once the location of a site was
identified by stimulation or by mapping the movement field, brief
pulses of air pressure of fixed intensity (30-80 psi) and duration
(4-20 ms) were applied by a picopump (World Precision Instruments) to release the muscimol contained within the pipette. The injected volumes
for each site in the two monkeys are listed in Table
1. We collected preinjection and
postinjection data on interleaved saccade and pursuit trials. Recovery
data were collected 24 h after the injections. Monkeys were
required to perform saccades along the horizontal meridian of 2, 5, 10, and 20° amplitude (8 trial conditions). Pursuit trials consisted of
ramps and step ramps of constant velocity targets moving at 15°/s
along the horizontal meridian in either direction. The location of the
step varied between 2 and 5° along the horizontal meridian in either
hemifield. Thus for pursuit trials, there were 10 possible conditions.
A step location either at 2 or 5° in the contralateral hemifield and
a subsequent ipsiversive or contraversive target motion (4 conditions),
or a step location of 2 or 5° in the ipsilateral hemifield and a
subsequent contraversive or ipsiversive direction of target motion (4).
Finally, ramp trials were those in which the target motion originated
at primary position and moved at a constant speed either ipsiversively
or contraversively (2).
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Data analysis
Voltage signals proportional to the horizontal and vertical
components of eye position were filtered (6 pole Bessel, 3 dB at 240 Hz) and then digitized at a resolution of 16 bits and sampled at 1 kHz.
The data were saved on disk for subsequent off-line analysis. An
interactive computer program was then used to filter, display, and
measure eye-position and eye-velocity signals. A signal encoding
horizontal eye velocity was obtained by applying a 29-point finite
impulse response filter (
3 dB at 96 Hz) to the eye-position signal.
The high frequency was used to insure detection of small saccades
(compare Abel et al. 1979
; Bahill et al.
1975
; Breznen and Gnadt 1997
). Also to maximize
detection of small saccades, we used stringent velocity (20°/s) and
acceleration (500-800°/s2) criteria. For the
pursuit-initiation measurements, data after the occurrence of detected
saccades were excluded from analysis as well as the saccades
themselves. Once individual eye-velocity records were obtained, the
computer program calculated average smooth eye velocity by aligning the
traces with respect to target motion onset and calculating the mean and
SD of the eye velocity for each millisecond of data. Measurements of
the data resulting from experiments manipulating pursuit speed or
pursuit maintenance, or during the muscimol experiments, were made on
the velocity traces in which each millisecond of the trace marked as a
saccadic velocity was excluded from the calculation of the average
smooth eye-velocity traces. These traces were defined as desaccaded
eye-velocity traces. For data passing normality tests run by
SigmaStat, we used Student's t-test for
statistical analysis; otherwise, we used the Mann-Whitney rank sum test.
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RESULTS |
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Electrical activation of the rostral SC
SACCADES AND PURSUIT INITIATION.
In two monkeys, we electrically stimulated the SC at rostral sites
within the central 5° of the visual field. To verify that we were
stimulating at the rostral SC locations that have previously been shown
to alter saccades, we first determined the effect on saccadic eye
movements made to large target steps (10-15°). Ipsiversive saccades
were suppressed completely and typically for the duration of the
stimulus train (Fig. 2A).
Contraversive saccades (Fig. 2E) were also suppressed
somewhat, and frequently small contralateral saccades intruded during
the stimulation. As the stimulation site in the SC was moved further
from the foveal representation, stimulation was less effective in
suppressing large saccades, even large ipsilateral saccades and more
frequently evoked small contralateral saccades (not shown). These
results are consistent with those reported previously (e.g.,
Munoz and Wurtz 1993) and serve to confirm the location
of our stimulating electrode within the rostral pole of the SC map.
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EFFECTS OF STIMULATION AT DIFFERENT SC LOCATIONS. Comparing the eye-velocity responses with and without electrical stimulation at different sites within the SC revealed a dependence on the SC site stimulated (Fig. 4). For a site at the very rostral end of the SC, which virtually never evoked saccades, pursuit eye velocity was slightly reduced during ipsiversive pursuit and unaffected during contraversive pursuit (Fig. 4, A and E). For a stimulation site slightly more caudal (Fig. 4, B and F), ipsiversive pursuit velocity was reduced more dramatically, whereas contraversive pursuit velocity was not. For a stimulating electrode even more caudal (Fig. 4, C and G) that evoked very small saccades during fixation, there was a reduction of ipsiversive pursuit eye velocity and a modest increase in contraversive pursuit. A site further caudal, which evoked on average a 4° saccade, produced no pursuit effect in either direction (Fig. 4, D and H).
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EFFECTS OF SC STIMULATION TIMING ON PURSUIT. As just described, the effects on pursuit frequently differed depending on when in the initial 100 ms of open loop pursuit the eye speed was measured. Specifically, the effect was largely restricted to the later 50 ms of the open loop period (compare Fig. 5, A and C and B and D).
This difference in the stimulation effect between the two intervals of pursuit initiation may reflect the known differences in early and late phases of pursuit initiation (e.g., Lisberger and Westbrook 1985STIMULATION OF SC AT DIFFERENT PURSUIT SPEEDS.
Up to this point, we have presented the results of SC stimulation on
pursuit eye movements of a single speed (15°/s). Past experiments
demonstrate that the pursuit system responds differently to target
perturbations depending on the speed of pursuit. For example, by
imposing small changes in the speed of a moving target that monkeys
were required to track, Schwartz and Lisberger (1991) demonstrated that the pursuit response to the speed perturbations increased as the target speed increased. Perturbations had a
dramatically smaller effect during fixation than during pursuit.
Similarly, Komatsu and Wurtz (1989)
demonstrated that
the effect of electrical stimulation of middle temporal/medial superior
temporal (MT/MST) depended on the speed of pursuit and was not
influential during fixation. Both sets of results were interpreted as
acting on the visual input to the pursuit system, which, in the case of
the stimulation, was subsequently combined with the information
obtained from the speed of the moving visual target. We tested whether the effects of SC stimulation also depended on pursuit speed to determine whether the SC signal could be combined with the visual input
to the pursuit system.
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SC STIMULATION AND PURSUIT MAINTENANCE. Stimulation of the rostral SC affected the monkeys' ability to maintain smooth-pursuit eye movements as well as to initiate them (Fig. 2C). Therefore we specifically tested the effects of rostral SC stimulation on maintained pursuit by presenting 300 ms trains of stimulation at 600 ms after the onset of target motion. By 600 ms, the initial catch up saccades, if any, had already occurred, and in most cases, pursuit attained a constant velocity approaching that of the target (as illustrated in Fig. 1). The effects on maintained pursuit with rostral SC stimulation mirrored the effects seen for pursuit initiation. For example, at a site close to the fovea, stimulation of the SC resulted in suppression of maintained pursuit at 15°/s ipsiversively (Fig. 9A). For this site, contraversive pursuit was suppressed also (Fig. 9B). We tested the effects of SC stimulation on pursuit eye velocity maintained at 5°/s as well and found that for most cases the trend was similar (not shown).
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SC STIMULATION AND THE VOR.
We next tested whether rostral SC stimulation affected smooth eye
movements simply because the stimulation affected all smooth eye
movements or because the effects of stimulation were specific for
smooth-pursuit eye movements. We did this by comparing the effects of
stimulation during smooth eye movements evoked by head rotationsthe
vestibular-ocular reflex (VOR)
to the effects of stimulation obtained
during smooth-pursuit eye movements. For pursuit in these
experiments, we presented monkeys with a target moving sinusoidally at
0.4 Hz and a peak-to-peak amplitude of 20°. To generate the VOR,
monkeys fixated straight ahead in the dark while the chair was rotated
sinusoidally at 0.4 Hz with a peak-to-peak amplitude of 20°. On
interleaved trials, SC stimulation was introduced for 400 ms beginning
during the phase in which the ipsiversive and contraversive eye
velocity was maximal. Stimulation within the SC during sinusoidal
pursuit when the peak eye velocity was maximal in the direction
ipsilateral to the stimulation suppressed smooth-pursuit eye velocity
(Fig. 11A; note that when
the velocity trace begins to turn downward, this reflects the time when
the eye velocity peaks and then declines indicating the turn around of
the sinusoidal movement). At the same SC site and stimulation conditions but during the VOR, there was only a modest effect on smooth
eye velocity (Fig. 11B). There were no effects on
contraversive pursuit or VOR at this site (not shown). Across our
sample of seven sites, six showed significantly different effects of
stimulation in the ipsiversive sinusoidal pursuit and VOR conditions
(Fig. 11C). Thus the effects of electrical stimulation
differ for pursuit and VOR eye movements and argue against the
possibility that the SC stimulation is a generic inhibitory signal that
affects all smooth eye movements similarly.
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STIMULATION OF SUPERFICIAL SC LAYERS.
Since our sites of stimulation in the SC were at locations where
low-threshold stimuli evoked saccades, it seems likely that the pursuit
effects resulted from activation of the premotor neuronal elements
within the intermediate and deep layers. Despite this, it is possible
that the effects on pursuit resulted from activation of the overlying
visual neurons within the superficial layers of the SC as well. The
significance of stimulating the superficial rather than the
intermediate layers is particularly important because it is known that
cortical areas encoding visual motion signals project directly to the
SC superficial layers (Ungerleider et al. 1984) and that
superficial layer visual neurons themselves convey motion signals
(Davidson and Bender 1991
).
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Muscimol inactivation of the SC
In contrast to electrical stimulation, which activates the underlying neuronal elements, muscimol injections should reduce the activity of the underlying neurons and produce opposite behavioral effects. Therefore if the signal generated by SC neuronal activity is used by the smooth-pursuit system, we expect unilateral inactivation of the SC to produce a reduced smooth eye velocity when the pursuit target is located within the region of visual space represented by the inactivated part of the SC (Fig. 13). To determine this, we inactivated the SC while monkeys performed smooth-pursuit eye movements in both directions. For these experiments, we switched to the step-ramp paradigm so that we could independently assess the interactions between the location of the target step and the direction of target motion with the location of the SC map inactivated.
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SACCADES.
As we did with electrical stimulation, we first confirmed that our
muscimol injections affected saccade generation as has been reported
previously (e.g., Aizawa and Wurtz 1998; Quaia et al. 1998
). To do this, we interleaved with the pursuit trials target step trials with stimuli located at 2, 5, 10, and 20° along the horizontal meridian in both hemifields and measured the saccades made to the target steps before and after the injections. We observed effects on saccades similar to those reported previously. First, contralateral saccades were hypometric, had reduced velocities and
increased latencies. Second, for many sites, even though the injection
was centered on a site evoking a 1° saccade with stimulation, saccades as large as 10° were affected by the muscimol. Third, in
some cases, ipsilateral saccades occurred with a slightly shorter latency (data not shown). Finally, shortly after the injection (within
5 min), a static fixation offset into the ipsilateral hemifield
developed (see also Hikosaka and Wurtz 1983
).
PURSUIT. We made eight unilateral SC injections in two monkeys. Seven of the injections were between 0.2° and 3.5° sites. One injection was made at an 8.8° site (see Table 1). Eye-velocity traces before and after a single muscimol injection into the rostral SC are shown in Fig. 14 and reflect a typical finding. For contraversive pursuit initiation, reduced eye velocity was observed, sometimes even when the target started slightly in the ipsilateral hemifield (Fig. 14G). For large steps into the ipsilateral visual field, pursuit was frequently enhanced (Fig. 14F). In contrast, an injection made more caudally had no effect and an injection made in the superficial layers had effects of the opposite sign (not shown).
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DISCUSSION |
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The results of our experiments demonstrate that the rostral SC influences smooth-pursuit eye movements. Activation of the rostral SC with electrical stimulation modifies pursuit in a manner similar to that for saccades (Fig. 2). Such stimulation reduces smooth-pursuit eye velocity ipsilateral to the site of stimulation and in some cases, also contralateral. Depending on the site of the stimulation, contraversive smooth eye velocity also could be slightly enhanced. We demonstrated a number of stimulation effects: the stimulation effects vary with the location of the stimulation on the SC map with most rostral sites producing the most effective suppression of ipsiversive pursuit (Figs. 4 and 5); the effects can occur immediately with the onset of pursuit (Figs. 6); pursuit eye movements are more affected as pursuit speed increases and are not evoked by stimulation during fixation (Figs. 7 and 8); the stimulation effects are evident for both pursuit initiation and maintenance (Figs. 9 and 10); the effects are not due to a generalized suppression because smooth eye movements evoked by head rotations are largely unaffected (Fig. 11); and it is the intermediate and deep layers of the SC that are responsible for the effects since superficial layer stimulation had either the opposite or no effect on pursuit (Fig. 12). In contrast to the stimulation, reduction in the activity of the rostral SC by injection of muscimol affects pursuit in an opposite manner; such injections reduce contraversive pursuit velocity and ipsiversive pursuit velocity is frequently enhanced (Figs. 14 and 15). These results of activating and inactivating the neurons in the rostral SC indicate that the activity of SC neurons contributes to smooth-pursuit eye movements. Moreover the results are consistent with the interpretation that the SC provides a position signal that can be used to drive the pursuit response.
The relationship of the results to the predictions of the position signal hypothesis outlined in the previous paper is not always obvious so we will consider the relationship in several steps. First, we will compare the effects of the rostral SC alterations on pursuit with those we obtained for saccades to compare the deficits of the pursuit system to those of the saccadic system, which is known to be driven by position signals. Next we will consider the extent to which the results of the pursuit experiments fit with the position signal hypothesis. Finally, we consider the possibility that the signal we are altering in the SC is a motion signal rather than a position signal.
Pursuit and saccade effects are similar
The first indication that effects on pursuit result from SC
activity related to position is the similarity of activation and inactivation of the rostral SC on pursuit and saccades. For pursuit of
targets moving in the ipsiversive direction, activation of the rostral
SC slows pursuit of moving targets just as such stimulation suppresses
saccades to ipsilateral stationary targets. In contrast, for pursuit of
targets moving in the contraversive direction, activation of the
rostral SC either increases pursuit speed or has little effect just as
such stimulation has less effect on saccades made to large,
contralateral stationary targets. When the SC is inactivated by
muscimol injections, the results are largely opposite the stimulation
results for both pursuit and saccades. Inactivation of the rostral SC
leaves pursuit of ipsiversive targets unaffected or speeds it. Saccades
to stationary, ipsilateral targets are largely unaffected or occur with
a slightly shorter latency (see also, Aizawa and Wurtz
1998; Quaia et al. 1998
). Inactivation decreases
pursuit speed to contraversive targets and small, contralateral
saccades are hypometric. Our experiments show that activation and
inactivation have opposite effects on pursuit, that these effects are
different for ipsiversive and contraversive movements, and that the
type of change is similar for both pursuit and saccades. Thus the
current results provide evidence that the activity in rostral SC
influences pursuit comparable to the previous evidence that this region
influences saccades. Moreover these results suggest that the two types
of eye movements are influenced by the same signal coded by rostral SC neurons.
The nature of the activity in the rostral SC fixation neurons has been
proposed to signal attentive fixation (Munoz and Wurtz 1993a,b
). The tonic activity of rostral neurons during
fixation, the pause in activity of these neurons during saccades, the
suppression of saccadic eye movements with electrical stimulation, and
the shorter latency of large saccadic eye movements resulting from temporary inactivation of these neurons support that interpretation. Our results on pursuit are very similar to those for saccades, and it is therefore possible that the effects we see on pursuit result
from a general signal that acts to suppress eye movements
pursuit as
well as saccades
and produce fixation. In the present experiments, when the stimulation was as close to the representation of 0° eccentricity on the SC map as was possible, we also found suppression of pursuit and saccades both ipsiversively and contraversively. We
think this activity reflects small target positions adjacent to the
fovea as described in our previous papers (Krauzlis et al. 1997
,
2000
) rather than a static fixation command for three reasons.
First, despite a suppression of pursuit in both directions, the effects
were asymmetrical
stimulation reliably suppressed ipsiversive pursuit
more than contraversive pursuit. Second, for some stimulation sites
where fixation neurons could be recorded, stimulation suppressed
ipsiversive saccades and pursuit but facilitated contraversive pursuit,
albeit modestly. Thus one stimulation site both increased and decreased
pursuit. Third, smooth eye movements produced by head rotations were
largely unaffected by rostral SC stimulation, precluding the
interpretation that these neurons code a signal to fixate or to
suppress all eye movements. It is important to note
therefore that we interpret the present pursuit result and the previous
saccade result in the same fashion. Specifically, the stimulation
mimics a small, contralateral target position signal that interacts
with the actual visual target. Thus during a 15° eccentric
ipsiversive saccade, or during pursuit of a target moving at 15°/s,
stimulation of the rostral SC representing a small, contralateral
target provides a position signal in the direction opposite the one
indicated by the visual stimulus and results in a reduced or suppressed movement.
SC provides a position signal for pursuit
Since the SC has long been known to provide a position signal for the saccadic system, the most likely interpretation of the effects of electrical stimulation and reversible inactivation of the rostral SC on pursuit eye movements is that it affects a position signal that is used by the pursuit system. We shall first describe the behavioral effects of imposed position signals on pursuit and then describe how we think the results of our experiments are consistent with this interpretation.
The smooth-pursuit response is generated primarily by visual motion
signals (see for review Lisberger et al. 1987). There is
evidence in both humans (Barnes and Asselman 1992
;
Barnes et al. 1987
; Carl and Gellman
1987
; Heywood and Churcher 1971
, 1972
; Pola and Wyatt 1980
) and monkeys (Krauzlis and
Miles 1996
; Morris and Lisberger 1987
;
Segraves and Goldberg 1994
) that smooth-pursuit eye
movements are also influenced by visual position signals. For example,
in humans, stepping a target to either side of the fovea creating a
small offset of the target with respect to the fovea results in changes
in smooth eye velocity in the direction of the target displacement
(Pola and Wyatt 1980
). Similarly, in monkeys, during
open-loop pursuit of a stabilized image, small steps in the direction
of target motion producing a static displacement of the target relative
to the fovea result in slight increases in smooth eye velocity.
Similarly stepping the target in the direction opposite the ongoing
target motion results in large decreases in smooth eye velocity
(Morris and Lisberger 1987
).
Whereas these results in monkeys demonstrate the use of a position
signal during maintained pursuit of a stabilized image, recently position signals were shown to influence pursuit during initiation in monkeys as well (for similar experiments in
humans, see also Carl and Gellman 1987; Krauzlis
and Miles 1996
). During step-ramp target motion, small
perturbations in target position were imposed at different times during
the first 100 ms of presentation of the target motion. For example, a
target would initially step to the left and then ramp to the right at
constant velocity. At different times during the presentation of the
constant velocity target motion the target position was changed either
forward in the direction of ongoing target motion or backward, opposite
the direction of ongoing target motion. When the target stepped
forward, pursuit was initiated with a slightly higher velocity than
when no target step was presented. In contrast, when the target stepped backward, pursuit was initiated with a much slower eye velocity relative to the no step condition.
A number of our results with SC manipulation are consistent with the
interpretation that the stimulation is acting to impose a slight
contralateral visual position error that influences the response of the
pursuit system. First, neurons in the rostral SC are tuned for small
contralateral target positions in both their visual and premotor
responses (Krauzlis et al. 1997, 2000
). Second, we
obtained different effects of SC stimulation at different locations on
the map where different target positions are located. For example,
sites very close to the fovea suppressed pursuit bilaterally but the
effects were always greater for ipsiversive than contraversive pursuit.
This is consistent with imposing a small contralateral position signal
producing a backward position error for both directions of pursuit but
a larger backward error for ipsiversive pursuit and thus a larger
slowing of eye velocity. A site slightly further caudal, representing a
slightly more contralateral position signal, suppressed only
ipsiversive pursuit, consistent with providing a large backward
position error for ipsiversive pursuit and no net position error for
contraversive pursuit.
In humans, position offsets created with retinal afterimages can
initiate pursuit (Heywood and Churcher 1971,
1972
; Pola and Wyatt 1980
), whereas in monkeys,
position offsets alone are less likely to initiate pursuit
(Morris and Lisberger 1987
). Our observations are
consistent with this since stimulation of the SC during fixation either
evoked small saccades or failed to evoke any response. We were never
able to initiate smooth pursuit with stimulation of the rostral SC
during fixation. This is in contrast to the findings in cat in which SC
stimulation may evoke smooth eye movements (Missal et al.
1996
; but see also Breznen and Gnadt 1997
).
Moreover, Segraves and Goldberg (1994)
demonstrated that
position signals as large as 3° can influence pursuit and we obtained
maximal effects on pursuit within this region of the SC map. Although
we did not systematically test sites further caudal on the map, one
site where we injected muscimol at 8° failed to influence our
step-ramp configuration of pursuit trials.
Finally, the results of our muscimol injections are also consistent with the position signal hypothesis. For example, when the target was stepped into the contralateral hemifield, in step-ramp pursuit trials, pursuit was suppressed in both directions. This demonstrates that the effects of the SC stimulation on pursuit is less influenced by the direction of pursuit but rather mostly depends on the location of the target step.
Indeed the idea that a position signal is used to drive a pursuit
response is not new. A number of models of the pursuit system incorporate a position-error signal as a drive for the pursuit system (see Lisberger et al. 1987; Pola and Wyatt
1980
). More recent models of oculomotor control have
incorporated both the position-error signal and the idea that the SC
was providing the position-error signal necessary to drive both types
of movements (Cova and Galiana 1995
;
Lefèvre et al. 1994
). Our single neuron evidence,
that the neurons are tuned for small positions of a visual target close
to the fovea (Krauzlis et al. 1997
, 2000
), and the
stimulation effects on pursuit as well as the inactivation of these
neurons resulting in pursuit deficits lend significant support to the
hypothesis that the rostral SC is involved in pursuit and that the SC
provides a position signal that assists in the drive for smooth-pursuit
eye movements.
Motion signal in SC?
We think that the effects of activation and inactivation are
consistent with a role for the SC in smooth-pursuit eye movements based
on a position signal conveyed by neurons in the rostral SC
(Krauzlis et al. 1997c, 2000
). However, it is still
possible that our experiments alter a visual motion signal, and there
are several ways in which this might come about.
First, the manipulation of the rostral SC may be efficacious on pursuit
due to the anatomical proximity and connections
(Büttner-Ennever et al. 1996) with the nucleus of
the optic tract (NOT), a structure intimately involved in smooth
eye-movement generation (Schiff et al. 1988
, 1990
). Our
results cannot be explained by this possibility for a number of
reasons. First, stimulation of NOT produces ipsiversive slow eye
movements while the monkey fixates, consistent with its role in
generating the slow phase of optokinetic nystagmus (Schiff et
al. 1988
). We were never able to evoke smooth eye
movements with stimulation of the SC while the monkey was maintaining
fixation. Second, stimulation of NOT produces ipsiversive pursuit
(Schiff et al. 1988
) while the effects of SC
stimulation typically produce the opposite, a suppression of
ipsiversive pursuit. Third, muscimol inactivation of NOT impairs
ipsiversive smooth eye movements (Schiff et al.
1990
), whereas muscimol inactivation of the SC, impairs contraversive smooth pursuit. Fourth, NOT inactivation very
rapidly (within 5 min) produces nystagmus with contralateral slow
phases (Schiff et al. 1990
), whereas, in our
experiments, if nystagmus developed it occurred typically 30-45 min
after an injection, consistent with diffusion into NOT. Thus our
results are not at all consistent with the interpretation that the
effects result from invasion of NOT.
A second possible way in which our experimental alterations in neuronal
activity might reflect changes in motion signal processing is by
altering the activity of superficial layer neurons. The superficial
layers of the SC are known to receive inputs from visual cortical areas
where the neurons are clearly related to the direction and speed of
target motion as well as to pursuit eye movements such as MT and MST
(Boussaoud et al. 1992; Ungerleider et al.
1984
). Moreover neurons in the superficial layers show an
effect of relative motion (Davidson and Bender 1991
),
and this may explain the results we obtained on pursuit. When we
tested the hypothesis that the visual superficial layers were
responsible for the effects on pursuit by stimulating the
superficial layers directly, we found that this effect on pursuit was
opposite to the stimulation of the intermediate and deep layers.
Furthermore our one muscimol injection located more dorsally, perhaps
inactivating the superficial layers preferentially, also had opposite
effects to those seen after inactivation of intermediate and deep layer neurons. Therefore we are confident that the effects on pursuit with
manipulation of the intermediate and deep layer SC neurons in our
experiments do not result from altering superficial layer activity.
Another possibility is that both our activation and inactivation
experiments are still acting on a visual motion signal but that motion
signal is in the intermediate and deep layers of the SC. This
possibility is relevant because recent experiments have shown that
neurons in the intermediate and deep layers of the SC can, with
extensive training in a visual motion discrimination task, display
responses to motion and directional tuning (Horwitz and Newsome
1999). If we were altering a visual motion signal in the
intermediate and deep layers, then we should get the same effects with
stimulation as those seen in MT and MST where the neurons are clearly
related to the direction and speed of motion. We see the opposite. In
MT/MST stimulation of the foveal region leads to an increase in
ipsiversive pursuit speed (Komatsu and Wurtz 1989
),
whereas we find that stimulation of the rostral SC leads to a
decrease in ipsiversive pursuit speed. Similarly,
inactivation of foveal MT/MST leads to a decrease in pursuit speed to
ipsiversive targets (Dürsteler and Wurtz 1988
),
but we frequently obtained an increase in ipsiversive pursuit. These
observations make it unlikely that the effects of activation and
inactivation of the rostral SC are the result of altering the
processing of motion information.
The role played by these neurons in pursuit seems to be similar to that
played in saccades; they convey a position rather than a motion signal.
This position signal used by both the saccadic and pursuit systems
might reflect a mechanism for modulating the gain of pursuit eye
movements seen with saccadic eye movements (Lisberger
1998). Alternatively, and since we demonstrated that the signal is independent of the actual movement made, this position signal might reflect a mechanism for selecting visual targets to serve
as common goals for these two eye-movement systems (Krauzlis and
Stone 1999
; Krauzlis et al. 1997c
). Increasing
the activity of the neurons results in biasing both the saccadic and
pursuit systems toward the location of target represented by the
stimulation. Similarly, reducing the activity of the neurons biases the
two eye movement systems away from the target location represented by
the zone of inactivation. Finally it is worth noting, that for the
activation or inactivation of the brain areas we have considered, the
effects fall into two categories depending on whether the area carries
a position or a motion signal. The effects of altering these areas are
so different that they might be useful for diagnosis of damage in the
oculomotor pathways, at least in the cortex and upper brain stem. If
the error conveyed by a region is one of position, the deficit will be
greater for movement to the contralateral field for either
saccades or for pursuit guided by position. If the signal conveyed by
an area is one for motion, the deficit will be greater for movement in
the ipsiversive direction. Pursuit may show a deficit in
either the contralateral field or the ipsiversive direction depending
on the signal used or compromised by damage.
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ACKNOWLEDGMENTS |
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We thank our colleagues at the Laboratory of Sensorimotor Research for comments on the manuscript. Additionally, we thank T. Ruffner and N. Nichols for machine shop assistance, J. McClurkin for data analysis software, J. Steinberg for administrative assistance, and M. Smith for technical assistance with the injection experiments. We also thank the Laboratory of Diagnostic Radiology Research at the National Institutes of Health for the magnetic resonance images.
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FOOTNOTES |
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Address for reprint requests: M. A. Basso, Laboratory of Sensorimotor Research, National Eye Institute, 9000 Rockville Pike, Bethesda, MD 20892 (E-mail: mab{at}lsr.nei.nih.gov).
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Received 8 December 1999; accepted in final form 30 March 2000.
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REFERENCES |
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