1Graduate Group in Bioengineering, University of California, San Francisco 94143; 2Graduate Group in Bioengineering, University of California, Berkeley 94720; and 3The Smith-Kettlewell Eye Research Institute, San Francisco, California 94115
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ABSTRACT |
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Gandhi, Neeraj J. and Edward L. Keller. Comparison of Saccades Perturbed by Stimulation of the Rostral Superior Colliculus, the Caudal Superior Colliculus, and the Omnipause Neuron Region. J. Neurophysiol. 82: 3236-3253, 1999. Over the past decade, considerable research efforts have been focused on the role of the rostral superior colliculus (SC) in control of saccades. The most recent theory separates the deeper intermediate layers of the SC into two functional regions: the rostral pole of these layers constitutes a fixation zone and the caudal region comprises the saccade zone. Sustained activity of fixation neurons in the fixation zone is argued to maintain fixation and help prevent saccade generation by exciting the omnipause neurons (OPNs) in the brain stem. This hypothesis is in contrast to the traditional view that the SC contains a topographic representation of the saccade motor map on which the rostral pole of the SC encodes signals for generating small saccades (<2°) instead of preventing them. There is therefore an unresolved controversy about the specific role on the most rostral region of the SC, and we reexamined its functional contribution by quantifying and comparing spatial and temporal trajectories of 30° saccades perturbed by electrical stimulation of the rostral pole and more caudal regions in the SC and of the OPN region. If the rostral pole serves to preserve fixation, then saccades perturbed by stimulation should closely resemble interrupted saccades produced by stimulation of the OPN region. If it also contributes to saccade generation, then the disrupted movements would better compare with redirected saccades observed after stimulation of the caudal SC. Our experiments revealed two significant findings: 1) the locus of stimulation was the primary factor determining the perturbation effect. If the directions of the target-directed saccade and stimulation-evoked saccade were aligned and if the stimulation was delivered within approximately the rostral 2 mm (<10° amplitude) of SC, the ongoing saccade stopped in midflight but then resumed after stimulation end to reach the original visually specified goal with close to normal accuracy. When stimulation was applied at more caudal sites, the ongoing saccade directly reached the target location without stopping at an intermediate position. If the directions differed considerably, both initial and resumed components were typically observed for all stimulation sites. 2) A quantitative analysis of the saccades perturbed from the fixation zone showed significant deviations from their control spatial trajectories. Thus they resembled redirected saccades induced by caudal SC stimulation and differed significantly from interrupted saccades produced by OPN stimulation. The amplitude of the initial saccade, latency of perturbation, and spatial redirection were greatest for the most caudal sites and decreased gradually for rostral sites. For stimulation sites within the rostral pole of SC, the measures formed a smooth continuation of the trends observed in the saccade zone. As these results argue for the saccade zone concept, we offer reinterpretations of the data used to support the fixation zone model. However, we also discuss scenarios that do not allow an outright rejection of the fixation zone hypothesis.
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INTRODUCTION |
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The superior colliculus (SC) has long been implicated as a
critical neural structure in controlling saccades -fast, conjugate eye
movements that realign the visual axis to objects in the periphery. Traditionally, the SC has been thought to participate strictly in the
generation of saccades (see Sparks and Hartwich-Young
1989 for a review) and, more generally, gaze shifts.
Microstimulation of SC during fixation evokes a fixed vector saccade
(FVS) in the head-restrained animal or an eye-head coordinated gaze
shift in the head-unrestrained animal, and the amplitude and direction of the stimulation-induced movement depend on both the site and parameters of stimulation (Freedman et al. 1996
;
Paré et al. 1994
; Robinson 1972
;
Schiller and Stryker 1972
; Stanford et al. 1996
). Suprathreshold stimulation in the head-fixed preparation elicits small saccades from rostral SC sites and larger eye movements from more caudal regions, whereas stimulation of medial and lateral areas of the SC generates saccades with upward and downward components, respectively. In agreement with the saccade motor map defined by the
simulation studies, the locus of neural activity in the deeper layers
of SC encodes the optimal saccade vector (McIlwain 1975
;
Schiller and Stryker 1972
; Sparks et al.
1976
; for head-free gaze, see Freedman and Sparks
1997
). On the basis of these studies, the topography in the
deeper layers is believed to consist only of a uniform saccade
zone (Fig. 1A)
(Robinson 1972
) that is in spatial register with the
retinotopic organization of the superficial layers (Cynader and
Berman 1972
).
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This long-held view recently has been questioned by studies that have
reported a subset of neurons that discharge vigorously during fixation
and show a pause in activity during most saccades (Munoz and
Guitton 1989, 1991
; Munoz and Wurtz 1993a
;
Peck 1989
). These cells, which have been called fixation
neurons, are located within the deepest portion of the intermediate
layers of an estimated 0.72 mm of the rostral SC (Munoz and
Wurtz 1995b
), a region that has been referred to as the
fixation zone or the rostral pole of the SC
(Guitton 1991
; Munoz and Istvan 1998
;
Munoz and Wurtz 1995b
; Munoz et al.
1993
). Neurons within the dorsal intermediate layers of the
rostral SC as well as all intermediate layer neurons in the remaining
caudal SC participate in saccade generation as in the traditionally
accepted saccade zone hypothesis. Figure 1B represents a
schematic of the deeper intermediate layers, in which the saccade zone
is defined as the region caudal to a discrete fixation zone (also see
Fig. 13 of Munoz and Wurtz 1995b
). Hence, the fixation
zone is composed of fixation neurons and the saccade zone constitutes
of burst and buildup neurons (Munoz and Wurtz 1995a
).
These electrophysiological and additional stimulation and lesion
studies in the rostral pole of the SC (Munoz and Wurtz 1993b
) have led to a developing notion that two functions and regions exist in the SC motor map: one encoding fixation and the other
saccade generation (Munoz and Guitton 1991
; Munoz
and Istvan 1998
; Munoz and Wurtz 1995a
,b
;
Munoz et al. 1991
, 1993
).
The fixation neurons are hypothesized to exert their saccade prevention
role by projecting to and exciting the omnipause neurons (OPNs) found
in the nucleus raphe interpositus on the midline within the paramedian
pontine reticular formation in the brain stem
(Büttner-Ennever et al. 1988). Like fixation
neurons, the OPNs stop firing during all saccades
(Cohen and Henn 1972
; Evinger et al.
1982
; Keller 1974
; Luschei and Fuchs
1972
) and also discharge tonically during fixation.
Functionally, the OPNs are thought to gate the saccade burst generator:
activity in OPNs results in fixation and absence of discharge leads to
a saccadic eye movement (Keller 1974
). On the basis of
similarities in activity and on known electrophysiological (King
et al. 1980
; Raybourn and Keller 1977
) and
anatomic connections (Langer and Kaneko 1984
, 1990
), an
excitatory projection from the fixation neurons of the SC to the OPNs
was hypothesized to control the saccade-related discharge characteristics in the latter neuronal group (Munoz and Guitton 1989
; Munoz and Wurtz 1993a
,b
; Munoz et
al. 1991
). Indeed, collicular projections to the OPN region
since have been shown to originate predominantly, but not exclusively,
from the rostral pole (Büttner-Ennever and Horn
1994
; Gandhi and Keller 1997
; Paré
and Guitton 1994
).
Although the fixation zone hypothesis has gained widespread acceptance,
a closer examination of the data provided in its support casts doubt on
at least its most rigid interpretation and therefore motivates a
reevaluation of this theory. Several observations noted in the papers
of Munoz and Wurtz (1993a,b
), who routinely are credited
for establishing the role of the primate rostral superior colliculus in
fixation, and in other reports also can be interpreted to support the
traditional uniform saccade zone concept or a theory of multiple
functionalities for the rostral pole of the SC (see
DISCUSSION). Most importantly, as mentioned earlier,
fixation neurons suppress activity during most saccades. But they also discharge a significant burst for small contraversive saccades (e.g., Figs. 10 and 11 of Munoz and Wurtz
1993a
; Fig. 1 of Krauzlis et al. 1997
; Fig. 3 of
Anderson et al. 1998
), strikingly similar to the burst
expected from a neuron in the saccade zone coding for an eye movement.
Then do these neurons in the proposed fixation zone encode saccades of
small vectors and form the continuation of the saccadic motor map? Or
do they function like the OPNs and act to preserve fixation?
Spatiotemporal trajectories of saccades perturbed by microstimulation
We addressed these questions by examining the effects of
stimulation of different SC sites on ongoing saccades. Previous studies have explored the interactions between visually guided and
SC-stimulation evoked saccades where the stimulation was applied to
either the posited fixation zone (Chaturvedi and Van Gisbergen
1999b; Munoz and Wurtz 1993b
) or the saccade
generation region (Chaturvedi and Van Gisbergen 1999a
;
Schlag-Rey et al. 1989
; Sparks and Mays 1983
). (For stimulation studies in the head-free cat, see
Pélisson et al. 1989
, 1995
.) However, effects on
saccades disrupted by stimulation of the fixation zone have not been
compared with the perturbations induced by stimulation of more caudal
regions of the SC. The general approach in these past studies has been
as follows: a persistent or briefly flashed visual target is presented in the periphery, and the monkey is required to make a saccade to the
target location. Before the large eye movement, a
target-activated response arises within an ensemble of
neurons in the caudal SC. At various intervals around the onset of the
saccade, different sites within the deeper intermediate layers of the
SC are stimulated, producing an interaction between the
stimulation-induced and target-activated population
responses, which then is reflected in the eye movement behavior.
Because of the hypothesized functional difference between the fixation
and saccade zones, stimulation of the SC in these two regions during
ongoing saccades makes different predictions on both the collicular
interactions and the resulting eye movement.
In the traditional saccade zone concept (Fig. 1A),
stimulation of the SC during a target-directed saccade should change,
at least momentarily, the metrics of the encoded movement. The new, desired goal may be, for example, a weighted vector average of the
saccades coded by the stimulation-induced and target-activated population responses (Chaturvedi and Van Gisbergen
1999a; Robinson 1972
; Van Opstal and Van
Gisbergen 1989
). Alternatively, it also could be equivalent to
the saccade retinotopically coded by the stimulation site but updated
by a lagged change in eye position from the beginning of the targeted
movement; the combined effect of the target-directed saccade and the
stimulation-evoked movement has been termed the colliding
saccade (Schlag and Schlag-Rey 1990
; Schlag-Rey
et al. 1989
). Or a combination of these and other hypotheses may be implemented. Whatever the exact mechanism, the ongoing saccade
curves and deviates in direction from its normal trajectory, and we
shall refer to this movement as a redirected saccade. The eye movement then stops, usually well short of the desired goal. Often
another saccade then is generated to bring the eyes near the original
target location.
To assign general terminology, we shall refer to the combination of the ongoing movement and the component perturbed by the stimulation as the initial saccade, the ensuing period when eyes have stopped in the orbits as the interruption duration, and the subsequent movement as the resumed saccade. If a resumed saccade is not observed, the eye movement is considered a truncated saccade.
According to the fixation zone hypothesis (Fig. 1B),
microstimulation in the fixation zone triggered on saccade onset also produces a perturbed eye movement with initial and resumed components, but the initial saccade does not exhibit spatial deviation and therefore is not a redirected saccade. Instead the disruption would be
similar to the interrupted saccade produced by stimulation of the OPNs
(Becker et al. 1981; Keller 1977
;
Keller et al. 1996
; King and Fuchs 1977
).
Artificial activation of fixation neurons is hypothesized to directly
activate the OPNs (Munoz and Wurtz 1993b
), which in turn
briefly stops the saccade in place without any directional deviation
from the original trajectory. After a variable duration, a resumed
movement is generated to bring the eyes near the original location of
the target. The reactivation of OPNs presumably does not change,
instead only momentarily suppresses, the encoded metrics of the desired
saccade because the target-activated population response in the SC is
reduced significantly when stimulation is delivered to either the OPNs
(Keller and Edelman 1994
) or the fixation zone
(Munoz et al. 1996
).
Previous studies that stimulated the fixation zone during large
saccades (Munoz and Wurtz 1993b; Munoz et al.
1996
), however, did not analyze the spatial trajectories of the
perturbed saccades to rule out nonfixation-zone mechanisms.
Consequently, it is unknown whether the stimulation of the rostral pole
produces redirected or interrupted saccades. In fact, no past reports,
to our knowledge, have analyzed systematically the effects of SC
stimulation site on the metrics of perturbed movements, much less
differentiate between redirected and interrupted saccades. Nor has any
study compared the results with those produced by stimulation in the OPN region in the same animal. In addition to the redirection of
saccades, we also measured the endpoint accuracy of the movements, the
amplitude of the initial component, the latency at which the stimulation effect is observed and the interruption duration. Although
not all the metrics address the fixation- and saccade-zone issue, they
do provide a quantitative and comparative description of the effects of
stimulation site on ongoing saccades.
Uniformly sampled collicular sites along the rostralcaudal dimension of its deeper intermediate layers were stimulated during large ongoing saccades, using parameters subthreshold to those that produce a FVS. Similarly, the OPN region also was stimulated to produce interrupted saccades. The spatial trajectories and metrics of all perturbed saccades were quantified and, for the SC stimulation saccades, analyzed as a function of the stimulation site. The perturbations induced by stimulation of the fixation zone also were compared with the interruptions produced by stimulation of the OPN region. We found that stimulation of the rostral pole of SC produced significant deviation in the spatial trajectories of the ongoing eye movement, a result that resembled the redirected saccades induced from the caudal SC. These results suggest that the mechanisms by which stimulation of the fixation zone perturbs saccades are, at least partially, different from the pathways by which the OPNs interrupt saccades.
The data presented here have appeared previously in preliminary form
(Gandhi and Keller 1995, 1998
; Keller and Gandhi
1998
).
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METHODS |
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Three juvenile, male, Macaca mulatta monkeys were used for this study. The experiments involved recording eye movements and stimulating sites in the deeper intermediate layers of superior colliculi and the omnipause region to perturb ongoing saccades. All experimental protocols were approved by the Institute Animal Care and Use Committee at the California Pacific Medical Center and complied with the guidelines of the Public Health Service policy on Humane Care and Use of Laboratory Animals.
Surgical preparation
Surgery was performed under aseptic conditions. Heart rate,
respiratory rate, body temperature, blood pressure, and oxygenation were monitored for the duration of the surgery. Four devices were implanted under isofluorane gas anesthesia in each monkey.
1) A stainless steel chamber was placed stereotactically on
the skull, slanted posteriorly at an angle of 38° in the sagittal
plane and aligned normal to both colliculi. 2) Another
stainless steel chamber was mounted stereotactically on the skull,
slanted laterally in the frontal plane at an angle of 25° and aligned
on the OPN region. 3) A head restraint consisting of two
light, stainless steel tubes was positioned transversely. The chamber
and the head bars were fixed to the skull with dental acrylic and small
titanium bone screws. And 4) a coil of Teflon-coated
stainless steel wire was set under the conjunctiva of one eye using the
method developed by Fuchs and Robinson (1966) and
modified by Judge et al. (1980)
. After surgery, the
monkeys were returned to their cage and were allowed to fully recover
from surgery. Antibiotics (Ancef) and analgesics (Buprenex) were
administered under the direction of a veterinarian during the
postoperative period.
Training
Each monkey was trained to climb out of his cage into a primate chair and sit in it during the experiment. Training and subsequent experimental sessions were conducted four to five times a week. The monkey was given water or juice rewards for correctly executing behavioral paradigms and was allowed to work until satiation. Daily records were kept of the animal's weight and health status. Supplemental water was given as necessary, and unlimited access to it was provided on days when training or experimental sessions were not performed.
Experimental setup
Behavioral paradigms, visual displays, and data storage were
under the control of a real-time program running on a laboratory PC
system. The targets were presented via a computer controlled, analogue
oscilloscope, which back-projected light spots on the 90 × 90°
translucent screen placed 40 cm in front of the monkey (Crandall
and Keller 1985). The targets were 15-min arc in diameter and 2 cd/m2 in intensity against a diffusely
illuminated dim homogeneous background illumination (0.05 cd/m2).
The eye movement signals were obtained by placing the head-restrained
animal with an implanted scleral coil in a pair of orthogonally aligned
20-kHz magnetic fields maintained electronically in temporal quadrature. The voltage induced in the coil was passed through a phase
detector, which separated the eye position signal into horizontal and
vertical components with a sensitivity of 0.25°, zero drift and a
bandwidth of 1 kHz (Robinson 1963). Horizontal and
vertical eye velocity were obtained by analogue differentiation (with a
cutoff frequency of 170 Hz) of the position signals yielding a root
mean square velocity noise of ~1°/s. Horizontal and
vertical eye position and velocity measurements were sampled by a
12-bit data acquisition card (Data Translation, DT-2831) at 1 kHz and stored on computer disk. Radial eye position and velocity were computed
off-line by the Pythagorean theorem.
Behavioral paradigms
SC STIMULATION.
Before each experiment, the SC chamber was opened and thoroughly
cleaned under aseptic conditions. A double eccentric micropositioning device with a single, drilled hole, which allowed access for a microelectrode track at virtually any location within its 12-mm diam,
was positioned in the chamber. A sharpened guide tube was placed in the
hole and gently pushed through the dura. By means of a hydraulic drive
system, a tungsten microelectrode (Frederick Haer; 0.5-1.5 M
impedance, tested at 1 kHz) was lowered through the guide tube into the
superficial layers of the SC (identified by neural "swishes" on the
audio amplifier as the monkey scanned the visual field). The
microelectrode then was lowered an additional 2.0-2.5 mm to place its
tip in the deeper intermediate layers of the SC. Neural activity was
monitored during saccades tasks to confirm that the electrode tip was
placed among fixation and buildup neurons (Munoz and Wurtz
1995a
). For the remainder of the experiment, this site was
stimulated to evoke as well as perturb saccades. Note that because the
microelectrode penetrations were normal to the SC motor-map, only one
site was typically stimulated on any given penetration.
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OPN STIMULATION.
The OPN chamber was cleaned under aseptic conditions and prepared for
electrophysiological experiments using the same methods described for
the SC chamber. A tungsten microelectrode was lowered through the guide
tube via a hydraulic drive system until the center of the OPN region
was encountered, a location determined by the unique discharge
characteristics of these neurons during saccades (Cohen and Henn
1972; Keller 1974
; Luschei and Fuchs 1972
). In addition, the interrupted saccade paradigm was used to validate the electrode's location. This site then was stimulated for the remainder of the experiment (see following text). At least once
in each monkey, the microelectrode was implanted, as described by
Keller and Edelman (1994)
, and used to stimulate the OPN
region for an extended period of time.
Data analysis
All off-line analyses were performed in Matlab (The Mathworks).
The velocity signals, collected from the analog differentiator, were
filtered digitally with a five-pole Butterworth filter in the forward
and reverse direction to produce zero phase distortion. This signal
then was differentiated, and a threshold criterion on the resulting
acceleration signal was used to detect saccade onset. As this method
sometimes erroneously marked the end of saccades particularly for large
eye movements, which were often slow when made to remembered target
locations (White et al. 1994), a velocity threshold
criterion (typically 90°/s) was used to mark the endpoint of all
saccades. In addition, all saccade onset and offset marks were checked
by an operator and manually changed if necessary.
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RESULTS |
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Forty-six sites in five colliculi of three monkeys
(monkey BA: n = 22;
monkey BZ: n = 19;
monkey HM: n = 5) were stimulated at the onset of large saccades. The stimulation parameters applied during ongoing saccades were subthreshold to those used to produce the
FVS or the site-specific maximal amplitude (Robinson
1972; Stanford et al. 1996
). The saccadic target
eccentricity was 30°, and the direction was either the preferred
direction or any of other three directions at integer multiples of
90° away from it (Fig. 3).
The results will be presented in the following order: first, we focus
on the type of saccadic perturbation induced by stimulation of SC sites
along the rostralcaudal axis when the directions of the target-directed
saccade and FVS are similar. These eye movements initially will be
examined in the temporal domain (radial amplitude vs. time). This
approach will demonstrate that the apparent interrupted saccade effect observed by stimulation of the fixation zone
(Munoz and Wurtz 1993b) can in fact be induced from a
larger region of the SC (Gandhi and Keller 1995
).
Second, we extend the qualitative assessment of the perturbations
observed for saccades in several different directions and consider the
effects of stimulation when illustrated as both spatial trajectories
(horizontal component vs. vertical component) and temporal plots
(radial amplitude as a function of time). These data will demonstrate
that stimulation trials must be examined in both coordinate systems to
accurately differentiate whether the perturbations are interrupted or
redirected saccades. Third, we quantify several metrics of the
perturbed saccades and report trends in the data as a function of
stimulation site within the SC. Fourth, we compare the metrics of
saccades perturbed from the fixation zone of the SC and the eye
movements interrupted from the OPN region. Fifth, and finally, we
briefly discuss the effects of stimulation parameters on the disrupted saccadic movements.
Site-specific perturbations (preferred direction)
SC sites uniformly sampled across the rostralcaudal dimension of
the SC were stimulated at the onset of large, visually triggered saccades the directions of which were similar to the FVS evoked from
each site. Figure 4 plots temporal
representations of radial amplitude and velocity of ongoing saccades in
the preferred direction for three sites chosen to span the
rostralcaudal extent of the SC. For the two rostral sites (Fig. 4,
A and B), one inside the fixation zone (FVS:
0.74@44°; amplitude@direction, the notation used henceforth) and
the other outside (FVS: 9.23@21°), stimulation at each site stopped
the saccade in midflight (). The eye movements resumed shortly after
stimulation offset and landed near the target location. In contrast,
stimulation of a more caudal site (FVS: 19.34@336°) did not stop the
ongoing saccades but, instead, slightly increased their peak velocity
(Fig. 4C) compared with the averaged control saccade
(- - -). These data suggest, albeit incorrectly, that the
hypothesized functional properties of the fixation zone extended beyond
the rostral pole in our experiments.
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Thus in examining the effects of stimulation on saccades in the
preferred direction, a dichotomous observation that depends on the
stimulation site was revealed. For each SC site, the stimulation either
stopped the saccade momentarily (Fig. 4, A and B)
or did not stop it at all (Fig. 4C). Figure
5 plots the location of the stimulation
sites (based on the FVS) on a schematic of the saccade motor map
(Ottes et al. 1986) and indicates whether stimulation at
onset of 30° saccades resulted in either two saccades (open symbols)
or a single eye movement (filled symbols). The spatial distribution
indicates that stimulation of any SC site within the rostral ~2 mm
(up to the 10° amplitude meridian) stopped the initial saccade short
of the desired target, and a resumed component was executed to bring
the eyes near the target location. Stimulation of sites caudal to this
landmark did not stop the initial saccade, and it reached the desired
goal with a single movement.
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The effects of stimulation site also was considered during small saccades (<10°) in a pilot study (data not shown). The stimulation, triggered on saccade onset, had no noticeable effect on the saccade trajectory because the desired eye movement ended near the flashed target location. Apparently the initial saccade had completed before the effects of stimulation could be observed. Thus we did not further explore effects of stimulation site during small saccades.
Spatial trajectories versus temporal representations
Temporal representation of perturbed saccades in the preferred
direction (Fig. 4) strikingly resembles saccades interrupted by OPN
stimulation (see Fig. 1) (Keller et al. 1996). However, an examination of perturbed saccades in preferred and nonpreferred directions and as both spatial trajectories (horizontal
component vs. vertical component) and temporal plots (radial
amplitude as a function of time) demonstrates the danger of incorrectly
classifying redirected saccades as interrupted saccades (Figs.
6-8). Data are presented for three SC
sites that spanned the rostralcaudal extent of the SC and exhibited the
battery of phenomena observed for all sites. In each figure,
A-D illustrate temporal representations of individual
stimulation trials (solid lines) and the average of control saccades
(dashed line) to targets presented in the four directions. The
equivalent spatial trajectories are shown in subplot E,
while two traces of the FVS evoked by stimulation during fixation is
presented in F.
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Stimulation of a relatively caudal site (FVS: 13.21@345°) during
saccades toward the preferred direction did not stop the eye movements
in midflight and minimally altered their trajectories (quadrant IV,
Fig. 6E), and the direction deviation is not obvious in the
temporal representation (Fig. 6A). The spatial redirections are, however, emphasized during saccades in the other three directions. The temporal plot in Fig. 6B, for example, was very similar
to a temporal representation of saccades interrupted by OPN stimulation (Fig. 1 of Keller et al. 1996) and fixation zone
stimulation (Fig. 5 of Munoz and Wurtz 1993b
). However,
the spatial trajectories of these saccades (quadrant I, Fig.
6E) were clearly redirected, i.e., the instantaneous
directions of stimulated saccades were altered dramatically relative to
control trials. Distinct deviations were not obviously detected in the
temporal plots because the amplitude of the saccades increased, albeit
more slowly, during the significant change in direction (see the ovals
encircling the approximately corresponding regions in the 2 representations). The same observation also held for the other
directions (Fig. 6, C and D). Note though that
stimulation sometimes reversed the direction of the ongoing saccade,
and this property was manifest as a decrease in the radial amplitude
(see corresponding trial referred to by the arrow in Fig. 6,
D and E). However, when the reversal was minor,
only a subtle decrease in amplitude was evident.
Saccades perturbed from a more rostral site (FVS: 5.32@342°), but still outside the fixation zone, are illustrated in both spatial and temporal representations in Fig. 7. Stimulation of this site at the onset of saccades in the preferred direction (Fig. 7A) stopped the movements in midflight with minimal deviation in its spatial trajectory (quadrant IV, Fig. 7E). Shortly after the end of stimulation, resumed saccades occurred and brought the eyes near the location of the flashed target. In contrast, saccades in other directions were curved significantly, although the temporal representation often failed to illustrate this point (Fig. 7D, for example).
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On the basis of the terminology presented in INTRODUCTION
and observation of saccades in the preferred direction only, one could
incorrectly conclude that stimulation of a site in the
saccade zone can interrupt large saccades. An examination of both
spatial and temporal representations for saccades in other directions also must be incorporated to establish that the stimulation redirected the eye movements. If the redirected saccades produced outside of the
fixation zone appear as interrupted saccades produced by OPN
stimulation, it is possible that the interrupted saccades reported to
occur after stimulation of the fixation zone (Munoz and Wurtz
1993b) are in fact redirected saccades. Therefore it is crucial
to consider whether saccades perturbed from the fixation zone also show
a redirection in their spatial trajectories.
Figure 8 plots the spatial and temporal
configurations of perturbed saccades from stimulation of a site with
FVS (0.78@18°; see F) <2°. On the basis
of the iso-amplitude marker that separates fixation and saccade zones
(Munoz and Wurtz 1995b), the site illustrated in Fig. 8
was in the fixation zone. Stimulation during saccades in the preferred
direction (Fig. 8A) temporarily stopped the eye movements in midflight and minimally altered the direction of their
spatial trajectories. For most saccades in other directions, the
redirection of the trajectories were too small to be noticeable in the
temporal representation (e.g., Fig. 8D) but still
present in the spatial profiles (see Fig. 8E,
). For
some directions, however, the spatial deviation was not noticeable even
in the spatial trajectories (upward saccades, Fig. 8E).
Nevertheless, a quantitative analysis (to be presented in the next
section) over all directions did indicate that the perturbations better resembled redirected saccades, not interrupted saccades.
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Saccade metrics
We now provide a quantitative analysis of how the characteristics of perturbed saccades varied with stimulation site. A schematic of a saccade in both temporal and spatial representations along with the metrics quantified for our analyses is illustrated in Fig. 9. A description of each measure and how it was computed will be provided with the results.
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Of the 46 tracks tested in three monkeys, sufficient data for quantitative analyses was collected for 32 sites from two (BA and BZ) monkeys. (The five tracks in monkey HM were used only to collect pilot data and, therefore, were not used for further study.) Stimulation was delivered during saccades in all four directions (see Fig. 3) in 19 of these tracks. For two sites, saccades were perturbed in all but the sameSC90 direction. Similarly, all but the preferred direction condition was fulfilled for one site. A total of six tracks contained data for only two directions (preferred and opposite: n = 3; sameSC90 and opposite: n = 1; sameSC90 and oppSC90: n = 1; preferred and sameSC90: n = 1). For the remaining four tracks, only the preferred direction was examined. In sum, the distribution of the number of sites stimulated for each of the four direction conditions are as follows: preferred, n = 29; sameSC90, n = 23; opposite, n = 26; oppSC90, n = 23.
Figures 10-14 summarize the metrics of
saccades perturbed by stimulation of SC sites. All figures contain four
subplots, each representing a different target direction relative to
the direction of the FVSrecall from Fig. 3 that target directions
were at integer multiples of 90° with respect to the direction of the
FVS. If stimulation at onset of a large saccade in the preferred
direction stopped the initial saccade well short of the desired
goal, the stimulation site was marked with an open symbol (
for
monkey BA and
for monkey
BZ). If the stimulation did not stop the ongoing saccade,
the stimulation site was indicated by
and
for the two monkeys.
This symbol convention also was used for the distribution plotted in
Fig. 5. It is worthwhile to reemphasize that stimulation of caudal
sites at onset of saccades in nonpreferred directions did not produce
single saccades but usually evoked a redirected saccade followed by an
interruption period, when the eyes were fixed, and then a resumed
movement which ended near the target location (Fig. 6). Nevertheless,
these caudal sites will be represented by
and
for all
directions in Figs. 10-14. Linear regression fits were applied to the
data plotted in Figs. 11
14, and only the statistically significant
trends (slope significantly >0; P < 0.05, 1-tailed t-test) are superimposed on the plots. Statistical measures
(Student's t-test) were performed on the mean final error
(Table 1) and on the slope measure of all
other metrics (Table 2).
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|
|
FINAL ERROR (E1).
An error measure (E1) was defined as the difference between the final
amplitude of perturbed and control saccades. Using the convention of
Keller et al. (1996), negative values of E1 indicated that the stimulated saccade fell short of the average amplitude of
control saccades (hypometria); consequently, positive values of E1
implied that the stimulated saccade overshot the control behavior
(hypermetria). Figure 10 shows the distribution of E1 as a function of
SC stimulation site. The subplots show that perturbed saccades tended
to be hypermetric compared with control saccades. The mean overshoot,
however, was <1° for all direction conditions and was significantly
different from zero only for directions orthogonal to the FVS direction
(Table 1).
INITIAL SACCADE AMPLITUDE (R1). The amplitude of the initial saccade (R1) was determined as the maximum radial displacement from the initial position achieved before the onset of a resumed component. In the case of stimulation of caudal sites during saccades in the preferred direction (sites marked by filled symbols in Fig. 5), the amplitude of the single eye movement was used for the initial amplitude. To minimize variability in saccadic accuracy, all initial amplitude measures were normalized by the average control saccade magnitude to the same target location. Figure 11 displays the normalized amplitude of the initial saccade as a function of stimulation site. Table 2 shows that the amplitude of the initial saccade increased as a function of stimulation site for all but the opposite direction conditions.
|
LATENCY OF PERTURBATION (L1).
The time from stimulation onset to the point when the effect of
stimulation was observed in the saccade trajectory was defined as the
latency of perturbation (L1). Not all previous studies that have
reported this measure explicitly mentioned how it was computed. For
example, Munoz and Wurtz (1993b) stimulated the rostral
SC at onset of large saccades and measured the latency from
"stimulation onset to saccade alteration" (p. 581) without providing the computation details. Similarly, Miyashita and
Hikosaka (1996)
stimulated the SC during saccades and
determined the equivalent latency measure by inspecting the velocity
trace "by eye" (p. 189). Keller et al. (1996)
, on
the other hand, computed L1 of saccades interrupted by OPN stimulation
using two objective methods. They measured the metric as the time from
stimulation onset to 1) the time of eye velocity peak in the
initial component and 2) the epoch when the initial
saccade's velocity trace separated >2 SE from the mean velocity plot
of the nonstimulated saccades for the same target amplitude and
direction and the same stimulation site. We compared the two sets of
values for L1 obtained with each method and found that the values were
similar. The same observation was reported by Keller et al.
(1996)
for saccades perturbed by stimulation in the OPNs. Only
results from the latter technique will be presented here, unless noted otherwise.
|
DIRECTION DEVIATION.
The method of computing the amount of redirection produced by
stimulation of SC sites is detailed in Fig. 9B. For each
target condition, the averaged control saccade direction
(c) was measured. For stimulation trials, the
direction of the eyes just before the onset of the resumed saccade was
determined (
p). Next, the absolute magnitude
of the difference between the two directions (
p
c) was
computed. This value was marked positive if the redirection occurred in
the direction of the FVS (as illustrated in Fig. 9B) and
considered negative if the redirection was in the opposite direction.
This final measure was labeled direction deviation (DD). For trials
without a resumed saccade, the eye position when the ongoing eye
movement stopped was used to compute
p.
|
INTERRUPTION DURATION.
The interruption duration (ID) was computed as the time from the peak
velocity of the initial component to the onset of the resumed
component. The time of peak velocity was chosen instead of the end of
the initial saccade because the initial component often did not come to
a complete stop (velocity does not reach 0) before the second component
resumed (Keller et al. 1996), particularly for smaller
stimulation parameters in the OPN region. Because a resumed component
must be present to compute ID, the analysis excluded tracks and
direction conditions for which the database included only truncated or
single saccades. Figure 14 plots the distribution of ID as a function of stimulation site for the four direction conditions. A weak positive trend was present only in the
preferred direction (Table 2).
|
Comparison with saccades interrupted by OPN stimulation
The results presented thus farthat, for most directions, the
metrics computed from stimulation of the rostral pole formed a
continuum with the corresponding measure obtained from stimulation of
the caudal SC
suggest that the perturbations induced by stimulation of
the posited fixation zone resemble the redirected saccades commonly
attributed to occur after stimulation of the saccade zone of SC during
ongoing saccades. We further tested this point by comparing significant
differences between perturbations produced by stimulation of the
rostral pole of the SC and saccades interrupted by stimulation of the
OPN region.
Eight (monkey BA: n = 5;
monkey BZ: n = 3) of the 32 total
sites stimulated in the SC of the two monkeys evoked FVS <2° and, therefore, were considered as loci located within the hypothesized fixation zone. Omnipause neuron region stimulation data were collected from 13 experiments, 4 from monkey BA and 9 from
monkey BZ. Because OPN stimulation induced
interruptions do not depend on saccade direction (Keller et al.
1996), data from all directions were pooled together for each
stimulation site. In accordance with the fixation zone hypothesis, all
four direction saccades perturbed by stimulation of each rostral pole
site were combined as well. The metrics illustrated in Fig. 9 then were
computed for each saccade and averaged to yield a mean value of each
measure per stimulation site. Each mean value then was averaged over
all stimulation sites within the rostral pole of SC or the OPN region,
and the results are summarized in Table
3.
|
The final amplitude of saccades disrupted by stimulation of both rostral pole of SC and OPN region tends to slightly overshoot the control behavior, although the final error (E1) was significantly different from zero for rostral pole stimulation only (P = 0.0189; 2-tailed t-test); for OPN region stimulation, P = 0.1469. However, the mean final error produced by stimulation of the rostral pole of SC and OPN region were not significantly different (P = 0.1413; 2-tailed t-test). Regardless, the hypermetria was small, suggesting that the local feedback system compensated for the perturbations. The mean normalized amplitude (R1) for the rostral pole stimulation, although slightly greater, was not significantly different from the mean value yielded for the OPN region stimulation (P = 0.2032; 2-tailed t-test). On the other hand, the ID was significantly longer for SC stimulation compared with OPN region stimulation (P < 0.0001; 1-tailed t-test). Similarly, the latency of perturbation (L1) for fixation zone stimulation trials was consistently longer by ~3 ms relative to OPN stimulation induced interrupted saccades (P = 0.0400; 2-tailed t-test).
For the eight fixation zone stimulation sites, the latency of perturbation values, determined using the 2 SE and the peak velocity methods, were 20.26 ± 4.84 ms and 19.08 ± 2.39 ms, respectively, and these means were not significantly different (P = 0.5481, 2-tailed t-test). For the 13 OPN stimulation tracks, the L1 measures were 16.69 ± 1.97 ms and 16.46 ± 2.21 ms for the SE and peak velocity approaches, respectively, and these means were also not significantly different (P = 0.8038, 2-tailed t-test). Thus for saccades perturbed by stimulation of the rostral pole of SC and the OPN region, these two methods to determine the latency of perturbation, when the stimulation is triggered on saccade onset, produced equivalent results.
For all stimulation data, the direction deviation (DD) was determined as the difference between the direction just before resumed saccade onset and the direction of the average control saccade to the same target location. For the rostral pole stimulation condition only, this measure was made positive if the deflection occurred toward the FVS direction and negative otherwise. The mean DD averaged over all rostral SC sites was significantly greater than zero (P = 0.0318; 1-tailed t-test). For OPN stimulation condition, the mean DD was not significantly different from zero (P = 0.5754; 2-tailed t-test). Furthermore the mean DD produced by rostral SC stimulation was significantly different from mean DD computed for OPN region stimulation (P = 0.0391; 2-tailed t-test; Table 3).
Because the DD parameters for rostral SC and OPN region stimulation
were not computed in the same way, the statistical comparison documented in Table 3 may be inappropriate. Therefore the DD metric for
the OPN stimulation condition, as computed in the preceding text, was
modified further as done for the SC stimulation analyses. We
arbitrarily selected a reference direction and the magnitude of the
difference between the direction just prior to resumed saccade onset
and the direction of average control saccade was made positive (or
negative) when the spatial redirection was toward (or away) from the
reference direction. With this implementation, the mean ± SD for
OPN stimulation condition was 0.51 ± 2.99°, which was not
significantly different from zero (P = 0.5532, 2-tailed t-test). However, the mean DD produced by rostral SC
stimulation was still significantly different from the mean DD computed
for OPN region stimulation (P = 0.0371; 2-tailed
t-test).
Note, however, that saccades interrupted by stimulation of the OPN region also were redirected, as indicated by a SD of ~3° (Table 3). This value is comparable with the variability observed for saccades perturbed by stimulation of the rostral pole of SC. The similarity might provide insights into the intrinsic variability present in the saccadic system. Nevertheless it is important to reemphasize that the mean direction deviation induced by stimulation of the rostral SC and the OPN region was significantly different.
Effects of stimulation parameters
The crucial factors determining the metrics and type of saccadic perturbation were the site of stimulation and the direction of the initial saccade relative to the direction of the FVS. A minor, secondary effect was produced by the choice of stimulation parameters. To minimize damage produced by repeated stimulation, we did not systematically vary the stimulation parameters to study their effects on saccadic trajectories. However, various stimulation current (10-30 µA) and duration (10-50 ms) parameters (frequency was kept constant at 400 pps) typically were used for most SC sites, allowing a qualitative treatment.
For stimulation of SC sites within the rostral 2 mm during saccades in
all directions, an increase in the stimulation parameters increased the
interruption duration. Further increase in stimulation parameters,
typically outside the range used in our experiments, raised the
proportion of truncated saccades. For sites caudal to the 2-mm region,
stimulation at onset of large saccades in the preferred direction did
not stop or alter the ongoing saccade. Instead, a minor increase in
peak velocity was observed. Stimulation of such caudal sites often
increased the peak velocity of the ongoing saccade, but this measure
was only weakly related to the stimulation parameters (see Munoz
et al. 1991; Stanford et al. 1996
). Unlike for
saccades in the preferred direction, saccades in the nonpreferred
directions did not show an increase in the peak velocity. For lower
stimulation parameters, the saccades usually paused in midflight and
slightly altered their spatial trajectories. An increase in the
stimulation parameters emphasized these effects.
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DISCUSSION |
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The experiments and analyses reported in this manuscript quantified the perturbations produced in ongoing saccades by electrical stimulation in the SC. Our approach was to stimulate sites along the rostralcaudal axis of the SC at onset of large saccades in several directions and to measure changes in the metrics of the saccadic perturbations as a function of stimulation site. The metrics computed from stimulation of the posited fixation zone formed a continuum with the trend observed for stimulation of more caudal sites (Table 2). For comparison, saccades also were interrupted by stimulation of the OPN region, and most of their metrics were found to differ significantly from the measurements of saccades perturbed by stimulation of the fixation zone (Table 3).
Rostral SC function: fixation, saccade generation, or both?
Munoz and Wurtz (1993a,b
) hypothesized that
fixation neurons in the rostral pole of the SC function to prevent
saccade generation by exciting the OPNs. They stimulated the region of
fixation neurons during saccades and interpreted the perturbations to
occur via the same mechanisms that interrupt saccades on stimulation of the OPNs. This claim was based on temporal domain (radial amplitude and
velocity as a function of time) analyses of rightward and leftward
saccades. In our study, we reanalyzed saccades perturbed by stimulation
of the fixation zone by examining their spatial trajectories (Figs.
6-8 and 13). Our results indicate that these perturbations more
closely resembled redirected saccades, particularly when the
target-directed saccades were orthogonal to the FVS, and that their
mean direction deviation was significantly different from the average
redirection observed for saccades interrupted by stimulation of the OPN
region. Thus our results provide evidence contrary to the fixation zone
hypothesis; however, they do not unequivocally refute it.
Munoz and Wurtz (1993a) reported finding visuomotor
burst neurons just dorsal to the fixation neurons they recorded in the rostral pole of the SC. As these cells exhibit a movement field (i.e.,
they discharge a burst during small saccades), it is possible that the
current from stimulation of the more ventral intermediate layers of SC
had spread to this dorsal region and/or the saccade zone, both in our
study and in the experiments of Munoz and Wurtz (1993b)
.
In other words, activation of neurons that discharge a burst during
small eye movements could have produced the redirected saccades. If so,
fixation neurons are equally likely candidates to contribute to
redirecting the spatial trajectories because most of these cells also
discharge a burst for small contraversive saccades (Fig. 10 and 11 of
Munoz and Wurtz 1993a
; Fig. 1 of Krauzlis et al.
1997
; Fig. 3 of Anderson et al. 1998
). How is it
possible, then, that fixation neurons are "critical for maintaining
active visual fixation and suppressing the generation of saccades"
(Munoz and Wurtz 1993a
, p. 567) when "for most
contraversive saccades, most [fixation] cells showed an increase in
discharge" (Munoz and Wurtz 1993a
, p. 565)? The
fixation zone hypothesis and the saccade-related discharge
characteristics of fixation neurons clearly suggest that these cells
have at least two seemingly contradictory functions
saccade generation
and saccade prevention. Although Munoz and Wurtz
(1993a
,b
) never explicitly stated that fixation neurons are not
involved in the generation of small saccades, they offered no
explanation to resolve the paradox.
Further studies are required to investigate how the saccadic system
parses the two opposing signals from the same neuron, and we contribute
to this research effort by suggesting a conceptual model. A simple
scheme that would preserve saccade initiation and termination is mutual
inhibition between the OPNs and the excitatory burst neurons (EBNs) in
the paramedian pontine reticular formation (PPRF). Well before saccade
onset, the ensemble SC response is a low-frequency discharge from the
fixation and buildup neurons that are concentrated within the rostral
SC (see population response figures in Anderson et al.
1998; Munoz and Wurtz 1995b
). The activation of
OPNs prevails because the net excitation of the EBNs is below threshold. Closer to saccade onset, intracollicular and/or
extracollicular processing causes a subset of SC neurons to discharge a
high-frequency burst, and this excitatory input surpasses the threshold
of EBNs causing them to burst rigorously and inhibit the OPNs
(indirectly) (see Moschovakis and Highstein
1994
).
For large saccades, the locus of the high-frequency burst in SC occurs
in a caudal region of the contralateral SC. Inhibitory interactions
within distant regions of the same SC (Meredith and Ramoa
1998; Munoz and Istvan 1998
) reduce activity in
rostral SC neurons, which suppress the facilitatory input to the OPNs and thus aid in shifting the balance of activity from the OPNs to EBNs
(see Gandhi and Keller 1997
). For small contraversive saccades, however, the rostral SC neurons do not exhibit a pause but,
instead, many discharge a high-frequency burst, suggesting that they
project to both the OPNs and EBNs (see Scudder et al. 1996
). Again, the small eye movement is triggered when the net excitation of EBNs reaches threshold, but the total excitatory input
required to overcome the increased excitatory input to the OPNs may
also be greater. A superposition of the population buildup neuron
response for 2.5 and 25° saccades (Fig. 15 of Anderson et al.
1998
) qualitatively supports this hypothesis.
To place validity on the fixation zone theory, as defined by Munoz and
colleagues, the functional importance of rostral SC projections to the
OPNs must be demonstrated, at least for large saccades during which the
SC neurons exhibit a pause in activity. In particular, the fixation
neurons are expected to modulate the discharge properties of OPNs.
However, a quantitative analysis, based on extracellular recordings,
has revealed that OPN activity does not consistently follow the
temporal evolution of fixation neuron discharge (Everling et al.
1998b). Also for large saccades perturbed by stimulation of the
rostral pole of SC, the resumption of OPN activity does not occur at
monosynaptic latency but, furthermore, is delayed even
more than during control trials (Gandhi and Keller 1999
). These studies
suggest that collicular projections to the OPNs provide at most a minor
functional contribution to fixation (also see Kaneko
1996
).
Therefore the primary function of SC neurons, including
the so-called fixation neurons located deeper within the intermediate layers in the rostral pole of the SC, may conform to the hypothesis of
a saccade zone across the motor map even though the distribution of
connections to OPNs and EBNs may vary systematically across the map
from caudal to rostral SC. Then how does this theory explain the
evidence used to support the fixation zone theory? In the text that
follows, we reinterpret the data originally used to support the
fixation zone hypothesis (Munoz and Wurtz 1993a,b
) in
terms of the saccade zone hypothesis.
NEURAL ACTIVITY.
As argued in the preceding text, neurons in the deeper intermediate
layers of the rostral SC discharge a burst of action potentials for
most contraversive saccades. Although Munoz and Wurtz
(1993a) emphasized the tonic prelude response and linked it to
fixation, the lack of pause during these saccades make them equally
qualified to contribute to saccade generation.
REVERSIBLE CHEMICAL INJECTIONS.
Munoz and Wurtz (1993b) showed that inactivation
(activation) of the rostral SC by small injections of muscimol
(bicuculline) reduced (increased) the latency of large saccades. This
observation was used to support the idea of a fixation zone because a
decrease (increase) in the fixation function expedited (delayed) the
motor preparation and initiation of saccades. In other words, the
weights of a mutually inhibitory circuit between the rostral SC (which is active because a fixation target is present before saccade onset)
and the caudal SC (which is active because a saccade target is
presented in the periphery) were altered by the injections. Inactivating (activating) the rostral SC, for example, decreases (increases) the processing time required to produce a high-frequency burst in the caudal SC.
STIMULATION OF THE ROSTRAL SC.
The rostral SC has been stimulated during fixation, just before saccade
onset, and during large, ongoing eye movements (Munoz and Wurtz
1993b; present study), and all the results can be interpreted in terms of the uniform saccade zone hypothesis. The data from stimulation during saccades already have been discussed in
terms of redirection of the spatial trajectories.
Mechanisms of saccadic perturbations
In our experiments, we observed that whenever the target-directed
saccade and stimulation-evoked saccade were separated by 90°, the
ongoing saccade was noticeably redirected from its spatial trajectory
and then stopped in midflight. Frequently a resumed saccade was
generated to bring the eyes near the (flashed) target location. If the
directions of the initial large saccade (to a target at 30°
eccentricity) and FVS were roughly aligned, the initial and resumed
saccade combination was observed when the stimulation site was within
the rostral ~2-mm region. Stimulation of more caudal sites appears to
accelerate the initial saccade, which ends when the desired goal is reached.
We hypothesize that stimulation of any SC site during large saccades activates a population of neurons which interacts through local circuit connections with the ensemble of SC cells, which are already active and are coding the ongoing movement. Thus when the stimulation-induced and target-activated populations of neurons overlap or are near neighbors, they excite each other and the ongoing saccade does not stop. If the two populations are more distant, they have inhibitory influences on each other such that the initial saccade is stopped well short of the desired goal. This hypothesis suggests that the influence of a neuron on its neighbors follows a Mexican hat function: excitation of proximal cells and inhibition of distant neurons, including those in the opposite colliculus.
These hypothesized interactions between local excitation and distant inhibition also may partly explain the trend observed for the latency of perturbation metric (L1; Fig. 12). When the stimulation-induced and target-activated mounds of activity are as far away as possible (in our experiments, the rostral pole and the 30° site, respectively), they have inhibitory influences on each other and the initial saccade stops with a specific L1. As the stimulation electrode is placed more caudally, the two ensembles of locally excited neurons begin to overlap, which, we speculate, increases the time required for the inhibitory network to overcome the excitatory one. Consequently, the value of L1 increases as a function of the caudal distance of the stimulation site. When the locally excited populations of neurons overlap substantially, the intracollicular inhibition is ineffective, and only a single saccade is generated to reach near the target location.
The range of stimulation sites sampled in our study allows us to
approximate the extent of the excitatory zone. Because all sites
rostral to approximately the 2-mm site (<10° amplitude meridian) stopped all 30° saccades, the distance in SC coordinates between the
most caudal open symbol in Fig. 5 and the site encoding the control
saccade was considered a conservative estimate of the minimal distance
necessary to observe intracollicular inhibition. Using the formulae to
transform visual space into SC coordinates (Optican
1995; Ottes et al. 1986
), the extent of local
excitation is ~1.3 mm, a value smaller than the 1.5 mm reported by
McIlwain (1982)
in the cat. Our smaller estimate,
however, may be due to subthreshold stimulation parameters (for a
review on stimulation induced current spread, see Tehovnik
(1996)
. In addition, the dendritic and axonal arborizations of
SC neurons, which typically extend
2 mm (Behan and Kime
1996
; Ma et al. 1990
; Moschovakis et al.
1988
), suggest a large excitatory span for these neurons. The
anatomic organization of SC neurons thus constrains the region of SC
capable of stopping ongoing saccades in the preferred direction to ~2
mm in the head-fixed preparation. Perhaps a similar effect can be
produced from a broader region for larger saccades or head-unrestrained gaze shifts.
The local excitation and distant inhibition weighting of SC neurons
also have been suggested by neural network models (Arai et al.
1994; van Opstal and van Gisbergen 1989
) and
electrophysiological experiments (Lee et al. 1997
;
Meredith and Ramoa 1998
; Munoz and Istvan
1998
; Pettit et al. 1999
). Note that the distant
inhibition is not exclusively between the rostral pole and the caudal
region. In fact, stimulation of sites within the caudal SC also
inhibits activity at sites within other, distant caudal regions of the same and opposite SC (Munoz and Istvan 1998
). Our
finding that stimulation of the caudal SC during large saccades in an
orthogonal direction (sameSC90) stops the saccade in midflight is in
accordance with suppression of the target-activated discharge.
Assessment of the metrics
The perturbations induced by stimulation of either the entire SC or the OPN region typically were followed by a resumed saccade that brought the eyes near the location of the flashed target. The resumed movements tended to slightly overshoot the control behavior independent of stimulation site, but the hypermetria compared with control (unstimulated saccades) was statistically significant only for the rostral SC (Table 3) and the orthogonal directions across the entire SC (Table 1). Nevertheless the magnitude of the mean final error was <2° even for these sites and directions, suggesting that the local feedback system for the saccadic system can compensate effectively for these extreme spatiotemporal perturbations in saccade trajectory.
The initial amplitude increased as a function of stimulation site for
nearly all direction conditions (Table 2). This trend is expected if
the stimulation momentarily replaces the desired goal by the FVS or by
a weighted average of the saccade vectors coded by the
stimulation-induced and the target-activated regions, as discussed in
the previous section. Vector averaging also has been reported by
psychophysical studies that varied the placement of distractors to
perturb the saccades (cf., Walker et al. 1997).
The latency of perturbation values measured in our study are
significantly greater than those documented in previous reports (<10
ms, Miyashita and Hikosaka 1996; ~12 ms, Munoz
and Wurtz 1993b
). One possible cause for the discrepancy is the
measurement methods (see RESULTS). Yet another, and we
believe, more likely explanation is the timing of the microstimulation.
As both collicular and reticular burst neurons discharge more
vigorously near saccade onset than around saccade end, the effects of
stimulation may be observed with a longer latency in the former case.
The mean latency of perturbation was also greater by ~3 ms for saccades perturbed from the rostral pole of the SC than from the OPN region. This value suggests that, relative to stimulus-induced activation applied directly to the OPNs, the stimulation train delivered to the SC needs to travel across one or more synapses to inhibit activity in the MBLNS, and one obvious candidate would be the projection from fixation neurons to the OPNs. However, if the mechanisms of perturbation are different, a 3-ms difference does not necessarily imply extra synapses for the signal to cross. The latency of perturbation is on the order of 20 ms, which also could reflect processing at a network level, leading to inhibition of the saccadic burst generator. That the mean interruption duration is significantly different for stimulation of the rostral pole and the OPN region (Table 3) also supports the notion that the perturbations may manifest via partially nonoverlapping mechanisms. In particular, the inhibition appears more potent when the stimulation is applied to the SC.
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ACKNOWLEDGMENTS |
---|
We thank Drs. L. M. Optican and L. Goffart for commenting on an earlier version of this manuscript.
This work was funded by National Institutes of Health Grants 5 T32 GM-08155 (University of California, San Francisco and Berkley, Graduate Groups in Bioengineering) and R01 EY-06860 (E. L. Keller) and a UCSF Regents Fellowship (N. J. Gandhi).
Present address of N. J. Gandhi: Division of Neuroscience, S-515, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030.
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FOOTNOTES |
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Address for reprint request: E. L. Keller, The Smith-Kettlewell Eye Research Institute, 2318 Fillmore St., San Francisco, CA 94115.
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 24 May 1999; accepted in final form 17 August 1999.
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REFERENCES |
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