 |
INTRODUCTION |
The human infant has
limited gaze-stabilizing abilities at birth, but rapidly develops
better control over the next 6 mo (Aslin 1987
;
Naegele and Held 1982
; Shupert and Fuchs
1988
). Normal development and the capacity to calibrate these
gaze-stabilizing systems may depend on normal vision during infancy.
Monocular deprivation of pattern vision from lid suture for the first 2 wk of life or artificial induction of esotropia induced during early
infancy in monkeys results in decreased monocular optokinetic nystagmus (OKN) in the nasal to temporal (N-T) direction (Kiorpes
et al. 1996
; Sparks et al. 1986
; Tychsen
et al. 1996
). In addition, strabismic humans with infantile
esotropia syndrome and infant monkeys with surgical strabismus often
show latent nystagmus (LN) when viewing monocularly (Kiorpes et
al. 1996
; Kommerell and Mehdorn 1982
; Schor 1983
; Tychsen et al. 1996
). This
immature pattern of OKN is found when cortical binocularity is
disrupted early in simian or human development (see Schor
1983
for review). These types of deprivation result in
significant competition between the two eyes. Psychophysical and
physiological studies in visual cortex in monkeys show that sensory
deficits caused by abnormal early visual experience as a result of
monocular form deprivation in monkeys is much more severe than those
associated with bilateral form deprivation (Crawford et al.
1993
; Harwerth et al. 1991
). The differences in
the severity of visual deficits have been attributed to the
consequences of binocular competition associated with unilateral form
deprivation. There is no information on ocular motor behavior in
monkeys with early binocular deprivation where there is no competition
between the two eyes. Based on a study in cats, we believe that
gaze-holding deficits can occur even with binocular deprivation. At the
end of 1 yr of dark rearing, cats have gaze-stabilizing deficits
similar to those of the newborn human infant including decreased
monocular OKN in the N-T direction and decreased velocity storage in
the vestibuloocular reflex (VOR) (Cynader 1985
).
In the current study, we have examined the VOR, optokinetic
response, and fixation of three monkeys with binocular lid suture initiated within 1 day of birth. We also examined ocular alignment, refraction, and visual acuity in these animals. We examined monkeys deprived for 25, 40, and 55 days of life to determine the duration of
deprivation critical for causing ocular motor defects. The overall
objective of this study was to determine to what extent the development
of gaze-stabilization in monkeys depends on normal visual input during
infancy, and to what extent visual deprivation results in irreversible
gaze-stabilizing deficits and spontaneous nystagmus. Brief reports of
some of these results have been presented elsewhere (Tusa et al.
1992
, 1994
).
 |
METHODS |
Subjects and general rearing conditions
Three infant rhesus monkeys (Macaca mulatta, 1 male and 2 females) born on the Johns Hopkins Primate Farm were used.
All of the experimental and animal care procedures were in strict
adherence with the National Institutes of Health Guide for the Care and Use of Laboratory Animals. Eyelids were sutured closed similar to the
method of Raviola and Wiesel (1985)
. The animals were
sedated with tiletamine and zolazepam and ketamine, and
then the epithelial margins of the upper and lower eyelid lateral to
the lacrimal papilla were trimmed. The cut surfaces of the lids of both
eyes were joined by 4-0 nylon mattress sutures from the lateral
canthus to the lacrimal papilla. After 7-10 days the sutures were
removed. After 25, 40, and 55 days, the eyelids were opened with sharp dissection. The ocular motor behavior of these three monkeys was compared with that of six normal control rhesus monkeys.
Ocular examination
These methods were previously described (Repka and Tusa
1995
; Tusa et al. 1991
). In brief, ocular
alignment, refraction of the eyes, axial length of the eye, and
clinical examination of spontaneous eye movements during binocular and
monocular viewing were assessed in all animals on the first day of
birth, and repeated at 3, 6, and 12 mo of age. Ocular alignment was
measured using a cover test with the monkey fixating on a toy at 33 cm
combined with a Krimsky corneal light reflex test. A photographic
determination of ocular alignment was also performed. Refractive error
was measured by retinoscopy with the pupils dilated with
cyclopentolate and the animal sedated with ketamine. Visual
spatial acuity was measured using Teller Acuity Cards (VisTech
Consultants, Dayton, OH).
Eye movement recordings
Eye movement recordings using the magnetic-field search coil
technique began at day 60. A 14-mm eye coil was implanted
around each eye, and the end of each wire was soldered to a small
electrical plug anchored onto the skull with a small inverted flat-head
screw (Judge et al. 1980
). The entire skull assembly
including plug, cement, and screw weighed 5 g. For the first few
months of life, the eye movement recording system was calibrated by
rotating the magnetic field coils 20° in each horizontal direction
around the stationary animal in the dark while measuring average eye
position. Calibration was also checked by rotating the field coils at a fixed velocity (30°/s) around the animal in the dark. We were usually
able to record eye movements for 20-30 min before the infants became
drowsy, at which time they were returned to their cages. Eye movements
were recorded while the monkey sat in a small adjustable, primate
chair. During eye movement recordings, the head was held stationary by
lightly padded braces and Velcro straps attached to the chair. By 6 mo
of age, the skull sutures were fused, and the skull was thick enough to
accept a light-weight, removable aluminum halo, of the type used on
human beings, to fix the head to the chair. The halos were removed
every 2 wk for at least 1 wk to prevent infection and skull erosion. By
6 mo of age, the monkeys stayed alert in the chair for 1-2 h and were easily trained to fixate and follow a small target light rear-projected onto a tangent screen located 75 cm in front of the animal. The animal's performance was reinforced with a sweetened liquid.
Spontaneous eye movements, OKN, and VOR were measured at 90, 180, and
365 days of age.
SPONTANEOUS EYE MOVEMENTS.
These were measured while the monkey viewed a stationary OKN drum or a
Ganzfeld (1/2 of a clean Ping-Pong ball placed over the eye).
FIXATION.
Fixation was measured while the monkey viewed a 0.5° target light
that was located in the primary and eccentric positions of gaze. The
target light was always surrounded by a full-field grating background.
In addition, fixation was measured while the monkey viewed a blinking
0.5° target light (0.5 Hz, duration 50 ms) in an otherwise dark room.
This test was done to avoid visual stabilization by retinal-slip
mediated tracking eye movements.
VOR.
The VOR was generated by rotating the monkey chair and the magnetic
field coils en bloc at a constant velocity (60°/s and 240°/s) in
the dark. Four trials were done to the left and four to the right at
each speed. Velocity of the chair was measured by a tachometer. The VOR
gain (eye velocity/chair velocity) for each trial was measured as the
average of three consecutive peak slow-phase eye velocities, once
maximum chair speed was obtained. The VOR time constant was measured as
the time taken for the slow-phase eye velocity (SPEV) to decrease to
one-third of its peak value.
OKN.
OKN was generated by rotating a full-field drum around the animal. The
drum contained a random pattern of black circles each subtending a
visual angle of 8-16° on a white background. Optokinetic response
gain (SPEV/drum velocity) under both monocular and binocular viewing
conditions was measured. The drum moved at a constant velocity ranging
from 5 to 180°/s for 60 s or until eye velocity reached a
steady-state value based on a chart-recorder printout. OKN gain was
measured during its initial rapid rise in slow-phase velocity (peak
SPEV during the 1st second the light was turned on), and during steady
state (the average velocity of the last 5 slow phases before the light
was turned off). The initial value OKAN (optokinetic after nystagmus)
was also examined (the average velocity of the 1st 3 slow phases
beginning 1 s after the light was turned off).
 |
RESULTS |
Ocular examination
Table 1 summarizes the ocular
findings for the three rhesus monkeys that had binocular eyelid suture
(BD) for the first 25, 40, and 55 days of life and the six controls.
Visual acuity was measured in cycles per degree and was displayed in
both LogMAR (Log10 [1/decimal]) and its snellen equivalent. Visual
acuity was measured with both eyes open. Visual acuity was better at 12 mo compared with 6 mo of age in each animal, but less than normal
controls. The visual acuity for the animal with the longest deprivation
was not as good as that of the animal with the shortest deprivation.
The 25-day monkey had an esotropia of 10 prism diopters when the
eyelids were opened, but it resolved 35 days later (2 mo of age). The
40- and 55-day monkeys developed a persistent exotropia. The 55-day
animal also developed a persistent hyperopia in both eyes. The
refractions of each eye of the controls were combined.
LN
GENERAL PROPERTIES.
All animals had a jerk nystagmus, which persisted through the duration
of the study (Fig. 1). When the right eye
was covered there was a conjugate, left-beating nystagmus. The term
left beating is used here based on the direction of the quick phases of
the nystagmus. When the left eye was covered, there was a right-beating nystagmus. When both eyes were open, all animals had a
low-amplitude, horizontal nystagmus. This combination of a
low-amplitude horizontal nystagmus with both eyes viewing, and a
strong horizontal nystagmus when only one eye was viewing (with slow
phases always toward the nose in the viewing eye) resembles "manifest
latent nystagmus" found in some human subjects (Dell'Osso et
al. 1979
). We will to refer to this as latent nystagmus (LN)
throughout the paper. LN was not seen at birth in any of the animals,
but LN was noted as soon as the eyes were opened after binocular
deprivation.

View larger version (15K):
[in this window]
[in a new window]
|
Fig. 1.
Eye movement trace showing latent nystagmus (LN) in the 55-day monkey
at 6 mo of age while viewing a stationary optokinetic nystagmus (OKN)
drum. Viewing conditions were right eye covered, left eye covered, and
both eyes viewing. With right eye covered, there was a conjugate
left-beating nystagmus, with the left eye covered the nystagmus became
right beating, and with both eyes viewing there was mild left-beating
nystagmus. RHe, right eye horizontal eye position; RVe, right eye
vertical eye position; LHe, left eye horizontal eye position; LVe, left
eye vertical eye position. One-second tick mark is shown above the
trace. Upward deflections of traces indicate rightward (or upward) eye
motion. This convention will be used throughout the paper.
|
|
SPEV of LN are plotted in Fig. 2. In the
55-day monkey, when the left eye was covered, SPEV increased over the
course of 60 s to plateau at ~90°/s (Fig. 2A). When
the patch was switched to the right eye, SPEV increased over a period
of ~40 s to plateau at ~40°/s. For the 40-day animal, the
plateaus were ~40°/s with either eye viewing. The SPEV of LN in the
25-day animal was low and variable (Fig. 2B).

View larger version (22K):
[in this window]
[in a new window]
|
Fig. 2.
Slow phase eye velocity (SPEV) of LN plotted against time in the 55-day
(A) and 25-day (B) monkey at 1 yr of age.
Data were collected on 2 separate days for each monkey. When either eye
was covered in the 55-day monkey, the SPEV builds up in intensity until
a plateau level was reached (mean and 1 SD listed during time when SPEV
reached a steady-state value). The open eye was viewing a stationary
OKN drum. When both eyes were viewing, the data illustrated came from
the right eye, but eye movements were conjugate in all animals. When
one eye was covered, the data illustrated came from the viewing eye.
This convention of illustrating eye movements from the viewing eye will
be used throughout the paper.
|
|
SENSORY CONDITIONS THAT INITIATE AND MAINTAIN LN.
The stimulus that initiates LN does not appear to depend on retinal
slip information in the viewing eye as the nystagmus could occur even
when the monkeys viewed a Ganzfeld. Figure
3A shows the mean and 1 SD of
SPEV recorded approximately every 10 s in the 55-day monkey when
this animal viewed a stationary OKN drum (A) and a Ganzfeld
(B). The average of the last five data points before the
patch was moved to the other eye was determined for each condition
(plateau). There was no significant difference (P > 0.01, t-test) between conditions A and
B. The plateau velocity of LN partly depends on the
luminance of the Ganzfeld stimulus (Fig.
4). As luminance was increased, velocity
of LN increased until eye velocity saturated at ~110°/s.

View larger version (20K):
[in this window]
[in a new window]
|
Fig. 3.
Sensory conditions that initiate and maintain LN. SPEV of LN was
plotted during different viewing condition of the open eye in the
55-day monkey at 1 yr of age. Data in both viewing conditions were
collected on 2 separate days. The mean and 1 SD are shown of the
plateau level (when SPEV reached a steady-state value). The open eye
was viewing a stationary OKN drum (A) or a Ganzfeld
(B). ANOVA revealed there was no significant difference
in SPEV in conditions A and B
(P > 0.01).
|
|

View larger version (14K):
[in this window]
[in a new window]
|
Fig. 4.
Effect of using neutral density filters to alter light intensity to the
viewing eye on LN in the 55-day monkey. Maximum horizontal eye velocity
(H ) of LN was plotted against the luminance of a Ganzfeld
stimulus. The nonviewing eye was covered with a black patch. Eye
velocity increased as luminance was increased from 0.1 to 10 cd/m2.
|
|
ADAPTATION OF LN.
The maximum velocity of LN decreased in the viewing eye if the animal
wore a patch over the other eye continuously for at least 1 day. Figure
5 shows the mean and 1 SD of SPEV in the
55-day monkey during monocular viewing before and after 1 and 3 days of
continuous occlusion of the left eye. Before occlusion, SPEV reached a
plateau of 172°/s when the left eye was covered and 31°/s when the
right eye was covered (Fig. 5A). The plateau was defined
when there was no significant change in SPEV over a period of 10 s
or more. After 1 day of occlusion of the left eye, SPEV was 94°/s
when the left eye was covered and 110°/s when the right eye was
covered, both of which represented significant changes from baseline
(P < 0.001, t-test). After 3 days of
occlusion (C), SPEV decreased further when the left
was covered and increased when the right eye was covered compared with
condition B (P < 0.001, t-test). In summary, a velocity bias of approximately
100°/s to the right developed when the left eye had been continuously occluded. Before occlusion, this animal fixated primarily from the left
eye, which explains why SPEV was initially lowest when the right
eye was covered during testing of LN. Thus the maximum SPEV of
the habitually viewing eye decreases over the course of several
days.

View larger version (23K):
[in this window]
[in a new window]
|
Fig. 5.
Adaptation of LN in the 55-day monkey induced by prolonged monocular
occlusion. Mean and 1 SD of LN is plotted. SPEV is plotted 1st when the
left eye was covered with a black patch and then when the right eye was
covered. Values of mean and 1 SD are listed when SPEV reached a
steady-state value. A: before occlusion, SPEV was much
higher when the left eye was covered. B: after the left
eye was occluded continuously for 1 day, steady-state SPEV decreased
significantly by 78°/s during the left eye covered condition, and
increased by 80°/s for the right eye covered condition (ANOVA,
P < 0.001). C: after 3 days of
occlusion, SPEV decreased further during the left eye covered condition
and increased for the right eye condition (ANOVA, P < 0.005). This experiment was done twice on 2 consecutive months. The
data were similar so were combined. Eye movements were conjugate, but
only data from the viewing eye are illustrated.
|
|
Other forms of nystagmus
GAZE-EVOKED NYSTAGMUS.
All monkeys had a conjugate, horizontal gaze-evoked nystagmus,
which was quantified by having the animals fixate a blinking target
(0.5 Hz, duration 50 ms) in a dark room to avoid reduction of the
nystagmus from visual-tracking mechanisms. When the 25-day animal
fixated targets to the left, slow phases of nystagmus moved the eyes
back toward the right (Fig.
6A). This testing was
performed during binocular viewing to evaluate gaze-evoked nystagmus
without LN. Similarly, when the animal fixated targets to the right,
slow phases of nystagmus were directed to the left. The SPEV decreased during each single slow phase as the fixation target was positioned closer to the center of gaze. Figure 6B shows the eye
velocity of each slow phase while the animal fixated a small target
located at different eccentricities. The estimates of SPEV decreased
exponentially with decreases in the eccentricity of the fixation
target. To determine the time constant (Tc) of the gaze-holding
integrator, we fitted an exponential curve through the data. The Tc for
the gaze-holding integrator in this animal was 15 s. A similar
analysis in the 40-day animal revealed a Tc of 12 s. Eye velocity
was frequently not symmetric across the midline due to a small amount
of spontaneous nystagmus in primary gaze. Vertical gaze-evoked
nystagmus was not present in any of the animals while they fixated
targets that moved vertically. The waveform of the slow phases of LN
was velocity decreasing in the 25- and 40-day animals, and SPEV varied
with orbital eye position (Fig. 6C). Gaze-evoked
nystagmus was not observed at birth and was observed immediately after
the eyelids were opened, but it was not quantified in a dark room at
these times.

View larger version (21K):
[in this window]
[in a new window]
|
Fig. 6.
Gaze-evoked nystagmus in the 25-day monkey at 1 yr of age.
A: horizontal eye position traces during binocular
viewing of a target at center of gaze and eccentrically. In all cases
the direction of slow phases brings the eye back toward the center of
gaze. B: plot showing the relationship of horizontal eye
velocity and the fixation point. In this animal, eye velocity was
higher for orbital positions to the left of center of gaze because of
the spontaneous left-beating nystagmus when both eyes are open.
C: LN while the monkey fixated target at center of gaze
(right eye covered). Slow phases were velocity decreasing. This is best
seen in the velocity trace. He, horizontal eye position; H ,
horizontal eye velocity.
|
|
VELOCITY-INCREASING JERK NYSTAGMUS.
In contrast to both the 25- and 40-day animals, the eye velocity
of the 55-day animal had velocity-increasing slow phases in eccentric
gaze. This was most apparent in the light when the animal fixated a
small target light (arrows in Fig. 7).
This animal also had a spontaneous left-beating nystagmus in the dark,
which primarily had linear or velocity-increasing slow phases.

View larger version (16K):
[in this window]
[in a new window]
|
Fig. 7.
Spontaneous, jerk nystagmus with velocity-increasing slow phases and
pendular nystagmus in the 55-day monkey at 1 yr of age. Recordings were
made while the monkey had both eyes open while sitting in the dark, or
while viewing a 0.5° light. In the dark there was a left-beating
nystagmus with linear and velocity-increasing slow phases. In the
light, this animal had marked velocity-increasing slow phases in
eccentric gaze (arrows). Transient bursts of pendular nystagmus were
also present (horizontal bars). RHe, right eye horizontal eye position;
RVe, right eye vertical eye position; LHe, left eye horizontal eye
position; LVe, left eye vertical eye position. One-second tick mark is
shown above the trace.
|
|
PENDULAR NYSTAGMUS.
All monkeys had a low-amplitude, conjugate pendular nystagmus.
This is illustrated in Fig. 7 (horizontal bars) for the 55-day monkey
and Fig. 8 for the 25-day monkey. The
peak-to-peak amplitude was 0.5-2.0°, and the frequency was 7-10 Hz.
Pendular nystagmus was not readily apparent when the eyelids were first
opened, but did become apparent by age 1 yr.

View larger version (14K):
[in this window]
[in a new window]
|
Fig. 8.
Low-amplitude, high-frequency pendular nystagmus in the 25-day monkey.
He, horizontal eye position; Ve, vertical eye position; H ,
horizontal eye velocity; V , vertical eye velocity. One-second
tick mark is shown above the trace.
|
|
VOR
All monkeys had mildly reduced VOR gains but normal time
constants for 60 and 240°/s constant-velocity chair rotations
compared with six normal monkeys tested at 1 yr of age (Table
2). The gain was measured as the average
of the three consecutive peak slow-phase eye velocities once chair
velocity reached peak velocity.
OKN
A robust OKN response was elicited in all three animals when both
eyes were viewing, but the response was severely impaired in the N-T
direction during monocular viewing. The rapid rise, steady-state OKN
and OKAN for the 25-day monkey is plotted in Fig.
9. For both eyes viewing there was a good
response to constant velocity steps (Fig. 9A). During
monocular viewing, OKN was reduced in the N-T direction, especially for
OKAN (Fig. 9, C and D). Table 3 compares the OKN responses in both the
25- and 55-day monkeys to six normal controls tested at 1 yr of age.
For the 25-day monkey, steady-state OKN was slightly reduced in the N-T
direction, and OKAN was significantly reduced in the N-T direction
compared with controls. It is likely that the LN present during
monocular viewing contributed to this reduced response in the N-T
direction. The OKN response for the 55-day monkey was more severely
impaired (Table 3). For both eyes viewing, steady-state OKN and OKAN
was reduced at high target velocities. During monocular viewing, OKN was severely impaired for all drum velocities in the N-T direction for
all three components of OKN. In the T-N direction, OKN was impaired for
high drum velocities.

View larger version (35K):
[in this window]
[in a new window]
|
Fig. 9.
Plots of SPEV plotted against OKN drum velocity in the 25-day monkey at
1 yr of age. A: mean and 1 SD of steady-state OKN during
a stimulus that increased in small velocity steps with both eyes open
(the fine dashed line represents perfect tracking). B:
mean OKN to constant-velocity drum rotations at 15, 30, 60, and 90°/s
rotations. The rapid rise (RR), steady-state OKN (SS), and optokinetic
afternystagmus (OKAN) components are illustrated. These OKN components
are shown for left eye viewing (C) and for right eye
viewing (D). For each plot, data were collected on 3 separate days and combined. Because spontaneous nystagmus occurred
whenever one eye was covered (LN), monocular viewing OKN was measured
in the following way. The animal faced a stationary OKN drum in the
light with both eyes open. The lights were turned off, the drum was
rotated at constant velocity, one eye was patched, and then the lights
were turned on. This technique reduced the spontaneous nystagmus of LN
during the rapid rise portion of OKN.
|
|
When OKN is tested to constant velocity steps, a high retinal-slip
velocity is delivered. To determine whether the reduced OKN response of
the 55-day monkey to N-T velocity steps was due to an impairment in the
processing of high retinal-slip velocities, we measured steady-state
OKN to a stimulus that started out at a velocity slightly greater than
the animal's LN velocity and then decremented in 5°/s steps at 15-s
intervals (Fig. 10). The mean and 1 SD
of SPEV of LN every 50 s is plotted during right eye view
(A) and left eye view (B). The staircase line
represents the velocity of the OKN drum. There was small trend in SPEV
in response to the stimulus (eye velocity = 0.07 times target
velocity in A and 0.06 times target velocity in
B), but there was no significant change in SPEV
(t > 0.01, Pearson correlation). This helped confirm that there was no significant monocular OKN response in the N-T direction in the 55-day monkey.

View larger version (14K):
[in this window]
[in a new window]
|
Fig. 10.
Inability of monocular OKN in the N-T direction to suppress LN in the
55-day monkey. Means and 1 SD of the velocity of LN (circles) are
plotted during right eye view (A) and left eye view
conditions (B). The staircase line represents the
velocity of the OKN drum. At time 0, the drum was
rotating near the same speed as the slow phases of LN to create little
retinal slip. The drum was then slowly decelerated by 5°/s steps
every 15 s. For each figure, data were collected on 2 separate
days and combined.
|
|
 |
DISCUSSION |
Images are stabilized on the retina by several gaze-stabilizing
systems, including the VOR, OKN, and fixation (Leigh et al. 1988
). Table 4 summarizes our
findings on gaze-stabilizing systems and fixation instability in the BD
monkeys tested at 12 mo of age. The most significant defect was the
impaired monocular OKN response in the N-T direction and the presence
of nystagmus.
OKN
In human infants, OKN is depressed in the N-T direction compared
with the T-N direction during monocular viewing at birth and becomes
symmetric by 6 mo of age (Naegele and Held 1982
). If
normal visual development is disrupted by unequal visual inputs from
the two eyes due to strabismus, anisometropia, or a congenital cataract
in one eye, then monocular OKN asymmetry persists (Maurer et al.
1983
; Schor and Levi 1980
; Shawkat et al.
1995
; Westall and Schor 1985
). This monocular
OKN asymmetry has also been found in monkeys following 14 days of
monocular eyelid suture starting at 7-14 days of age (Sparks et
al. 1986
). Our study has extended these findings. We have
examined both the rapid rise and the velocity storage components of OKN
(OKAN). Our results suggest that the velocity-storage component of OKN
in the N-T direction is the component most impaired by binocular
deprivation in monkeys. When the duration of deprivation increases, the
rapid rise component of OKN is also impaired in the N-T direction and
eventually, OKN deficits may start to occur in the T-N direction at
high target velocities, as was found in the 55-day monkey. It is likely
that the reduced OKN in the N-T direction is partially due to the
presence of LN. We chose not to subtract the LN from OKN, as these
visual tracking systems may be nonlinear. Our testing using a moving OKN drum that changed speeds in small steps indicates that these deficits in OKN were not simply due to an inability to process high
retinal-slip velocities, but represented a true deficit in generating
an OKN response.
A schematic diagram illustrating the possible basis for a
decreased monocular OKAN response in the nasal-to-temporal direction is
shown in Fig. 11. Neural activation of
the nucleus of the optic tract (NOT) evokes ipsiversive eye movements
(dashed lines above NOT) (Mustari and Fuchs 1990
;
Schiff et al. 1988
). NOT neurons are activated by
ipsilaterally directed retinal slip. Normally, NOT receives inputs
directly from the contralateral eye (T-N motion) and indirectly (via
cerebral cortex) from the ipsilateral eye (Mustari and Fuchs
1990
). In the BD monkey, NOT loses its input from the
ipsilateral eye (cortical input) and responds only to T-N motion viewed
from the contralateral eye. Consequently, the BD monkey cannot generate
OKN to N-T stimuli during monocular viewing. This loss of visual input
to NOT from the ipsilateral eye may be due to a defect in any number of
sites indicated by the "X" marks.

View larger version (31K):
[in this window]
[in a new window]
|
Fig. 11.
Schematic diagram of the proposed disruption within the circuit
mediating the velocity-storage component of OKN. Dashed lines indicate
target motion and slow-phase eye movement (SPEM) directions. Continuous
lines indicate anatomical projections. A cortical afferent system
includes a projection from the dorsolateral geniculate nucleus (dLGN)
to striate cortex (V1) to the middle temporal area (MT). This system
processes information about target motion from each eye. The cortical
efferent system includes a projection from the medial superior temporal
(MST) area to the nucleus of the optic tract (NOT). NOT also receives a
direct retinal projection from the contralateral eye. Each NOT
generates ipsilateral slow-phase eye movements via a projection to the
medial vestibular nucleus (MVN), 6th nerve nucleus (6th) and 3rd nerve
nucleus (3rd). In the schematic, black and open arrows indicate the
visual pathways from the left and right eyes, respectively. Gray arrows
indicate pathways downstream from NOT. Most neurons in NOT are normally
activated only by target motion toward the ipsilateral side (indicated
by the 3 small dashed lines above NOT).
|
|
VOR gain
Human infants have VOR gains similar to adults (Ornitz et
al. 1985
; Weissman et al. 1989
). In contrast,
VOR velocity storage is poorly developed at birth, although it improves
rapidly over the course of 2 mo and then slowly reaches adult values
over the course of 2 yr (Ornitz et al. 1985
;
Weissman et al. 1989
). In cats reared for 1 yr in the
dark, VOR gain is reduced, and the VOR velocity-storage is poor
(Cynader 1985
; Harris and Cynader 1981
).
These deficits endure despite subsequent exposure to a normal visual
environment. VOR gain has not been previously examined in visually
deprived monkeys. In our study, 25-55 days of binocular derivation
beginning at birth resulted in a small decrease in VOR gain and no
change in the velocity storage system compared with normally reared
monkeys. These results suggest that the vestibular system still
received adequate retinal-slip information to be maintained and
calibrated in these animals despite the presence of the monocular OKN deficits.
Nystagmus
CRITICAL PERIOD.
Based on our study along with others, it appears that
deprivation-induced nystagmus in monkeys only occurs if deprivation is
initiated during the first few weeks of life. Furthermore, nystagmus
may persist even with as little as 25 days of deprivation. Nystagmus
resembling LN occurs in monkey following artificial induction of
esotropia within the first 2 wk of life (Kiorpes et al.
1996
), and nystagmus resembling congenital nystagmus occurs following monocular lid suture initiated within 1 day of life as long
as the fellow eye is suture closed within 3 wk (Tusa et al.
1991
). Spontaneous nystagmus has not been reported in monkeys reared with monocular or bilateral eyelid suture starting 30 days or
later after birth for up to 4-18 mo of deprivation (Crawford et
al. 1993
; Harwerth et al. 1991
).
Based on these studies the critical period in which visual deprivation
causes gaze instability may be over by the first few weeks of life in
monkeys. This brief duration for motor deficits from visual deprivation
is in striking contrast to purely visual perceptual problems from
visual deprivation. Based on monocular deprivation studies in monkeys,
the development of scotopic threshold spectral sensitivity has a
critical period of 3 mo, the critical period for development of
photopic threshold sensitivity is complete by 6 mo of age, and
binocular visual function is complete by 2-3 yr of age
(Crawford et al. 1993
; Harwerth et al.
1986
).
All of the BD monkeys had strabismus when the eyelids were
opened. It is possible that ocular motor function of our monkeys may
have deteriorated further after the eyelids were opened due to visual
deprivation from strabismus and amblyopia. It is even possible that
some ocular motor deficits may have occurred due to competition between
the two eyes behind closed eye lids. The hairless eyelids of macaque
monkeys allow transmission of 10% of light in the adult, perhaps more
in the infant (Crawford and Marc 1976
; Robinson
et al. 1991
). Competition between the two eyes from strabismus
during the first few weeks of life may be the cause of LN in both
lid-sutured monkeys and induction of artificial esotropia.
CHARACTERISTICS OF LN IN BD MONKEYS.
Certain features of LN in monkeys are similar to LN in human
subjects. First is the presence of horizontal nystagmus elicited by
closing one eye whose direction depends on which eye is closed (slow
phases are directed toward the closed eye). Second, the maximum
velocity of LN decreases in the viewing eye if the animal wears a patch
over the other eye continuously for a few days, similar to that
reported by patients with LN (Simonsz 1989
). This reduction of SPEV by patching one eye continuously appears to be due to
the development of a constant velocity bias whose slow phases are
directed toward the habitually viewing eye. The direction of this bias
can be reversed after patching the eye for 1 day. Remarkably, this
reduction in SPEV occurred even in the 55-day monkey, which suggests
that this animal can still decrease SPEV of LN even without any
monocular OKN in the N-T direction. Thus this type of adaptation may
not rely solely on retinal-slip in the viewing eye.
We found three additional features of LN in monkeys that we
believe help elucidate potential neural mechanisms. First, when one eye
is patched, the slow phases of LN build up slowly over the course of
30-60 s. Second, LN occurs even when the open eye is viewing a
Ganzfeld. Thus the stimulus that evokes LN when one eye is closed does
not appear to require retinal slip. The stimulus may in part be due to
a difference in light intensity in the two eyes. Third, the peak SPEV
of LN varied in each monkey, but was correlated inversely with the
amount of monocular OKN in the N-T direction. Thus retinal slip in the
viewing eye may not be inducing LN, but it may activate OKN that, in
turn, decreases LN. Consider the 25-day monkey that had a partial
monocular OKN response in the N-T direction. When one eye was closed,
LN was induced such that retinal slip occurred opposite to the
direction of the slow phases N-T. This retinal slip should stimulate
the OKN system to generate slow phases opposite to the LN. When the
monocular OKN response is completely normal, no LN may be seen, whereas when the monocular OKN response in the temporal direction is completely absent, maximum LN may be seen. These three properties of LN suggest that the NOT may be involved in LN. When the NOT is electrically stimulated on one side, horizontal nystagmus is elicited whose SPEV
builds up over 60 s or less (Mustari and Fuchs
1990
; Schiff et al. 1988
). Cells in NOT respond
to both retinal slip and transient light changes, and NOT is involved
in the generation of OKN.
In the companion paper we examine specifically the physiological
properties of the NOT neurons in two of these monkeys (Mustari et al. 2001
).
We are grateful for the technical assistance of J. R. Economides.
Address for reprint requests: R. J. Tusa, Yerkes Research Center,
954 Gatewood Rd. NE, Emory University, Atlanta, GA 30322 (E-mail:
rtusa{at}rmy.emory.edu).