1Eye and Ear Research Unit,
Thurtell, Matthew J.,
Ross A. Black,
G. Michael Halmagyi,
Ian S. Curthoys, and
Swee T. Aw.
Vertical eye position-dependence of the human vestibuloocular reflex
during passive and active yaw head rotations. The effect of
vertical eye-in-head position on the compensatory eye rotation response
to passive and active high acceleration yaw head rotations was examined
in eight normal human subjects. The stimuli consisted of brief, low
amplitude (15-25°), high acceleration
(4,000-6,000°/s2) yaw head rotations with respect to the
trunk (peak velocity was 150-350°/s). Eye and head rotations were
recorded in three-dimensional space using the magnetic search coil
technique. The input-output kinematics of the three-dimensional
vestibuloocular reflex (VOR) were assessed by finding the difference
between the inverted eye velocity vector and the head velocity vector
(both referenced to a head-fixed coordinate system) as a time series.
During passive head impulses, the head and eye velocity axes aligned
well with each other for the first 47 ms after the onset of the
stimulus, regardless of vertical eye-in-head position. After the
initial 47-ms period, the degree of alignment of the eye and head
velocity axes was modulated by vertical eye-in-head position. When
fixation was on a target 20° up, the eye and head velocity axes
remained well aligned with each other. However, when fixation was on
targets at 0 and 20° down, the eye velocity axis tilted forward
relative to the head velocity axis. During active head impulses, the
axis tilt became apparent within 5 ms of the onset of the stimulus. When fixation was on a target at 0°, the velocity axes remained well
aligned with each other. When fixation was on a target 20° up, the
eye velocity axis tilted backward, when fixation was on a target 20°
down, the eye velocity axis tilted forward. The findings show that the
VOR compensates very well for head motion in the early part of the
response to unpredictable high acceleration stimuli For the angular vestibuloocular reflex (VOR) to
stabilize an image on the retina, it must generate an eye movement
equal in speed but exactly opposite in direction to the head movement
stimulus. Hence the eye and head velocity axes must be parallel to one
another, and the magnitude of the eye velocity must be equal to that of the head. In many experiments, the three-dimensional VOR in humans has
been investigated with the eye initially positioned in the center of
the ocular motor range at the onset of the head rotation stimulus. In
these experiments, the responses to yaw, pitch, and roll head movements
have been investigated, and the eye velocity axis was found to remain
approximately parallel with the head velocity axis (Aw et al.
1996 Fetter et al. (1992) Misslisch et al. (1994) Misslisch et al. (1994) In all of the previous experiments, the eye position-dependence of the
VOR was investigated using predictable, passive, low-frequency, steady-state stimuli. Furthermore, only the spatial characteristics of
the eye position-dependence were investigated; the temporal characteristics were not described. Our aim was to measure the effect
of vertical eye-in-head position on the response to high acceleration
yaw head rotations, which we have called head "impulses" (Halmagyi and Curthoys 1988 Paradigms and subjects
We conducted two experiments. In the first, the effect of
vertical eye-in-head position on the response to passive yaw head impulses (Halmagyi and Curthoys 1988
ABSTRACT
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
APPENDIX
REFERENCES
the eye position-
dependence of the VOR does not become apparent until 47 ms after the
onset of the stimulus. In contrast, the response to active high
acceleration stimuli shows eye position-dependence from within 5 ms of
the onset of the stimulus. A model using a VOR-Listing's law
compromise strategy did not accurately predict the patterns observed in
the data, raising questions about how the eye position-dependence of
the VOR is generated. We suggest, in view of recent findings, that the
phenomenon could arise due to the effects of fibromuscular pulleys on
the functional pulling directions of the rectus muscles.
INTRODUCTION
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
APPENDIX
REFERENCES
; Tweed et al. 1994
). Similar observations have been made in monkeys (Crawford and Vilis 1991
).
investigated the effect of
different initial eye-in-head positions on the three-dimensional
characteristics of the human VOR during the first 1-2 s of the
response to constant velocity (150°/s) rotations of the whole body in
yaw, pitch, and roll. They found that the eye velocity output of the
VOR systematically depended on eye-in-head position. When the initial
eye-in-head position was moved away from the center of the ocular motor
range, the eye velocity axis was observed to tilt away from its optimal orientation, thereby compromising retinal image stability.
made similar observations when
studying the response to sinusoidal (0.3 Hz) whole-body rotations in yaw, pitch, and roll. Specifically, during yaw rotations, the eye
velocity axis was observed to tilt away from its optimal position when
the initial eye-in-head position was either up or down. During pitch
rotations, the eye velocity axis was observed to tilt away from its
optimal position when the initial eye-in-head position was left or
right. During roll rotations, the eye velocity axis tilted away from
its optimal position when the initial eye-in-head position was up,
down, left or right. Misslisch et al. (1994)
noted that
the axis tilts were such that the foveal image always remained
stabilized during the rotations being studied; only peripheral retinal
image stability was compromised.
concluded that the axis tilts
arose due to a compromise between perfect image stabilization and
Listing's law. Listing's law is a constraint on ocular kinematics
observed during fixations, saccades and smooth pursuit. The law states that for any eye position, there is an associated plane (the
displacement plane) such that the eye assumes only those
positions that can be reached from the initial position by a single
rotation about an axis in that plane (von Helmholtz
1962
). To keep these axes in the displacement plane during an
eye movement, the eye velocity vectors must systematically tilt
away from the displacement plane (because the time
derivative of angular eye position does not equal angular eye velocity)
(see Tweed and Vilis 1987
). Consequently, the velocity
vectors are found to lie in distinct planes (called velocity
planes) that have unique orientations depending on eye-in-head position
(Tweed and Vilis 1990
). Hence, if the VOR does partially obey Listing's law, then, in response to a head rotation stimulus, the
eye velocity axis will tilt toward the velocity plane for the current
eye-in-head position. One of the models presented by Misslisch
et al. (1994)
used a VOR-Listing's law compromise strategy, in
which the eye velocity vector was positioned exactly halfway between
its optimal position and the velocity plane as predicted by Listing's
law. As this model could predict, both qualitatively and
quantitatively, the mean axis tilts observed in the subjects,
Misslisch et al. (1994)
concluded that the
VOR-Listing's law compromise was responsible for the eye
position-dependence of the VOR. The compromise strategy was thought to
be neural in origin. There is now evidence that the functional pulling
directions of the rectus muscles change with eye-in-head position
(Demer et al. 1995
). Therefore the observed axis tilts
could arise as a result of orbital mechanics.
; Halmagyi et al.
1990
). The responses to passive, unpredictable head rotations
were contrasted with the responses to active predictable head
rotations. To characterize the response to both stimuli, we sought to
describe both the spatial and temporal characteristics of any eye
position-dependence observed in the responses.
METHODS
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
APPENDIX
REFERENCES
; Halmagyi et
al. 1990
) was investigated. The passive yaw head impulse is an
unpredictable, low-amplitude (15-25°), high-acceleration
(4,000-6,000°/s2) horizontal head rotation. It has a
peak velocity of 150-350°/s (the mean head velocities from each of
the subjects are plotted in Fig.
1A). During a passive yaw head
impulse, the axis of head rotation approximately aligns with the
z axis of the head (because the stimulus is delivered
manually, there is always a small vertical and torsional component to
the head rotation). In the experiment, the vertical position of the
fixation target was altered to be either straight ahead (0°), 20°
up, or 20° down relative to the subject's left eye. The head and eye
rotations were recorded during passive yaw head impulses for each of
the different vertical positions of the eye. The paradigm in which
passive yaw head impulses were applied with fixation straight ahead (at
0°) was exactly the same as that studied by Aw et al.
(1996)
.
View larger version (30K):
[in a new window]
Fig. 1.
A: mean horizontal, vertical, and torsional head
velocities from each subject during leftward and rightward
passive yaw head impulses. Impulse onset is indicated
(arrow). B: mean horizontal, vertical, and torsional
head velocities from each subject during active yaw head
impulses. Head velocity profiles generated during active head impulses
are similar to those generated during passive head impulses.
The second experiment was identical to the first except that the head
rotation stimulus used was an active (self-generated) yaw head impulse.
The head velocities recorded during the second experiment were similar
to those recorded in the first experiment (the mean head velocities
from each of the subjects are plotted in Fig. 1B). The use
of the active yaw head impulse stimulus has been reported previously
(Foster et al. 1997).
In the passive head impulse experiment, eight normal human subjects (26-55 yr, 37 ± 11 yr, mean ± SD) were tested. Eight normal human subjects (21-50 yr, 33 ± 10 yr, mean ± SD) were tested in the active head impulse experiment (6 of these subjects also were tested with the passive head impulse stimuli). None of the subjects had symptoms or signs of vestibular or ocular motor disease, and all were alert at the time of testing. Each subject gave informed consent before each test. The experimental protocols were approved by the Royal Prince Alfred Hospital Human Ethics Committee.
Recording system
Eye and head positions in three-dimensional space were measured
using the magnetic search coil technique (Collewijn et al. 1985; Robinson 1963
), with the subject seated in
the center of 1.9 × 1.9 × 1.9 m magnetic field coils
(CNC Engineering, Seattle, WA). Eye position was recorded with a dual
search coil (Skalar, Delft, The Netherlands) placed on the left eye.
Head position was recorded with a dual search coil secured to the
nosepiece of a lightweight spectacle frame. The spectacle frame was
strapped very tightly to the subject's head to prevent it from
slipping on the head. To confirm that movement of the spectacle frame
was coupled tightly to movement of the head, one subject was tested wearing the usual head coil on the spectacle frame and a search coil
attached to a bite bar. We assumed that movement of the bite bar was
coupled very closely to movement of the head. The difference between
the spectacle frame and bite bar coil velocities was very small (see
Fig. 2). The vertical components and
torsional components of the velocities were virtually identical
throughout the data analysis period. We did notice that, as the head
approached peak velocity, the horizontal component of the spectacle
frame coil velocity was slightly less than that of the bite bar coil.
However, the difference between the horizontal components of the
spectacle frame and bite bar coil velocities was always <5°/s.
|
The signal from the eye search coil was degraded significantly if the subject blinked during the head impulses. Hence the position of the eyelid in space was recorded with a 2-mm diam, two-dimensional induction coil that was lightly but securely attached to the eyelid to monitor for blinks. Data found to contain blinks were removed from any subsequent analysis.
The four signals from each search coil were recovered by phase detectors (CNC Engineering) and then passed through a custom-made antialiasing filter with a cutoff frequency of 100 Hz (only 2 signals were recovered from the "blink" coil and passed through the filter). The signals were digitized at 1 kHz with a 16-bit analog-digital converter (model AT-MIO-16X, National Instruments, Austin, TX) and then saved to the hard disk of an IBM-compatible PC running under Windows 3.11. Data acquisition programs for the PC were written in LabVIEW (Version 4.1, National Instruments).
Maximum peak-to-peak position noise of the search coil system was <1 min of arc, and maximum peak-to-peak velocity noise was ±3.6°/s. Because of the low system noise, the data did not require smoothing in software.
To preserve the linearity of the magnetic fields, all metallic objects
(except those essential for the normal functioning of the system) were
removed from the vicinity of the magnetic fields. Previous studies have
shown that this search coil system is not sensitive to translations of
the magnitude that occur during head impulses (Aw et al.
1996).
A fixation target was provided by a solid-state red laser, which was rear-projected onto a 2 × 1.5 m Plexiglas tangent screen placed exactly 94 cm from the front of the cornea. The laser position was altered by mirror galvanometers driven horizontally and vertically by the PC. The offset of the laser was adjusted so that the fixation spot was positioned in the exact center of the tangent screen (at the level of the subject's left eye).
Calibration procedures
Before each test, the head and eye search coils were calibrated
in vitro with a plexiglas Fick gimbal positioned in the exact center of
the magnetic fields. During the calibrations, the gimbal was moved
between ±20° (in 5° steps) for roll, pitch, and yaw positions
(each in a separate calibration). The signals from the search coils
were recorded at each calibration position. For the torsional,
vertical, and horizontal search coil channels, the signal voltage was
plotted against the sine of the calibration angle and an off-line
linear regression analysis (in Splus) was used to calculate the search
coil gain. The calibration was only considered acceptable if the square
of the multiple correlation coefficient (R2) for
the linear regression analysis was >0.99. R2
was always >0.9999 in these experiments. It was assumed that the gains
and offsets of the search coils were the same in vivo as during the in
vitro calibration (Aw et al. 1996; Haslwanter et
al. 1996
).
Experimental protocols
The subject was seated so that the head was positioned in the exact center of the magnetic fields. The front surface of the cornea of the left eye was positioned exactly 94 cm from the tangent screen.
In vivo calibration data were gathered while the subject was fixating
on a target placed in the center of the tangent screen. During this
calibration, the subject's head was positioned so that the yaw, pitch,
and roll signals from the head search coil were in a software window of
±1° from the zero position of the head. The in vivo calibration was
repeated at regular points during each test. The data from the in vivo
calibrations were used to correct for the misalignment of the search
coil on the eye (as in Tweed et al. 1990).
Listing's plane data were collected at the beginning of each test. The subject was instructed to fixate a number of dots arranged concentrically (from ±20°) on the tangent screen. At least 90 s of data were collected, to calculate the orientation of Listing's plane. During the acquisition of the data, the subject's head was held firmly so that the yaw, pitch, and roll signals from the head search coil were maintained steadily in the ±1° software window.
The head impulse experiments were conducted in soft lighting conditions, with the subject comfortably seated in the center of the magnetic fields. Before the onset of each head impulse (passive or active), the experimenter was required to alter the subject's head position so that the signals from the head search coil were in the ±1° software window. For the passive head impulses, once the head was positioned correctly, the data acquisition system was triggered manually. Subjects were instructed to stare at the fixation target while the head was rotated quickly to the left or the right by the experimenter. Data acquisition ceased a few seconds after the head impulse onset. For the active head impulses, once the head was positioned correctly, the experimenter removed his or her hands from the vicinity of the subject's head. The subject was required to maintain the head position, and, on command, quickly rotate their head to the predetermined side while maintaining fixation on the laser target. Data acquisition commenced ~1 s before the onset of the impulse and ceased a couple of seconds after the onset. Data from subjects who moved their head before the onset of the active head impulse were discarded. The subjects were carefully tutored and given ample time to practice before the search coil was placed on the eye.
Some of the active head impulse experiments were carried out with the subject in complete darkness to investigate whether the response changed when there was no visual input. The laser target was extinguished immediately before the onset of the impulse so that there were no visual cues during the impulse. During these tests, the experimenter wore a virtual reality headset (Virtual i-O, Seattle, WA), enabling them to view the head search coil signals (and therefore position the head so that the coil signals were in the ±1° software window) without compromising the dark environment in which the subject was placed.
Some of the passive and active head impulse tests were carried out on
more than one occasion to determine how consistent the responses from a
single subject were on repeated testing. In all cases, the data from
the initial test were used in the analysisthe data from the repeated
tests were only used for comparison with the previously collected data.
Data analysis
All data were analyzed off-line on a DECstation 5000/240 using C
and Splus (Becker et al. 1988), under Ultrix. The
analysis procedures applied to the data from both experiments were identical.
The horizontal and vertical Fick angles representing eye and head
position, with reference to a right-handed space-fixed coordinate system, were calculated from the raw data and the search coil gains
using the methods described by Haslwanter (1995). The
torsional Fick angle (with reference to a right-handed space-fixed
coordinate system) was calculated using the equation from Bruno
and van den Berg (1997)
to correct for nonorthogonality between
the direction and torsion induction coils of the search coil.
Nonorthogonality between the induction coils results in pseudotorsion
during purely vertical movements of the search coil. The correction
proved effective in eliminating the error (see APPENDIX).
The Fick angles were used to calculate the rotation matrices
representing the eye and head rotations in three-dimensional space. The
in vivo calibration data were used to calculate the offset rotation
matrix for both the eye and head in three-dimensional space. Using the
methods described by Tweed et al. (1990), the raw eye
and head rotation matrices were corrected for any position offset using
the offset rotation matrices. From the corrected rotation matrices, the
rotation vectors representing head and eye position were calculated
(Haslwanter 1995
; Haustein 1989
). The
velocity vectors of the head-in-space, eye-in-space, and eye-in-head were calculated from the corresponding rotation vectors using the
equation from Hepp (1990)
. We calculated head velocity
with reference to a head-fixed coordinate frame using the methods of Aw et al. (1996)
so that the eye and head velocities
were expressed with reference to the same coordinate frame for our
analysis. Head velocity with reference to a head-fixed coordinate frame is simply the velocity of the head-in-space expressed with respect to
the head-fixed coordinate frame. The concept is illustrated in Fig.
3.
|
Models presented later in the paper require that the orientation of
Listing's plane be known for each subject. The 90 s of Listing's
plane data were used to fit a plane of best fit, using a singular value
decomposition algorithm (Press et al. 1988)
![]() |
The time of onset of each head impulse was calculated using an
algorithm developed by Aw et al. (1996). The analysis of
the head-impulse data was restricted to a period of 100 ms, beginning 20 ms before the onset of the head impulse. Thus in the case of the
passive head impulses, the effects of non-VOR systems (such as the
cervicoocular reflex and smooth pursuit) were excluded because these
systems have latencies >90 ms after the onset of head rotation
(Bronstein and Hood 1986
; Carl and Gellman
1987
; Tychsen and Lisberger 1986
).
The data were not desaccaded because saccades and quick phases do not
normally occur within 100 ms of the onset of passive head impulses
(Aw et al. 1996) or, as we discovered, active head impulses. Nevertheless, all head impulse data were inspected visually to check for blinks, search coil slippage, and other artifacts; data
that showed such artifacts were not included in the analysis.
The spatial alignment of the head and eye velocity axes (with reference to a head-fixed coordinate frame) was displayed by plotting the head and eye velocity vectors in the pitch (xz) and roll (yz) planes. Data were not plotted in the yaw (xy) plane as these plots did not clearly illustrate the spatial arrangement of the vectors (the head and eye velocity vectors were aligned fairly closely to the z axis of the head, which is coincident with the origin of the yaw plane).
The temporal characteristics of any eye-head axis misalignment cannot
be illustrated clearly in the pitch and roll plane plots; a complete
three-dimensional VOR performance measure is required. The temporal
characteristics of VOR performance initially were measured using the
indices (misalignment angle, speed gain, and VOR gain) introduced by
Aw et al. (1996). At low eye and head velocities,
however, the indices cannot be calculated because of the presence of
erratic values introduced by the processing. To overcome this problem,
we developed a new performance measure that allowed complete
description of the input-output kinematics of the VOR in three
dimensions, regardless of eye or head velocity. The performance
measure, named the VOR error vector (
), is simply the
difference between the velocity vectors representing the head (
h) and eye (
e) rotations with reference
to a head-fixed coordinate frame
![]() |
|
For the first experiment (passive yaw head impulses), the analysis also
involved the calculation of misalignment angle, speed gain, and VOR
gain so that we could directly compare our results with those of
Aw et al. (1996). These indices were calculated 80 ms
after impulse onset, near the peak head and eye velocities, where the
low-velocity artifact would be minimal.
Means ± two-tailed 95% confidence intervals were computed for
the time series, misalignment angle, speed gain, and VOR gain. At
various stages in the data analysis, a standard two-sample t-test was performed to establish the existence of a
significant difference or otherwise between two samples. The
P value was set at 0.05, and the null hypothesis was that
the difference between the means of the two samples was equal to zero.
![]() |
RESULTS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
The results from the two experiments are considered separately. There are three categories of analysis for each experiment: position and velocity time series, spatial alignment of the head and eye velocity vectors in three-dimensional space, and three-dimensional analysis of the input-output kinematics of the VOR.
Position and velocity time series for passive head impulses
The horizontal, vertical, and torsional components of the VOR in response to leftward passive yaw head impulses, from one subject, with gaze directed toward each of the three vertical targets are plotted against time in Fig. 5A. Position and velocity data for head-in-space, eye-in-space, and eye-in-head are shown. Head rotation data with reference to a head-fixed coordinate frame are not displayed in this plot.
|
The horizontal and vertical eye-in-head components are the mirror
images of the corresponding head-in-space components, regardless of
vertical eye-in-head position. Consequently the horizontal and vertical
components of gaze remain constant throughout the impulses. The degree
to which the eye-in-head torsion component mirrors the head-in-space
torsion depends, however, on the vertical eye-in-head position. The
effect is most obvious in the velocity traces, when the torsional
eye-in-head components 125 ms after head impulse onset (large arrows in
Fig. 5A) are compared with each other. The torsional
eye-in-head response most closely matches the torsional head-in-space
stimulus when the vertical eye-in-head position is 20° up. As the
vertical eye-in-head position moves from 20° up to 20° down, the
torsional eye-in-head velocity becomes progressively more
counterclockwise relative to an ideal torsional eye-in-head
response. The eye-in-head torsional responses during rightward yaw head
impulses were the opposite of those observed during the leftward yaw
head impulsesas vertical eye-in-head position progressively moved
from up to down, the eye-in-head velocity became progressively more
clockwise relative to an ideal eye-in-head response. Any
mismatch between the torsional eye-in-head and head-in-space traces
resulted in a subtle torsional gaze offset at the end of the impulse.
The torsional gaze offset was least when vertical eye-in-head position
was 20° up and became progressively greater when fixation was on
targets at 0 and 20° down (see dashed traces in Fig. 5A).
The responses shown in Fig. 5A are representative of the data obtained from the entire group. In each subject, the direction and magnitude of the torsional eye-in-head response was consistent for each vertical fixation position, throughout each test and on repeated testing.
Velocity axis alignment in passive head impulses
Mismatch of the torsional eye-in-head and head-in-space velocities, especially when fixation was on the targets at 0 and 20° down, suggests misalignment of the head and eye velocity axes. To allow the velocities to be compared, both were calculated relative to the same head-fixed coordinate frame. The eye-in-head velocity vector also was inverted to facilitate comparison between the two vectors. The spatial alignment of the mean eye-in-head and head-in-head velocity vectors (averaged across all 8 subjects) for each of the vertical eye-in-head fixation positions is shown in Fig. 6A. In Fig. 6A, the vectors are shown in two planes (pitch and roll) to display the degree of vector alignment in all three dimensions.
|
The eye velocity vector most closely aligned with the head velocity vector, in both the pitch and roll planes, when the vertical eye-in-head position was 20° up. The vectors became increasingly misaligned in the pitch plane as the vertical eye-in-head position moved from up to down; the eye velocity vector tilted forward as eye position moved from up to down. Surprisingly, the eye and head velocity vectors remained aligned at low velocities for all vertical eye-in-head positions. The eye position-dependence of the response only became obvious when eye velocity was >75°/s. In contrast, the eye and head velocity vectors remained aligned in the roll plane, regardless of vertical eye-in-head position.
Input-output analysis for passive head impulses
To evaluate how closely eye velocity mirrored head velocity, the
VOR error vector () was calculated for each of the three vertical
eye-in-head fixation positions. The time series of the horizontal,
vertical, and torsional components of
are plotted for each vertical
eye-in-head fixation position (see Fig.
7A).
|
When the data from the left and right impulse sets were compared, no
large asymmetries were observed. There was a significant difference
(P < 0.05) when the left and right horizontal
components of (
z) in the center (0°) fixation
condition were compared at 80 ms after the impulse onset, indicating a
small left-right asymmetry in the VOR responses of the subject group
(see Fig. 7A). No significant difference was observed for
any of the other conditions.
z was consistently larger than the other
components
(mean maximum values were 20.8°/s for leftward impulses and 33.1°/s for rightward impulses), regardless of the vertical eye-in-head fixation position, in all subjects. Thus horizontal eye velocity did
not exactly match the horizontal head velocity in any of the fixation
conditions. There was, however, considerable variability in the extent
to which the horizontal eye velocity matched horizontal head velocity.
No significant differences were observed between
z (at
40 and 80 ms after impulse onset) for each of the vertical eye-in-head
fixation positions (P > 0.05), indicating no
dependence of
z on vertical eye-in-head position.
There was a small vertical component of (
y) in
most subjects
mean maximum values were <±10°/s for each of the
vertical eye positions. When
y for each of the vertical
eye-in-head fixation positions (at 40 and 80 ms after impulse onset)
were compared, they were not significantly different (P > 0.05).
In contrast, the torsional component of (
x)
varied systematically with vertical eye-in-head fixation position: it
was consistently small throughout the head impulses when the fixation
position was 20° up, it became larger when the fixation position was
central and larger again when the fixation position was 20° down.
However, for all vertical eye-in-head fixation positions, the magnitude of
x was similar for the first 40 ms after the onset of
the head impulse
only in the last 40 ms of the data analysis period
did the changes in
x magnitude become apparent. The
means ± two-tailed 95% confidence intervals of
x
at 40 and 80 ms after the onset of the head impulse, for the responses
to both leftward and rightward impulses, are listed in Table
1. When
x for each of the
vertical fixation positions was compared 40 ms after impulse onset, the differences were not significant (P > 0.05). However,
a significant difference (P < 0.05) was observed 80 ms
after the impulse onset. The time at which the vertical eye-in-head
position dependence becomes significant (P < 0.05),
defined as the point at which
x for the 20° up and
20° down conditions become significantly different, was 47 ms after
the onset of the head impulse.
|
Position and velocity time series for active head impulses
The three components of the response to leftward active yaw head impulses, from one subject, with fixation on each of the three vertical targets are plotted in Fig. 5B. For each of the different vertical eye-in-head fixation positions, the horizontal and vertical components of eye in head are, once again, the approximate mirror images of the corresponding components of head in space, and the horizontal and vertical components of gaze remain constant throughout the impulses. The torsional component of eye in head does not mirror the torsional component of head in space in the 20° up and 20° down conditions, but it does when fixation is at 0°. When vertical eye-in-head fixation position is 20° up, the eye-in-head torsion is clockwise relative to an ideal eye-in-head response; when fixation is 20° down, the eye-in-head torsion is relatively counterclockwise. Subsequently, there are torsional gaze offsets at the end of these two impulses, unlike when fixation is on the center target. Once again, the eye-in-head torsional responses during rightward yaw head impulses were the opposite of those observed during the leftward impulses.
The patterns observed in Fig. 5B are representative of the results from the whole subject group in response to leftward active head impulses. For each subject, the direction and magnitude of the response was very consistent for each vertical eye-in-head fixation position throughout the test, on repeated testing, and when tested in complete darkness. The magnitudes of the responses did differ between subjects (as with the passive head impulses).
Velocity axis alignment in active head impulses
The spatial alignment of the mean eye and head velocity vectors (averaged across all 8 subjects) for each of the vertical eye-in-head fixation positions is shown in Fig. 6B. Note that the head velocity profiles for the three vertical eye-in-head fixation positions are similar, indicating that the head rotation stimulus was consistent regardless of eye position.
The head and eye velocity vectors were most closely aligned in the
pitch and roll planes when the vertical eye-in-head fixation position
was at 0°, although the vectors did not align perfectly at low
velocities in the pitch plane. When the vertical eye-in-head fixation
position was 20° up or 20° down, the vectors did not align in the
pitch plane. The vectors remained well aligned in the roll plane,
regardless of vertical eye-in-head position. In general, the eye
velocity vectors tilted forward when the vertical eye-in-head position
was 20° down, and tilted backward when it was 20° up. It is clear
from the pitch plane plots that the eye and head velocity vectors do
not necessarily align well at low velocitiesthe degree of the
alignment does show some eye position-dependence. For example, in Fig.
6B, when the vertical eye-in-head position is 20° down,
the head and eye velocity vectors do not align well at the low
velocities, in contrast with the responses to the passive head impulses
(see Fig. 6A).
Input-output analysis for active head impulses
The means ± two-tailed 95% confidence intervals of
x,
y, and
z for the
subject group are shown in Fig. 7B with vertical eye-in-head
fixation position at 0°, 20° up, and 20° down. The responses from
leftward active head impulses are illustrated in black shading, whereas
those from the rightward active head impulses are illustrated in gray.
There were no significant left-right asymmetries (P > 0.05). The mean maximum values of z were 10.6°/s for
leftward active head impulses and 15.8°/s for rightward impulses.
Thus the horizontal eye velocity did not exactly match the horizontal
head velocity in any of the conditions. No significant differences were
observed when
z (at 40 and 80 ms after impulse onset) at
each of the vertical fixation positions was compared (P > 0.05), indicating no dependence of
z on vertical eye position.
The mean maximum values of y were < ±10°/s.
When
y at each of the fixation positions was compared
(at 40 and 80 ms after impulse onset), no significant differences were
observed (P > 0.05).
The profile of x did vary systematically depending on
the vertical fixation position: it remained closest to zero throughout the data analysis period when fixation was on the target at 0°. For
leftward impulses, it became increasingly negative when fixation was on
the 20° up target (indicating that the torsional eye velocity was
more clockwise than the ideal response). When fixation was on the 20°
down target, it became increasingly positive (indicating that the
torsional eye velocity was more counterclockwise than the ideal
response). The opposite was observed in the rightward active head
impulses. There was considerable intersubject variability in the
magnitude of the responses, in particular, when fixation was on the
20° up target. However, the directions of the responses were
consistent within the group.
The means ± two-tailed 95% confidence intervals of
x at 40 and 80 ms after active head impulse onset, for
the responses to both leftward and rightward impulses, are listed in
Table 2. When
x at 40 ms
after impulse onset was compared, a significant difference
(P < 0.05) was found between the 0° and 20° down
fixation positions and the 20° up and 20° down fixation positions.
At the 80-ms point, when
x for each of the fixation
positions were compared, there was a significant difference
(P
0.01).
x for the 20° up and
20° down fixation positions became significantly different (P < 0.05) within the first 5 ms after the onset of
the active head impulses. Thus
x depends on vertical
eye-in-head fixation position from 5 ms after the onset of an active
head impulse in contrast with the response to a passive head impulse,
which does not become eye position-dependent until 47 ms after onset.
|
![]() |
DISCUSSION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
VOR during central fixation
When fixation was on a target at 0° during the passive yaw head
impulses, the head and eye velocity axes did not remain perfectly aligned for the duration of the data analysis period, and the horizontal eye velocity was slightly less than that of the head. Aw et al. (1996) made similar observations. They
calculated time series of the angle between the eye and head velocity
axes (misalignment angle), the speed gain of the response (magnitude of
eye velocity divided by magnitude of head velocity), and the VOR gain
(speed gain multiplied by the cosine of misalignment angle). To compare our results directly with those of Aw et al. (1996)
, we
calculated the misalignment angle, speed gain, and VOR gain at 80 ms
after the head impulse onset. Our calculated values and those reported by Aw et al. (1996)
are listed in Table
3. The mean values from the present study
lie within the two-tailed 95% confidence intervals reported by
Aw et al. (1996)
.
|
In pilot experiments, we observed that the VOR became less compensatory
when head velocity was >350°/s during passive head rotation. Our
observation is in agreement with previous findings. Pulaski et
al. (1981) found that the VOR compensated well for head
velocities up to ~350°/s during both active and passive head rotation, provided there was an attempt to visualize a real or imagined
target in space.
We found that the eye and head velocity axes aligned better during the
active head impulses with fixation at 0° than during the passive head
impulses. Furthermore the horizontal components of eye and head
velocity were matched more closely during the active head impulses than
during the passive head impulses. z was significantly
smaller at 40 and 80 ms after impulse onset in the active head impulses
(P < 0.05). The horizontal head velocities of the two
stimuli were similar (see Fig. 1), so differing head rotation
kinematics would not explain why there is less horizontal error in
response to the active head impulses. We suggest that other neural
mechanisms (e.g., horizontal VOR gain enhancement) could be responsible
for improving the compensatory eye movement performance during active
head impulses in normal subjects.
VOR and vertical eye position
The three-dimensional orientation of the eye velocity axis changed
when vertical eye-in-head position was varied during both passive and
active head impulses. The shifts in eye velocity axis were most obvious
in the pitch plane: when the vertical eye-in-head position was 20°
up, the eye velocity axis tilted backward, when the vertical
eye-in-head position was 20° down, the eye velocity axis tilted
forward. The spatial characteristics and magnitudes of the axis shifts
agree with previous findings reported for both passive (Fetter
et al. 1992; Frens et al. 1996
; Misslisch
et al. 1994
) and active head rotations (Misslisch
1995
).
We found considerable intersubject variability in the magnitudes of the
axis shifts. Misslisch (1995), who also observed large intersubject variability, suggested that the variability could be
related to the level of alertness of the subject. In our experiments, subjects who were drowsy at the time of testing were noted to have
subtle axis tilts compared with when alert. Such a finding would be
consistent with the idea of a VOR-Listing's law compromise because
Listing's law fails during sleep (Nakayama 1975
).
However, the level of alertness in the subjects was not objectively
measured in the experiments. Therefore it cannot be concluded that
differing alertness levels were responsible for the observed variations in the magnitude of axis tilt. To the contrary, the majority of subjects who showed subtle responses during their initial test continued to do so on repeated testing regardless of their apparent alertness level. It appears then that the variation in the axis shift
magnitude is more likely due to variations between subjects, rather
than to the level of alertness of the subject.
The temporal courses of the axis tilts have not been previously
studied. Our measurements of the VOR error vector () show that
during passive head impulses, the head and eye velocity vectors show a
similar profile of misalignment in the first 47 ms after head impulse
onset, regardless of vertical eye-in-head position! It was only after
this period that differences appeared in
x for the
different vertical fixation positions. Also the head and eye velocity
axes were well aligned in the pitch plane at low velocities (<75°/s)
regardless of vertical eye-in-head fixation position. Whether the lack
of relative misalignment between the different vertical fixation
positions is velocity related or due to a latency in the response is
unclear. Evidence that suggests that the axis tilt is not velocity
related includes the finding that axis shifts are still present for the
different vertical eye positions at velocities <50°/s
(Misslisch et al. 1994
). Therefore it appears that after
the onset of a passive yaw head impulse there is a 47-ms delay before
the VOR becomes dependent on vertical eye position.
In contrast, after an active yaw head impulse there is <5 ms delay before the VOR becomes dependent on vertical eye position. Therefore the major finding from this study is that there is vertical eye position-dependence in the response to both active and passive high-acceleration head rotations; the eye velocity generated depends on both the head velocity stimulus and the current vertical eye-in-head position. The eye position-dependence is not apparent in response to the passive head impulses until 47 ms after impulse onset, whereas it is apparent within 5 ms of impulse onset when the stimulus is actively generated. The findings are summarized in Fig. 8, which shows the mean misalignment angle between the eye and head velocity axes in the pitch plane as a function of time for both passive and active head impulse stimuli.
|
Consequences for retinal image stabilization
To investigate the effect of the axis shifts on retinal image
stabilization for both sets of head impulse stimuli, a computer simulation was developed. In the simulation, an array of target points
on a tangential screen 94 cm from the eye was rotated passively using
representative rotation matrices from the eye-in-space position data.
The target points were, at each millisecond in time, projected on to
the back of a sphere corresponding to the retina of the eye. The
dimensions of the sphere and fovea corresponded to anatomic data
(Williams et al. 1989). The result of the simulation was a representation of the cumulative slip or smear of the retinal image
over the course of each head impulse.
First, we examined how much slip occurred in the first 60 ms of the data analysis period (from 20 ms before impulse onset to 40 ms after impulse onset). In response to the passive head impulses, very little retinal slip was evident. Therefore the VOR is very effective in stabilizing the retinal image in response to very short-duration (<40 ms) high-acceleration yaw head rotations regardless of the initial vertical eye-in-head position. In response to the active head impulses, there was little retinal slip when the vertical eye-in-head position was at 0°. When the vertical eye-in-head fixation position was 20° up and 20° down, there was slippage of the image in the periphery of the retina and over the fovea with the point of maximum stability being near the lower and upper poles of the retina, respectively. It seems then that the response in active head impulses is optimized to stabilize retinal images when the starting eye position is near the center of the ocular motor range.
We also investigated how much retinal slip occurred over the entire
duration of the data analysis period. The foveal image was not well
stabilized for any of the fixation positions or either of the stimuli.
The fact that the horizontal eye velocity did not exactly match the
horizontal head velocity resulted in a degree of horizontal image slip
over the fovea for each of the vertical eye positions. During the
passive head impulses, image stability was best when vertical
eye-in-head position was 20° up; during the active head impulses, it
was best when vertical eye-in-head position was at 0° (see Fig.
9). For the other vertical eye-in-head positions, there was increased torsional slippage of the retinal image
in the periphery, which was combined with the horizontal slippage so
that the point of maximal image stability was on the periphery of the
retina. The findings contrast with those of Misslisch et al.
(1994), who reported that the foveal image was well stabilized, whereas image stability on the periphery was compromised. The argument
that the VOR-Listing's law compromise strategy allows efficient
stabilization of the foveal image therefore is not supported by the
findings from the current experiment.
|
Possible axis shift mechanisms
The head velocity profiles for the different vertical eye-in-head
positions are almost identical. Hence differing inputs from the
semicircular canals with the different fixation positions cannot be
responsible for the observed axis shifts. In our experiments, the
possibility that search coil defects were responsible for the observed
patterns was eliminated by the use of an algorithm (Bruno and
van den Berg 1997) to correct for the effects of
nonorthogonality between the direction and torsion induction coils (see
APPENDIX). The mechanism responsible for producing the axis
tilts is therefore most likely the same as that responsible for
producing the phenomena observed in previous experiments (Fetter
et al. 1992
; Misslisch et al. 1994
).
For each of the vertical eye positions, the eye velocity vectors tilted
toward the velocity planes predicted by Listing's law, indicating that
the response could be due to a compromise between the ideal eye
velocity axis and that predicted by Listing's law. To investigate this
possibility, we developed a model similar to that presented by
Misslisch et al. (1994). Our model calculated the
eye-in-head torsional velocity to be exactly halfway between the
optimal eye-in-head torsional velocity, which would stabilize the
entire retinal image, and that predicted by Listing's law (calculated
from the subjects' Listing's plane data). The eye-in-head velocity
vectors predicted by the model, for both passive and active head
impulses, are shown in the pitch plane in Fig.
10 along with the actual data for
comparison. The model does predict the correct direction for the eye
velocity axis shifts, but it does not predict the correct magnitude of
the response; it also does not predict the initial good alignment of
the head and eye velocity vectors in the passive head impulses, as
expected. These findings contrast with those of Misslisch et al.
(1994)
, who reported that the averaged eye velocity responses
of their subject group were matched by the output of their model. A
simple VOR-Listing's law compromise strategy is therefore inadequate
to explain our findings and the mechanism responsible for bringing
about the eye position-dependence of the VOR now is called into
question.
|
In previous studies (Misslisch 1995; Misslisch et
al. 1994
), it was concluded that the eye position-dependence
of the VOR probably comes about due to neural processing and that
ocular motor plant mechanics could not (or at least not
solely) be responsible for producing it. Recently,
Demer et al. (1995)
demonstrated that the tendons of the
rectus muscles pass through fibromuscular pulleys near their insertions
on eyeball, keeping the paths of the muscle bellies relatively fixed so
that the functional pulling directions of the muscles change with
different eye-in-head positions. Because the functional pulling
directions of the rectus muscles are dependent on eye-in-head position,
the pulleys therefore could play a very important role in producing the
observed axis tilts.
Using a model-based approach, it has been shown that Listing's law is
obeyed when a two-dimensional (yaw-pitch) saccadic pulse is sent to an
ocular motor plant that incorporates pulleys (Quaia and Optican
1998; Raphan 1997
, 1998
). In other words, the
systematic tilts of the eye velocity vectors that occur during an eye
movement that obeys Listing's law are predicted by models that
incorporate pulleys, when the saccadic pulse has only yaw and pitch
components! In the case of the VOR, the commands being sent to the eye
muscles have three components (yaw, pitch, and roll); this would
explain why the VOR does not obey Listing's law when considered in the context of the pulley model. Indeed, Raphan (1997)
has
shown that after incorporation of the pulley system into a
vector-integrator model of ocular motor control, the eye
position-dependence of the VOR is predicted when a three-dimensional
eye movement command is sent to the eye muscles. To predict the eye
position-dependence of the VOR, Tweed also incorporated the pulley
effect into his quaternion model of ocular motor control so that
"the muscles' pulling directions move when the eye moves, in the
same direction but only about half as far" (Tweed
1997
).
Although it is likely that the pulleys have a role in bringing about
the eye position-dependence of the VOR, there is currently no
experimental evidence to support the hypothesis. Therefore a neural
mechanism in which the eye movement signal is altered depending on
eye-in-head position (as hypothesized by Misslisch et al.
1994) is still a possibility. We are unable to establish which
of the proposed mechanisms (if either) is responsible for the eye
position-dependence of the VOR based on the results from the current
experiment. Indeed, our findings serve more to highlight the complexity
of the issue. As discussed earlier, the eye and head velocity axes were
aligned better during the active head impulses than during the passive
head impulses when fixation was on a target at 0°. If the degree of
muscle contraction in the smooth muscle pulleys does not change, the
pulleys should exert a constant effect on the eye muscles given a
particular eye-in-head position regardless of whether the stimulus was
generated passively or actively. Such an argument initially may be
considered as evidence that the neural hypothesis is responsible for
the observed patterns in axis tilt. The argument is not as convincing
as one may think, however. It must be noted that the eye velocity
response to the head impulse depends on both the head velocity stimulus
and the current eye-in-head position. It is clear, from
Figs. 1 and 6, that although the stimuli are similar they are not
identical. On average, the head velocity axis tilted back from the roll
(yz) plane during the passive head impulses, whereas it
tilted forward from the roll plane during the active head impulses. The
eye velocity axis was, on average, tilted forward relative to the head
velocity axis during the passive head impulses when fixation was on the target at 0°, whereas the averaged head and eye velocity axes remained well aligned during the active head impulses for the same
fixation position. Hence it is certainly possible that the differing
stimulus profiles partly explain the differences between the responses
to passive and active head impulses. We also found that the horizontal
eye velocity was a much better match for horizontal head velocity
during the active head impulses (resulting in a smaller horizontal
error vector component
see Fig. 7). Therefore, at the very least,
there is a degree of enhancement of the horizontal VOR gain to reduce
horizontal retinal image slip during the active head impulses. The
mechanism responsible for the improved performance is unclear, but in
any case there has to have been some neural modification of the eye
movement command to bring about these changes. Hence for head movements
with identical kinematics, the neural commands traveling to the eye
muscles probably are altered depending on whether the eye movement is
generated in response to a passive or active head impulse. Consequently
the differing axis tilt patterns in response to passive and active head
impulses do not provide sufficient evidence to rule out the possibility that a pulley system has an effect on the VOR.
The observed latency in the axis shift, after the passive head impulse onset, is difficult to explain in the context of both pulley and neural hypotheses. It is possible that, if the eye position-dependence of the VOR arises primarily due to the effects of the pulleys, the initial alignment of the axes results from some neural effort to improve the early VOR performance. Alternatively, if the eye position-dependence of the VOR arises primarily due to a neural mechanism, the delay before the axis tilt may occur due to some processing delay in the CNS.
In summary, the degree of misalignment between the eye and head velocity axes depends on vertical eye-in-head position during both passive and active yaw head impulses. The initial 47 ms of the response to passive head impulses is not eye position-dependent. The response to the active head impulses is eye position-dependent almost immediately. The findings show that the initial lack of eye position-dependence in the VOR after the onset of an unpredictable head rotation results in almost perfect stabilization of the retinal image during that time. In view of the current evidence, the eye position-dependence of the VOR probably arises due to the effects of fibromuscular pulleys on the pulling directions of the rectus eye muscles.
![]() |
APPENDIX |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Nonorthogonality correction
The algorithm to correct for the nonorthogonality between the
direction and torsion induction coils was based on formulae presented
in Bruno and van den Berg (1997). To establish that the
correction does improve the estimation of the torsional Fick angle, a
search coil with nonorthogonal induction coils was placed in the gimbal
and moved through a combination of different horizontal, vertical, and
torsional angles. Two graphs are presented in Fig. A1: in the first, the torsional Fick
angle without the correction for nonorthogonality is plotted; in the
second, the torsional Fick angle with the correction for
nonorthogonality is plotted. On the x axis, the actual value
of the torsional Fick angle, according to the gimbal, is given. It can
be seen clearly that the best estimation of the torsional Fick angle is
seen when the signal is corrected for the nonorthogonality between the
induction coils.
|
![]() |
ACKNOWLEDGMENTS |
---|
The authors thank all of the subjects who participated in the experiments, M. Todd and G. Serdaris for assistance with the engineering aspects of the study, A. Burgess and A. Migliaccio for assistance with the computing aspects of the study, and J. Ramsay for assisting in some of the tests. In addition, the authors acknowledge Prof. A. Sefton, Dr. J. Demer, and Dr. T. Raphan for valuable comments and Dr. D. Tweed for supplying his VOR model.
This work was supported by the Royal Prince Alfred Hospital Department of Neurology Trustees.
![]() |
FOOTNOTES |
---|
Address for reprint requests: M. J. Thurtell, Eye and Ear Research Unit, Dept. of Neurology, Royal Prince Alfred Hospital, Camperdown, Sydney, NSW 2050, Australia.
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 15 June 1998; accepted in final form 25 November 1998.
![]() |
REFERENCES |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|