1Department of OtolaryngologyHead and Neck
Surgery, 2Department of Biomedical Engineering,
and 3Department of Neuroscience, The Johns
Hopkins University School of Medicine, Baltimore, Maryland 21287-0910
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ABSTRACT |
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Clendaniel, Richard A., David M. Lasker, and Lloyd B. Minor. Horizontal Vestibuloocular Reflex Evoked by High-Acceleration Rotations in the Squirrel Monkey. IV. Responses After Spectacle-Induced Adaptation. J. Neurophysiol. 86: 1594-1611, 2001. The horizontal angular vestibuloocular reflex (VOR) evoked by sinusoidal rotations from 0.5 to 15 Hz and acceleration steps up to 3,000°/s2 to 150°/s was studied in six squirrel monkeys following adaptation with ×2.2 magnifying and ×0.45 minimizing spectacles. For sinusoidal rotations with peak velocities of 20°/s, there were significant changes in gain at all frequencies; however, the greatest gain changes occurred at the lower frequencies. The frequency- and velocity-dependent gain enhancement seen in normal monkeys was accentuated following adaptation to magnifying spectacles and diminished with adaptation to minimizing spectacles. A differential increase in gain for the steps of acceleration was noted after adaptation to the magnifying spectacles. The gain during the acceleration portion, GA, of a step of acceleration (3,000°/s2 to 150°/s) increased from preadaptation values of 1.05 ± 0.08 to 1.96 ± 0.16, while the gain during the velocity plateau, GV, only increased from 0.93 ± 0.04 to 1.36 ± 0.08. Polynomial fits to the trajectory of the response during the acceleration step revealed a greater increase in the cubic than the linear term following adaptation with the magnifying lenses. Following adaptation to the minimizing lenses, the value of GA decreased to 0.61 ± 0.08, and the value of GV decreased to 0.59 ± 0.09 for the 3,000°/s2 steps of acceleration. Polynomial fits to the trajectory of the response during the acceleration step revealed that there was a significantly greater reduction in the cubic term than in the linear term following adaptation with the minimizing lenses. These findings indicate that there is greater modification of the nonlinear as compared with the linear component of the VOR with spectacle-induced adaptation. In addition, the latency to the onset of the adapted response varied with the dynamics of the stimulus. The findings were modeled with a bilateral model of the VOR containing linear and nonlinear pathways that describe the normal behavior and adaptive processes. Adaptation for the linear pathway is described by a transfer function that shows the dependence of adaptation on the frequency of the head movement. The adaptive process for the nonlinear pathway is a gain enhancement element that provides for the accentuated gain with rising head velocity and the increased cubic component of the responses to steps of acceleration. While this model is substantially different from earlier models of VOR adaptation, it accounts for the data in the present experiments and also predicts the findings observed in the earlier studies.
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INTRODUCTION |
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The angular
vestibuloocular reflex (VOR) adapts its behavior in response to image
motion across the retina associated with head movements. The
combination of signals required for such adaptation occurs naturally in
instances such as changes in the peripheral vestibular system
associated with aging or illness, as well as with optically induced
changes in vision. Continuously worn spectacles that either magnify or
minimize the visual world can also induce changes in VOR gain
(Miles and Eighmy 1980). While the compensatory changes
to these manipulations of the visual inputs are in the direction
required to enhance image stabilization, the adapted gain typically
does not reach the value required for complete image
stabilization. When rhesus monkeys were tested in darkness with
sinusoidal rotations of 0.5-2.0 Hz (±20-50°/s), the VOR gain increased to 1.5-1.8 following adaptation to ×2 spectacles and decreased to 0.2-0.3 following adaptation to ×0 spectacles
(Lisberger 1984
; Lisberger et al. 1983
).
Thus the adapted gain typically does not reach the value required
for complete image stabilization.
Previous studies have identified different components to the dynamics
of the VOR following spectacle-induced adaptation. Responses to
transient changes in head velocity were studied in rhesus monkeys before and after adaptation to spectacles that produced an increase (×2.2) or decrease (×0.25 or ×0) in image motion relative to the head. The horizontal VOR was measured in darkness after an adaptation period of several days in which the animals made free head movements. The stimulus was a passive change in head velocity (of 30°/s) with an
acceleration of 600°/s2 for 50 ms to a peak
velocity of ±15°/s, followed by a velocity plateau of 250 ms. The
initial trajectory of the eye velocity in response to this stimulus was
identical regardless of the adapted state of the monkey (normal,
magnified gain, or minimized gain) (Lisberger 1984). The
ratio of the peak eye velocity, reached during the acceleration, to the
steady-state eye velocity, measured during the velocity plateau,
changed depending on whether the VOR gain had been increased or
decreased. This ratio was increased with adaptation to the minimizing
spectacles and decreased following adaptation to the magnifying
spectacles (Lisberger and Pavelko 1986
). These findings
were interpreted as indicating that the initial 4 to 9 ms of the VOR
evoked by this stimulus was not modifiable, whereas the VOR measured
during the remainder of the stimulus showed an increase or decrease in
gain in relation to the spectacles. In the latter study, single-unit
recordings from vestibular-nerve afferents revealed a correspondence
between the responses of irregularly discharging afferents and the
initial VOR during the acceleration portion of the stimulus. Lisberger
and Pavelko hypothesized that irregularly discharging afferents provide
inputs to the nonmodifiable VOR pathway, whereas regularly discharging
afferents provide inputs to the modifiable pathway.
Adaptation of the VOR with other paradigms and testing with other
stimuli following spectacle-induced adaptation has led to different
conclusions about the dynamics of the adapted VOR. Khater et al.
(1993) paired horizontal sinusoidal vestibular stimulation with
phase-synchronized vertical optokinetic stimulation in cats. The VOR
evoked by 4,000°/s2 accelerations given in
darkness after a 2-h adaptation period had horizontal and vertical
components from the onset of the head rotation (i.e., there was no
discernible latency between modified and nonmodified components). In
another study using spectacle-induced adaptation, rhesus monkeys had
eye movements evoked by brief current pulses delivered through an
electrode implanted in the labyrinth (Broussard et al.
1992
). These evoked responses differed in amplitude according
to whether the VOR had been adapted with magnifying or minimizing
spectacles. In this paradigm, there was no latency to the onset of the
adapted responses, as the modified responses began at the onset of the
evoked eye movements.
Frequency selectivity has also been demonstrated in the processes that
mediate adaptation of the VOR. When monkeys were rotated at a single
frequency of 0.2 or 2 Hz while wearing magnifying or minimizing
spectacles and then tested over a range of frequencies (0.1-4 Hz), the
change in VOR gain is the greatest at the adapting frequency
(Lisberger et al. 1983). The phase and gain data
suggested that the adaptation process was controlled by a series of
parallel, frequency-specific channels each consisting of a low-pass
filter with a corner frequency at the frequency of adaptation. When
adapting frequencies of 5-10 Hz (peak-to-peak velocity of 20°/s)
were used, the adapted changes in VOR gain and frequency specificity
were less than those noted at lower frequencies (Raymond and
Lisberger 1996
). Directional selectivity of the
adaptation process has been demonstrated in monkeys (Bello et
al. 1991
; Yakushin et al. 2000
). When adapted
with magnifying or minimizing spectacles to yaw, pitch, or roll
rotations for six hours, changes in gain were observed when the monkey
was tested with rotations that were in the same plane as the adapting
rotations. There was no transfer of the adaptation response to
orthogonal rotations.
We have recently described a nonlinearity in the horizontal VOR evoked
by high-acceleration, high-frequency head rotations in the squirrel
monkey; the gain of the reflex rises with velocity at higher rotational
frequencies (Minor et al. 1999). The contribution of
this nonlinear component to the dynamics of the VOR is clearly evident
for frequencies and accelerations that are within the range of
naturally occurring head movements in primates. We have further shown
that this nonlinear component of the response augments the response to
an excitatory stimulus but is driven into cutoff at stimulus velocities
of ~30°/s for high-frequency, high-acceleration stimuli that are
inhibitory. Based on the frequency dynamics of the linear and nonlinear
components of the response and the velocity-dependent gain enhancement,
we have modeled the VOR as being comprised of linear and nonlinear
pathways that combine centrally to generate the observed responses.
Preferential modification of the gain of the nonlinear pathway induced
by retinal slip following unilateral plugging of the three semicircular
canals (Lasker et al. 1999
) or unilateral
labyrinthectomy (Lasker et al. 2000
) accounts for the
rapid return of the gain of the VOR for contralesional rotations to
values that are close to the prelesion values.
The purpose of this study was to investigate the contributions of the linear and nonlinear pathways inherent in the dynamics of the VOR to the responses following spectacle-induced adaptation of VOR gain. We show that the nonlinear pathway is highly modifiable and that the gain after adaptation to magnifying spectacles to stimuli that evoke a contribution from the nonlinear pathway is greater than that observed to stimuli that do not have a contribution from this pathway. A model in which the VOR receives inputs from linear and nonlinear pathways and the process of adaptation is driven by a signal related to a low-pass filtered representation of head velocity accounts for these data. The findings from earlier studies of spectacle-induced adaptation of the VOR are also predicted from this model.
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METHODS |
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Surgical procedures and eye movement recording
Surgery was done under sterile conditions in six adult squirrel
monkeys anesthetized with inhalation of halothane/nitrous oxide/oxygen.
The experimental procedures used for recording eye movements were
identical to those that have previously been described for this
laboratory (Minor et al. 1999). All surgical and other animal care procedures used in this study were done in accordance with
a protocol approved by the Animal Care and Use Committee of the Johns
Hopkins University School of Medicine. Each animal was seated in a
plastic chair with its head restrained by securing the implanted bolt
to a chair-mounted clamp. The chair was connected to a superstructure
that was mounted to the top surface of a servo-controlled rotation
table capable of generating a peak torque of 125 N-m (Acutronic,
Pittsburgh, PA). The horizontal VOR was tested with the animal
seated in the upright position in the superstructure and aligned such
that the horizontal canals were in the earth-horizontal plane of rotation.
Two pairs of field coils, each with a side length of 45 cm, were rigidly attached to the superstructure and moved with the animal. A detection circuit (Remmel Labs) that extracted signals proportional to horizontal and vertical eye position monitored voltages induced in the scleral search coils. The peak-to-peak noise at the output of the circuit was equivalent to an eye movement of 0.02°. All signals transducing motion of the head or the eye were passed through eight-pole Butterworth anti-aliasing filters with a corner frequency of 100 Hz. These signals then were digitized with a sampling rate of 1,000 Hz for acceleration steps and sinusoidal rotations at frequencies 2 Hz and above. A sampling rate of 200 Hz was used for sinusoidal rotations <2 Hz.
The eye-coil system was calibrated in two ways. A search coil identical
to the one implanted about each eye was placed in a gimbal located
where the animal's head was positioned in the field coil. This search
coil then was moved to angles of 5, 10, and 15° right-left and up
down with respect to center, and calibration factors relating volts to
degrees were determined. The second method involved sinusoidal rotation
of the animal, before spectacle-induced adaptation, in light at 0.5 Hz, ± 60°/s, a stimulus in which the gain of the visual-VOR reflex has
been shown to be 1.0 (Minor and Goldberg 1990;
Paige 1983
). Calibration factors obtained from these
methods typically agreed to within 5% and varied by <5% between
testing sessions.
Rotational testing
Responses to steps of acceleration were recorded with the animals in darkness. The stimuli consisted of 3,000, 1,000, 500, and 100°/s2 accelerations to a peak velocity of 150°/s followed by a plateau of head velocity lasting 0.9-1.1 s and then deceleration at 3,000, 1,000, 500, or 100°/s2 to rest, or 3,000°/s2 acceleration to a peak velocity of 60°/s followed by a plateau of head velocity lasting 0.9-1.1 s and then deceleration at 3,000°/s2 to rest. The acceleration direction, duration, and interstimulus interval were varied randomly from one trial to the next. Sinusoidal head rotations (0.5-15 Hz, peak velocity 20-150°/s) were given with animals in darkness. Each stimulus frequency was given for 60 s. The order in which different frequencies and velocities were tested was varied.
Adaptation paradigms
To induce adaptation, monkeys were fit with magnifying (×2.2) or minimizing (×0.45) spectacles that were attached to the acrylic skullcap. The monkeys wore the magnifying lenses for 5-7 days, 24 h a day, were housed in their normal environment, and were allowed to move about freely. Twice a day the monkeys were brought to the lab, and the spectacles were cleaned while the monkeys were kept in the dark. To ensure adequate exposure to a range of rotational stimuli, twice a day the monkeys were rotated for 2 h using a sum-of-sines stimulus (0.5, 1.1, 2.3, and 3.7 Hz, peak velocity of 20°/s).
Data analysis
The data were analyzed off-line using software that we wrote in
the Matlab (The Math Works) programming environment. The methods of
analysis are similar to those that we have described previously (Lasker et al. 1999; Minor et al. 1999
).
ACCELERATION STEPS. The eye-position data first were passed through a 50-point, finite-impulse-response filter with a corner frequency of 100 Hz (to calculate latency) or 40 Hz (to assess dynamics of the response). Eye velocity was obtained from a seven-point central difference algorithm. The data from 10-30 trials in each direction were averaged to obtain a representation of the response.
The latency to the onset of the adapted response was measured for 3,000, 1,000, 500, and 100°/s2 accelerations preadaptation and postadaptation with the magnifying spectacles. Responses to 30 steps of acceleration in each condition were averaged. The latency to the onset of the adapted response was determined by the time it took the adapted response to intersect the line representing one SD above the mean response obtained under the preadaptation condition. Measurements of the gain of the VOR for the 3,000°/s2 to 150°/s acceleration steps were made during three components of the stimulus: the acceleration phase, after the plateau of head velocity had been reached, and the deceleration step to rest. The acceleration gain of the VOR, GA, was measured for each trial as the ratio of the slope of a line through the eye-velocity points to the slope of a line through the head-velocity points during a 20-ms period starting 20 ms after the onset of the stimulus. During this time interval the head velocity was increasing from 60 to 120°/s. The velocity gain of the VOR, GV, was measured from the ratio of the mean eye and head velocity evaluated at 100-300 ms after the plateau head velocity had been reached for each trial. For display of the data, fast phases were removed from each trace, and an average response was calculated at each point based on the traces without a fast phase at that point. This method avoided any distortion of the data due to interpolation or smoothing at the time of the fast phases. The deceleration gain of the VOR, GD, was measured for each trial as the ratio of the slope of a line through the eye-velocity points to the slope of a line through the head-velocity points during the period of 15-45 ms after the onset of the stimulus. During this time interval the head velocity was decreasing from 105 to 45°/s. To compare the acceleration and deceleration responses, the acceleration gain was remeasured over the same time interval (15-45 ms). Thus the responses to accelerations were measured while the head velocity was increasing from 45 to 105°/s, and the deceleration responses were measured while the head velocity was decreasing from 105 to 45°/s. For the 3,000°/s2 to 60°/s acceleration steps, we also determined the dynamic index (DI) of the response. As in previous studies (Lisberger and Pavelko 1986SINUSOIDAL ROTATIONS. Eye-position data were differentiated with a four-point central difference algorithm to obtain eye velocity. Saccades were removed from responses at frequencies <4 Hz, and an average cycle was obtained based on the data representing slow-phase eye velocity at each point in time. Responses at frequencies 4 Hz and greater were not desaccaded, and only cycles without saccades were included in the analysis. Successive cycles (5-10 at 0.5 Hz, 10-35 at 2-6 Hz, and 25-75 at 8-15 Hz) were averaged. The amplitude and phase of the response fundamental were obtained from a Fourier analysis as were the corresponding values for the head-velocity signal. Gains and phases for eye with respect to head velocity were expressed with the convention that a unity gain and zero phase imply a perfectly compensatory VOR. A negative phase indicates that eye movements lag head movements.
Modeling of the VOR
Mathematical models of the VOR were formulated in Simulink (The Math Works). The Dormand-Prince method with a fixed step size of 0.0001 s was used for simulation of the ordinary differential equations. Fourier analysis was used to calculate gain and phase of the simulated responses to sinusoidal inputs.
Statistical analysis
Results were described as means ± SD. Repeated measures ANOVA were used to compare the data from more than two groups. Post hoc t-tests or one-way ANOVA tests were performed when the ANOVA demonstrated significant main effects or interactions, and the post hoc analyses are reported in the results section. Data from two groups were compared with unpaired t-tests. Paired t-tests were used when preadaptation and postadaptation data in one animal were analyzed.
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RESULTS |
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Adaptation of the horizontal VOR was studied in six squirrel monkeys (M1-M6). The adapted responses were evoked by steps of head acceleration and by sinusoidal rotations in the dark. The adaptation conditions used in each of the monkeys were as follows: normal responses and responses following adaptation to both magnifying and minimizing spectacles (M1 and M2); normal responses and responses following adaptation with magnifying spectacles (M3 and M4); and normal responses and responses following adaptation with minimizing spectacles (M5 and M6).
Responses to steps of acceleration
The VOR evoked by steps of acceleration following adaptation with magnifying spectacles demonstrated increased gain during both the acceleration and constant velocity components of the stimulus. Similarly, the VOR gain during both components of the stimulus was reduced following adaptation to the minimizing spectacles. Examples of responses preadaptation, after adaptation to the magnifying spectacles, and after adaptation to the minimizing spectacles are shown in Fig. 1. For the four monkeys that were adapted with the magnifying spectacles, the mean GA during 3,000°/s2 to 150°/s acceleration steps was 1.05 ± 0.08 (mean ± SD) preadaptation and 1.96 ± 0.16 postadaptation (Table 1). For the same animals, the mean GV prior to adaptation was 0.93 ± 0.04, and postadaptation the mean GV was 1.36 ± 0.08. These increases in GA and GV postadaptation with the magnifying spectacles were significant. In addition, while both GA and GV increased with adaptation, there was a significant difference in the relative increases of the two components of the response [F(1,15) = 61.41, P < 0.01]. The acceleration gain increased by a factor of 1.92, while the velocity gain only increased by a factor of 1.46. Similar increases in gain were observed for acceleration steps of 3,000°/s2 to a peak velocity of 60°/s and 500°/s2 to a peak velocity of 150°/s (Table 2). In the 3,000°/s2 to 60°/s steps of acceleration, there was no difference between the increase in GA and GV. This is most likely due to the lower peak velocity of the stimulus and the shorter duration of the acceleration component.
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Due to the presence of fast phases, which generally occurred either during (500°/s2 to 150°/s steps) or at the peak (3,000°/s2 to 150°/s) of the acceleration portion of the steps, we were only able to measure the DI during the 3,000°/s2 to 60°/s acceleration steps. DI is the ratio of peak eye velocity during the acceleration phase of the stimulus divided by the eye velocity during the constant velocity phase of the stimulus (see METHODS). Following adaptation to the magnifying spectacles, we observed no change in the DI as compared with the preadaptation condition. Average responses for one animal are presented in Fig. 2. For the two monkeys that were adapted to the magnifying spectacles, the mean postadaptation DI was 1.12 ± 0.10, and the mean preadaptation index was 1.17 ± 0.09. This difference was not statistically significant [t(4) = 0.562, P > 0.1].
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For the four monkeys that were adapted to the minimizing spectacles, the gain during the acceleration component of the 3,000°/s2 to 150°/s acceleration steps decreased from 1.04 ± 0.05 to 0.61 ± 0.08 postadaptation. For the same animals, GV prior to adaptation was 0.94 ± 0.03, and the postadaptation GV was 0.59 ± 0.09. Paired t-tests of preadaptation and postadaptation measures of GA and GV showed that the decreases in gain during both components of the response were statistically significant. However, there was no difference between GA and GV following adaptation to the minimizing spectacles. Unlike the asymmetric increases in GA and GV following adaptation with the magnifying spectacles, the monkeys displayed essentially identical decreases in both GA and GV (61 and 65%, respectively). Similar symmetrical decreases in GA and GV were seen for acceleration steps of 3,000°/s2 to 60°/s and 500°/s2 to 150°/s (Table 2). There was no change in the DI measured in the responses to the 3,000°/s2 to 60°/s acceleration steps following adaptation to the minimizing spectacles (Fig. 2). For the four monkeys that were adapted to the minimizing spectacles, the postadaptation DI was 1.16 ± 0.14, and the preadaptation index was 1.18 ± 0.08. This difference was not significant [t(8) = 0.321, P > 0.1].
Latency
The latency to the onset of the adapted response was measured for 3,000, 1,000, 500, and 100°/s2 accelerations steps to peak velocities of 150°/s preadaptation and postadaptation with the magnifying spectacles. Responses to 10-30 steps of acceleration in each condition were averaged. The results from one animal, which were typical of findings in all the animals tested, are displayed in Fig. 3. For the purposes of this analysis, the latency to the onset of the adapted response was defined as the time required for the adapted response to rise above a reference line (1 SD above the mean response for the preadaptation acceleration steps). For this animal, the adapted response intersected the reference line 25 ms after the onset of the 3,000°/s2 accelerations. For the 1,000 and 500°/s2 accelerations, the adapted response intersected the reference line 29 and 32 ms, respectively, after the onset of the stimulus. The responses to the 100°/s2 accelerations are not shown for this animal; however, the adapted response intersected the reference line 69 ms after the onset of the stimulus. For all the animals tested, the latencies of the adapted response were 19 ± 5 ms, 29 ± 8 ms, 30 ± 4 ms, and 81 ± 72 ms for the 3,000, 1,000, 500, and 100°/s2 accelerations, respectively. These differences were statistically significant (t-tests, P < 0.01). For the 3,000°/s2 accelerations, the adapted response intersected the reference line at an average velocity of 45.9 ± 18.76°/s. Similarly, the adapted response crossed the reference line at average velocities of 31.8 ± 12.61°/s, 20.2 ± 3.39°/s, and 23.5 ± 16.47°/s for the 1,000, 500, and 100°/s2 accelerations, respectively. Thus there was no apparent velocity threshold for the onset of the adapted response.
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Response dynamics
The initial VOR during the step of acceleration was evaluated with
linear and polynomial fits relating eye to head velocity (Fig.
4). The coefficients for the first-
through third-order fits to the data records formed by concatenating
responses to leftward and rightward rotations, the mean square error
for each fit, and the Baysean information criterion (see description in METHODS) for each polynomial are presented in Table
3. As seen in earlier work describing
responses to these stimuli (Minor et al. 1999), there
was a significant cubic component to the responses under normal
conditions and essentially no difference between the linear and a
second-order polynomial fits to the data. In all six monkeys, there was
a significant reduction in the BIC value when comparing the third-order
to the linear fit. Also, there was no significant decrease in the BIC
values when comparing fifth-order to third-order fits to the responses.
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There was an increase in the cubic component to the responses following adaptation to the ×2.2 magnifying spectacles. In the four monkeys that underwent adaptation to the ×2.2 spectacles (M1-M4), there was little change in the BIC values between the linear and second-order fits to the responses. There was, however, a significant reduction in the BIC value between the linear and third-order fits. The coefficient to the linear term in the third-order polynomial fit to the data increased by <40% following adaptation to the magnifying spectacles, while the coefficients to the cubic term increased by at least 200% (3.42 to 16.81).
The relationship between eye velocity and head velocity can be
described by a third-order polynomial of the following general form
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In the four monkeys that were adapted with the ×0.45 minimizing spectacles, there was still a slight reduction in the BIC values between the linear fit and third-order fit to the response. This reduction in BIC value was smaller following adaptation with the minimizing spectacles than in the normal condition. There was a 26-43% reduction in the value of the linear coefficient of the third-order equation and a 75-90% reduction in the value of the cubic term coefficient following adaptation to the minimizing spectacles.
When the coefficients for the third-order polynomials for the four monkeys that subsequently underwent adaptation with the minimizing spectacles (M1, M2, M5, and M6) were pooled (Table 4), we observed decreases in the values of the coefficients with an apparent greater modification of the nonlinear component of the response. While there were slight differences between the preadaptation coefficients and those for the four monkeys that were used in the VOR magnification portion of the study, the coefficients were quite similar. When Eq. 1 is evaluated with HV equal to 100°/s and the coefficients for the postminimization response, the linear term contributes 107% of the response, the second-order term diminishes the response by 4%, and the third-order term diminishes the response by 1%. The decreases in both the linear and cubic terms between the normal and adapted conditions were significant. While the values of both the linear and cubic coefficients decreased significantly, the change in the coefficient for the third-order term was significantly greater than that for the linear term coefficient [F(1,12) = 71.83, P < 0.01]. The pooled coefficient of the linear term was reduced by 34% after minimization, and the pooled coefficient of the cubic term was reduced by 94%. These results suggest that with adaptation to minimizing spectacles there is a significant modification of both the linear and nonlinear pathways, with the gain of the nonlinear pathway being reduced essentially to zero. The greater changes seen in the coefficients for the third-order term following adaptation to either magnifying or minimizing spectacles suggest that there is greater, or preferential, modification of the nonlinear component of the response with adaptation.
Responses to deceleration steps
The gains during both the acceleration (GA) and deceleration (GD) components of the stimulus were recorded in four monkeys preadaptation and postadaptation to the magnifying spectacles. The dynamics of the acceleration and deceleration stimuli were identical (3,000°/s2) except that the acceleration ramp started at 0°/s and rose to 150°/s while the deceleration ramp, which followed the 0.9-1.1 s velocity plateau, started at 150°/s and declined to 0°/s. The time period for the calculation of values of GA and GD was adjusted so that the range of stimulus velocities and time periods would be identical. The gain was measured over a 20-ms interval starting 15 ms after the onset of the ramp. The corresponding stimulus velocities were 45 to 105°/s for the acceleration ramp and 105 to 45°/s for the deceleration ramp. The GA, GD, and GV values are presented in Table 5. Preadaptation there was no difference in the gain values between the acceleration and deceleration ramps. However, after adaptation to the magnifying spectacles, there was a significant asymmetry to the response with the acceleration response being greater than the deceleration response (Fig. 5). In contrast to the difference between GA and GD postadaptation, there was no difference between GD and GV postadaptation. This finding is consistent with the nonlinear component of the response being present only during the acceleration portion of a rotation.
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Responses to sinusoidal rotations
The gain and phase plots of responses to sinusoidal rotations (0.5-15 Hz, ±20°/s) preadaptation, postmagnification, and postminimization are displayed in Fig. 6. There was no frequency-dependent change in gain under the preadaptation condition; however, a frequency-dependent change in gain was noted following adaptation with magnifying spectacles. Greater gains were observed at the lower testing frequencies [F(7,16) = 13.54, P < 0.01]. Post hoc analyses with Fisher's pair-wise comparisons showed that for the testing frequencies from 0.5-6 Hz there were significant differences between the testing frequency and all remaining frequencies, except for the immediately adjacent frequency. For example, there was no difference between 0.5 and 2.0 Hz, but there were differences between 0.5 Hz and all testing frequencies from 4 to 15 Hz (P < 0.05). There was no significant difference for the gains at 8 Hz and higher frequencies. After adaptation with the minimizing spectacles, there was again a frequency-dependent change in gain, with the greatest decrease in gain evident at the lower testing frequencies [F(7,19) = 2.87, P < 0.05]. Post hoc analyses (Fisher's pair-wise comparisons) showed differences only between the postadaptation gains at 15 Hz and testing frequencies of 2-8 Hz (P < 0.05).
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Following adaptation with the magnifying spectacles, there were significant increases in gain at all testing frequencies as compared with the normal condition. The gain increases varied across frequencies, with the greatest increases occurring at the lower frequencies. At 0.5 and 2 Hz, the gain postmagnification increased by 70%, while at 12 and 15 Hz, the gain increased by 30%. Paired t-tests showed a significant difference between pre- and postmagnification gains at all frequencies. After adaptation with the minimizing spectacles, there were decreases in gain at all testing frequencies. As seen in the postmagnification condition, the greatest changes were present at the lower testing frequencies. At 0.5 and 2 Hz, the gain decreased by 40%; at 12 and 15 Hz the gain decreased by 23%. Paired t-tests showed a significant difference between pre- and postminimization gains at all frequencies.
The phase of the adapted responses varied with frequency in an adaptation-specific manner (Fig. 6B). Following adaptation with magnifying spectacles, there was a frequency-dependent phase change, with progressively greater phase lags at the higher testing frequencies [F(7,16) = 4.35, P < 0.01]. After adaptation with the minimizing spectacles, there was again a frequency-dependent change in phase, with progressive phase leads at the higher frequencies of stimulation [F(7,19) = 13.42, P < 0.01].
Following adaptation with the magnifying spectacles, there were significant increases in phase lag at the higher testing frequencies as compared with the normal condition. There was a 1.5° phase lead at 0.5 Hz and a 10.4° greater phase lag at 15 Hz postmagnification. Paired t-tests showed a significant difference in phase between the preadaptation and postmagnification values at frequencies of 4 Hz and greater. There was no difference between the preadaptation and postmagnification phases at 0.5-2 Hz. After adaptation with the minimizing spectacles, there were marked increases in phase lead at the higher testing frequencies. There was a 0.5° phase lag preadaptation and a 16.3° phase lead postminimization at 15 Hz. As with the postmagnification results, post hoc paired t-tests showed a difference (P < 0.05) in phase at frequencies 4 Hz and greater. Again there were no significant differences in phase at testing frequencies between 0.5 and 2 Hz.
The frequency- and velocity-dependent nonlinearity in the response to
sinusoidal rotations noted in normal monkeys (Minor et al.
1999) was observed in the monkeys following adaptation to
magnifying spectacles. When tested at 4 Hz preadaptation, there was an
increase in the gain of the response with increasing stimulus velocity.
Following adaptation to magnifying spectacles, this gain increase with
rising stimulus velocity was enhanced as compared with the normal
condition (Fig. 7), consistent with a
greater enhancement of the nonlinear pathway. After adaptation to the minimizing spectacles, there was little difference in the gain of the
response with increasing velocity of stimulation. If the nonlinear
portion of the response were used to lower the gain after adaptation to
minimizing spectacles, then one would expect a progressive gain
decrease with increasing velocity of rotation. The absence of a
difference in gain with increasing velocity of rotation after
adaptation with the minimizing spectacles argues that the nonlinear
component is not used to actively lower the gain after adaptation.
These results are consistent with the findings observed in the
responses to steps of acceleration, in that the nonlinearity
contributes to the enhanced response after adaptation with magnifying
spectacles but does not contribute to or actively lower the response
after adaptation with the minimizing spectacles.
|
Polynomial fits were made to the data from the 4-Hz rotations at
100°/s preadaptation and postadaptation to both the magnifying and
minimizing spectacles (2 animals magnifying spectacles and 4 animals
minimizing spectacles). As reported previously in the preadaptation
condition (Minor et al. 1999), there was little difference between the second-order and first-order fits to the data.
The greatest improvement in the fit to the data was noted between the
first-order and third-order polynomial fits (Table 6). On the basis of the response to
acceleration and deceleration steps, it appears that the nonlinear
portion of the VOR is evident only during ipsilateral acceleration.
Consequently, we compared the first- and third-order coefficients
during the acceleration and deceleration portions of the sinusoidal
rotations separately. We did this by measuring the two quarter cycles
during which the absolute value of the stimulus velocity was increasing
or decreasing. Since we were using discontinuous portions of the
stimulus and response, and concatenation of these two segments could
alter the fits due to phase shifts, we analyzed each set of quarter cycles independently. The quarter cycles in one direction were inverted
and then concatenated with the original signals at the origin. The best
fit to the data was an odd-order polynomial without contribution from
the even-order terms, because the method of forming the signal ensured
the responses were symmetric about the origin (Lasker et al.
1999
). The relationship between eye velocity and head velocity
can be described by a third-order polynomial of the following general
form:
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(2) |
|
|
The linear and cubic term coefficients were analyzed separately to determine whether there was a differential effect on these terms depending on the nature of the stimulus (acceleration or deceleration). The linear term coefficients showed a significant increase following adaptation to the magnifying spectacles [F(1,7) = 102.70, P < 0.01], and a significant decrease following adaptation to the minimizing spectacles [F(1,15) = 55.71, P < 0.01]. In both cases there was no difference in this term between the postadaptation acceleration and deceleration quarter cycles. These findings indicate that the linear component of the response is not dependent on whether the stimulus is accelerating or decelerating.
Analysis of the coefficients for the cubic term following adaptation to the magnifying spectacles showed a significant increase from the preadaptation values for the acceleration quarter cycles [F(1,7) = 12.16, P < 0.05] and no difference in the preadaptation and postmagnification deceleration quarter cycles. This pattern of change is consistent with the observed behavior during the steps of acceleration and deceleration postadaptation to the magnifying spectacles. Following adaptation to the minimizing spectacles, there was a significant decrease in the cubic term coefficients [F(1,15) = 7.12, P < 0.05] for the acceleration quarter cycles as compared with the preadaptation levels. There was no difference in the cubic term coefficients for the deceleration quarter cycles pre- and postadaptation to the minimizing spectacles. In addition, there was no difference between the postminimization acceleration and deceleration cubic term coefficients. This lack of difference between the acceleration and deceleration cubic term coefficients can be interpreted as a loss of the excitatory input from the nonlinear pathway postadaptation to the minimizing spectacles.
To determine whether there were differential effects on the linear and cubic terms with adaptation, the linear and cubic terms were analyzed with two-factor ANOVA. Since there was such a large difference between the actual values of the coefficients for the linear and cubic terms, which would obscure any interaction between the terms, we standardized the terms by multiplying the coefficients of the cubic term by 105. There was a significant increase in the values of the linear and cubic term coefficients postadaptation with the magnifying spectacles [linear: F(1,4) = 34.24, P < 0.01; cubic: F(1,4) = 9.52, P < 0.05]. In addition, there was a significant interaction between the linear and cubic term coefficients and the adaptive state. This interaction indicates that the increase in the coefficient for the cubic term was greater than that for the linear term, consistent with the preferential enhancement of the nonlinear component of the response. Following adaptation to the minimizing spectacles, there were significant decreases in both the linear and cubic terms [linear: F(1,6) = 26.28, P < 0.01; cubic: F(1,6) = 9.62, P < 0.05]. While there was no significant interaction between term and condition with the adaptation to the minimizing spectacles, there was a 10-fold decrease in the value of the cubic term. In contrast, the linear term decreased by less than half. The lack of significant interaction may be due to the variability in the coefficients of the cubic term.
The responses during the deceleration quarter cycles were analyzed in a similar fashion. Following adaptation to the magnifying spectacles, there was a significant increase in the linear term coefficients [linear: F(1,4) = 78.33, P < 0.01], but no change in the cubic term coefficients. A similar result was seen following adaptation to the minimizing spectacles; there was a decrease in the linear term coefficient postadaptation [F(1,6) = 29.44, P < 0.01] but no change in the cubic term coefficients. The lack of change in the cubic term coefficients during the deceleration portion of the stimulus is further support for the hypothesis that the nonlinear pathway on one side only enhances the response during the acceleration portion of an ipsilateral rotation.
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DISCUSSION |
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The previous three papers in this series have described the linear
and nonlinear components of the VOR in response to high-acceleration rotations, and the modifications that occur in these responses following canal plugging and unilateral labyrinthectomy (Lasker et al. 1999, 2000
; Minor et al.
1999
). There are several lines of evidence that have led us to
model this behavior as separate linear and nonlinear pathways that
converge centrally. First, there are different frequency dynamics for
the linear and nonlinear components. Second, the linear component fits
well with the transfer function for regularly discharging canal
afferents, and the frequency dependence of the nonlinear component fits
with the dynamics of the irregularly discharging afferents. Third, the
asymmetry between ipsilesional and contralesional rotations following
unilateral canal plugging and labyrinthectomy fits the cutoff
characteristics of the irregularly discharging afferents. Fourth, the
observed differences between acceleration and deceleration responses
are predicted from the behavior of the two classes of afferents. These results could be explained simply by the differences in the response properties of the afferents that are converging at the level of the
secondary vestibular neuron. However, there is further evidence that
suggests the linear and nonlinear pathways combine beyond the level of
the secondary vestibular neuron. First, the dynamics of the irregularly
discharging afferents do not predict the rise in gain with velocity for
higher frequency rotations, so this aspect of the nonlinearity must
arise centrally. Since the velocity-dependent gain enhancement is not
observed at low frequencies, the enhancement must occur separately from
the linear pathway. Second, to model the data following
spectacle-induced adaptation, we need to change the gains of the linear
and nonlinear components independently. The gains of the two components
do not change in parallel. Thus the linear and nonlinear pathways are
hypotheses suggested by the behavioral data, but the neural elements
mediating these pathways will need to be defined through further
studies and single-unit recordings. We proceed to discuss the findings
of this study in light of these hypotheses and in comparison to
previous studies on adaptation.
As expected, the gain of the VOR increased following adaptation with
×2.2 magnifying spectacles and decreased following adaptation with
×0.45 minimizing spectacles. Our findings extend the understanding of
the adaptive processes of the VOR to high-frequency, high-acceleration rotations, stimuli for which the VOR is of critical importance for
image stabilization (Grossman et al. 1988,
1989
; Minor et al. 1999
). The results
indicate that both the linear and nonlinear components of the VOR, as
described in earlier studies, are modified during the adaptation
process. The first major finding of the study is that there does not
appear to be a fixed latency to the onset of the adapted response, as
the latency changes with the intensity of the stimulus. The second
finding is that, following adaptation to magnifying spectacles, the
response during the acceleration component of a high-acceleration,
high-velocity rotational stimulus is nearly equal to the magnifying
power of the spectacles and is considerably greater than the gain
during the constant velocity component of the stimulus. In addition,
there is a greater nonlinearity in the acceleration response following
adaptation to the magnifying spectacles as compared with the
preadaptation condition. A reduction in both acceleration and velocity
gains is seen after adaptation to the minimizing spectacles. These
responses fit with our understanding of the nonlinear and linear
components of the VOR. We can model these responses by simply eliciting
changes in the central gain elements for the linear and nonlinear
pathways, and we suggest that there is a greater, or preferential,
modification of the nonlinear component, or pathway, with adaptation.
During the high-acceleration, high-velocity steps, we also observed
that, although the metrics of the accelerations were equal, the
response during the deceleration component (or off-ramp) differed from
the acceleration (or on-ramp) response. In addition, the gain during
the off-ramp did not differ from the gain during the constant velocity
component of the stimulus. The greater enhancement of the nonlinear
pathway is also seen in the responses to sinusoidal stimuli, although
the differences in the response dynamics are subtle compared with those
seen in the acceleration steps. All of the observed behaviors can be
modeled with slight changes to our previously published model
(Lasker et al. 1999
, 2000
; Minor
et al. 1999
).
Latency of the adapted response
The present results indicate that there is not a temporally fixed
latency to the onset of the adapted response. Rather, the dynamics of
both the stimulus and the central adaptation mechanisms determine the
latency to the onset of the adapted response. There is a progressive
decrease in the latency of the adapted response as the acceleration
steps increase from 100 to 3,000°/s2. These
findings are in contrast with earlier reports of a temporally fixed
latency, which was thought to be a consequence of modifiable and
nonmodifiable pathways for the VOR (Lisberger 1984).
This hypothesis of modifiable and nonmodifiable pathways for the VOR came from the observation that there was a fixed latency between the
onset of the normal VOR and the beginning of the adapted response to
both magnifying and minimizing spectacles. In these earlier studies,
the monkeys were rotated with only one set of stimulus parameters
(600°/s2 accelerations to velocities of
±15°/s, a 30°/s change in velocity); thus a latency that varies
with the dynamics of the stimulus would not be evident. In the present
study we rotated the monkeys at four different accelerations, which
enabled us to show that the onset of the adapted response was linked to
the dynamics of the stimulus and not fixed in terms of time or velocity.
Responses to steps of acceleration
Following adaptation with the magnifying and minimizing
spectacles, we observed changes in the gain of the VOR during the constant velocity component of the rotation
(GV) that were similar to previously
reported values (Lisberger 1984; Lisberger et al. 1983
). The gain changes seen with adaptation during the
acceleration component of the stimuli have not been previously
reported. After adaptation to the magnifying spectacles, there was a
consistent increase in the value of the acceleration gain
(GA), which was significantly greater
than the corresponding GV values and
approached the magnifying power of the spectacles. Thus there was a
greater VOR response to the acceleration component of the stimulus in comparison to the constant velocity component. After adaptation to the
minimizing spectacles, we did not see differences between GA and
GV.
Previous studies have identified a nonlinear component to the VOR in
addition to the recognized linear behavior (Minor et al.
1999). This nonlinear component is seen as an enhancement of
the gain of the VOR to increasing velocities of stimulation at
frequencies above 2 Hz. It is also observed in the trajectory of the
eye responses to steps of acceleration
(3,000°/s2 to a peak velocity of 150°/s),
which are better described by a third-order polynomial than linear fit.
Under the present adaptive conditions, asking for essentially either a
doubling or halving of the VOR gain, we see comparable changes in the
gain of the linear pathway (28% increase postmagnification and 33%
decrease postminimization). We also see substantially greater gain
changes in the nonlinear pathway (420% increase postmagnification and 100% decrease postminimization). We hypothesize that the greater change in GA as compared with
GV following adaptation to the
magnifying or minimizing spectacles can be explained by a greater, or
preferential, adaptation of the nonlinear pathway. The findings
indicate that the nonlinear pathway can be used to enhance the gain of
the VOR, but it cannot be used to actively lower the gain of the VOR.
The gain during the acceleration (on-ramp) portion of the stimulus was
markedly greater than that during the deceleration (off-ramp) portion
(GD) of the stimulus following
adaptation to the magnifying spectacles. This asymmetric response to
acceleration and deceleration steps with identical stimulus profiles
can also be explained by a greater enhancement of the nonlinear
pathway. We have modeled the nonlinear pathway as a frequency- and
velocity-dependent excitatory pathway that can boost the gain of the
response during rotation in the excitatory direction. From this model,
we predict that the inputs to the nonlinear pathway for a leftward step
of acceleration arise from the left labyrinth, and the inputs for the
deceleration response should arise from the right labyrinth. If this is
the case, why then is there an asymmetry in the response? Since
regularly discharging afferents innervating the semicircular canal
display linear behavior with respect to frequency, acceleration, and
velocity (Hullar and Minor 1999), these afferents could
not cause the acceleration-deceleration asymmetry. The irregularly discharging afferents then would be a possible source of the nonlinear response. Simulation of irregularly discharging afferents using the
Goldberg and Fernandez transfer functions (Fernandez and
Goldberg 1971
; Goldberg and Fernandez 1971
)
shows that the acceleration and deceleration responses will differ.
Preliminary evidence also suggests that the irregular afferents respond
differently to identical accelerations starting from rest and starting
from a constant velocity rotation to the contralateral side
(Hullar et al. 2001
). For example, an irregular afferent
on the left side will respond with a brisk increase in firing rate with
an acceleration step to the left from rest. However, if the animal is
rotating at 150°/s to the right, the irregularly discharging afferent
is silent. If the animal is then decelerated with the same stimulus
profile, the irregularly discharging afferent on the left will not
start firing until the animal has decelerated to approximately 3°/s. As such, the VOR during the deceleration phase is due almost entirely to the input from regularly discharging afferents. This asymmetry in
irregular afferent discharge could account for the differences in the
acceleration gain values between the on-ramp and off-ramp responses.
This would also explain why, following adaptation to the magnifying
spectacles, the gain during the off-ramp response was no different from
the gain during the constant velocity portion of the stimulus.
Responses to sinusoidal rotations
Following adaptation to the magnifying and minimizing spectacles,
we observed changes in gain and phase that were similar to those
reported earlier (Lisberger et al. 1983; Melvill
Jones and Gonshor 1982
; Paige and Sargent 1991
).
As in these earlier studies, the changes in VOR gain, particularly
following adaptation to magnifying spectacles, were greatest at the
lower testing frequencies. The decrease in amount of adaptation at the
higher testing frequencies is consistent with previously published
results (Raymond and Lisberger 1996
). In that study,
monkeys were adapted to ×2 or ×0 viewing conditions at either 0.5, 2, 5, 8, or 10 Hz and showed frequency-dependent gain changes, following
adaptation at the lower frequencies. When adapted at the higher
frequencies, the monkeys demonstrated less robust changes, and there
was no frequency dependence. There were also similar
frequency-dependent changes in gain reported in monkeys following
compensation for a unilateral labyrinthectomy (Lasker et al.
2000
). For stimuli that do not invoke the nonlinear pathway, the process that leads to adaptation in situations that require an
increase in the gain of the VOR behaves as a low-pass filter. Conversely, the process that leads to adaptation in situations that
require a decrease in the gain of the VOR behaves as a high-pass filter. In both situations the behavior of the system is consistent with a low-pass filtered adaptation response being added to
(postadaptation to magnifying spectacles) or subtracted from
(postadaptation to minimizing spectacles) the VOR. The nature of
retinal slip, the presumed error signal, may provide an explanation for
these findings. Retinal slip is dependent on visual following
mechanisms, which have been shown to degrade at higher frequencies
(Martins et al. 1985
).
The frequency-dependent changes in gain seen in the sinusoidal
responses would not be predicted from the asymmetrical gain changes
(GA > GV) observed in the response to steps
of acceleration. In the case of the sinusoidal responses, the greatest
changes in gain were observed at the lower frequencies, whereas the
greatest change in gain during the steps of acceleration was seen
during the acceleration component (or higher frequency portion) of the step. This apparent difference in the adaptation response may be due to
the inherent difference between the unpredictable acceleration steps
and the predictable sinusoidal stimuli. Another possible explanation
for this discrepancy is that the responses to sinusoidal stimulation
were measured at peak velocities of 20°/s, which is below the
threshold for activation of the nonlinear pathway (Minor et al.
1999), while the steps of acceleration were of sufficient intensity to recruit the nonlinear component of the response. Thus the
greater adaptation of the nonlinear pathway may account for the
difference between responses to sinusoidal rotations and steps of acceleration.
While the preferential adaptation of the nonlinear pathway was not seen when tested with sinusoidal stimuli with peak velocities of 20°/s, the adaptation of this pathway was found in the response to sinusoidal stimuli at stimulus intensities of sufficient frequency and velocity to recruit the nonlinearity. When the responses to 4-Hz stimuli of increasing velocity were analyzed, there were proportionally greater increases in gain with increasing velocity of stimulation following spectacle-induced magnification of the VOR (see Fig. 7). Thus this aspect of the sinusoidal responses following spectacle-induced adaptation would be predicted from the responses to steps of acceleration. However, the postmagnification gain of the VOR during the 4 Hz, 100°/s sinusoidal stimuli was still less than the GA measured during the 3,000°/s2 acceleration steps. There are two other factors that could contribute to this difference. First, the gains that were measured during the response to sinusoidal stimulation were derived from the full cycle (both acceleration and deceleration portions of the stimulus), and we have shown that there was a significant difference between the acceleration and deceleration gains postmagnification. Second, there are substantial differences in the relationship between acceleration and velocity for sinusoidal stimuli and steps of acceleration. For the steps of acceleration, we measured GA over an interval of constant acceleration where the stimulus velocity was increasing from 60 to 120°/s. For the sinusoidal stimuli, however, the peak acceleration occurs at 0°/s head velocity and decreases to 0°/s2 as the stimulus reaches peak velocity. Thus during comparable segments of increasing stimulus velocity, the acceleration is constant during the steps of acceleration and decreasing during the sinusoidal stimuli. The nonlinear pathway would be contributing to the VOR during this period of increasing velocity during the step of acceleration (see the discussion of the model in the APPENDIX and Fig. 12). However, during the period of increasing velocity for the sinusoidal stimulus, the contribution of the nonlinear pathway would be decreasing. Due to these differences in the stimulus parameters, the responses to sinusoidal rotations and steps of acceleration are qualitatively similar, but differ quantitatively.
The responses to the acceleration and deceleration portions of the sinusoidal stimuli were consistent with the responses observed during the steps of acceleration and deceleration. For both preadaptation and postadaptation conditions, there were no differences between the linear term coefficients for the acceleration and deceleration quarter cycles. This is consistent with the similarity between the values of GV and GD, which, we propose, are responses due to the linear pathway. With adaptation to the magnifying spectacles, we observed an enhancement in the cubic term for the acceleration portions of the sinusoidal stimulus. We did not observe a similar enhancement of the cubic term for the deceleration portions of the sinusoidal stimulus. These results fit with the greater increase in GA as compared with GV and GD during the steps of acceleration. We hypothesize that the greater increase in GA and the cubic component of the acceleration quarter cycles are due to greater enhancement of the nonlinear pathway.
Relationship to previous studies of VOR adaptation
The findings in this study would, on first inspection, appear to disagree with those reported in earlier investigations of VOR adaptation. Differences in the rotational stimuli used in the present study and those used in earlier studies can account for the different findings. As we shall show, the VOR model we present and validate with our data predicts the findings noted in the earlier studies. Thus we view the previous results as a subset of a broader profile of the adaptation processes described within the present study. In this section, we will review the findings and suggested interpretations from the earlier studies. We will then discuss the data from our studies that suggest a different interpretation of the results, and we will demonstrate that our model predicts the results from the previous studies.
The first difference between our results and those from the earlier studies is that we did not observe a fixed latency to the onset of the adapted response. The absence of a fixed latency to the adapted response calls into question the notion of discrete pathways that are either modifiable or nonmodifiable. Yet, there is an obvious latency to the onset of the adapted response. How do we reconcile these findings? The most likely explanation is that the adaptation is frequency dependent (see Fig. 6). With adaptation to both magnifying and minimizing spectacles, the greatest change in the response gain is seen at the lower frequencies. Following adaptation to the magnifying spectacles, the response to the initial portion of the acceleration step, which contains the highest frequencies, shows less gain enhancement than the later portion of the response. In a similar fashion, the response to the initial portion of the acceleration step postadaptation to the minimizing spectacles demonstrates less gain attenuation than the later portions of the response. This frequency dependence would give rise to a stimulus-dependent latency to the onset of the adapted response.
Since the onset of the adapted response occurs at a velocity lower than
the threshold for the nonlinear pathway (Minor et al.
1999), the variability in the latency could not be due to recruitment of the nonlinear pathway. Therefore the initial responses are presumably due to adaptation of the linear pathway. Further support
for the frequency-dependent adaptation process as being the cause of
the variable latency is demonstrated by comparison of two models of VOR
adaptation. The first model contains a frequency-specific adaptation
process, as described in the APPENDIX. The second model is
comprised of a nonmodifiable pathway and a parallel modifiable pathway
that contained a fixed gain modification element and a fixed time delay
(Lisberger 1984
; Lisberger and Pavelko
1986
). The parameters of the nonmodifiable pathway were
determined from a least-squares fit to the data from sinusoidal
rotations prior to adaptation. The value of the modified gain element
was determined from the adapted response gains at 0.5 Hz. The fixed
latency of the modifiable pathway was determined by averaging the phase
values (in seconds) of the adapted responses to the sinusoidal stimuli (0.5
15 Hz). We then modeled the response of this pathway to
acceleration steps of 3,000 and
500°/s2.
Figure 8A shows that the responses generated from the model with the frequency-dependent adaptation process are similar to the observed behavior after adaptation to both the magnifying and minimizing spectacles. There is a latency to the onset of the adapted response that varies with the stimulus parameters, and, once the adapted response starts, it demonstrates appropriate changes in gain. Figure 8B shows the responses generated from the model containing the nonmodifiable pathway and parallel modifiable pathway. This model generates responses that are in the appropriate directions, but regardless of the stimulus parameters the latency to the onset of the adapted response is constant, which does not fit with the observed data. As a further evaluation of the model containing parallel modifiable and nonmodifiable pathways, we analyzed the predicted responses to sinusoidal stimuli of 0.5-15 Hz with a peak velocity of 20°/s. The gains and phases predicted after adaptation to magnifying and minimizing spectacles are shown in Fig. 8, C and D, respectively. While the phase values are appropriate, the gain values do not demonstrate the frequency-dependent changes observed in the actual data (see Fig. 6). These findings provide further support to the notion that all components of the VOR are modified in response to both magnifying and minimizing spectacles.
|
While previous studies have not measured
GA following adaptation,
Lisberger and Pavelko (1986) measured the DI, which was defined as the ratio of the maximum eye velocity to the steady-state eye velocity. These authors reported that, although the peak and steady-state eye velocities increased following adaptation to the
magnifying spectacles, there was a decrease in the DI. Conversely, while the peak and steady-state eye velocities decreased following adaptation to the minimizing spectacles, there was an increase in the
DI. Thus there was a greater peak eye velocity relative to the
steady-state eye velocity after adaptation to the minimizing spectacles. This increased DI following adaptation to the minimizing spectacles was thought to be due the presence of the nonmodifiable pathway in the VOR circuitry. In addition, based on recordings from the
primary vestibular afferents, the authors concluded that the irregular
afferents provided the input to the nonmodifiable pathway.
We measured the DI for the 3,000°/s2 to 60°/s stimulus, and the results differed from the previously reported responses. There was no significant change in the DI postadaptation to either the magnifying or minimizing spectacles. There are several differences between the present study and the earlier study. First, the acceleration steps used in the two experiments are vastly different. In the present study we used accelerations of 3,000°/s2, to a peak velocity of 60°/s. The acceleration steps used in the earlier studies were significantly lower (600°/s2 to a peak velocity of 30°/s) and would not have been expected to evoke an appreciable response from the nonlinear pathway. Recruitment of the nonlinear pathway under normal conditions could account for the lack of decrease in the DI seen following magnification in the present study.
Another significant difference between the two studies is the degree of VOR gain attenuation obtained during the adaptation process. In the earlier study, decreased VOR gain was obtained using a head-fixed visual scene (×0) or ×0.25 minimizing spectacles. In the present study, we used minimizing spectacles of ×0.45 power. Consequently, the velocity gains of the minimized VOR differed in the two studies (0.32 in the earlier study and 0.60 in the present study). We can view the VOR following minimization to be a high-pass filtered response (see Fig. 6). With greater decreases in the low-frequency VOR gain, one would expect that the dynamics of the high-pass filtered central adaptation element would change to reflect a greater decrease at the lower frequencies. This would lead to a proportionally greater initial overshoot and larger values of DI to steps of acceleration.
Figure 9 shows the simulated responses, from our current model of the VOR, to 600°/s2 to 30°/s acceleration steps. The two solid lines are the simulated responses following adaptation with the magnifying (top solid line) and minimizing spectacles (bottom solid line). The parameters of the frequency-dependent adaptation process were derived from the actual responses to sinusoidal stimuli and were identical to those used for the previous simulations. As seen in the previously reported data for responses to 600°/s2 to 30°/s acceleration steps, the model predicts an increase in the DI with adaptation to the minimizing spectacles. We next estimated the frequency-dependent responses that would be observed with adaptation to ×0.25 minimizing spectacles. We used these data to generate the appropriate parameters for the frequency-dependent adaptation element in our model. The simulated results are shown in the lowest dotted line in Fig. 9. With the greater reduction in VOR gain, we observe an even greater increase in the DI. Our model of the VOR, therefore predicts the findings that have been observed with the stimuli used in other studies.
|
Most of the data presented in earlier papers describing the DI were
obtained on a daily basis during the adaptation process. The values of
DI presented here were obtained after one week of adaptation to the
magnifying or minimizing spectacles. It is possible that the DI is a
manifestation of differing rates of adaptation for the static and
dynamic components of the response, with the static component adapting
faster than the dynamic component. There is evidence in support of
differential adaptation of the VOR across frequencies (Lisberger
et al. 1983; Melvill Jones and Gonshor 1982
;
Raymond and Lisberger 1996
). There is also some evidence to suggest that there are differential rates of adaptation in the
static and dynamic components of the response. Melvill Jones and
Gonshor (1982)
noted a difference in the rate of de-adaptation to the removal of vision-reversing spectacles when the VOR was tested
at frequencies from 0.5 to 6.0 Hz. They found that the changes in the
VOR could be described as an interaction of a simple gain attenuation
acting across all frequencies and a more complex frequency-dependent
modulation of both gain and phase. This complex effect was present at
the lower frequencies and absent at frequencies above 3 Hz. With
removal of the vision-reversing spectacles, they observed a rapid
reduction in the complex component of the adapted response and a
prolonged decline of the simple gain attenuation response. If the
de-adaptation process is a mirror image of the adaptation process, then
one could interpret their results as suggesting that the
lower-frequency component of the VOR would adapt faster than the
higher-frequency component. This could explain the difference in the
measures of DI between the present study and the earlier study of
Lisberger and Pavelko. In one animal, we obtained data on day
4 and day 9 during adaptation to minimizing spectacles,
and the observed results do not support this explanation. The DI was
1.07 on day 4 and 0.96 on day 8. While there is a
minimal decrease in the DI from day 4 to 9, these
data do not show the same degree of overshoot described in the previous
studies. A further explanation for the discrepancy between the studies
could be the use of different species of monkeys. However, in all other respects, the adaptation data are comparable with the previously described results in rhesus monkeys. In addition, previous
investigations of VOR adaptation in squirrel monkeys have demonstrated
results that are consistent with the results in rhesus monkeys
(Bello et al. 1991
).
Concluding remarks
We have presented evidence that requires a reassessment of previously held ideas regarding adaptation of the VOR. Our findings provide evidence of linear and nonlinear pathways involved in control of the horizontal angular VOR. The gains of both pathways are modified by exposure to magnifying or minimizing spectacles; however, the nonlinear pathway is more modifiable than the linear pathway. The nonlinear pathway is responsible for the increase in VOR gain to values that approach the power of the spectacles in response to high-frequency, high-velocity rotations. The model that we have proposed for VOR adaptation is similar to the one that has accounted for our findings in squirrel monkeys with normal vestibular function and following unilateral plugging of the three semicircular canals or unilateral labyrinthectomy. This model also predicts the responses that have been observed in other studies of VOR adaptation.
Our analysis of acceleration steps of different amplitudes has shown that there is not a fixed latency to the onset of the adapted response. Rather, the latency that is measured is dependent on the dynamics of both the stimulus and the adaptive processes. From the responses to acceleration step stimuli that were of sufficient intensity to recruit the nonlinear pathway, which is inherent in the dynamics of the VOR, we observed changes in the dynamics of the VOR that were different from those reported in earlier studies. A model of the VOR circuitry containing modifiable and nonmodifiable pathways cannot directly explain these findings. We propose a model of VOR adaptation in which both the linear and nonlinear pathways are modified. Based on the observed changes in the dynamics of the response during the acceleration and deceleration steps, we suggest that the nonlinear pathway is the more modifiable pathway and derives its input from the irregularly discharging afferents innervating the semicircular canals.
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APPENDIX |
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The model we have used to simulate responses after
spectacle-induced adaptation is similar to the one we described for the VOR in animals with intact vestibular function, following unilateral canal plugging of the three semicircular canals, and following unilateral labyrinthectomy (Lasker et al. 1999,
2000
; Minor et al. 1999
). This bilateral
model, shown in Fig. A1, has inputs to
the reflex coming from both linear and nonlinear pathways. The linear
pathway contributes to the reflex during all types of rotational
stimuli. The nonlinear pathway, however, makes an appreciable
contribution to the reflex only at frequencies greater than 2 Hz and at
velocities greater than ~30°/s.
|
There are two stages to each pathway. The first stage of the linear
pathway describes the dynamics of regularly discharging vestibular-nerve afferents innervating the semicircular canals. These
afferents have a rotational sensitivity that is constant with respect
to frequency and velocity for the stimuli used in this study
(Hullar and Minor 1999). The first stage of the
nonlinear pathway consists of a transfer function describing the
dynamics of irregularly discharging afferents and a cubic term
representing the dependence of the gain of this pathway on head
velocity. The transfer function of irregular afferents describes the
increase in response gain based on frequency and also the propensity of these afferents to be driven into inhibitory cutoff at higher stimulus
velocities. The gain of the nonlinear pathway also varies with the cube
of head velocity.
The second stage of the linear pathway shows the dependence of adaptation on the frequency of the stimulus. With adaptation to magnifying spectacles, the transfer function is a low-pass filter because there is a larger increase in gain for responses to low- in comparison to high-frequency rotations. The inverse of this relationship between gain and frequency is noted for adaptation to minimizing spectacles; therefore a high-pass filter is used to describe this process. The frequency-specific adaptation process is represented by a first-order transfer function with one zero, one pole, and a gain term with coefficients determined from a least-squares fit to the data from sinusoidal rotations after adaptation to the magnifying or minimizing spectacles. The coefficients are k = 1.9, TZ = 0.0123, and TP = 0.0196 after adaptation to magnifying spectacles and k = 0.7, TZ = 0.0272, and TP = 0.018 after adaptation to minimizing spectacles. The second stage in the nonlinear pathway is described by a modifiable gain element (kN) that increases during adaptation to magnifying spectacles and decreases to 0 during adaptation to minimizing spectacles. The two pathways are then summed to provide a representation of the complete response.
The transfer function providing a representation of the inputs to the
nonlinear pathway in our initial description of this pathway
(Minor et al. 1999),
[sTc(sTh)]/[(sTc + 1)(sTh + 1)], has been changed to a
somewhat different form,
[sTc(sTh + 1)]/(sTc + 1), in the current
model. There are two reasons for this change in the mathematical
representation of the high-pass filter. First, the new transfer
function provides a better description of the dynamics of irregularly
discharging semicircular canal afferents (Fernandez and Goldberg
1971
; Goldberg and Fernandez 1971
). These afferents have a gain enhancement that increases with the frequency of
rotational stimulation making them candidates for mediating the
nonlinear pathway. Second, the dynamics of the present transfer function provide a better representation of the asymmetric responses to
the acceleration and deceleration portions of the
3,000°/s2 steps. Even though there are subtle
differences in the responses arising from these two high-pass filters,
the fundamental dynamics of each are the same: a rise in gain and phase
lead with increasing frequency.
The gain of responses at 4 Hz were simulated prior to adaptation, following adaptation to ×0.45 spectacles, and following adaptation to ×2.2 spectacles. Preadaptation, the model led to an approximate 5% increase in gain for responses to rotations with a peak velocity of 100°/s in comparison with those at a peak velocity of 20°/s. There was no increase in gain with peak velocity in the simulated responses after adaptation to ×0.45 spectacles when the modifiable gain for the nonlinear pathway element was decreased to 0. The gain of the simulated responses at 100°/s peak velocity after adaptation to ×2.2 spectacles was approximately 10% greater than that for the rotations with a peak velocity of 20°/s. Figure A2, A and B, shows the simulated responses to a 3,000°/s2 to 150°/s step of acceleration. Gain values were kept the same as those used during the simulation of 4-Hz responses. The model predicts the overall elevation in gain and the asymmetrical gains during the acceleration, constant velocity, and deceleration portions of the step following adaptation to the magnifying spectacles (Fig. A2A). The increase in the acceleration gain occurs because of contributions from both the linear and nonlinear pathways. This is expected due to the high-frequency content during the initial acceleration as well as the increasing velocity. The gain during the constant velocity portion of the stimulus is not as elevated since there is no contribution of the nonlinear pathway due to the low-frequency content during this part of the stimulus. The gain during the deceleration portion of the stimulus was less than the gain during the acceleration portion of the stimulus due to the high sensitivity and cutoff properties of irregular afferents. The model also predicts the decreased gains of all three components of the response following adaptation to the minimizing spectacles (Fig. A2B). The similar decreases in gain are due solely to changes in the linear pathway, as the nonlinear pathway gain was decreased to 0. Thus the model is able to replicate the actual responses to the steps of acceleration when the data from the sinusoidal stimuli are used to determine the parameters of the central gain elements.
|
A simulated response to a leftward
3,000°/s2 stimulus that reaches a plateau
velocity of 150°/s and then decelerates to rest at
3,000°/s2 is shown in Fig.
A3. A shows the simulated
response of a horizontal canal irregular afferent (determined from the
transfer function given in Fig. A1) in the left () and right
(- - -) vestibular nerve. Note that the right irregular afferent
response is in inhibitory cutoff for the acceleration and plateau
portions of the stimulus. The excitatory response of the right
irregular canal afferent during deceleration (emerging from inhibitory
cutoff) is not equivalent to the excitatory response of the left
horizontal canal irregular afferent at the onset of the rotation.
Figure A3B shows the contribution of the nonlinear pathway
to the VOR after the cubic nonlinearity described in Fig. A1. The
relative contribution from the right excitatory response during the
deceleration portion of the stimulus is less than the left excitatory
response during the acceleration portion of the stimulus. The cubic
term accentuates this asymmetry between the acceleration and
deceleration portions of the response due to its nonlinear behavior.
Figure A3C shows the symmetric responses predicted for the
regular horizontal canal afferents (Hullar and Minor
1999
) to excitatory and inhibitory stimuli. The summed
responses from the linear and nonlinear pathways are shown in
D. As observed in the data, the acceleration response has a
larger gain than the deceleration response.
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ACKNOWLEDGMENTS |
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This work was supported by National Institute on Deafness and Other Communication Disorders Grants K08 DC-00150 and R01 DC-02390 and by the National Aeronautics and Space Administration Cooperative Agreement NCC 9-58 with the National Space Biomedical Research Institute.
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FOOTNOTES |
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Address for reprint requests: R. A. Clendaniel, Dept. of
OtolaryngologyHead and Neck Surgery, Johns Hopkins Medicine, 601 North Caroline St., Rm. 6245, Baltimore, MD 21287-6214.
Received 12 December 2000; accepted in final form 6 June 2001.
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REFERENCES |
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