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Adaptations and Deficits in the Vestibulo-Ocular Reflex After Third Nerve Palsy
Agnes M. F. Wong, MD, PhD;
James A. Sharpe, MD
Arch Ophthalmol. 2002;120:360-368.
ABSTRACT
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Objective To analyze the vestibulo-ocular reflex (VOR) in patients with unilateral
peripheral third nerve palsy.
Participants and Methods Ten patients and 15 healthy subjects were studied using magnetic search
coils. Subjects made sinusoidal ±10° head-on-body rotations in
yaw, pitch, and roll in darkness and during monocular viewing in light.
Results Horizontal VOR and visually enhanced VOR (VVOR) gains of the paretic
eye were decreased during both abduction and adduction. Vertical VOR and VVOR
gains of the paretic eye were decreased during both elevation and depression.
Dynamic and static torsional VOR and VVOR gains of the paretic eye were reduced
during both excyclotorsion and incyclotorsion. Horizontal, vertical, and torsional
VOR and VVOR gains were normal in the nonparetic eye.
Conclusions Adducting VOR gains were reduced as anticipated from medial rectus palsy.
Abducting gains were also reduced; the reduction is attributed to an adaptive
decrease in innervation to the lateral rectus to achieve symmetry of the horizontal
VOR in the paretic eye. Torsional VOR gains were reduced during excyclotorsion
from palsy of the inferior oblique muscle. Gains were also reduced during
incyclotorsion, which can be explained by an adaptive decrease in innervation
to the superior oblique to restore symmetry of the torsional VOR in the paretic
eye.
Clinical Relevance Monocular adaptation in the VOR of the paretic eye reduces asymmetrical
movement of retinal images during head motion, prevents nystagmus, and reduces
retinal image disparity.
INTRODUCTION
THE EFFECTS of third nerve palsy on the vestibulo-ocular reflex (VOR)
have not been systematically investigated. Clinical testing of ocular motor
nerve palsies emphasizes examination of static deviations of the eyes. The
VOR stabilizes retinal images by generating compensatory smooth eye movements
that are nearly equal in amplitude and opposite in direction to head rotations.
Adaptive changes in the VOR occur in response to visual stimuli.1-5
When healthy subjects wear reversing prisms for several days, VOR gains are
substantially reduced.3 After 3 to 4 weeks
of vision reversal, the phase of the VOR actually reverses; head rotations
cause eye rotations in the same direction, so that
retinal images are once again stabilized.3
Disconjugate VOR adaptation has been elicited in response to different prisms
in each eye6 and experimental weakening of
the horizontal rectus muscles of one eye in monkeys.7-8
Adaptive changes in the VOR might also improve defective visual stabilization
of images caused by third nerve palsy.
In this study, we investigated patients with unilateral third nerve
palsy to examine their VORs and their adaptations, if any, in 3 dimensions.
The third (oculomotor) nerve innervates 4 extraocular muscles: the medial
rectus, superior rectus, inferior rectus, and inferior oblique. Because the
primary action of the medial rectus is adduction, we hypothesized that weakness
of the medial rectus in third nerve palsy would cause a reduction in VOR gains
during adduction. We also anticipated a decrease in vertical VOR gains during
both elevation and depression in third nerve palsy, as these are the primary
actions of the superior and inferior rectus muscles.9
Similarly, because the primary action of the inferior oblique is excyclotorsion,9 we also predicted a decrease in VOR gains during excyclotorsion
in third nerve palsy. We identified changes in the VOR that signify monocular
adaptation by the vestibulo-ocular system.
PARTICIPANTS AND METHODS
CLINICAL ASSESSMENT AND IMAGING STUDIES
We recruited 10 patients with unilateral peripheral third nerve palsy
from the Neuro-ophthalmology Unit at the University Health Network, Toronto,
Ontario. A complete history was taken, and detailed ophthalmic and neurologic
examinations were performed, recording the duration and age at onset of diplopia,
the presence or absence of risk factors for ischemia (diabetes mellitus and
hypertension), and associated neurologic symptoms and signs. The magnitude
of strabismus was measured objectively using the prism and cover test and
subjectively using the Maddox rod and prism test. The range of ductions was
estimated independently by 2 examiners (A.W. and J.A.S.), and the degree of
duction defect was graded according to the estimated percentage of the normal
duction in the fellow eye. When indicated, appropriate tests were performed
to rule out myasthenia gravis, thyroid ophthalmopathy, other orbital diseases,
or intracranial lesions. Informed consent was obtained for all subjects.
In this investigation, magnetic resonance (MR) or computed tomographic
(CT) imaging was performed on all patients, although imaging is not our standard
practice for all such patients. We obtained CT images of the head with contrast
in all patients with ischemic risk factors and for patients older than 50
years. Those with abnormal findings on CT scans were further investigated
with MR imaging. Serial axial and sagittal T1-weighted and T2-weighted MR
images with gadolinium enhancement were obtained (slice thickness, 5 mm) for
all patients younger than 50 years. In addition, MR imaging was performed
on all patients with pupillary involvement; if the MR image was normal, cerebral
angiography was performed.
EYE MOVEMENT RECORDINGS
Experimental Protocol
With one eye occluded, subjects viewed a red laser spot 0.25° in
diameter that was rear-projected on a uniformly gray vertical flat screen
1 m from the nasion. Subjects made active sinusoidal ±10° head-on-body
rotations in yaw to elicit the horizontal VOR and in pitch to elicit the vertical
VOR at approximately 0.5 and 2 Hz. Torsional VOR was elicited by head rotation
in roll at approximately 0.5, 1, and 2 Hz. Head movements were paced by a
periodic tone. The examiner placed his or her hands on each parietal area
of the subject's skull to maintain the desired amplitude and frequency of
head movements. The procedure was performed in light with one eye viewing
to elicit the visually enhanced VOR (VVOR) then repeated with the other eye
fixating and the fellow eye occluded. The VOR was then recorded in complete
darkness while subjects were instructed to fixate on an imaginary earth-fixed
target.
To measure the static torsional VOR, subjects fixated on the center
target with one eye occluded as we measured their ocular responses to static
head rolls of about 30° toward each shoulder, as measured with search
coils. The procedure was then repeated with the other eye fixating and the
fellow eye occluded and also in total darkness.
Recordings of Eye Movement and Calibration
The positions of each eye were simultaneously measured by a 3-dimensional
magnetic search coil technique, using an 183-cm (6-ft) diameter coil field
arranged in a cube (CNC Engineering, Seattle, Wash). In each eye, the subject
wore a dual-lead scleral coil annulus designed to detect horizontal, vertical,
and torsional gaze positions (Skalar Medical, Delft, the Netherlands). Head
position was recorded by another coil taped to the subject's forehead. Each
subject's head was centered in the field coils. Horizontal, vertical, and
torsional movements were calibrated by attaching the scleral coil to a rotating
protractor before each experiment. After scleral coils were inserted in the
subject's eyes, horizontal and vertical eye movements were calibrated with
saccades from the straight-ahead reference position to steps of a laser target.
Consistency of calibrated positions before and after coils were inserted provided
evidence that the gimbal calibrations were valid. Because torsional eye position
depended on the same magnetic field as vertical eye position, the accuracy
of vertical calibration before and after coil insertion provided further evidence
that the torsional calibration was also accurate. Phase detectors employing
amplitude modulation as described by Robinson10
provided signals of torsional gaze position within the linear range. Torsional
precision was about ± 0.2°. There was minimal cross-talk; large
horizontal and vertical movements produced deflections in the torsional channel
of less than 4% of the amplitude of the horizontal and vertical movement.
Any coil slippage was assessed by requiring subjects to repeatedly refixate
at the straight-ahead reference position after each eye movement. Consistency
of calibrated torsional coil signals after each eye movement provided evidence
that the coil did not slip on the eye. Eye position data were filtered with
a bandwidth of 0 to 90 Hz and digitized at 200 Hz. They were recorded on disc
for off-line analysis. Analog data were also displayed in real time by a rectilinear
thermal array recorder (Model TA 2000; Gould Electronics Inc, Eastlake, Ohio).
Data Analyses
Eye position was derived by subtracting head position from gaze position
signals. Fast phases of vestibular nystagmus were identified by a computer
program using velocity and acceleration criteria.11
Results of fast-phase identification were edited on a video monitor, allowing
the operator to verify cursor placement for fast-phase removal. Eye positions
between 80 milliseconds before and after the identified fast phases were removed,
and the gaps were replaced with quadratic fits. The average slopes were used
to calculate the contribution of the ongoing slow phase during the fast phase.
The offset due to the fast phase was then removed, and the ongoing slow phase
was interpolated to yield a cumulative trace of eye position.
Using position data, each cycle of rotation was identified by marking
adjacent peaks with the opposite direction, and the frequency was computed.
Using a least-square sinusoidal fit,12 eye
and head positions were fitted with one cycle, and the phase and amplitude
were computed. The ratio of the amplitude of the eye and the amplitude of
the head was the gain, and the difference between the phase of the eye and
the phase of the head was the phase shift.
To calculate the gain in each direction, eye and head position data
from each half cycle were used and reflected to form a full cycle. Each cycle
was then fitted using a least-square sinusoidal fit,12
and the gain was computed for each direction. In addition, we plotted head
velocity against eye velocity and performed a linear regression for each direction.
The slopes of the fitted lines were the gains, and the results were comparable
to those computed by the least-square sinusoidal fit technique (Figure 1).
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Figure 1. Plots of head velocity vs eye
velocity of the paretic right eye (A) and the nonparetic left eye (B) of Patient
1 with severe right third nerve palsy during horizontal head rotation about
an earth-vertical axis at 2 Hz in darkness. Gains in the vestibulo-ocular
reflex, defined as the slopes of the lines of best fit, were reduced in the
paretic right eye in both directions (A), whereas gains were normal in the
nonparetic left eye in both directions (B). Open circles indicate data during
rightward movements; dashed line, line of best fit for data during rightward
movements; filled circles, data during leftward movements; and solid line,
line of best fit for data during leftward movements.
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Subjects wore spectacles, if habitually worn, during VOR testing. To
account for the prismatic effect or rotational magnification induced by spectacle
adaptation,5, 13 horizontal and
vertical VOR gains were adjusted by using the formula: Mpred =
40/(40 - D), where D is the lens power in diopters and Mpred
is the predicted magnification.5, 13
For example, a patient with hyperopia who habitually wears +10 D spherical
lenses has an Mpred of 40/(40 - 10) or 1.3. This means that
while wearing +10 D, a VOR gain of 1.3, instead of 1.0, is required to prevent
the visual scene from moving on the retina during head rotations.
For the measurement of static torsional VOR, head and gaze position
signals were sampled for 6 seconds in each of 20 positions of 30° lateral
tilt. The position of the eye in the head was derived from the difference
between head and gaze position signals. Head and eye positions were computed
off-line over each 6-second period after the eye had come to a torsional resting
position (defined as having angular velocity less than 1° per second).
Responses containing blinks or rapid drifts were not analyzed. Change of torsional
eye position was plotted as a function of static change of head position after
roll, and a linear regression was performed. Static torsional VOR gain, defined
as the change in torsional eye position divided by the change in head position
in static roll, was calculated from the slope of the regression line.
Oculography was performed at one point in each patient's course (Table 1). Thus, deviations from normal
results, rather than serial intrasubject changes, were analyzed. Statistical
analyses of horizontal, vertical, and torsional VOR and VVOR gains and phases
were performed using t tests with 2-tailed, unequal
variance. Values were defined as significant when P<.05.
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Table 1. Characteristics of Patients With Third Nerve Palsy*
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RESULTS
GENERAL CHARACTERISTICS OF PATIENTS
The mean ± SD age was 54 ± 13 years (median age, 54 years;
age range, 38-70 years). There were 8 women. The duration of symptoms ranged
from one week to 50 months, with a mean duration of 18 months. Mean follow-up
duration was 38 months (range, 11-72 months). In all patients, the third nerve
palsy affected both the superior and inferior divisions, with or without pupillary
involvement. No patients had any clinical signs of misdirection involving
the eyelid or pupil. Six patients had idiopathic, presumed ischemic, peripheral
lesions. Four had normal MR images, and 2 had normal CT scans. Four of these
6 patients had ischemic factors, namely hypertension or diabetes, and had
a complete resolution of their palsy within 4 to 6 months. Four other patients
had intracranial lesions: head injury (n = 1), neurosarcoidosis with enhanced
meninges at the cavernous sinus (n = 1), posterior communicating artery aneurysm
(n = 1), and pituitary tumor extending into the cavernous sinus (n = 1). All
4 patients with intracranial lesions had neurologic symptoms and signs in
addition to diplopia. None of them had signs or MR evidence of involvement
of the third nerve nucleus or fascicle. Fifteen healthy subjects served as
controls (mean ± SD age, 52 ± 15 years; median age, 58 years;
age range, 19-69 years; 8 women).
GAIN AND PHASE IN THE VOR
In darkness (Figure 2A), horizontal VOR gains of the paretic eye were reduced symmetrically
(P<.05) during both abduction and adduction, whereas
those of the nonparetic eye remained normal in both directions (Table 2). During viewing with either eye in light (Figure 2B and C), horizontal VVOR gains of the paretic eye were
low in both directions (P<.05), whereas VVOR gains
of the nonparetic eye were normal (Table
2). In light and darkness, the mean phase differences between the
eye and head positions approximated 180°, designated as zero phase shift.
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Figure 2. Mean horizontal vestibulo-ocular
reflex (VOR) gains in controls (n = 15) and patients with peripheral third
nerve palsy (n = 10) in darkness (A); and mean horizontal visually enhanced
VOR (VVOR) gains in light during paretic (B) and nonparetic (C) eye viewing.
Adducting and abducting VOR and VVOR gains are reduced symmetrically in the
paretic eye, so their VVOR plots overlap (B and C). Error bars indicate one
SD.
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Table 2. Horizontal, Vertical, and Torsional VOR and VVOR Gains in
Patients With Third Nerve Palsy*
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In darkness (Figure 3A), vertical VOR gains of the paretic eye were reduced (P<.01) during both elevation and depression, whereas
gains of the nonparetic eye were normal (Table 2); upward and downward gains did not differ. In light, during
paretic or nonparetic eye viewing (Figure
3B and C), vertical VVOR gains of the paretic eye remained reduced
(P<.05), whereas gains in the nonparetic eye were
normal (Table 2). Neither eye
showed any significant phase shift from zero in light or darkness.
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Figure 3. Mean vertical vestibulo-ocular
reflex (VOR) gains in controls (n = 15) and patients with peripheral third
nerve palsy (n = 10) in darkness (A); and mean vertical visually enhanced
VOR (VVOR) gains in light during paretic (B) and nonparetic (C) eye viewing.
Upward and downward VOR and VVOR gains are reduced symmetrically in the paretic
eye, so their VVOR plots overlap (B and C). Error bars indicate one SD.
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In darkness (Figure 4A), torsional VOR gains of the paretic eye were reduced during
both incyclotorsion and excyclotorsion (P<.01),
whereas gains of the nonparetic eye were normal (Table 2). In light, and during viewing with either eye (Figure 4B and C), torsional VVOR gains of
the paretic eye remained reduced (P<.01), whereas
gains in the nonparetic eye were normal (Table 2). Neither eye showed any significant phase shift from zero
in light or darkness.
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Figure 4. Mean dynamic torsional vestibulo-ocular
reflex (VOR) gains in controls (n = 15) and patients with peripheral third
nerve palsy (n = 10) in darkness (A); and mean torsional visually enhanced
VOR (VVOR) gains in light during paretic (B) and nonparetic (C) eye viewing.
Excyclotorting and incyclotorting VOR and VVOR gains are reduced symmetrically
in the paretic eye. Error bars indicate one SD.
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Static torsional VOR gains did not differ between
viewing with the paretic or nonparetic eye. Therefore, they are reported as
the pooled mean for each eye with either eye fixating, in light and darkness
(Table 3). Static torsional VOR
and VVOR gains of the paretic eye were reduced during incyclotorsion and excyclotorsion
(P<.05); they were normal in the nonparetic eye.
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Table 3. Static Torsional VOR Gain (Ocular Counterroll) in Controls
and Patients With Third Nerve Palsy*
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COMMENT
In subjects with third nerve palsy, horizontal VOR and VVOR gains of
the paretic eye were decreased during both abduction and adduction, whereas
gains in the nonparetic eye were normal. Vertical VOR and VVOR gains of the
paretic eye were decreased during both elevation and depression, consistent
with palsy of the superior and inferior rectus muscles in third nerve palsy.
In the nonparetic eye, vertical gains were normal. Dynamic and static torsional
VOR and VVOR gains of the paretic eye were reduced during incyclotorsion and
excyclotorsion. Torsional gains were normal in the nonparetic eye. In light,
horizontal, vertical, and torsional VVOR gains in the paretic eye remained
reduced, indicating that visual input does not enhance VVOR to normal in third
nerve palsy.
Changes in the VOR in our patients, who were tested at one point in
the course of their palsies, are expressed as changes from normal, rather
than serial intrasubject changes. Any recovery toward normal values was not
assessed. Abnormalities are interpreted as deficits or adaptations to those
deficits.
HORIZONTAL VOR IN UNILATERAL THIRD NERVE PALSY
During rotation in darkness, horizontal VOR gains were reduced during
adduction of the paretic eye in all patients, as anticipated in palsy of the
medial rectus muscle from third nerve palsy. VOR gains during abduction of
the paretic eye were also reduced. In contrast, in the nonparetic eye, VOR
gains were normal during both abduction and adduction (Figure 2). Apparently, the innervation to the lateral rectus of
the paretic eye is reduced, along with the reduced innervation to the medial
rectus resulting from the palsy, without changes in the innervation to the
horizontal rectus muscles of the nonparetic eye.
A functional adaptation to unilateral third nerve palsy can explain
this adjustment in abducting VOR gain. Without it, the VOR would be asymmetrical
in the paretic eye, being reduced in adduction but normal in abduction. The
asymmetry would drive the paretic eye farther into abduction with each cycle
of head rotation, soon "pinning" it at its temporal limits and aggravating
the patient's diplopia. There are several strategies that might seem to rectify
this problem. The brain might increase its innervation to the paretic medial
rectus to increase VOR gain during adduction, but this strategy is limited
by the palsy itself. Or, the brain might generate adducting saccades in the
paretic eye to correct for low VOR gains during adduction. However, adduction
paresis would limit the saccades. Moreover, if common premotor signals are
sent to both the abducens motoneurons and internuclear neurons in the abducens
nucleus, the result might be unwanted abducting saccades in the nonparetic
eye, taking it off its target. A better option would be to reduce the innervation
just to the lateral rectus of the paretic eye, decreasing its abduction gain
to make the VOR symmetrical in that eye, while leaving the VOR in the nonparetic
eye intact. Apparently, the brain adopts this adaptive strategy when challenged
by retinal image disparity caused by paresis of the medial rectus muscle.
TORSIONAL VOR IN UNILATERAL THIRD NERVE PALSY
In third nerve palsy that affects both the superior and inferior divisions,
3 of 4 cyclovertical extraocular muscles are involved, namely, the superior
rectus, inferior rectus, and inferior oblique muscles. The cyclotorsional
actions of the superior rectus and the inferior rectus are opposed; the superior
rectus incyclotorts, and the inferior rectus excyclotorts.9
If both vertical rectus muscles were equally palsied, the net effects of third
nerve palsy on torsional VOR would be determined by weakness of the inferior
oblique, whose primary action is excyclotorsion. As anticipated, dynamic and
static torsional VOR gains are reduced during excyclotorsion. However, we
found that torsional VOR gains are also reduced during incyclotorsion. Unequal
involvement of the superior and inferior rectus muscles, with the superior
rectus being more severely affected than the inferior rectus, might make some
contributions to reduction of incyclotorting gains. However, symmetry of upward
and downward gains indicate that differential paresis of the vertical rectus
muscles was not a factor.
The reduced VOR gains during incyclotorsion in the paretic eye, without
any change in gains in the nonparetic eye, can be attributed to a functional
adaptation in unilateral third nerve palsy. Without it, the VOR would be asymmetrical
in the paretic eye: weak in excyclotorsion but normal in incyclotorsion. The
asymmetry would drive the paretic eye farther into incyclotorsion with each
cycle of head rotation, resulting in increased torsional disparity between
the 2 eyes and diplopia. Using similar rationale discussed for the horizontal
VOR, this adaptation in the paretic eye could be achieved by decreasing the
innervation to the ipsilateral superior oblique (but not to the yolked contralateral
inferior rectus) of the paretic eye.
PROPRIOCEPTION AND VOR ADAPTATION
A decrease in proprioceptive signals from extraocular muscles of the
paretic eye might have also contributed to the VOR changes in our patients.
Extraocular muscle afferents leave the ocular motor nerves near the apex of
the orbit or in the region of the cavernous sinus and travel via the ophthalmic
branch of the trigeminal nerve and the gasserian ganglion to reach the spinal
trigeminal nucleus.14-19
There is disagreement as to whether some afferents also project centrally
via the ocular motor nerves.19-24
Sectioning of the trigeminal nerve reduced horizontal VOR gains in rabbits25-27 and pigeons.28 Immediately after unilateral sectioning of the trigeminal
nerve in pigeons, horizontal VOR gains of the deafferented eye were dramatically
reduced, whereas gains in the contralateral eye were little affected.28 In our patients, horizontal VOR gains of the paretic
eye were reduced in both directions, whereas gains of the nonparetic eye remained
normal. Our results might be explained by defective transmission of afferent
signals from the paretic eye to the brainstem because of a lesion in the oculomotor
nerve, which normally carries proprioceptive signals from extraocular muscles
to the ophthalmic branch of the trigeminal nerve and the spinal trigeminal
nucleus.
ORBITAL MECHANICS AND VOR ADAPTATION
Changes in normal orbital plant mechanics might contribute to the decreased
VOR gains of the paretic eye in third nerve palsy. The relative contribution
of agonist contraction and antagonist relaxation varies with orbital position,29 and it may be altered when one muscle of an agonist-antagonist
pair is palsied. In paralytic strabismus, "contracture" (shortening and increased
stiffness) occurs in the nonparetic antagonist muscle,30-33
whereas the paretic muscle lengthens in response to a change in orbital position
of the globe. Anatomical and histological study34
showed that shortening or contracture of the nonparetic antagonist is associated
with a decrease in the number of sarcomeres, whereas lengthening of the paretic
muscle is accompanied by an increase in its number of sarcomeres.34 In addition, denervation atrophy in the paretic muscle
and changes in orbital tissues have been documented in paralytic strabismus.35-36 These changes may alter VOR gains
in both directions of the 3 axes of rotation.
MONOCULAR ADAPTATION IN UNILATERAL THIRD NERVE PALSY
Hering37 suggested that the brain circuitry
controlling gaze consists of 2 systems: one for conjugate movements, the other
for vergence. Conjugate control operates in the vestibulo-ocular, saccade,
smooth pursuit, and optokinetic systems. Premotor neurons encode common signals
to both abducens motoneurons and internuclear neurons in the abducens nucleus.38-40 The abducens motoneurons
innervate the ipsilateral lateral rectus, whereas the internuclear neurons
innervate the medial rectus motoneurons in the contralateral oculomotor nucleus.41-43
Because the neuronal connectivity is suitable for conjugate motion,
it might be presumed that only conjugate plasticity is possible. However,
experiments on primates have shown that ocular motor systems are capable of
selective, monocular adaptation.7-8,44
In monkeys, surgical weakening of the horizontal rectus muscles of one eye
elicits an adaptation that selectively increases saccadic and VOR gains in
the affected eye, whereas those of the unaffected eye remained normal.7-8 Disconjugate ocular motor adaptation
has also been demonstrated in normal humans45-46
and monkeys6 in response to image disparity
induced by anisometropic spectacles45 or prisms.6 Disconjugate saccades and pursuit are generated to
compensate for the disparate retinal errors produced by the optical displacement
of images.45-46
This investigation is the first, to our knowledge, to demonstrate monocular
adaptive change in the VOR in humans with third nerve palsy. We found that
VOR gains are selectively decreased during abduction and incyclotorsion of
the paretic eye, without a conjugate decrease in gains of the nonparetic eye.
These results exemplify monocular adaptation in humans with peripheral neuromuscular
deficits. Differences in slippage of retinal images between the 2 eyes is
a stimulus that can drive the monocular adaptation we have recorded.
Changes in neural drive to each eye might occur independently at the
level of motoneurons. Selective adaptation might be achieved by changing the
sensitivity of each motoneuron pool to innervation from premotor neurons.
The cerebellum, which mediates ocular motor adaptation, may have direct projections
to ocular motoneurons.47 Using the Nauta method
for tracing wallerian degeneration, Carpenter and Strominger47
suggested that cerebello-oculomotor fibers from all parts of the dentate nucleus
project to the inferior rectus subdivision of the contralateral oculomotor
nucleus, whereas fibers from ventral portions of the dentate nucleus project
to the superior rectus subdivision of the contralateral oculomotor nucleus.
However, a more modern retrograde tracer technique identified no afferents
from the dentate nucleus to the oculomotor nucleus.48-49
Supranuclear neural circuitry is not exclusively conjugate. For example,
for saccades, different populations of burst neurons mediate a pulse of innervation
to each eye. In monkeys, 79% of premotor excitatory burst neurons in the caudal
pontine paramedian reticular formation that were thought to encode conjugate
velocity commands for saccades38-40
actually encode monocular commands for either the ipsilateral or contralateral
eye.50 Similarly, different populations of
vestibular neurons provide innervation to the horizontal muscles of each eye.
In addition to a major excitatory horizontal VOR pathway that mediates conjugate
eye movements via motoneurons and internuclear neurons in the abducens nucleus,
a second direct excitatory horizontal VOR pathway exists. This second pathway
originates from the ventral lateral vestibular nucleus and ascends through
the ascending tract of Deiters to the ipsilateral medial rectus subdivision
of the oculomotor nucleus.51-52
Furthermore, neurons in the feline medial vestibular nucleus are activated
antidromically only by local stimulation of the contralateral abducens nucleus,53 whereas another group of medial vestibular nucleus
neurons are activated only by stimulation of the ipsilateral medial rectus
motoneurons pool, but not by stimulation of the contralateral abducens nucleus.53
The cerebellum plays important roles in adaptive control of saccades54-57 and
the VOR, including disconjugate control.55, 58-61
Experimental inactivation of the deep cerebellar nuclei (including the fastigial
nucleus) causes disconjugate saccadic dysmetria, so that both saccade magnitude
and peak velocity differ in the 2 eyes.62 Patients
with cerebellar degeneration or dysgenesis also show disconjugate dysmetria
during and immediately after horizontal or vertical saccades,63
although brainstem circuits are typically not spared in spinocerebellar degenerations
or malformations. The flocculus modulates VOR responses, and unilateral lesions
of the rabbit flocculus cause different VOR gain changes in the 2 eyes.64 Thus, the cerebellum exerts selective, dysconjugate
control and may participate in the monocular adaptation of the horizontal
and torsional VOR that we have identified after third nerve palsy.
AUTHOR INFORMATION
Submitted for publication June 13, 2001; final revision received November
16, 2001; accepted December 13, 2001.
This study was supported by the E. A. Baker Foundation, Canadian National
Institute for the Blind, Toronto, Ontario; the Vision Science Research Program,
University of Toronto; and grants MT 15362 and ME 5504 from the Canadian Institutes
of Health Research, Ottawa, Ontario.
We thank Douglas Tweed, MD, PhD, and the late Phat Nguyen, MSc, for
their advice and assistance.
Corresponding author and reprints: James A. Sharpe, MD, Division
of Neurology, University Health Network, EC 5-042, Toronto Western Hospital,
399 Bathurst St, Toronto, Ontario, Canada M5T 2S8 (e-mail: sharpej{at}uhnres.utoronto.ca).
From the Division of Neurology, the Department of Ophthalmology, and
the University Health Network, University of Toronto, Ontario.
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