Department of Neurobiology, Pharmacology and Physiology, University of Chicago, Chicago, Illinois 60637
![]() |
ABSTRACT |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Chen-Huang, Chiju and Robert A. McCrea. Effects of viewing distance on the responses of horizontal canal-related secondary vestibular neurons during angular head rotation. The eye movements generated by the horizontal canal-related angular vestibuloocular reflex (AVOR) depend on the distance of the image from the head and the axis of head rotation. The effects of viewing distance on the responses of 105 horizontal canal-related central vestibular neurons were examined in two squirrel monkeys that were trained to fixate small, earth-stationary targets at different distances (10 and 150 cm) from their eyes. The majority of these cells (77/105) were identified as secondary vestibular neurons by synaptic activation following electrical stimulation of the vestibular nerve. All of the viewing distance-sensitive units were also sensitive to eye movements in the absence of head movements. Some classes of eye movement-related vestibular units were more sensitive to viewing distance than others. For example, the average increase in rotational gain (discharge rate/head velocity) of position-vestibular-pause units was 20%, whereas the gain increase of eye-head-velocity units was 44%. The concomitant change in gain of the AVOR was 11%. Near viewing responses of units phase lagged the responses they generated during far target viewing by 6-25°. A similar phase lag was not observed in either the near AVOR eye movements or in the firing behavior of burst-position units in the vestibular nuclei whose firing behavior was only related to eye movements. The viewing distance-related increase in the evoked eye movements and in the rotational gain of all unit classes declined progressively as stimulus frequency increased from 0.7 to 4.0 Hz. When monkeys canceled their VOR by fixating head-stationary targets, the responses recorded during near and far target viewing were comparable. However, the viewing distance-related response changes exhibited by central units were not directly attributable to the eye movement signals they generated. Subtraction of static eye position signals reduced, but did not abolish viewing distance gain changes in most units. Smooth pursuit eye velocity sensitivity and viewing distance sensitivity were not well correlated. We conclude that the central premotor pathways that mediate the AVOR also mediate viewing distance-related changes in the reflex. Because irregular vestibular nerve afferents are necessary for viewing distance-related gain changes in the AVOR, we suggest that a central estimate of viewing distance is used to parametrically modify vestibular afferent inputs to secondary vestibuloocular reflex pathways.
![]() |
INTRODUCTION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
The vestibuloocular reflex (VOR) functions to
stabilize images on the retina during head movements by rotating the
eyes. The angular vestibuloocular reflex (AVOR) is evoked by angular
rotations of the head that stimulate the vestibular semicircular
canals. The eye movements evoked by the AVOR vary inversely as a
function of viewing distance (Chen-Huang and McCrea
1998b; Snyder and King 1992
; Viirre et
al. 1986
).
Several observations suggest that the increase in AVOR eye movement
gain during near viewing reflects changes in the processing of
vestibular signals in brain stem VOR pathways. During near target
viewing, sudden step changes in head velocity evoke eye movements with
an enhanced gain at latencies that are shorter than even the shortest
visual feedback-driven eye movements (Crane and Demer
1997, 1998
; Snyder et al. 1992
;
Viirre et al. 1986
). A viewing distance-related
increase in AVOR gain has been demonstrated to occur before the
convergent eye movements that produce a change in viewing distance
(Snyder et al. 1992
). This gain increase persists in the
absence of a target in complete darkness (Chen-Huang and McCrea
1998b
; Hine and Thorn 1987
; Snyder et al.
1992
). Finally, viewing distance gain increases in the AVOR are
significantly reduced when irregular vestibular afferents are silenced
(Chen-Huang and McCrea 1998b
). These observations have
led to the suggestion that some, or possibly all of the central
vestibular signals that drive the VOR are multiplied by an internal
estimate of vergence angle or viewing distance (Chen-Huang and
McCrea 1998b
; Paige and Tomko 1991
;
Viirre et al. 1986
).
If the changes in the AVOR are due to parametric changes in central
pathways that mediate the reflex, it is not clear how or where these
changes occur. Recently, McConville et al. (1996) carried out a single-unit recording study in rhesus monkeys in which
the AVOR responses of eye movement-related units were recorded during
viewing of near and far targets. They found that some classes of eye
movement-related units were more sensitive to viewing distance than
others. Specifically, the rotational responses of
eye-head-velocity (EHV) units (whose response to vestibular stimulation
typically reverses when the VOR is voluntarily canceled or suppressed)
were significantly enhanced during near target viewing. On the other hand, the responses of position-vestibular-pause (PVP) units were usually unaffected by viewing distance, once the eye position sensitivity of those cells was taken into account. The rotational responses of units that were not sensitive to eye movements were not
affected by viewing distance (Tomlinson et al. 1996
).
Although based on a relatively small sample of cells, these
observations suggest that viewing distance-related changes in the AVOR
may be mediated by a specialized subset of the available VOR pathways.
In this study we examined in further detail the viewing
distance-related changes in the angular head rotation sensitivity of
different classes of horizontal canal-related secondary vestibular neurons. We focused particularly on eye movement-related neurons in
the rostral part of the medial vestibular nucleus of the squirrel monkey, because such neurons are likely to be related to the VOR (Cullen et al. 1993; Scudder and Fuchs
1992
). We report that the signals generated by most of the
horizontal canal-related neurons putatively involved in mediating the
VOR change as a function of viewing distance. The changes in
sensitivity to head rotation appear to be more than sufficient to
produce viewing distance-related changes in the VOR. We hypothesize
that viewing distance modifications in the AVOR are produced by
modifying the gain of indirect inhibitory vestibular afferent inputs to
VOR pathways.
Some of these results have been previously described in a preliminary
report (Chen-Huang and McCrea 1998a).
![]() |
METHODS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Surgical procedures
Two squirrel monkeys were prepared for chronic recording of bilateral eye movements, single-unit activity and for electrical stimulation of both labyrinths. Surgeries were carried out under sterile conditions on anesthetized animals (pentobarbital sodium, 20 mg/kg, initial dose; supplemental doses of 1-2 mg/kg administered as necessary). A flattened stainless steel bolt, to be used for head restraint in the plane of the horizontal semicircular canal, was attached to the occipital bone with dental acrylic. A Plexiglas cylindrical recording chamber (15 mm diam), was stereotaxically implanted on the surface of the left parietal bone for introducing recording microelectrodes into the brain stem. A search coil was sutured to the sclera of the right eye, and the twined leads of the coils were soldered to a connector that was cemented to the skull.
On a subsequent day, a second search coil was implanted on the left eye, and bipolar stimulating electrodes were implanted into both labyrinths. One of each pair of labyrinthine stimulating electrodes (chlorided silver wire, 0.25 mm diam and Teflon insulated to within 1 mm of tip) was inserted into the perilymphatic space through a hole in the bony promontory midway between the round and oval windows. The second electrode was placed in the ventral aspect of the middle ear. Leads from both electrodes were led out of the middle ear near the insertion of the tympanic membrane and soldered to a skull-mounted connector.
Experimental recording conditions
During experiments the monkey was seated in a Plexiglas chair on
a vestibular turntable. Each animal was trained to fixate two types of
visual targets. Rewards were contingent on vergence angle and vertical
eye position. In some experimental paradigms (Fig.
1A) the monkey fixated small
targets that were projected onto a blank cylindrical screen 90 cm
distant from the axis of rotation. In other paradigms the monkey looked
through a door in the screen at an earth-stationary far target
1.52 m distant from the axis of rotation (Fig. 1). All experiments
were carried out in a dimly lit room (2 × 4 m in size) in
which the monkey was isolated. Squirrel monkeys typically fixated
targets for brief periods (0.5-2 min) on demand for periods of 6 h
or more.
|
Turntable rotation and head movement recording
Passive head rotations in the plane of the horizontal semicircular canals (15° nose down from the stereotaxic plane) were produced with a position servo-control system whose output modified the command of a velocity servo turntable controller (Inland model 832). The axis of turntable rotation, which was parallel to earth-vertical, passed through the squirrel monkey's midsagittal plane, where it intersects with the line connecting the two external auditory meatuses. The responses of single units were typically recorded during rotations at several different frequencies and velocities of table rotation (most commonly, 0.7 Hz, peak velocity 20-40°/s; 1.9 Hz, 10-20°/s and 4.0 Hz, 6-10°/s). Each stimulus frequency produced a slightly higher peak head acceleration (88, 119, and 150°/s2 for the 0.7-, 1.9-, and 4.0-Hz stimuli, respectively) and a significant decrease in head displacement (4.55, 0.84, and 0.24° for the 0.7-, 1.9-, and 4.0-Hz stimuli, respectively). Angular table velocity was recorded with an angular velocity transducer (Watson Industries).
Eye movement recording
Eye movements were measured with a magnetic search-coil system (40 cm diam, Neurodata Instruments) that was mounted on a movable superstructure on top of the vestibular turntable. The system was linearly related to eye position throughout the monkey's oculomotor range of ±20°. The root-mean-square (rms) noise level of the system was equivalent to ±0.2° (0-7 kHz). The gain of each eye coil was calibrated independently by assuming that the AVOR gain recorded in the light in response to a 1.9-Hz, 10°/s sinusoidal head rotation had a gain of unity. Zero horizontal eye position for each eye was defined as the position of the eye during fixation of a target 8 mm lateral to the midline (half of the interpupillary distance) when the other eye was patched. These calibrations were checked periodically by recording smooth pursuit eye movements evoked by a 0.7-Hz, 20°/s moving target. The vergence angle was obtained from the difference between right and left eye positions. Negative values indicate convergence.
Visual target characteristics and behavior control
Smooth pursuit eye movements were evoked with a laser projected onto a cylindrical screen 90 cm from the monkey with a pair of mirrors attached to position controlled galvanometers. Two retractable ceiling-mounted earth-stationary visual targets were used to study viewing distance-related changes in the VOR. Each target was a red light-emitting diode (LED) affixed to the tip of a motorized telescoping rod attached to the ceiling. The far and near LEDs were 5 mm (0.2°) and 1 mm (0.5°) in diameter, respectively. The far target was positioned on the midline 152 cm from the monkey. The near target was positioned on the midline 12.25 cm from the interaural plane (10 cm from a plane passing through the meridian of the 2 eyes). A third head-stationary near target was attached to the monkey chair with a hinge that allowed it to be positioned 10 cm from the eyes. The monkey was intermittently rewarded for fixating a visual target with drops of vanilla-flavored milk. The milk rewards were typically given at a frequency of ~1/s when the horizontal and vertical position of both eyes converged within 1° of the target.
Single-unit recording techniques
The techniques used for obtaining single-unit recordings have
been previously described (Chen-Huang et al. 1997;
Cullen and McCrea 1993
). Briefly, Epoxy-insulated
tungsten microelectrodes (4-7 M
impedance) were advanced into the
cerebellum with a manually operated micromanipulator. A hydraulic
microdrive (Trent Wells) was then used to move the microelectrode into
the vestibular nuclei. The location of each electrode probe into the
brain was determined with respect to a skull-mounted reference point
inside the recording chamber and verified by the location of vestibular
field potentials evoked after electrical stimulation of the ipsilateral
vestibular nerve (0.1-ms monophasic perilymphatic cathodal pulses, 200 µA). Single isolated vestibular unit potentials were conventionally amplified and discriminated. The output pulse of a window discriminator was used to trigger the event channel of a CED 1401 data acquisition system, which stored the time of the spike at a 100-µs resolution (see Data acquisition and data analysis).
SYNAPTIC ACTIVATION OF VESTIBULAR UNITS FROM THE VESTIBULAR NERVE. For most of the units encountered, the ipsilateral vestibular nerve was electrically stimulated (0.1-ms pulses, 50-300 µA) to determine the presence and latency of synaptically evoked responses. Units whose response latency was <1.4 ms were considered to have monosynaptic inputs from the vestibular nerve. The lack of a response to vestibular nerve stimulation was not considered to be strong negative evidence for the lack of direct inputs from the vestibular nerve. The maximum currents used were not sufficient to activate all of the fibers in the vestibular nerve, and, in a few cases (particularly with those units not tested) the unit potential was too small to recognize in the presence of the vestibular field that was concomitantly evoked by the stimulus.
Most of the cells included in this report were located in the vestibular nuclei, based on the latency and amplitude of the field potentials recorded in the vicinity of each unit. Estimates of the rostral, medial, and lateral borders of the nuclei were based on the amplitude of monosynaptic field potentials recorded following electrical stimulation of the vestibular nerve and the firing behavior of neurons in regions judged to be outside the borders of the vestibular nuclei.ANTIDROMIC IDENTIFICATION OF ASCENDING TRACT OF DEITERS
NEURONS.
In one monkey, a concentric bipolar electrode (platinum-irridium;
150 µm OD, 75 µm ID; tip separation 300 µm) was placed ~400 µm dorsal to the left ascending tract of Deiters (ATD) after
determining the location of the left medial longitudinal fasciculus at
a rostrocaudal level that was 0.5 mm caudal to the caudal pole of the
trochlear nucleus. Some of the data from these units have been
presented in a preliminary report (Chen-Huang and McCrea
1998a).
Single-unit recording protocol
Only isolated units whose firing behavior was related to head
rotation in the horizontal semicircular canal plane (either during
fixation of an earth-stationary target or during fixation of a
head-stationary target) were studied. Once encountered, horizontal semicircular canal-related units were tested for their responses following electrical stimulation of the ipsilateral vestibular nerve
and/or the ipsilateral ATD (see ANTIDROMIC IDENTIFICATION OF
ASCENDING TRACT OF DEITERS NEURONS). The response of each unit was then recorded in the following paradigms (~30-60 s per
paradigm):
1 | |
AVOR during fixation of a far target (152 cm distant; 0.7 Hz, ±20°/s; 1.9 Hz, ±10°/s; 4.0 Hz, ±6°/s) | |
2 | |
AVOR during fixation of a near target (12.25 cm distant; 0.7, 1.9, and 4.0 Hz) | |
3 | |
Smooth pursuit of a moving target (90 cm distant; 0.7 Hz, ±20°/s) | |
4 | |
Cancellation of the AVOR; head stationary far target (90 cm distant; 0.7 Hz) | |
5 | |
Spontaneous eye movements in the absence of table rotation | |
6 | |
Cancellation of the AVOR; head stationary near target (12.25 cm distant; 0.7 Hz) |
Data acquisition and data analysis
DATA ACQUISITION. Eye positions, eye velocity, head velocity, and table position were acquired at 16-bit A/D resolution with the CED 1401 system at 500 Hz. Single-unit spike data were stored as event times (100-µs resolution) using the CED 1401 event channel for off-line analysis. Off-line analysis was carried out on a Macintosh microcomputer with the aid of IGOR, a data analysis and programming software (WaveMetrics).
UNIT FIRING RATE. Unit clock values were converted to firing rate values that were assigned to each 2-ms A/D bin using a time-symmetric algorithm. All of the quantitative analysis in this study was carried out using these records of unit firing rate. In some illustrations, the bin size was increased from 2 to 10 ms to improve graphic presentation; this change in bin size is noted in the figure legend.
UNIT STATIC EYE POSITION SENSITIVITY. Static eye position sensitivity was assessed from firing behavior generated during periods (500 ms to 2 s) of spontaneous fixation in the absence of a target. Multiple regression estimates of the sensitivity to horizontal and vertical eye position were computed from at least 20 stable eye positions (>100 ms after a saccade). For units that demonstrated nonlinearity in the rate-position relationship, multiple fits of firing rate were made to subranges of eye position where the relationship appeared to be linear by visual inspection. In some units whose firing rate approached zero during off-direction gaze, eye position coefficients were determined with an iterative fitting technique that used changes in residual variance to estimate the point at which the fit became nonlinear. Static eye position coefficients were used to correct records for eye position-associated signals.
Little effort was made to determine unit sensitivity to monocular eye position. A rough estimate of the ocular dominance of a unit's eye position sensitivity (McConville et al. 1994ANALYSIS OF UNIT DATA OBTAINED WITH SINUSOIDAL STIMULI. All of the unit data related to smooth pursuit, VOR cancellation, and the VOR were obtained during sinusoidal target or turntable rotations. Typically, unit responses during two or more 30-s duration trials were obtained for each of the behavioral paradigms described above. Only cycles in which the positions of both eyes were within 2° of the target were included in the analysis. In the analysis of records related to the VOR, cycles were rejected if an appropriate vergence angle was not maintained during the cycle. The included cycles were concatenated, desaccaded, averaged, and fit with sinusoidal functions.
The desaccading, or "de-quickphase" algorithm involved a comparison of the estimated slow phase eye velocity to the actual eye velocity recorded from one eye in selected cycles (usually the right eye). When the recorded eye velocity deviated from estimated slow phase velocity by a criterion amount (usually 10-30°/s), the records were considered to be saccades or artifacts, and all of the data within a window around the saccade were eliminated from further analysis. The saccade window was usually 30 ms before the saccade and 40 ms after the end of the saccade. The window was adjusted so that saccade-related bursts and pauses in firing rate were eliminated from records. It was sometimes not feasible to entirely eliminate firing behavior related to postsaccadic "slide," because its duration could be longer than the mean quick-phase interval. In these cases (particularly EHV omnibursters), the time constant of the saccade slide was estimated, and the saccade window was adjusted to extend at least one time constant after the end of the saccade. The efficacy of the desaccading algorithm was evaluated by careful visual comparison of desaccaded records to the original records. Desaccaded, selected records were then duplicated. One set of records was averaged and fit with sinusoidal functions whose frequency was the same as the fundamental frequency of the stimulus. An iterative fitting technique was used to eliminate low firing frequency responses that deviated significantly from linearity during periods of inhibitory saturation (Chen-Huang et al. 1997Methods for calculating viewing distance-related changes in unit and eye movement responses
The rotational responses of many vestibular units were
significantly different during near target viewing (AVORn)
than during far target viewing (AVORf), but the phase of
these responses did not change significantly as a function of viewing
distance. It was convenient to define a scalar quantity (GVD) that
was an estimate of change in response gain (
G) related to viewing
distance (VD) of a unit, based on the difference in responses recorded during AVORn and AVORf. A ratio of a unit's
VOR response gains during AVORn and AVORf (N/F
ratio) was also calculated.
The vergence angles required to fixate the far and near targets were
0.2 and 9.6°, respectively. The ideal gain of the VOR required to
maintain image stability during head rotation calculated from the
equations described by Viirre et al. (1986) was 1.02 for
the far target and 1.22 for the near target. Thus the change in VOR
gain required by kinematic considerations was 0.20. In previous
behavioral studies we found that the AVOR gain change was inversely
related to the frequency of turntable rotation, and even at low
stimulus frequencies it had a variable gain that rarely matches the
kinematic requirement (Chen-Huang and McCrea 1998b
). In
the present study, the change in AVOR gain recorded concomitantly with
unit recordings varied from 0.0 to 0.25. The mean gain change was
0.17 ± 0.02 (mean ± SE) during 0.7-Hz table rotations,
0.09 ± 0.01 during 1.9-Hz rotations, and 0.03 ± 0.01 during
4.0-Hz rotations (Fig. 1B). These values were slightly smaller than those recorded in the absence of single-unit recordings. Because the target was located on the midline, very little change in
the phase of the eye movements was predicted, or, on average, recorded
(Fig. 1C). Variances in both eye movement and unit responses reported in figures, text, and tables are means ± SE.
![]() |
RESULTS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Location and classification of vestibular units
The effects of viewing distance on the responses of 105 vestibular nucleus neurons to sinusoidal angular head rotation in the plane of the horizontal semicircular canals were recorded in two squirrel monkeys. Every unit encountered was classified on the basis of its firing behavior during 1) sinusoidal rotation while the monkey fixated an earth-stationary LED target, 2) VOR cancellation evoked by fixation of a head-stationary target projected onto a cylindrical screen, and 3) sinusoidal smooth pursuit of a target projected onto the screen. Units whose firing rate was not related to horizontal rotation or horizontal eye movements during pursuit were discarded. Most of the units tested (84/105) were activated at monosynaptic (77/84) or disynaptic (1/84) latencies following electrical stimulation of the ipsilateral vestibular nerve (Fig. 2, A and B).
|
Most of the units in this study were located in the rostral half of the vestibular nuclei. The estimated location of the tracks in one monkey is illustrated in a diagrammatic horizontal section through the vestibular nuclei in Fig. 2C. The diagram is a dorsal view of the vestibular nuclei constructed in a plane orthogonal to the orientation of electrode tracks. Reconstruction of electrode tracks suggested that neurons in the medial, superior, and lateral vestibular nucleus were included in our sample. The majority of horizontal canal-related secondary vestibular neurons were encountered in the ventral lateral vestibular nucleus and adjacent regions of the rostral medial vestibular nucleus. Four units recorded on one track were included in this study even though the reconstruction suggested they were located in the rostral prepositus nucleus [starred track at rostral end of nucleus prepositus hypoglossi (PH) in Fig. 2C]. These burst-position units were included because the synaptic field potential recorded in that track was large and because adjacent nonhorizontal canal-related units were activated at monosynaptic latencies following stimulation of the vestibular nerve.
Horizontal canal-related vestibular neurons were classified on the
basis of their firing behavior during the VOR, VOR cancellation, smooth pursuit eye movements, fixation, and spontaneous saccadic eye
movements. The classification scheme and nomenclature used here are
similar to that previously described for segregating the responses of
primate vestibular neurons (Cullen and McCrea 1993;
Miles 1974
; Scudder and Fuchs 1992
;
Tomlinson and Robinson 1984
). These categories include
the following:
1 | |
Type I vestibular only (VI) units (n = 10) | |
2 | |
Burst-position (BP) units (n = 10) | |
3 | |
PVP units (n = 47) | |
4 | |
EHV units (n = 22) | |
5 | |
Position-vestibular (PV) units (n = 6) | |
6 | Other eye movement-related vestibular units (n = 10) |
All of the VI, PVP, and PV units, and the majority of the EHV
units exhibited type I (ipsilateral on direction) rotational responses
during fixation of earth-stationary targets. Most eye movement-related
BP units, some EHV units, and most of the unclassified units exhibited
type II responses (see below). The predominance of PVP and EHV
units in this sample was due to the fact that a concerted attempt was
made to record from regions of the vestibular nuclei that contained
horizontal canal-related secondary vestibular neurons that project to
the abducens nucleus or the medial rectus subdivision of the oculomotor
nucleus. Six EHV units and one PVP unit included in this study were
antidromically activated following electrical stimulation of the
ascending tract of Deiters. Some of the firing characteristics of these
cells have been described in a preliminary communication
(Chen-Huang and McCrea 1998a). In the following
paragraphs the characteristic firing behavior of each class of units
will be described.
Vestibular-only units
The firing behavior of a typical VI unit during smooth pursuit, VOR cancellation and during the VOR evoked while fixating the far target (AVORf) and while fixating the near target (AVORn) is illustrated in Fig. 3. In each paradigm the stimulus frequency was 0.7 Hz and the peak velocity was 20°/s. Figure 3, A1-D1, shows sample records obtained from the cell. Figure 3, A2-D2, shows the averaged, desaccaded responses of the same cell.
|
The firing characteristics of VI units are summarized in Table 1. All of the VI units tested (8/8) were activated at monosynaptic latencies following stimulation of the vestibular nerve and were sensitive to ipsilateral head velocity during sinusoidal turntable rotation (mean gain = 0.96 ± 0.16 spikes/s/deg/s at 0.7 Hz). Their head velocity sensitivity was slightly higher during VOR cancellation (mean gain = 1.08 ± 0.15 spikes/s/deg/s). VI units were not sensitive to eye position and saccades and were not modulated during sinusoidal smooth pursuit eye movements.
|
The rotational responses of most VI units were not significantly affected by viewing distance. One VI unit's response gain decreased from 1.4 spikes/s/deg/s to 1.1 spikes/s/deg/s during near target viewing (22% decrease in gain). This exceptional unit caused the average rotational responses of VI units to be slightly lower during near target viewing (Table 2).
|
Burst position units
Burst-position units were usually encountered in probes through the medial aspect of the rostral medial vestibular nucleus. They are included in this study because most of them were located in the vestibular nucleus and because they presumably could be involved in producing the AVOR. BP units were sensitive to horizontal eye position, usually (9/10) in the ipsilateral direction, and generated bursts of spikes during on-direction saccades. Only the contralateral eye movement-related BP unit could be monosynaptically activated following electrical stimulation of the ipsilateral vestibular nerve. Sample records and averaged responses of an ipsilateral BP unit are illustrated in Fig. 4. The firing characteristics of ipsilateral on direction BP units are summarized in Table 1.
|
BP units were sensitive to eye position during steady fixation (static eye position sensitivity, Ks = 2.6-32; median Ks = 11.1 spikes/s/deg; Fig. 5A) and to eye velocity during pursuit. In six units the background firing rate during near and far target viewing was significantly different, which presumably reflected the preference of the units to the position of one eye. The eye position signals appeared to be related primarily to the contralateral eye in three units and to the ipsilateral eye in three other units. In the remaining four units, the difference in background firing rate was too small, or inconsistent, to allow an estimate of ocular dominance. BP units were typically more sensitive to on-direction saccades than to off-direction saccades. The unit illustrated in Fig. 4, A1-D1, for example, generated bursts of spikes during leftward, on-direction saccades and quick phases of nystagmus, but was weakly, and inconsistently inhibited during off-direction saccades.
|
BP units were strongly modulated during sinusoidal smooth pursuit eye movements (Fig. 4, A1 and A2). Their mean sensitivity re eye velocity was 3.40 ± 0.55 spikes/s/deg/s; n = 10). During VOR cancellation (Fig. 4, B1 and B2) the rotational response of these cells was related primarily to the small, unsuppressed eye velocity.
The rotational responses of most (9/10) BP units increased as a
function of inverse viewing distance (e.g., GVD ranged from 0.3 to
1.4 spikes/s/deg/s at 1.9 Hz). One unit exhibited a significant decrease in rotational gain during AVORn (
GVD =
0.5 spikes/s/deg/s). On average, BP unit sensitivity to head velocity
increased from 2.82 sp/s/deg/s during far target viewing to 3.68 spikes/s/deg/s during near target viewing at 1.9 Hz, whereas response
phase was not significantly affected by viewing distance. A large
increase in the mean BP unit response gain was also observed during
0.7-Hz rotation. These rotational responses are summarized in Table 2. The mean BP
GVD, of 0.71 and 0.86 spikes/s/deg/s at 0.7 and 1.9 Hz,
corresponded to an average increase in modulation of 23%. The 23%
increase in modulation was larger than 17% increase in VOR gain
recorded concomitantly, and the average increase in modulation (
16
spikes/s) was larger than the increase that would be predicted from
their sensitivity to pursuit eye velocity and static eye position
(
12 spikes/s).
Position-vestibular-pause units
The effects of viewing distance on the AVOR responses were recorded for 47 PVP units that were sensitive to ipsilateral head rotation in the plane of the horizontal semicircular canal. One unit was antidromically activated following electrical stimulation of the ipsilateral ATD, and thus presumably projected to the medial rectus subdivision of the ipsilateral oculomotor nucleus. Sample records and averaged responses of one PVP unit are illustrated in the left and middle columns of Fig. 6. The gain and phase of the responses of each PVP unit during 0.7-Hz smooth pursuit eye movements, VOR cancellation, and the VOR are illustrated in the polar plots in Fig. 6, A3-D3. The firing characteristics of PVP units are summarized in Table 1.
|
Most of the PVPs tested (38/40) were activated at a monosynaptic latency following electrical stimulation of the ipsilateral vestibular nerve (Fig. 2A). During steady fixation in the absence of a target, the tonic firing rate of these units was related to eye position (range 0.4-10.6 spikes/s/deg; mean Ks = 4.1 ± 0.4 spikes/s/deg). The spatial tuning of this static position signal calculated from multiple regression analysis varied considerably from cell to cell (see Fig. 5B) but was always contralateral. On the basis of their background firing rate during near and far target viewing, the eye position sensitivity of most PVPs (23/25) appeared to be better related to the position of the contralateral eye than to the ipsilateral eye (Fig. 5B). PVPs were either inhibited or stopped firing altogether during saccades; although the inhibition was typically weak or nonexistent when the saccade was in the unit's on-direction. A few (6) PVP units generated bursts of spikes during on-direction saccades.
PVP units tended to be more sensitive to head rotation during the VOR than to eye movements alone. The modulation in their firing rate during horizontal smooth pursuit of a moving visual target (0.7 Hz, 20°/s) was 1.52 ± 0.15 spikes/s/deg/s re eye velocity (Fig. 6, A1-A3). This pursuit response phase-lagged contralateral eye velocity by an average of 40.2 ± 5.6°. When the monkey fixated a far, earth-stationary target, rotation of the turntable at the same velocity and frequency evoked a response whose gain was 1.71 ± 0.14 spikes/s/deg/s re ipsilateral head velocity and contralateral eye velocity during the VOR. The PVP unit responses phase-lagged head and eye velocity by 13 and 12°, respectively. During VOR cancellation (Fig. 6, B1-B3) the gain of PVP rotational responses decreased by ~50% (mean gain re head velocity = 0.88 ± 0.09 spikes/s/deg/s; see Table 1).
The rotational responses of most (34/47) PVP units increased as a
function of viewing distance (Fig. 7),
although in several of those units (9/34) the increase was small and
statistically insignificant. On average, PVP head velocity sensitivity
increased from 1.73 spikes/s/deg/s during far target viewing to 2.04 spikes/s/deg/s during near viewing at 0.7 Hz (see Table 2 and Fig. 7).
The average PVP GVD was 0.28 ± 0.08 spikes/s/deg/s; a 20%
change in gain that was comparable with the concomitantly recorded VOR
gain change of 17%. This small unit gain change was statistically
significant (P < 0.01; t-test for paired
observations) in spite of the fact that the viewing distance-related
changes in response gain of individual PVP units varied considerably
(Fig. 7, B and C). Thus the change in PVP unit
population response was appropriate for generating the viewing
distance-related changes in the AVOR that was concomitantly recorded,
even though a significant fraction of units of this type were
insensitive to viewing distance.
|
Eye-head-velocity units
The effects of viewing distance on the AVOR responses of 22 EHV units that were sensitive to head rotation in the plane of the horizontal semicircular canal were recorded. Six of these units were antidromically activated following electrical stimulation of the ipsilateral ATD. Sample records and averaged responses of one EHV unit are illustrated in the left and middle columns of Fig. 8. The gain and phase of the responses of each EHV unit during 0.7-Hz smooth pursuit eye movements, VOR cancellation, and the VOR are illustrated in the polar plots in Fig. 8, A3-D3. The firing characteristics of EHV units are summarized in Tables 1 and 2. During VOR cancellation, 10 EHV units increased their firing rate during ipsilateral head rotation (EHVI units, + in Fig. 8, A3-D3), and 12 units increased their firing rate during contralateral rotations (EHVII units, square symbols in Fig. 8, A3-D3). Most of the EHVI and EHVII cells that were tested were activated at monosynaptic latencies following electrical stimulation of the ipsilateral vestibular nerve (16/17 tested; Fig. 2B).
|
Most EHV units were sensitive to eye position during steady fixation,
but the preferred on direction and ocular preference were idiosyncratic
for each cell (Fig. 5C). Several EHVI units were more
sensitive to vertical eye position and vertical smooth pursuit eye
movements than to horizontal eye movements and position. EHVI units
tended to be weakly related to ipsilateral conjugate horizontal eye
position (mean gain = 1.1 ± 0.5 spikes/deg), whereas EHVII
units were related to contralateral conjugate horizontal eye position
(mean gain = 1.8 ± 1.0 spikes/deg). The ocular preference of
3 EHV units was for the ipsilateral eye, and for 10 other EHV units the
contralateral eye. The tonic firing rate of EHV units that projected
into the ATD, and presumably to the ipsilateral medial rectus
subdivision of the oculomotor nucleus, was not necessarily related to
the ipsilateral eye. The ocular preference of two ATD units was for the
ipsilateral eye, and four others were related primarily to the
contralateral eye (Chen-Huang and McCrea 1998a). EHV
units also exhibited idiosyncratic responses during saccades. Most
units (13/22) were either inhibited or stopped firing altogether during
saccades in the oculomotor off-direction. Four EHV units generated
bursts of spikes during on-direction saccades, and the firing rate of
six others was not related to saccades in any direction. EHV units
tended to be more sensitive to smooth pursuit eye movements (mean
gain = 1.94 spikes/deg/s eye velocity) than to head velocity during the VOR (mean gain = 1.35 ± 0.18). The head movement
on direction of this class of cells reversed during VOR cancellation, although the gain re head velocity during cancellation was, on average,
less than half that recorded during the VOR evoked by fixation of an
earth-stationary target (mean gain = 0.60 ± 0.08).
Two peculiar features of many EHV units were that their sensitivity to
static eye position was frequently nonlinear, and that the eye
movement-related signals exhibited during smooth pursuit eye movements
were often different from the signals generated during steady fixation.
Figure 9 illustrates an analysis of the firing behavior of three ATD EHV units in the left vestibular nucleus
during steady fixation (top panels) and during smooth pursuit eye movements (bottom panels). Note that the
modulated discharge of all three units led contralateral eye velocity
during 0.7-Hz ocular pursuit, but the signals generated by each cell during steady fixation (between spontaneous saccades) were
idiosyncratic. The firing rate of the cell in Fig. 9A was
correlated with ipsiversive eye position, the cell in B was
related to contraversive eye position, whereas the cell in C
was related to both ipsi- and contraversive eye position. Similar
observations have been reported for secondary vestibular units that
receive inputs from the ipsilateral flocculus (Lisberger et al.
1994).
|
The effects of viewing distance on the AVOR responses of EHV units were
not uniform. The response gain of most (13/22) EHV units increased
during near target viewing (Figs. 8 and
10, Table 2). However, near viewing had
no significant effect on the AVOR response of five units, produced a
decrease in gain in three units, and a reversal of response phase in
the response of another. On average, the GVD of EHVII units was
0.75 ± 0.24 spikes/s/deg/s at 0.7 Hz, which corresponded to a
gain increase of 38%. EHVI units tended to be less sensitive to head
velocity during the VOR, and consequently their
GVD was smaller on
average (0.41 ± 0.20 spikes/s/deg/s at 0.7 Hz). However, the
average increase in rotational gain of EHVI units was 49%. On the
whole, the viewing distance-related change in firing rate was
significantly larger for EHV units than for PVPs (t-test,
P < 0.01).
|
Viewing distance significantly affected the response phase of most EHV
units. In most cases the near response significantly phase lagged the
response recorded during far target viewing. At 0.7 Hz, the
AVORn response phase lagged the AVORf response by 34 ± 6° in the nine EHVII units that exhibited a significant GVD increase. The response phase of EHVI units was more mixed. The
AVORn responses of most of these units also lagged the
AVORf responses. However, the AVORn response of
four EHVI units phase led their AVORf responses by
11-54°. All of those EHVI units were sensitive to vertical eye
movements and had AVORf responses that lagged contralateral
head velocity by >70°.
In sum, viewing distance-related changes in the AVOR response gain of EHV units were, on average, larger than the change in response recorded from any other class of vestibular unit, and more than twice as large as the concomitant changes in eye movements.
Position vestibular units
PV units were encountered in the same region where PVP units were
found. Most of the PV units (5/6) were activated at a monosynaptic latency following electrical stimulation of the ipsilateral vestibular nerve. The firing rate of these cells was correlated with static eye
position but was unaffected during saccadic eye movements. The
responses of PV units during smooth pursuit, VOR cancellation, and the
far or near viewing VOR are summarized in Tables 1 and 2. In general,
the smooth pursuit eye movement sensitivity of PV units was much lower
than PVP and EHV units. The gain and phase of the rotational responses
of PV units were similar to PVPs when the animal was fixating an
earth-stationary target or was canceling its VOR (Table 1). On average,
PV units were more sensitive to changes in viewing distance than PVPs.
Their mean GVD was 0.38 ± 0.53 (spikes/s/deg/s), and their N/F
ratio was 1.41 ± 0.25 during 0.7-Hz rotation. In sum, PV units
were not as sensitive to eye movements as EHV and PVP units, but the
sensitivity of their rotational responses to viewing distance was quite high.
Other vestibular units
Ten units were encountered in the vestibular nuclei that could not
be readily classified in one of the five cell classes described above.
Nine of the units were activated at monosynaptic latencies following
electrical stimulation of the vestibular nerve. Six of the cells were
eye movement-related type II neurons (EVII units), whose firing rate
was modulated in phase with contralateral head velocity during rotation
and with ipsilateral eye velocity during smooth pursuit. The rotational
responses of EVII units were also sensitive to viewing distance. During
1.9-Hz table rotations, where the result for every unit was available,
the mean GVD increased 24 ± 19%. The responses of EVII units
are summarized in Tables 1 and 2.
Two monosynaptically activated units were related to contralateral smooth pursuit eye velocity but not to static eye position. One monosynaptically activated unit did not respond to any type of eye movements but showed large differences between VOR cancellation and AVORf. One other unit paused during saccades but exhibited no other signals related to eye movements. The rotational responses of the pausing neuron and one of the two pursuit units increased during near viewing. The rotational responses of the other two units were unaffected by viewing distance.
Effects of stimulus frequency on AVOR GVD
Most of the results described above were obtained with a sinusoidal vestibular stimulus (0.7 Hz, 20°/s) that matched the stimulus frequencies used to evoke smooth pursuit eye movements and to evaluate the responses of units during VOR cancellation. The AVOR responses were also recorded during higher frequencies of vestibular stimulation in many (87/105) units. Figure 11 illustrates examples of the averaged AVOR responses of a PVP unit and an EHVII unit evoked at three rotation frequencies (0.7 Hz, 20°/s; 1.9 Hz, 10°/s, and/or 4.0 Hz, 6°/s).
|
Graphic summaries of the responses of 13 PVP and 7 EHV units that were tested at all 3 frequencies of rotation are illustrated in Fig. 11, D1 and D2. The average response gain and phase of both classes of cells tended to increase slightly during far target viewing as stimulus frequency increased, although there was considerable individual variability within each class. During near target viewing the average PVP unit gain decreased slightly from 2.04 ± 0.18 spikes/s/deg/s at 0.7 Hz to 1.53 ± 0.24 spikes/s/deg/s at 4 Hz, whereas the average EHVII unit gains were nearly the same at each stimulus frequency. Viewing distance had larger, significant effects on the average response gain of the 32 vestibular units tested at 0.7 Hz, but it did not affect the average response gain of these vestibular neurons recorded at 4 Hz, which corresponded to the changes in AVOR gain as a function of viewing distance at these frequencies.
The AVOR near target responses of both PVP and EHVII units slightly phase lagged their responses during far target viewing at every frequency (Fig. 11, D1 and D2). The phase lag in unit response produced by a reduction in viewing distance was remarkably constant at different frequencies.
Firing behavior of vestibular units during voluntary cancellation of AVORn
The responses of 16 vestibular units, including 5 EHVII and 11 PVP units, were recorded during cancellation of a head-stationary target located on the midline 10 cm from the monkey's eyes. The firing behavior of vestibular neurons during 0.7-Hz VOR cancellation in the presence of near (VORCn) and far (VORCf) head-stationary targets was compared, and the effects of viewing distance on rotational gains were assessed.
Cancellation of the VOR during fixation of a head-stationary near target (mean VOR gain = 0.07 ± 0.01 re head velocity) was equal or better than VOR cancellation during fixation of a head stationary far target (mean gain = 0.14 ± 0.01). EHV units, as noted above, characteristically reversed the direction of their response during VOR cancellation, whereas PVP units characteristically exhibited a reduction in their rotational response. The response of one unit during cancellation of AVORn and AVORf is illustrated in Fig. 12A. The filled, shaded histogram is the averaged response recorded during fixation of an earth-stationary near target, whereas the superimposed thin and thick traces show the averaged responses recorded during fixation of head-stationary far and near targets, respectively. The unit's modulation during VORCn and VORCf was similar, regardless of the distance of the target, although there was a small decrease in the background firing rate during near target viewing that was related to the more medial deviation of the contralateral eye during VORCn.
|
In each of the PVP and EHV units tested, the response recorded during
VORCn was comparable with the response recorded
during VORCf cancellation (Fig. 12B). During
VORCn the average gain of PVP responses was 0.8 ± 0.2 spikes/s/deg/s compared with 1.0 ± 0.2 spikes/s/deg/s during
VORCf. The mean response phase led head velocity by 45°
during VORCn and 17° during VORCf. The small
differences in response gain recorded during AVORn
cancellation and AVORf cancellation (VORC GVD; Fig.
12C) were not correlated with viewing distance sensitivity.
The comparability of the single-unit responses during VOR cancellation
might be interpreted to be a reflection of the fact that the
GVD
signals on secondary VOR neurons were related to their eye movement
sensitivity. An alternative possibility is that the inputs that reduce
or modify the rotational responses of PVP and EHV units during VORC are
also modified as a function of viewing distance. The comparison of unit
viewing distance sensitivity and eye movement sensitivity in the next
section suggests that the latter interpretation is more likely.
Relationship of AVOR GVD to pursuit eye velocity sensitivity and
static eye position sensitivity
The viewing distance-related changes in AVOR responses of central
vestibular neurons were not well correlated with their sensitivity to
eye velocity during smooth pursuit. The correlation coefficient of the
linear relationship between smooth pursuit eye velocity sensitivity and
AVOR GVD was 0.51 for PVP units and 0.05 for EHVII units. On the
other hand, unit sensitivity to viewing distance was better correlated
with their static eye position sensitivity. The correlation between eye
position sensitivity and the increase in unit modulation during near
target viewing was
0.76 for EHVI units, +0.85 for EHVII units, and
+0.58 for PVP units (Fig. 13).
|
The positive correlation between AVOR GVD and static eye position
sensitivity was not readily attributable to the increase in the
amplitude of eye movements during near viewing per se. The slopes of
the regressions illustrated in Fig. 13 suggest that PVP and EHVII units
tended to be three times more sensitive to the increased amplitude of
eye movements during near viewing than their static eye position
coefficients would predict. Subtraction of static eye position signals
from vestibular unit rotational responses affected both their gain and
phase, particularly at the 0.7-Hz stimulus frequency, but on average
this removal had little effect on the increase in response gain
recorded during near viewing. The effects of subtraction of eye
position signals on the average responses of representative BP, PVP,
and EHVII units during 1.9-Hz rotation are illustrated in Fig.
14, A-C. The mean eye
position-corrected 1.9-Hz AVORn responses of BP, PVP, and
EHVII units are summarized in the polar plots at the bottom of Fig. 14 (see also Table 2). Subtraction of static eye position signals produced a phase lead in both BP and PVP unit responses (Fig.
14, A and B), but the gain change produced by
changing viewing distance was not significantly affected. Subtraction
of static eye position signals had little effect on the gain or phase
of EHVII unit rotational responses during near and far target viewing (Fig. 14C). Subtraction of static eye position signals also
did not account for viewing distance-related unit responses during 0.7-Hz rotation (Table 2), although the eye position changes evoked at
that frequency were larger.
|
In sum, static eye position sensitivity and viewing distance sensitivity were correlated, but the increase in rotational gain of eye movement-related central vestibular units during near target viewing was not directly attributable to eye position and eye velocity oculomotor signals they carry.
Relationship between vestibular nerve signals and viewing distance related unit and eye movement signals
In a previous study we showed that viewing distance-related
changes in the AVOR were significantly reduced when irregular afferents
were selectively silenced by bilateral application of galvanic anodal
currents (Chen-Huang and McCrea 1998b), whereas the
AVORf was unaffected. We suggested that the central AVOR
GVD signals might reflect the addition of an irregular afferent
input to secondary AVOR pathways. Figure
15 is a polar plot of the difference between the AVORn and AVORf uncorrected 1.9-Hz
responses of the three classes of neurons illustrated in Fig. 14. These
phasors represent the signals added to each unit class during near
target viewing. The dashed arrow corresponds to the phase of the vector difference between AVORn and AVORf eye
movements. The shaded sector of the polar plot represents the response
phase of squirrel monkey vestibular nerve irregular afferents at 2 Hz
(Lysakowski et al. 1995
). Considered together, PVP and
EHV viewing distance signals lagged the mean vestibular nerve irregular
afferent signals by ~91°. On the other hand the viewing distance
signals generated by BP units had nearly the same phase as the viewing
distance-related eye movements.
|
In Fig. 15, the phasor sum of the viewing distance signals related to BP, PVP, and EHV units (labeled B, P, and E, respectively) was 134° when the signals related to BP and PVP units were inverted. The inversion could occur anatomically in the case of units that project to the contralateral abducens nucleus or ipsilateral medial rectus subdivision of the oculomotor nucleus. The sum of the inverted EHV and PVP signals with BP signals had nearly the same phase as the viewing distance-related eye movement at 1.9 Hz. This suggests that inputs from these three groups of units to the oculomotor plant are sufficient to produce AVORn at 1.9 Hz.
![]() |
DISCUSSION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
The gain of the VOR evoked by semicircular canal stimulation needs
to increase as an inverse function of viewing distance to compensate
for the differences in the axis of rotation of the eyes and head
(Viirre et al. 1986). In the squirrel monkey the rotational sensitivity of many secondary vestibular neurons is altered
as a function of viewing distance. These changes in sensitivity related
to viewing distance,
GVD, were found only in classes of vestibular
neurons that have been shown in previous studies to project to the
extraocular motor nuclei. Although putative secondary VOR neurons
varied considerably in their sensitivity to viewing distance; on the
whole, our results suggest that the signals carried by direct VOR
pathways from the vestibular nuclei to extraocular motoneurons are
sufficient to generate the behavioral changes in VOR gain that were observed.
Two notable features of the central signals related to AVOR GVD in
putative secondary VOR neurons were that they phase lagged head
velocity by nearly 90° and were correlated with static eye position
sensitivity. These observations, together with the low band-pass
characteristic of the viewing distance AVOR gain adjustment in squirrel
monkeys suggest that viewing distance-related changes in the AVOR
utilize central circuits that are involved in temporal integration of
the AVOR. In the following discussion, we will first address certain
technical issues related to the variability in the AVOR
GVD. We will
then briefly discuss our neurophysiological observations in light of
previously described anatomy and physiology of central horizontal
canal-related AVOR pathways. Finally, we will discuss the nature of
the neural mechanisms related to viewing distance-related changes in
the AVOR and advance a specific hypothesis for how AVOR signals are
modified as a function of viewing distance.
Technical issues related to viewing distance-related changes in the AVOR
We previously reported that viewing distance-related gain changes
in the squirrel monkey AVOR are variable both within and between
animals (Chen-Huang and McCrea 1998b). The distance of the squirrel monkey's interaural axis from the center of the eye is
~2.25 cm, and in our experiments the gain of the VOR needed to be
increased by ~20% to stabilize a visual target on the retina that
was 12.25 cm in front of the axis of head rotation. Indeed, each of the
squirrel monkeys in this study increased the gain of their AVOR,
although, on average, the increase was 17% at the lowest stimulus
frequencies used. This mean increase in AVOR gain while viewing a near
target was slightly higher than the change in gain we previously
reported in a study of the effects of functional ablation of irregular
afferents on the AVORn (Chen-Huang and McCrea 1998b
). One problem in estimating single-unit AVOR
GVD
values was that a 17% gain change represented a relatively small
change in firing rate (<6 spikes/s at 0.7 Hz, <3 spikes/s at 1.9 Hz) in most cells, even though unit
GVD was slightly larger on average than the change in eye movement. The small changes in firing rate and
variable changes in AVORn gain may partially explain why
the responses of many putative secondary VOR units were not
significantly affected by viewing distance, and why these changes in
response gain were not observed in a previous study by
McConville et al. (1996)
.
A second behavioral issue relates to the relationship between vergence angle and AVOR gain. Although vergence angle and AVOR gain were positively correlated, the correlation was not perfect. AVORn gain varied from trial to trial, but the vergence angle generated by a particular monkey was relatively stereotyped and fixed. The fluctuation in AVORn gain was thus not attributable to fluctuations in vergence angle. Other factors may be involved in triggering viewing distance-related gain changes in the AVOR. Unfortunately vergence angle is the only variable we measured or controlled.
Neural substrate for generating viewing distance-related gain changes in the AVOR
The results of a number of anatomic and electrophysiological
studies suggest that the immediate premotor substrate for generating the horizontal canal-related AVOR includes direct secondary VOR pathways made up of PV, PVP, and EHV units and more indirect pathways from the vestibular nerve to medial and lateral rectus motoneurons (Cullen and McCrea 1993; McCrea et al.
1980
, 1987
; Reisine and Highstein
1979
; Scudder and Fuchs 1992
). The latter
include primarily pathways from BP units in the rostral prepositus and
adjacent regions of the medial vestibular nucleus (Cullen et al.
1993
; McFarland and Fuchs 1992
; Scudder
and Fuchs 1992
). The identification of putative VOR-related
vestibular units in this study depends primarily on observations made
in those previous studies, although a few units that projected into the
ascending tract of Deiters were identified by antidromic
activation following stimulation of that tract (see Chen-Huang
and McCrea 1998a
).
McConville et al. (1996) reported that vestibular units
whose rotational responses were modified by viewing distance also carried signals related to eye movements. In this study, we also found
that all of the vestibular units whose firing behavior was related to
viewing distance were eye movement-related cells. Although it has
certainly not been demonstrated that all eye movement-related vestibular neurons are premotor neurons, there is evidence that virtually every major subcategory of eye movement-related secondary vestibular neurons projects to one or more of the extraocular motor
nuclei. In any case, it is not unreasonable to suggest that most eye
movement-related vestibular units whose firing rates are modulated
during the VOR are probably involved, in some way, in controlling or
generating the VOR. This assumption seems particularly valid for the
four classes of eye movement-related units described in this study:
PVP units, EHV units, BP units, and PV units.
The change in gain of the signals carried to the extraocular motor
nuclei by direct central secondary VOR pathways appears to be at least
as large as the concomitant change in eye movement gain. The average
increase in rotational gain exhibited by PVP and BP units during near
target viewing was larger than the concomitant increase in eye
movements, and the signals generated by EHV and PV units increased in
gain more than twice as much as the eye movements. It seems likely that
the AVOR-related signals carried by the other, indirect, central
pathways are similarly affected by viewing distance. For example, all
except one of the vestibular BP units described in this study were
activated at disynaptic latencies following electrical stimulation of
the vestibular nerve and were more likely related to these indirect
AVOR pathways. Because the firing behavior of many EHV cells and BP
cells is similar to that described for vestibular units that are
inhibited following electrical stimulation of the cerebellar flocculus
(Lisberger et al. 1994), it seems likely that the AVOR
pathways receiving inputs from the flocculus are particularly sensitive
to viewing distance.
Viewing distance adjustments in vestibular sensitivity make sense for
neurons involved in controlling the VOR, but the function of this
adjustment for cells involved in other vestibular functions, for
example vestibulospinal pathways, is not obvious. Tomlinson et
al. (1996) found that viewing distance did not modify the
rotational responses of vestibular units whose firing behavior was not
related to eye movements. We also were unable to observe viewing
distance-related changes in the angular rotational responses of most
VI units. Currently there is no evidence that vestibular neurons of
this type project to the extraocular motor nuclei in the primate.
Contribution of smooth pursuit and visual feedback signals to vestibular unit viewing distance sensitivity
The AVOR responses of EHV and BP units were on average more than twice as sensitive to viewing distance as PVP units. EHV and BP vestibular units also tended to be more sensitive to smooth pursuit eye movements than PVP units. These observations, together with the low-pass filtered characteristic of the viewing distance-related changes in the squirrel monkey AVOR, raise the question of whether viewing distance-related changes in the AVOR are mediated by a visual feedback or smooth pursuit mechanism.
There are several reasons why it is unlikely that ocular pursuit and/or
visual feedback are essential for viewing distance gain changes in the
AVOR:
In sum, visual feedback mechanisms may supplement or add to the viewing distance adjusted signals carried by central AVOR pathways, but the existing evidence suggests that these inputs are neither necessary nor sufficient to change the gain of the AVOR as a function of viewing distance.
It is reasonable to assume that viewing distance-related changes in the gain of the AVOR are usually, if not always, triggered by a visual estimate of target distance. It also appears that the central premotor pathways that are most important for generating these gain changes in the AVOR are those that are most sensitive to visual feedback. However, the weight of evidence suggests that the change in gain of the AVOR is accomplished by multiplication of a vestibular signal that is then added onto secondary VOR pathways rather than an addition of a visual signal.
Relationship between viewing distance-related changes in the AVOR and AVOR cancellation
Squirrel monkeys were at least as capable of suppressing or canceling near viewing VOR as they were the VOR evoked during far target viewing. VOR cancellation tended to be more complete when a near LED target was fixated than when the 90-cm distant head-stationary laser spot was fixated. The improvement in VOR cancellation may have been related to the fact that the visual angle subtended by the near target was larger than that subtended by the far target. However, it is clear that the mechanisms involved in AVOR cancellation are capable of canceling the viewing distance-enhanced AVOR as well.
One possible interpretation of these results is that the "vestibular" signals carried by secondary vestibular EHV and PVP neurons were largely unaffected by viewing distance. The problem with this idea is that many vestibular neurons may receive inputs that are specifically related to cancellation of the VOR and function to cancel, or reduce vestibular signals on VOR pathways during fixation of head-stationary targets. For example, EHV units may receive modulated inputs from gaze velocity cerebellar flocculus Purkinje cells during VOR cancellation but not during the VOR. A more plausible explanation of the VOR cancellation results is that the central signals that modify signal processing in VOR pathways during VOR cancellation are sensitive to viewing distance.
Relationship between vestibular unit static eye position signals and viewing distance sensitivity
The AVOR viewing distance sensitivity of central vestibular units
was weakly but positively correlated with their sensitivity to eye
position. The most striking correlation between static eye position
sensitivity and AVOR GVD was in EHV units, but the smaller response
changes observed in PVP units were also positively correlated with
their static eye position sensitivity. This correlation, together with
the observation that
GVD signals tend to phase lag head velocity,
suggests that
GVD signals might be related to the central AVOR
velocity-position integrator.
The static eye position signals on secondary VOR neurons are clearly
not, by themselves, sufficient to cause the changes in rotational
response observed during near target viewing. Subtraction of static eye
position signals from unit rotational responses only reduced the mean
AVOR GVD signal generated by PVP units by half and had virtually no
effect on the mean response of EHV units. The latter observation is
consistent with the idea presented below that the input to the AVOR
integrator is multiplied to produce the enhanced signal on secondary
VOR neurons during near viewing.
If the GVD signals generated by secondary VOR neurons are related to
pathways that feed back integrated head velocity signals to secondary
VOR neurons (see below), it is reasonable to expect that these signals
would be mixed with static eye position signals. No central neuron has
been identified whose firing behavior is specifically related to the
AVOR integrator, but there are many neurons in the vicinity of the
vestibular nuclei, particularly in the rostral medial vestibular
nucleus and the prepositus nucleus, that receive disynaptic inputs from
the vestibular nerves and generate signals that phase lag head velocity
by 40-90° (Escudero et al. 1992
; Lopez-Barneo
et al. 1982
). These integrated vestibular signals usually
coexist with static eye position signals and dynamic eye position
signals related to ocular pursuit, although the latter two signals may
differ significantly in various types of VOR neurons (Cullen et
al. 1993
; Tomlinson and Robinson 1984
).
Monocular static eye position signals on vestibular neurons
The eye position signals generated by most, if not all, of the
neurons in the regions of the brain that are likely to be immediately involved in eye velocity-position integration are monocular
(McConville et al. 1994; Zhou and King
1996
, 1997
). Although this issue was not studied
systematically, we also found that most of the units in this study were
dominantly related to the movements of one eye. Presumably, the
difference between the signals generated by the neural integrators
related to each eye could represent an internal estimate of viewing
distance. This viewing distance estimate could then be used to amplify
vestibular afferent inputs to VOR pathways.
Scheme for amplifying vestibular signals by viewing distance
The polar plot in Fig. 15 illustrates that the change in the signals produced by secondary vestibular neurons during near target viewing is comparable with the change in eye movement gain. The phase of the viewing distance-related signals lagged vestibular irregular afferent signals by an average of ~90°. We suggest that this viewing distance-related change in the responses of secondary vestibular pathways is produced primarily by the addition of multiplied, temporally integrated vestibular irregular afferent inputs.
Most secondary vestibular neurons receive inputs from a combination of
regular and irregular vestibular nerve fibers (Goldberg et al.
1987). The latter inputs can be selectively silenced by application of galvanic currents, which reveals that most central neurons receive not only direct excitatory inputs from irregular vestibular nerve afferents but also inhibitory inputs that are on
average just as powerful as the direct excitatory inputs
(Chen-Huang et al. 1997
). Thus individual secondary
vestibular neurons receive both excitatory and inhibitory inputs from
irregular vestibular afferents. On average the excitatory and
inhibitory irregular afferent inputs are roughly equal
(Chen-Huang et al. 1997
).
In a previous study we showed that viewing distance-related
gain changes in the AVOR could be attenuated or even abolished by
silencing irregular vestibular nerve afferents using galvanic currents
(Chen-Huang and McCrea 1998b). That observation
suggested the possibility that one of the functions of the irregular
afferent inputs to secondary VOR pathways is to provide additional VOR gain when behavioral circumstances require it. Viewing
distance-related gain changes in the AVOR could be generated in part
by inhibiting or partially silencing an irregular afferent inhibitory
pathway to secondary vestibular neurons, thereby parametrically
increasing the gain of VOR pathways.
One way the gain of the AVOR could be adjusted as a function of viewing distance is illustrated in Fig. 16A. In this scheme, the inhibitory irregular afferent inputs to secondary VOR neurons are relayed through a set of inhibitory interneurons that receive inputs from irregular vestibular nerve afferents whose threshold is set by another inhibitory input whose gain is inversely related to viewing distance. Individual elements of this viewing distance multiplier could code viewing distance by receiving excitatory inputs related to the position of one eye and inhibitory inputs related to the position of the other. The difference between the two inputs would be equal to a central estimate of viewing distance. When the two inputs are equal, viewing distance would be infinite, and the inhibitory feedback pathway could cancel irregular afferent inputs to secondary VOR neurons. As the two eyes converge on a near target, the inhibitory eye position signal would drive progressively more interneurons into inhibitory saturation and effectively increase the irregular afferent input to secondary VOR pathways. Alternatively, the viewing distance signal could be a signal related to vergence angle.
|
Although the direct parametric adjustment in irregular afferent inputs to secondary VOR pathways would be an elegant way to modify the gain of the AVOR as a function of viewing distance, several observations suggest that the viewing distance multiplied inputs to secondary VOR pathways are low-pass filtered. First of all, if irregular afferent inputs to AVOR pathways were gated in a manner similar to that shown in Fig. 16A, their AVORn signals would phase lead, rather than phase lag their AVORf responses. Second, the gain of the near viewing AVOR would be expected to progressively increase as a function of stimulus frequency rather than decrease (Fig. 1B). Because the viewing distance-related rotational signals generated by EHV and PVP units typically phase lag irregular afferent signals by ~90° (Fig. 15), it seems likely that a large fraction of the viewing distance multiplied irregular afferent signal input to secondary VOR neurons is low-pass filtered or integrated. One place this could occur is in the AVOR velocity-position integrator itself, as illustrated in Fig. 16B. The correlation between the viewing distance sensitivity of EHV and PVP units and contralateral static eye position sensitivity shown in Fig. 13 suggests that the central pathways involved in changing the gain of the AVOR as a function of viewing distance also transmit contralateral static eye position signals to secondary VOR pathways. The idea is attractive in part because the sensitivity of secondary vestibular units to viewing distance was correlated with their eye position sensitivity, and in part because it relieves the necessity to postulate the existence of a separate neural integrator specifically related to viewing distance changes in the AVOR. Clearly additional study is required to determine whether regions that are considered to be related to central integration of the AVOR, such as the prepositus nucleus, generate signals that are necessary or sufficient to produce viewing distance-related changes in eye movements or secondary VOR pathways that have been observed in this study.
Conclusion
The results of this study suggest that the central premotor pathways that mediate the horizontal canal-related AVOR also mediate viewing distance-related changes in the reflex. We suggest that a central estimate of viewing distance modifies the gain of indirect, centrally integrated, vestibular semicircular canal irregular afferent inputs to secondary VOR neurons to produce the change in gain in the AVOR observed.
![]() |
ACKNOWLEDGMENTS |
---|
This work was supported by National Eye Institute Grants EY-08041 and EY-06485 and by the Women's Council of University of Chicago Brain Research Foundation.
Present address of C. Chen-Huang: Dept. of Physiology, Northwestern University, Chicago, IL 60611.
![]() |
FOOTNOTES |
---|
Address for reprint requests: R. A. McCrea, Dept. of Neurobiology, Pharmacology and Physiology, 947 E. 58th St. (MC 0926), University of Chicago, Chicago, IL 60637.
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 26 June 1998; accepted in final form 31 December 1998.
![]() |
REFERENCES |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|