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The Journal of Neurophysiology Vol. 87 No. 6 June 2002, pp. 2946-2963
Copyright ©2002 by the American Physiological Society
Department of Biophysics, University of Nijmegen, 6500 HB Nijmegen, The Netherlands
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ABSTRACT |
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Van Beuzekom, A. D. and J.A.M. Van Gisbergen. Collicular Microstimulation During Passive Rotation Does Not Generate Fixed Gaze Shifts. J. Neurophysiol. 87: 2946-2963, 2002. We investigated whether saccades evoked by electrical stimulation (E-saccades) in the superior colliculus can compensate for passive sinusoidal head rotation in yaw so as to keep the rapid gaze shift constant. After accounting for variations in E-saccade onset position, we found significant horizontal metric changes, proportional to head velocity, in 31 of 37 experiments in 2 monkeys. Vertical effects were small. In a substantial fraction of the experiments (14/37), these metric changes represented significant but often insufficient compensatory adjustments in the horizontal component, opposite to the direction of head movement. However, very robust violations of gaze-shift constancy were remarkably common: significant anticompensatory changes in the horizontal component occurred in 17/37 experiments. In these cases, typically involving larger E-saccades, the horizontal component increased in size with rotation into the half field containing the E-saccade and became smaller during opposite rotation. Further analysis showed that, instead of showing a dichotomy, the metric effect actually varied along a continuum from compensatory to strongly anticompensatory. In addition to these metric changes, we found a robust kinematic effect of head rotation in metrically matched E-saccades. In all experiments where the effect was significant (34/37), horizontal peak velocity increased for rotation into the half field where the E-saccade was directed and decreased for opposite rotation. This kinematic effect was again proportional to head velocity and predominant in the horizontal component. Comparison of yaw and pitch rotation at the same stimulation site showed that both expressions of vestibular-saccade interaction (metric and kinematic) tended to align with the direction of rotation. The component-specific nature of the modulation suggests that the effects may have been caused by convergence of saccadic and vestibular signals at a component-coding stage downstream of the colliculus. We suggest that the quick-phase system got access to the common pulse generator as soon as the collicular stimulation had opened the pause-cell gate. Adding such an anticompensatory signal would act to increase the E-saccade horizontal component when the monkey was rotated in the same direction and bring about a decrease in size and peak velocity when it was opposite. In the large majority of experiments the metric changes failed to maintain gaze-shift constancy, either because they were in the wrong direction or because they were too small. Possible reasons for this major departure from the properties of natural gaze shifts are discussed.
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INTRODUCTION |
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There is general
agreement that the control of rapid eye movements relies on a common
circuit involving burst neurons that is called into action both for
goal-directed saccades to a selected target and during quick phases
generated by the vestibuloocular reflex (VOR). Studies on VOR quick
phases have typically side-stepped the issue how they might interact
with goal-directed saccades. However, preliminary findings by
Kitama et al. (1992)
in the cat may have interesting
implications for this question. These authors reported
saccade-vestibular interactions in electrically induced collicular
saccades (E-saccades) involving an anticompensatory vestibular signal.
Since, if confirmed, such results would seem to provide an interesting
window on the neglected topic of saccade-quick phase interaction, we
have performed similar experiments in the passively rotated monkey. Our
major motivation to pursue the basic observation of Kitama and
co-workers is that it argues against the notion of gaze constancy that
has become a key feature of most current gaze-control models. To
provide a more detailed account of the relevant issues, the subsequent
sections will briefly review the literature on the neural control of
fast eye movements and on current ideas concerning saccade-vestibular interaction.
Neural control of rapid eye movements
It is well-established that signals for the generation of
goal-directed saccades and quick phases of nystagmus finally converge on a common brain stem circuit, involving excitatory burst cells (EBNs)
and omnidirectional pause neurons (Fig.
1), known as the pulse generator (for
reviews see Hepp et al. 1989
; Keller
1991
; Moschovakis et al. 1996
; Scudder et
al. 2002
). EBNs specialized for horizontal and for
vertical/torsional rapid eye movements have been identified in the
pontine reticular formation and the rostral midbrain, respectively.
They burst both during goal-directed saccades and quick phases into
their ON-direction.
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Omnipause neurons show a steady discharge during fixation and slow
phases of nystagmus, but cease firing during both types of rapid eye
movements in any direction. By disinhibiting burst neurons in
this fashion, the omnipause neurons gate the pulse generator and
control the timing of rapid eye movements (Gandhi and Keller
1999
; Keller 1974
).
In principle, this picture of how the pulse-generator circuit works can
explain the stereotyped and intermittent nature of rapid eye movements
(Robinson 1975
; Van Gisbergen et al.
1981
; Zee et al. 1976
). The wider question of
how and when this system is called into action has been pursued mainly
in studies concentrating on more central saccadic control mechanisms
(for reviews, see Guitton 1991
; Sparks and
Hartwich-Young 1989
; Wurtz 1996
). This work has
provided clear evidence that the pathways for saccades to visual,
auditory, and tactile targets have already converged at the level of
the superior colliculus (SC), which plays an important role in the
sensory-motor transformation for the control of saccadic eye movements
(Groh and Sparks 1996
; Jay and Sparks
1987
; Sparks 1986
). Burst cells in the deeper
layers of the SC exhibit a vigorous burst, tightly linked to saccade
onset. In contrast to the temporal coding of saccade components in
EBNs, collicular neurons are organized into a two-dimensional
topographic map, representing the contralateral hemifield, that
specifies the relation between the locus of activity in the map and the
saccade vector (Robinson 1972
) (see also Fig. 1).
Collicular saccade-related burst cells have limited movement fields
(Schiller and Stryker 1972
; Wurtz and Goldberg
1972
).
The generation of quick phases by vestibular signals has received much
less attention. Experiments in the cat (Kitama et al. 1995
; Ohki et al. 1988
; see Markham
1996
for review) have suggested an important role for burster
driving neurons (BDNs) in activating the pulse generator during these
rapid eye movements (see Fig. 1). The possible role of the SC in the
control of quick phases has received only very scant attention, but
there is some evidence that quick phases also have a neural
representation in the colliculus map. For example, Schiller and
Stryker (1972)
found that collicular burst cells that become
active during goal-directed saccades, may also show movement-related
activity during quick phases. Furthermore, Wurtz and Goldberg
(1972)
described cells in the SC that were active both before
horizontal visually guided saccades and before quick phases of caloric
nystagmus of equal amplitude. A systematic movement-field study,
however, has never been undertaken so that virtually nothing is known
on how the spatial distribution of this activity relates to the layout
of the collicular map. Reversible-inactivation experiments in the
monkey by Hepp et al. (1993)
showed that the SC plays an
essential role in the generation of voluntary and goal-directed
saccades: after inactivation, hardly any saccades were made. Quick
phases, on the other hand, could still be generated, although their
peak velocities were clearly reduced.
Earlier studies on saccade-vestibular interactions
These results on the afferent signals to the pulse generator for
saccades and quick phases, pictorially summarized in Fig. 1, were
mostly obtained in dedicated studies concentrating on either system
that left open how they operate in conjunction. For example, the fact
that gaze shifts often involve a combined eye-head movement immediately
raises questions on how collicular targeting signals and oculomotor
signals of vestibular origin are combined. The prevailing view is that
the SC, long seen as an area for the control of eye saccades, is
actually a control center for combined eye-head gaze shifts
(Freedman et al. 1996
; Freedman and Sparks
1997
; Roucoux et al. 1980
). If the brain decides that the head should contribute to a voluntary gaze shift, will this
simply lead to the addition of the vestibularly driven eye movements
that normally accompany head movements when there is no explicit
target? Investigations concerning this question have mostly
concentrated on the slow-phase signal of the VOR and have provided
mixed evidence for slow-phase suppression during large gaze shifts
(Guitton and Volle 1987
; Laurutis and Robinson
1986
; Pélisson et al. 1988
; Tabak
et al. 1996
; Tomlinson and Bahra 1986
).
Position-vestibular-pause (PVP) cells, which are thought to carry a VOR
slow-phase signal, are inhibited during voluntary gaze shifts
(Roy and Cullen 1998
), possibly by inhibition mediated by the pulse generator (see Fig. 1). On this basis, it has been suggested that the PVPs may play a role in VOR suppression.
If gaze shifts can affect the generation of VOR slow phases, how about
the quick-phase mechanism? While it is not hard to see a rationale for
suppressing slow-phase signals, which would counteract the gaze shift,
predicting the fate of the anticompensatory quick phases is not trivial
from a theoretical point of view. In any case, since different neurons
are involved, slow-phase suppression does not automatically imply
quick-phase suppression. Experimental and theoretical studies
considering the issue of whether quick-phase signals may contribute to
goal-directed rapid eye movements when the head is moving have been
rare (but see, e.g., Barnes 1981
; Barnes and
Prosser 1981
; Guitton and Volle 1987
). Against
this general background, the present study was undertaken with the
objective to clarify how collicular saccadic commands and vestibularly
related signals are combined when both systems are activated. We asked
how E-saccade properties would be affected by yaw rotation in either
direction, at various velocities. One potential scenario is that
gaze-shift constancy is maintained by modifying the E-saccade to
compensate for the ongoing head movement so as to keep the sum of eye
and head movement constant (see Fig. 2).
Alternatively, as suggested by earlier findings of Kitama et al.
(1992)
in the cat, vestibular stimulation may add an
anticompensatory component to the E-saccade (see Fig. 2). Such loss of
spatial constancy in anticompensatory E-saccades was seen in many
experiments. The anticompensatory effect may come about when electrical
SC stimulation opens the pause-cell gate, thereby allowing the
expression of an anticompensatory movement from the quick-phase system.
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This result raised the important further question of whether this
putative quick-phase contribution was generated at 1) the vectorial coding stage embodied by the SC motor map or 2) at
downstream oculomotor centers carrying component-related signals. Since
vector averaging (Robinson 1972
) would be expected if
quick phases have a collicular origin, the data were analyzed to check
for this possibility. The results show no sign of averaging but rather reflect changes in the component aligned with the direction of rotation
and therefore seem compatible with the second hypothesis.
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METHODS |
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Animal preparation and neurophysiological procedures
The experiments were performed in two adult male rhesus monkeys (Macaca mulatta), weighing 6-7 kg, that had been trained to accurately fixate visual targets. The animals will be denoted as BR and GI. All surgical and experimental procedures were reviewed and approved by the university committee for the use of experimental animals. Surgery was carried out in the local central animal facility, which was responsible for housing, feeding, and veterinary care.
SURGERY.
To prepare the animals for chronical neurophysiological experiments,
two separate sterile surgical procedures were performed under inhalant
anesthesia with N2O/O2 and ethrane, in
combination with infusion of pentobarbital sodium. Blood pressure,
heart rate, oxygen saturation, and body temperature were continuously
monitored during surgery. The animal was artificially ventilated, and
end-tidal CO2 was maintained around 4%. A venous canule
was inserted in a hind leg to allow a steady infusion of pentobarbital
and saline. In the first surgical session, a thin gold-plated copper
ring (diameter about 17 mm) was implanted underneath the conjunctiva of
the right eye, following a method similar to Judge et al.
(1980)
. The ring, which became firmly attached to the eye by
connective tissue, served to record two-dimensional eye movements (see
below for details). In the second operation, a solid cap was tightly fitted to the skull. This was done by placing 14 tapered titanium bone
screws (length 7.5 mm, diameter 2.7 mm) in drilled and tapped holes in
the skull and embedding them in sterile orthopedic bone cement
(Palacos). Four stainless steel bolts were fixed in the cement cap to
allow rigid fixation of the head during experiments. A stainless steel
recording chamber (11 mm ID) was stereotaxically implanted over a
trephine hole, centered on the midline above the intersection of the
midsagittal plane and the interaural line, such that both colliculi
could be reached by microelectrode penetrations.
RECORDING OF NEURONAL ACTIVITY.
The localization of the SC was based on a number of neurophysiological
criteria (Melis and Van Gisbergen 1996
). Extracellular activity in the SC was recorded using glass-coated tungsten
microelectrodes (impedance 0.3-1.2 M
). The electrode was placed
inside a stainless steel guide tube to prevent damage to the tip during
penetration of the dura and was moved downward by a hydraulic stepping
motor (Trent Wells), mounted on the chamber. After amplification (BAK Electronics, Model A-1) and filtering (bandpass 100 Hz to 10 kHz), the
electrode signal was monitored on an oscilloscope and fed into a level
detector such that individual action potentials could be detected with
a time resolution of 10 µs.
Experimental procedures and setup
All experiments were conducted in a completely dark room. While seated in a primate chair, the head-restrained monkey was rotated about either a vertical or horizontal axis through the cyclopean eye using a motor-driven vestibular stimulator. Chair position was measured using a digital position encoder with an angular resolution of 0.04° (sample rate: 500 Hz). Visual targets were presented using an array of red light-emitting diodes (LEDs). The array was attached to the vestibular stimulator, with the center LED on the monkey's naso-occipital axis at 0.39 m from the cyclopean eye, so that it moved with the monkey during rotations. LEDs were positioned on the intersections of seven circles at 5, 10, ... , 35° and 12 meridians every 30°. To calibrate the eye-ring signals, sessions started with a run in which the monkey made refixations from the central fixation LED to each of all 84 peripheral targets and maintained fixation as long as it was visible.
EYE POSITION RECORDING.
Two-dimensional eye position relative to the head was recorded using
the double-magnetic induction technique (Bour et al. 1984
). Two oscillating perpendicular magnetic fields
(horizontal: 48 kHz, vertical: 60 kHz) induced an
eye-position-dependent electrical current in the implanted eye ring,
which, in turn, induced secondary currents in a sensitive pickup coil
that was mounted directly in front of that eye. A nulling coil, placed
some distance away from the recording eye on a rigid manipulator,
electronically canceled the primary eye-position-independent signal
component induced by the magnetic fields. After amplification and
demodulation by lock-in amplifiers (PAR 128A), the raw horizontal and
vertical eye position signals were low-pass filtered (
3 dB at 200 Hz, 4th-order Bessel filter) and sampled with 12-bit resolution at 500 Hz
per channel (CED 1401plus). This technique provides a
high-resolution eye-position recording (~0.2° in all directions)
with only small nonlinearities that can be easily accounted for using a
relatively simple calibration procedure (see Data
analysis).
Paradigms combining collicular microstimulation and vestibular stimulation
VESTIBULAR STIMULATION. The experiments were designed to investigate how E-saccades were affected by vestibular stimulation compared with control data collected in absence of vestibular stimulation. In all sessions, vestibular stimulation was applied by rotation about the vertical axis, using a 0.15-Hz sinusoidal profile with a maximal velocity of 66°/s and an amplitude of 70°. In each run, the monkey was rotated continuously for 80 s. In six sessions, the monkey subsequently was also rotated about a horizontal axis (0.2 Hz, 57°/s, 45°). In these combined yaw-pitch sessions, we used the same velocity profile also for yaw rotation.
What was intended as yaw rotation led to slow phases with a small pitch component indicating that the monkey's sagittal head plane was not perfectly aligned with the earth-vertical rotation axis. The deviation was quantified by determining the relation between horizontal and vertical eye velocity. The slope of this relationship describes the deviation of the body axis from earth vertical. Deviations were small, 2.47 ± 0.91° (mean ± SD) for all sessions of monkey BR, 0.49 ± 0.60° for all experiments of monkey GI. Quick phases had a slight downward component in both rotation directions (see Fig. 3C), but this effect is probably related to drift compensation and would not be expected on the basis of the small pitch component in vestibular rotation.ELECTRICAL STIMULATION.
E-saccades were elicited by electrical stimulation of sites in the
deeper layers of the caudal SC with a train of constant-current biphasic pulses (BAK Electronics, Model BPG-1). The train always had a
pulse frequency of 500 Hz with each pulse lasting 0.2 ms. We reliably
elicited various amplitude saccades at 26 different collicular sites
(nBR = 20, nGI = 6). At
each site, threshold was determined by gradually increasing the current
strength. Stimulation threshold was defined as the current intensity
where at least 90% of all stimulations led to a saccadic response
while the monkey was scanning the experimental room. Experiments were
then conducted with a current up to 2.5 times threshold. With respect
to train duration, two different stimulation paradigms were in use. In the long paradigm (nBR = 21, nGI = 5), we used train durations between 34 and
66 ms, ensuring that the site-specific maximum amplitude E-saccade
(Stanford et al. 1996
) was elicited. At some sites
(nBR = 7, nGI = 4),
we also applied a short 20-ms pulse train (short paradigm). Since the
two paradigms typically yielded different E-saccades, we will describe
the results as coming from different experiments. As a result, the
total number of experiments (37) exceeds the number of sites.
Data analysis
CALIBRATION OF EYE POSITION.
Horizontal and vertical eye-coil signals were calibrated off-line using
fixation data obtained in the eye-coil calibration run at the beginning
of each experimental session. Two neural networks, one for each
position component, were trained to fit the raw fixation data to the
target locations, using a back-propagation algorithm based on the
gradient-descent method of Levenberg-Marquardt (Matlab, the Mathworks).
This algorithm was used to correct for the inherent nonlinearity of the
double-magnetic induction technique. Each network consisted of two
input units, representing the raw horizontal and vertical signal, three
hidden units and one output unit, representing either the desired
calibrated horizontal or vertical position signal (Melis and Van
Gisbergen 1996
). Raw eye-coil signals were subsequently
calibrated by applying the resulting feed-forward networks. Calibration
errors, i.e., the remaining error between actual target position and
corrected signal, were typically less than 0.5°, on average. In all
figures rightward and upward eye and chair position will be denoted as positive.
SACCADE DETECTION AND SELECTION. Saccade detection was performed on the calibrated eye position signals on the basis of separate velocity and acceleration/deceleration criteria for saccade onset and offset, respectively. All detection markings were checked by the experimenter and adjusted if necessary.
A rapid eye movement was considered an E-saccade if it started between 16 and 60 ms after the onset of the electrical stimulation train. E-saccades starting within 140 ms after a previous rapid eye movement were discarded from further analysis, to minimize temporal interaction effects of the type reported by several groups (Kustov and Robinson 1995| |
RESULTS |
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To investigate the effect of vestibular stimulation, E-saccades were elicited by electrical microstimulation in the SC during passive head rotation and during rest. We will first provide data on the rapid and slow eye movements during vestibular stimulation and present an overview of the range of E-saccade vectors tested in the yaw-rotation experiments. Subsequently we describe the effect of vestibular stimulation on the metric and kinematic properties of E-saccades.
Characteristics of nystagmic eye movements and range of tested E-saccade vectors
Figure 3A shows eye
position traces during yaw rotation. At the time marked by the arrow,
the electrical pulse train started and after a short latency an
E-saccade was made to the left and down. Since the E-saccade was
elicited during ongoing sinusoidal rotation, it occurred against a
background of nystagmus eye movements. The compensatory slow phase
moved the eye in a direction opposite to the head rotation (average
gain: 0.79 ± 0.08), while the anticompensatory quick phases
prevented the eyes from getting stuck at the border of the oculomotor
range. As noted before, the quick phases did not just reset the eye to
the straight-ahead position, but typically ended at a more eccentric
position, displaced into the direction of rotation (see, e.g.,
Chun and Robinson 1978
). This so-called shift of the
beating field is further illustrated in Fig. 3B, which shows
quick phase end positions relative to the head as a function of
head-velocity phase, revealing a clear relation between the end points
of quick phases and instantaneous head velocity (gray line).
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As shown by the gray-shaded density plot in Fig. 3C, the
metric properties of quick phases in the absence of electrical
stimulation showed wide scatter. The mean quick-phase vector (+) had a
horizontal component of 23.0°. The downward component of the mean
quick-phase vector may reflect compensation for the clear upward eye
position drift in the dark (see trace V in A), as
proposed by Fuchs et al. (1996)
. The upward drift
(velocity ~5°/s) was present in both monkeys. For comparison, the
open circles in Fig. 3C represent all mean E-saccade vectors
that were obtained in the control experiments performed in monkey
BR (stimulation in right SC). As can be seen, their amplitudes
varied between 3.2 and 27.6°, and their directions covered the range
from 113 to 243°.
Dependence of E-saccade metrics on head velocity
Qualitative observations by Kitama et al. (1992)
in
the cat suggest that vestibular stimulation may change E-saccade
metrics. We checked to what extent this is also true in the monkey and pursued the suggestion from this earlier work that yaw rotation affects
primarily the horizontal component. Our results show convincing metric
changes in most experiments but also revealed that not all effects were alike.
Figure 4 shows results from an experiment
where rotation introduced an obvious change in end point distribution.
E-saccades in the stationary control condition, represented by gray
squares, were directed to the left and down. Filled circles indicate
E-saccades elicited when the monkey was rotated to the right at chair
velocities exceeding 20°/s; open circles denote saccades elicited
during leftward yaw rotation in the same velocity range. Note that
during rotation, saccade vectors scattered more widely than the
controls. It is clear that saccades elicited during rightward rotation
generally had smaller horizontal components than those elicited during
leftward rotation, i.e., into the half field of the E-saccade vector.
In addition, in this experiment, the vertical component also showed an
effect of yaw rotation. So, effectively, yaw rotation into the half
field of the E-saccade tended to make it bigger while opposite rotation
made it smaller than in the control condition. However, as further
analysis will show, just looking at end points may be deceiving since
effects of head velocity are superimposed on effects of initial eye
position. A statistical analysis was performed to isolate these two
effects. First, vestibular stimulation gave rise to nystagmic eye
movements that caused some variability in E-saccade starting positions,
despite measures to limit this effect (see METHODS). Since
it is known that E-saccade vectors may depend on initial eye position
(Freedman et al. 1996
; Klier et al. 2001
;
Segraves and Goldberg 1992
), it was essential to quantify the impact of this phenomenon on E-saccade metrics. Second, we
ascertained to what extent the variability in E-saccade metrics could
be related to the direction and magnitude of head velocity. Both
factors were investigated separately for horizontal and vertical components.
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To quantify how horizontal (
EH) and vertical
components (
EV) of E-saccades in a given
experiment were related to initial eye position at saccade onset and to
head velocity, we performed a multiple-linear regression
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(1) |
yaw represents
horizontal head velocity. Figure 5 shows
the linear regression results for the horizontal (left-hand
panels) and vertical (right-hand panels) component of
all E-saccades elicited during the same experiment as shown in Fig. 4.
For both components there was a reasonable correlation between data and
model fit (goodness-of-fit values 0.69 and 0.49, A and
B). Model fits were generally better for the horizontal component (mean R2 for horizontal 0.47 ± 0.25; vertical 0.30 ± 0.21, based on all data from the 2 monkeys).
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As can be seen from the coefficient values
(aH =
0.45 ± 0.04 and
aV =
0.55 ± 0.06), significant at
the P < 0.001 level (t-test), the
experiment in Fig. 5 had a clear E-saccade onset-position effect in
both components. To visualize this effect of initial eye position in
isolation, the partial-regression plots in Fig. 5, C and
D, show how variations in E-saccade onset position correlate to changes in component size. The slopes of the regression lines reflect coefficients aH and
aV, respectively. The effects of initial eye
position in this experiment were far from negligible, as the range of
approximately 10° in associated component variations indicates. Note
that both components showed a similar onset position dependence, with
comparable slopes and goodness-of-fit values. The position effect was
significant (t-test, P < 0.05) in the majority of experiments, both for the horizontal (26/37) and the vertical component (33/37).
However, initial eye position accounted only partly for the observed E-saccade scatter. As shown by the partial-regression plots in Fig. 5, E and F, there was an additional clear relationship between head velocity and saccade component size. Note that changes in component size increased linearly with head velocity, and that leftward and rightward rotation altered the metrics of the E-saccade in opposite directions. The effect, however, was more pronounced in the horizontal component as expressed by the difference between coefficients mH = 0.095 ± 0.006 s and mV = 0.025 ± 0.005 s.
If the two factors in the multiple regression equation (initial eye
position and head velocity) are strongly correlated, caution is
warranted to avoid erroneous conclusions. Collinearity becomes a
possible point of concern for correlations beyond r = 0.80 (Glantz and Slinker 1990
). We found that the actual
correlations between the two factors remained below this value without
a single exception (horizontal: r = 0.40 ± 0.16;
vertical r = 0.22 ± 0.15). As an additional
check, we compared goodness-of-fit values (R2)
for Eq. 1 and a reduced version lacking the head velocity
term. The results showed that the head velocity term significantly
improved the R2 values of the model in 31 of 37 experiments for the horizontal component. This number was considerably
smaller for the vertical component (20/37). The partial
R2 for head velocity ranged from 0.00 to 0.91 (mean: 0.37 ± 0.28) for the horizontal component. In the vertical
component we found a range from 0.00 to 0.37 (mean: 0.09 ± 0.11).
An additional indication that the analysis yielded consistent results
is the similarity of the initial eye position dependence in rest and
during rotation (correlation coefficient r = 0.90, slope 0.88 ± 0.06). The bias (coefficients
bH and bV) was also
similar during rest and during yaw rotation (correlation coefficient
r = 0.99, slope 0.98 ± 0.01).
We focused the regression analysis on head velocity, but could the relation with head velocity actually represent a hidden relation with head position? Since in a sinewave each head position has two head velocities associated with it, it is unlikely that variations in head position would produce a tight relation with velocity. Indeed, only two experiments that showed a significant relation with head velocity displayed a stronger relation with head position when we did the regression with head position rather than head velocity. Only one experiment without a significant head velocity relation yielded a significant effect of head position. Since head position and head acceleration are perfectly negatively correlated in a sinusoidal profile, this result also argues against a hidden relation with head acceleration in the overwhelming majority of experiments.
In summary, the multiple-regression analysis is an adequate approach to separate and quantify two distinct sources of variability in E-saccades with consistent results. Most sites show a robust relation between the size of the horizontal component and head velocity.
Characteristics of the metric rotation-effect
In what follows, we found it convenient to visualize the isolated
metric effect of head rotation as a vector, termed M-vector. The
M-vector was defined as the change in the E-vector in response to a
50°/s rotation into the half field of the E-saccade. As illustrated in Fig. 5, its components were computed by taking
mH ×
50°/s for the horizontal (Fig.
5E) and mV ×
50°/s for the
vertical component (Fig. 5F). Note that each experiment
yields one M-vector. So, the experiment in Fig. 5 yielded an M-vector
with a horizontal component of
4.75° (0.095 s ×
50°/s)
and a vertical component of
1.25° (0.025 s ×
50°/s) that
was directed to the left and downward. Since the M-vector was directed
into the left half field, just as the E-vector (see Fig. 4), the
head-velocity effect was anticompensatory. If the system were to keep
the rapid gaze shift constant in the presence of head rotation (see
Fig. 2), the M-vector should have been directed away from the E-saccade
(rightward in this case). The M-vector was also slightly downward, but
less than suggested by the raw data in Fig. 4, which still contain the
initial eye position effect. Our further analysis will first concentrate on the question to what extent these M-vectors had the
appropriate characteristics (sign and amplitude) to maintain E-saccade
gaze constancy during head rotation.
In Fig. 6 we show all E-saccade vectors (left-hand column) and the corresponding M-vectors (right-hand column), both for monkey BR (top row) and for monkey GI (bottom row). Since the monkeys were stimulated in different colliculi, their E-saccades were directed into opposite hemifields. M-vectors occupied a much narrower direction range than the E-saccades, mostly close to the horizontal axis.
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VIOLATIONS OF GAZE CONSTANCY. Recall that adjusting the E-saccade for the head rotation, in order to keep the gaze shift constant, requires a horizontal M-vector that is directed away from the E-saccade. Such oppositely directed M-vectors were found in 14 of 37 experiments (t-test, P < 0.05), but these vectors were always relatively small. By contrast, in 17 experiments we saw typically very robust anticompensatory effects (t-test, P < 0.05). In the remaining experiments (6/37), the M-vector was not significant.
In Fig. 7A we have pooled the M-vector results from both monkeys, rotating all M-vectors from monkey GI by 180° as if they were obtained from E-saccades directed into the left hemifield, just as in monkey BR (see Fig. 6, A and B). The solid line shows the horizontal M-vector component required for gaze-shift constancy, as a function of E-saccade duration. It represents the compensation that would null out a 50°/s head rotation occurring during the E-saccade and shows that larger saccades require larger M-vectors because they last longer. The different symbols denote results obtained in the long (
) and short stimulation paradigm (
). The shorter duration paradigm tended to yield smaller shorter-lasting saccades, but, as will become clear, our conclusions apply equally to
both experimental conditions.
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DIRECTIONAL SCATTER. A plausible explanation of the trend toward anticompensatory effects is that the electrical stimulation may have enabled both the saccadic and the quick-phase system. If so, the question arises whether the putative quick-phase system contribution had a collicular or a more peripheral origin (see INTRODUCTION). With this issue in mind, we analyzed the directional variability in M-vectors (Fig. 6) from the perspective of two hypotheses, each with different predictions.
The first hypothesis, suggested by Kitama et al. (1992)
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50°/s rotation. For 22 of 37 of experiments, it was not possible to predict an M-vector according to
the vector-averaging hypothesis since the direction of its horizontal
component already violated the idea. Further discussion of the
averaging predictions will concentrate on the remaining
experiments. The rotation-alignment hypothesis was applied to all data.
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Specific kinematic changes in E-vectors induced by yaw rotation
This section will provide evidence to show that, in addition to
the metric effect described earlier, vestibular stimulation often also
had clear consequences for the kinematic properties of metrically
matched E-saccades. Figure 11 shows the
relation between component size and component peak velocity for an
experiment yielding left-down E-saccades
(
EH =
21.9°,
EV =
8.1°). Open circles represent
E-saccades during leftward rotation; filled circles denote E-saccades
when the monkey was rotated to the right, both at chair velocities
exceeding 50°/s. There was a distinct effect of vestibular
stimulation on the kinematic properties of the horizontal component as
indicated by the vertical offset in the two clusters. E-saccades with
comparable horizontal components exhibited an approximately 100°/s
higher horizontal peak velocity during leftward rotations (i.e., into
the half field of the E-vector). The vertical component showed hardly
any change in peak velocity during leftward rotations (Fig.
11B).
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Relying on a multiple-regression analysis, the dependence of horizontal
and vertical peak velocity in the E-saccade,
Hmax and
Vmax, on component size
(
EH and
EV) and
horizontal head velocity (
yaw) was
quantified with
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(2) |
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Correlations between the terms of the multiple regression were modest (horizontal: r = 0.49 ± 0.25, with 4 experiments exceeding r = 0.80; vertical r = 0.22 ± 0.15), indicating that collinearity was generally not a point of concern. The head velocity term contributed a significant increase in R2 values for the horizontal component in 30 of 37 experiments, and in 19 experiments for the vertical component. Partial R2 values for the head velocity term ranged from 0.00 to 0.75 (mean: 0.27 ± 0.21) for the horizontal component and from 0.00 to 0.28 (mean: 0.08 ± 0.09) for the vertical component.
Figure 13 provides an overview of the
effects of vestibular stimulation on E-saccade kinematics in the two
monkeys. Using a similar approach as in the metric analysis (see
section "Characteristics of the metric rotation-effect"), the
change in peak velocity due to a 50°/s rotation into the half field
of the saccade, based on the coefficients kH and
kV as illustrated in Fig. 12, E and F, was taken as a measure of the kinematic effect (denoted
as K-vector). Figure 13, A and C, displays the
peak-velocity vectors of the E-saccades whose directions show a close
resemblance to the E-vectors in Fig. 6, indicating that E-saccades
followed a roughly straight path. The corresponding K-vectors (Fig. 13,
B and D) scatter about the horizontal axis, with
on average a slight downward component. Kinematic changes were more
pronounced in the horizontal component, the horizontal range was
approximately three times the vertical range. The typical kinematic
effect, seen in almost all (34/37) experiments, was that horizontal
peak velocity increased for rotation into the half field containing the
-vector (see also Fig. 12).
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To allow comparison with the metric data in Fig. 7A, we show the horizontal components of K-vectors from both monkeys as a function of E-saccade duration in Fig. 7B. The solid line denotes the horizontal K-vector component expected in case of addition of a perfect VOR signal, slowing the E-saccade. Instead, the majority of experiments yielded negative horizontal K-components, reflecting increased peak velocities caused by an anticompensatory effect of rotation. K-vectors clearly fail to show the inverse relation with saccade duration seen in M-vectors (Fig. 7A). As a further sign that the metric effect and the kinematic effect are independent, at least to some extent, there were 23 experiments where M-vector and K-vector were directed in opposite hemifields. In other words, irrespective of whether rotation into the half field of the E-saccade made it larger or smaller, the resulting saccade almost invariably showed velocity enhancement.
As Fig. 14, A and
B, shows, K-vectors clustered more tightly about the
horizontal axis than the
-vectors. Nevertheless, since the
vertical K-components are not negligible, the question arises how the
data should be interpreted. We compared two hypotheses. 1)
K-vectors are aligned with the direction of rotation and 2) K-vectors represent a change in vectorial peak velocity. As in the
metric analysis, we found that the rotation-alignment hypothesis provided the best description of the data (Fig. 14C). The
vertical K-vector components predicted on the basis of the vectorial
hypothesis (line marked "vector") fail to match the observed data,
which are close to the rotation-alignment prediction (marked
"align"). An analysis of residual errors (listed in Table 1,
right-hand side) further substantiated that the
rotation-alignment hypothesis was clearly better, in both monkeys.
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Yaw versus pitch rotation
The yaw-rotation data presented above, strongly suggest that changes in metrics and kinematics of E-saccades predominate in the horizontal component, aligned with rotation direction. To test whether the rotation-alignment hypothesis has a more general validity, we performed separate horizontal and vertical rotation experiments in six different sites and determined M- and K-vectors for each rotation direction. According to the rotation-alignment hypothesis, M- and K-vectors should be aligned with the horizontal axis during yaw rotation, and be aligned with the vertical axis during pitch rotation.
The top panels of Fig. 15 display the results of the metric analysis. E-saccades had various directions into the left hemifield (A), but most yielded horizontally directed M-vectors during yaw rotation (B). During pitch rotation, E-saccades elicited at the same site showed mainly changes in the vertical component (C). Even more convincing support for the alignment hypothesis was provided by the kinematic analysis (bottom panels). Note that during yaw rotation all K-vectors pointed to the left, in the same half field as the peak-velocity vectors. By contrast, pitch rotation changed the picture entirely (F). The fact that peak-velocity vectors showed both positive and negative vertical components (D) explains why there were both upward and downward K-vectors during pitch rotation. A summary of a quantitative comparison is listed in Table 2.
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DISCUSSION |
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Overview of main experimental findings
This investigation into the effect of passive vestibular
stimulation on rapid eye movements has shown clear changes in the metrics of E-saccades that were most pronounced in the component aligned with the direction of rotation and were proportional to instantaneous head velocity. The regression analysis yielding this
result was designed to rule out that these metric changes were due to
changes in the starting position of the E-saccades. Our results confirm
the original observation by Kitama et al. (1992)
in the
cat that vestibular stimulation may give rise to considerable
anticompensatory changes (see Fig. 6). However, other experiments
yielded the opposite result, compensatory changes in E-saccade metrics,
as if the system was attempting to maintain a degree of gaze-shift
constancy. The results show that there actually was a gradual
transition between these two opposite extremes (see Fig. 7).
A further major finding in the present study is that rotation into the half field containing the E-saccade nearly always made it faster (see Fig. 13). This robust kinematic effect was again essentially limited to the rotation-aligned component, reversed with the direction of rotation and was proportional to head velocity. When the monkey was subsequently rotated in pitch, the metric and the kinematic effect became predominant in the vertical component of E-saccades (see Fig. 15). The kinematic effect is not a trivial epiphenomenon of the metric effect. We took great care to show that it occurred in metrically matched E-saccades. Furthermore, the two effects can even be opposite. In the next section, we try to delimit the neural stage where the convergence of saccadic and vestibular signals may have occurred.
Evidence that the modulation occurs downstream of the SC
As outlined in the INTRODUCTION, it has been shown
that the pathways for saccades to visual, auditory, and tactile targets have already converged at the level of the SC where movement vectors are coded spatially in a motor map. It is not clear whether vestibular quick phases may be controlled by the SC. Neural activity related to
quick phases has been demonstrated in the SC (Schiller and Stryker 1972
; Wurtz and Goldberg 1972
), but its
functional significance has always been enigmatic. If the spatial
distribution of quick-phase activity conforms to the collicular map,
there may have been two loci of collicular activity during our
experiments: one due to the electrical stimulation, the other
corresponding to the metrics of the quick phases evoked by vestibular
stimulation. There is evidence from double-target experiments
(Edelman and Keller 1998
; Glimcher and Sparks
1993
; Van Opstal and Van Gisbergen 1990
) and double electrical-stimulation experiments (Robinson
1972
) that having two areas of collicular activity may give
rise to a phenomenon called saccade averaging, resulting in a
compromise movement. If averaging was responsible for the metric
modulation effect during vestibular rotation, one would expect the
M-vector to be directed toward the site near the horizontal meridian
where the vestibular activity locus would be expected (see Fig. 8,
right-hand section). As our results have shown, the actual
M-vector directions did not square at all with this hypothesis (see
Figs. 9C and 10, C and D). So our
study does not provide evidence for a collicular role in the observed
interaction effects.
Since we found that the metric and kinematic effects were predominant
in the E-saccade component aligned with the direction of rotation (see
Figs. 10D and 14C), the most parsimonious
explanation is to assume that they occurred at a level where components
are specified, rather than at a vectorial-coding stage. If so, the interaction site must have been somewhere downstream of the superior colliculus, in line with earlier models for the generation of quick
phases that emphasized the role of brain stem mechanisms (Anastasio 1997
; Galiana 1991
). All
significant kinematic effects indicate involvement of an
anticompensatory signal, just as many of the metric findings. In
addition, both metric and kinematic changes were proportional to head
velocity. To explain these observations, we assume that a head-velocity
signal, that carries the appropriate sign, was added to the horizontal
component of the E-saccade. More specifically, since BDNs carry such a
head velocity signal (see Fig. 1), we suggest that cells of this type
(or a neural equivalent) may have been involved. Normally, during
vestibular rotation applied in isolation, the head-velocity signal of
BDNs will not come to expression since EBNs are shut off by the
pause cells. Only if the BDNs carry a burst, their activity will be strong enough to enforce a rapid eye movement (a quick phase). However,
the situation becomes different in the conditions of our experiment
when the pause cell gate has already been forced open by the collicular
E-stimulation. Once the gate is open, we suggest, the added
head-velocity signal can augment or decrease the burst cell signal
imposed by SC stimulation, depending on the direction of rotation
relative to the direction of the saccade. Since the head-velocity
signal is only present on horizontal BDNs, only horizontal burst cells
would be affected in this fashion, leaving the vertical burst cells
unmodified. Such a scheme can nicely explain the kinematic modulation
effect typical of virtually all experiments, including the observation
that the effect was proportional to head velocity. It should be noticed
that the more specific version of our hypothesis can only be
preliminary, since BDNs, which have been amply studied in the cat, have
only been found in the vertical channel in the monkey, so far
(Kaneko and Fukushima 1998
).
The involvement of an anticompensatory signal in the kinematic data is
obvious (see Fig. 13), but why did this not always lead to
anticompensatory metric changes? Recall that compensation for the
ongoing head movement was almost never complete and was seen only in
smaller E-saccades (see Fig. 7A). Could VOR slow-phase addition have played a role as well, in this amplitude range, by adding
a compensatory signal (see Fig. 1)? It is thought that the gain of the
VOR is attenuated during large gaze shifts, leaving the VOR active
during small saccades (Guitton and Volle 1987
; Laurutis and Robinson 1986
; Pélisson et al.
1988
; Roy and Cullen 1998
; Tabak et al.
1996
; Tomlinson 1990
; Tomlinson and Bahra
1986
). By itself, the addition of such a VOR signal may account
for the partial compensation seen in small E-saccades (see Fig.
7A). Yet, several phenomena are not well understood at
present. First, experiments yielding a compensatory metric effect may
still have an anticompensatory kinematic effect. In other words, the
size of the horizontal component may decrease, but its peak velocity
may still be higher than expected for that amplitude. Second, we found
that the sizes of the metric and kinematic effects obtained in the same
experiments were uncorrelated and did not share the same relation with
saccade duration (see Fig. 7, A and B). Third,
within a given experiment, saccade-by-saccade deviations from the
metric regression line (yielding the M-vector) typically were not
correlated with deviations with the kinematic regression line (yielding
the K-vector). Taken together, these findings indicate that the
processes determining E-saccade component amplitude during rotation and
those affecting its peak-velocity/amplitude relation are not simply two
sides of the same coin. Even when both effects are in the
anticompensatory direction, as was often the case, their magnitudes are
not rigidly coupled. Settling these questions concerning the precise
neural origin of the compensatory and anticompensatory signals awaits
further investigation. Our results also raise a quite different issue
that we will have to discuss: The occurrence of anticompensatory metric
effects appears directly at odds with firmly based notions about the
spatial accuracy found in natural gaze shifts.
Spatial accuracy in natural and electrically induced gaze shifts
An important question is how the oculomotor system can generate
accurate gaze shifts, both when the head is still and when it is
moving. There is considerable evidence that the gaze control system can
produce accurate gaze shifts, even though the head contribution varies
from trial to trial (for review, see, e.g., Guitton
1992
). It also has become apparent that sudden perturbations of
the head movement, as well as passively imposed head movements, are
taken into account so that gaze accuracy is maintained (Guitton and Volle 1987
; Laurutis and Robinson 1986
;
Pélisson et al. 1988
, 1995
; Tomlinson
1990
; Tomlinson and Bahra 1986
). The problem for the brain, in controlling accurate gaze shifts, is to implement an
eye-head strategy that allows all involved subsystems (saccadic system,
quick-phase system, VOR, and the head control system) to cooperate.
The question of how this is possible has been subject of extensive
investigation and modeling efforts. Bizzi and colleagues (Bizzi
et al. 1971
; Dichgans et al. 1973
;
Morasso et al. 1973
) suggested that even when the
saccadic command for a given target location would always be fixed,
independent of whether the head is fixed or free, the variable head
contributions would be nulled out by the VOR. Since it appears that the
VOR is at least partially suppressed during large gaze shifts
(Guitton and Volle 1987
; Laurutis and Robinson
1986
; Pélisson et al. 1988
; Roy and
Cullen 1998
; Tabak et al. 1996
; Tomlinson
and Bahra 1986
), this so-called linear addition hypothesis
fails to explain the data during large gaze saccades. As an alternative
explanation of gaze accuracy, several models have suggested that the
control signal in the head-free situation is a desired
gaze-displacement command (Guitton and Volle 1987
;
Laurutis and Robinson 1986
; Roucoux et al.
1980
; Tomlinson and Bahra 1986
; for reviews see
Becker 1991
and Guitton 1991
, 1992
). In these schemes, gaze
feedback adjusts the saccadic control system for the variable head
contributions that may change from trial to trial. However,
Freedman (2001)
recently proposed a gaze control model
that accurately mimics metric and kinematic properties of gaze shifts
without relying on gaze feedback.
If the electrical stimulation in the SC evokes a desired gaze shift to
a spatially fixed location, the oculomotor system somehow needs to
correct the eye contribution for any ongoing head movement to maintain
gaze-shift constancy and ensure spatial accuracy. Actually, our results
show that in a clear majority of experiments vestibular rotation led to
violations of spatial accuracy, ranging in a continuum from
undercompensation to changes in the wrong direction (see Fig.
7A). Looking for a plausible source of the anticompensatory
vestibular signal, responsible for these violations, we have already
proposed that the quick-phase system may have been responsible (see
section Evidence that the modulation occurs downstream of the
SC). This suggestion is not new: the possibility that the
quick-phase system may be active when the head rotates is one of the
major features in the models proposed by Barnes (1981)
and by Guitton and Volle (1987)
. In their schemes, the brain stem pulse generator is driven by the saccadic and the
quick-phase systems, working in conjunction, but gaze feedback ensures
that spatial accuracy is maintained.
Such a contribution from the quick-phase system may have been
responsible for "some extra source of innervation" to the pulse generator invoked by Laurutis and Robinson (1986)
who
investigated the eye contribution during gaze shifts when subjects were
passively rotated toward the target. They found that these saccades
became faster (reminiscent of our kinematic findings) but nevertheless retained their accuracy (no metric effect): a clear difference with the
present results. Our frequent failure to see gaze accuracy is also in
stark contrast to several other studies showing that natural gaze
saccades to a visual target do maintain spatial accuracy, independent
of whether the head movement is normal, perturbed, or passively
generated (Guitton and Volle 1987
; Pélisson
et al. 1988
, 1995
; Tomlinson 1990
; Tomlinson and
Bahra 1986
). Recently, we have studied saccadic responses to
flashed targets in head-fixed human subjects during passive vestibular
rotation (Van Beuzekom and Van Gisbergen 2002
).
Refixations to the remembered target often consisted of several
saccades and showed clear evidence of compensation for intervening
vestibular eye movements.
Furthermore, there is evidence that eye-head coordination mechanisms
governing normal gaze shifts to visual targets and those determining
electrically induced gaze shifts in the head-free and the head-fixed
animal may be different as well. Coimbra et al. (2000)
observed in the cat that increasing the moment of inertia of the head
led to compensatory changes in the eye saccade when the target was a
visual flash, but these adjustments were absent when the gaze shift was
elicited by collicular electrical stimulation. Freedman et al.
(1996)
have emphasized that there are strong similarities in
the partitioning of the total gaze shift into eye and head contributions in both paradigms (electrical stimulation against natural
behavior) when the head is free to move. For example, the eye
contribution in both types of experiment is strongly dependent on
initial eye position. However, if the same collicular site is then
activated by electrical stimulation while the head is kept fixed, the
typical result is that the eye still maintains the same initial eye
position dependence without compensating for the lost head
contribution. By contrast, when there is a natural target, the eye
makes a larger movement to keep the total gaze shift normometric. This
discrepancy can be seen as another indication that electrically induced
gaze shifts seem to ignore crucial information that is available to the
normal system. It is as if gaze shifts caused by electrical stimulation
follow rigid default rules for specifying eye and head contributions
that fail to take into account that certain conditions may make this
default strategy inadequate.
It is still unclear why E-saccades lack the ability of normal saccades
to maintain gaze constancy during passive rotation. The hypothesis that
the putative gaze feedback system is corrupted during E-stimulation
(Coimbra et al. 2000
) is interesting but requires
rigorous further testing and more refinement. A problem for the model
is that an electrically induced gaze disturbance of the natural
response to a visual remembered target is properly corrected
(Pélisson et al. 1995
), indicating that the
internal feedback loop can monitor even these artificial movements
accurately. Motor strategies based on feed-forward mechanisms,
calibrated by training, deserve more attention than they have received
so far. As work on saccadic adaptation has shown (Melis and Van
Gisbergen 1996
), if a natural saccade has been adapted to new
circumstances, this change in the control signals does not transfer to
comparable E-saccade vectors. Since E-saccades lack several signals
accompanying normal saccades, feed-forward contributions recruited by
these signals may also be different. For this reason, Freedman's
model, which was developed for head-free voluntary gaze shifts
(Freedman 2001
), cannot be applied to our experimental
conditions in a straightforward manner. By providing a tool to corrupt
spatial accuracy, the paradigm used in this study may be valuable in
further exploration of its underlying mechanisms.
Conclusion
Our data show that vestibular stimulation modulated E-saccade metrics and kinematics. Since the effect predominated in the E-component aligned with the direction of rotation, we suggest that saccadic and vestibular signals converge downstream of the colliculus. Addition of an anticompensatory signal, attributed to the quick-phase system, often led to clear violations of spatial accuracy. Why E-saccades deviate from normal saccades in this respect remains to be determined.
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ACKNOWLEDGMENTS |
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The staff of the central animal facility provided excellent care for our monkeys. We thank G. Windau, G. Van Lingen, H. Kleijnen, and T. Van Dreumel for technical support. The authors also acknowledge helpful discussions with C. Kaneko, G. Barnes, and D. Guitton. P. Medendorp gave useful critical comments on an earlier version of the manuscript. Two anonymous referees gave valuable comments that substantially improved the paper.
This work was supported by the Council for Earth and Life Sciences (ALW-NWO).
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FOOTNOTES |
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Address for reprint requests: A. D. Van Beuzekom, 231 Dept. of Biophysics, University of Nijmegen, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
Received 13 August 2001; accepted in final form 30 January 2002.
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REFERENCES |
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This article has been cited by other articles:
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A. D. Van Beuzekom and J.A.M. Van Gisbergen Interaction Between Visual and Vestibular Signals for the Control of Rapid Eye Movements J Neurophysiol, July 1, 2002; 88(1): 306 - 322. [Abstract] [Full Text] [PDF] |
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