State-of-the-Art Review
Section Editors: Vale
Cerebellar Control of Eye Movements
Shin C. Beh, MD, Teresa C. Frohman, PA-C, Elliot M. Frohman, MD, PhD
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Background: The cerebellum plays a central role in the
online, real-time control, and long-term modulation of eye
movements.
Evidence acquisition: We reviewed the latest (fifth) edition
of Leigh and Zee’s textbook, The Neurology of Eye Move-
ments, and literature in PUBMED using the following terms:
cerebellum, flocculus, paraflocculus, vermis, oculomotor
vermis, dorsal vermis, caudal fastigial nucleus, fastigial
oculomotor region, uvula, nodulus, ansiform lobule, eye
movements, saccades, ipsipulsion, contrapulsion, smooth
pursuit, vergence, convergence, divergence, gaze-holding,
down beat nystagmus, vestibulo-ocular reflex (VOR), angu-
lar VOR, translational VOR, skew deviation, velocity storage.
Results: The cerebellum is vital in optimizing the perfor-
mance of all classes of gaze-shifting and gaze-stabilizing
reflexes. The flocculus-paraflocculus are crucial to VOR gain
and direction, pulse-step matching for saccades, pursuit
gain, and gaze-holding. The ocular motor vermis and caudal
fastigial nuclei are essential in saccadic adaptation and
accuracy, and pursuit gain. The nodulus and ventral uvula
are involved in processing otolothic signals and VOR re-
sponses, including velocity storage.
Conclusions: The cerebellum guarantees the precision of
ocular movements to optimize visual performance and
occupies a central role in all classes of eye movements
both in real-time control and in long-term calibration and
learning (i.e., adaptation).
Journal of Neuro-Ophthalmology 2017;37:87–98
doi: 10.1097/WNO.0000000000000456
© 2016 by North American Neuro-Ophthalmology Society
T he goal of the efferent visual system is to direct and
maintain the angle of gaze on an object of regard,
thereby guaranteeing the best possible visual acuity and
clarity. Several mechanisms are crucial in attaining this goal:
Departments of Neurology (SCB, TCF, EMF), and Ophthalmology
(EMF), University of Texas Southwestern Medical Center, Dallas, Texas.
T. C. Frohman has received speaker and consultant fees from Gen-
zyme, Novartis and Acorda. E. M. Frohman has received speaking and
consulting fees from, TEVA Neuroscience, Genzyme, Acorda, and
Novartis. The remaining author reports no conflicts of interest.
Address correspondence to Shin C. Beh, MD, UT Southwestern
Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75235;
E-mail: scjbeh@gmail.com
Beh et al: J Neuro-Ophthalmol 2017; 37: 87-98
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!rie Biousse, MD
Steven Galetta, MD
(A) saccades, which direct the eyes to the object of regard; (B)
fixation and pursuit tracking, which detects (and corrects for)
retinal image drift, and suppresses unwanted saccades; (C) the
vestibulo-ocular reflex (VOR) that compensates for head per-
turbations at short latency to preserve visual acuity during
locomotion; and (D) the gaze-holding system, which counter-
acts the elastic forces of orbital tissue (1–3). In species with
frontally directed eyes with central foveas, the vergence sys-
tem enables bifoveal fixation of a single object of regard by
correctly aligning the visual axes (1). The cerebellum plays
a vital role in ensuring the precision and accuracy of ocular
movements regardless of changes in head or body positions
and is intimately involved in controlling gaze-shifting and
gaze-stabilizing reflexes, both in their real-time, immediate
modulation, and in their long-term calibration (1).
Three cerebellar regions are especially important for
ocular motor control (Fig. 1):
1. ocular motor vermis (OMV) and caudal fastigial nuclei
(CFN);
2. ventral uvula and nodulus; and
3. flocculus and paraflocculus
To maintain visuomotor precision, the cerebellum
continuously monitors and adapts the network’s perfor-
mance. The cell groups of the paramedian tract (PMT)
receive collaterals from all ocular motor neurons and in turn
convey efference copy signals to the flocculus, paraflocculus,
and vermis (1). In addition, retinal slip signals are conveyed
from the inferior olivary nucleus (ION) to the contralateral
flocculus via climbing fibers (1,4).
The main afferents to the flocculus and paraflocculus are
mossy fibers from the medial vestibular nucleus (MVN),
superior vestibular nucleus (SVN), nucleus prepositus hypo-
glossi (NPH), nucleus reticularis tegmenti pontis (NRTP), and
cell groups of the PMT, as well as climbing fibers from the
ION (1,4). The main efferents from the flocculus and paraf-
locculus travel to the ipsilateral SVN, MVN, and Y-group (1).
Major inputs to the nodulus and ventral uvula are mossy
fibers arising from the ipsilateral vestibular nerve (with
preferential input from the semicircular canals to the nodulus,
and the sacculus to the ventral uvula), SVN, MVN, and NPH,
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 State-of-the-Art Review

FIG. 1. Structures of the cerebellum subserving visuomotor function. The principal structures that play an important role in
cerebellar visuomotor function are the ocular motor vermis (lobules VI and VII), caudal fastigial nuclei (or fastigial oculomotor
region), ventral uvula, nodulus, flocculus, and paraflocculus. The ventral uvula and nodulus together form the caudal vermis.
The flocculus-paraflocculus and caudal vermis together constitute the vestibulocerebellum.

as well as ION climbing fibers (1,4). Important efferents pro-
ject to the SVN, MVN, and the Y-group (1).
The OMV receives mossy fiber afferents from the pontine
paramedian reticular formation (PPRF), NRTP, vestibular
nuclei, NPH, and dorsolateral and dorsomedial pontine nuclei,
as well as ION climbing fibers (1,4,5). Efferent projections
from the OMV Purkinje cells are directed to the ipsilateral
CFN (1). The CFN also receive climbing fiber afferents from
the ION and mossy fibers from pontine nuclei (particularly
the NRTP) (1,6). CFN efferents project primarily to the con-
tralateral CFN, before travelling via the uncinate fasciculus in
the superior cerebellar peduncle to the omnipause neurons in
the pontine raphe, contralateral brainstem burst neurons (ros-
tral medulla, PPRF, and rostral interstitial nucleus of the
medial longitudinal fasciculus [riMLF]), NRTP, central mes-
encephalic reticular formation, periaqueductal gray, nucleus of
the posterior commissure, vestibular nuclei, thalamus, and
bilateral rostral poles of the superior colliculi (1,4–6).
VERGENCE
Clinical observations indicate an important role for the
cerebellum in vergence eye movements. A range of
disorders in cerebellar disease has been reported including
convergence insufficiency and esodeviation during dis-
tance viewing (1).
The OMV, CFN, and posterior interposed nuclei (PIN)
are involved in vergence (7–10). Neurons controlling

88 Beh et al: J Neuro-Ophthalmol 2017; 37: 87-98

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vergence project to the NRTP from the medial superior
temporal area (MST), supplementary eye field (SEF), fron-
tal eye field (FEF), superior colliculi, and mesencephalic
pretectum. The NRTP subsequently projects to the
OMV and deep cerebellar nuclei (5,11–13).
Esodeviation at distance has been recognized in
cerebellar disease (1,7). To understand how cerebellar
lesions affect vergence, it is important to note that neural
pathways for convergence and divergence are separately
organized; divergence-related neurons in the PIN receive
input from the ventral paraflocculus and OMV, while the
convergence is controlled by the OMV-CFN pathway
(1,9,10,12–16). Further, since divergence-related neurons
in the OMV may be more susceptible to injury, and
convergence may be better compensated for (7), vermal
lesions are more often associated with incomitant esode-
viation (5,17).
SKEW DEVIATION
Skew deviation is a vertical misalignment of the eyes
resulting from lesions disrupting otolithic input to the
interstitial nucleus of Cajal (1). When skew deviation is
associated with ocular torsion (with the upper poles of the
eyes rotated toward the lower ear) and a head tilt (toward
the lower eye), this combination is called the ocular tilt
reaction (OTR) and is often associated with deviation of
the subjective visual vertical (1). The OTR is believed to
arise from an imbalance in the otolith-colic reflexes, part of
the phylogenetically ancient righting response to a lateral
head tilt (1).
Skew deviations have been long recognized as a feature of
cerebellar disease (1,17). Sometimes, the vertical misalign-
ment may change with horizontal position, with the abduct-
ing eye being higher (the alternating skew deviation)
(17–23). The cerebellum (specifically, the uvula, nodulus,
biventer lobe, and dentate nucleus) is involved in otolithic
signal processing, ensuring the accuracy of the internal rep-
resentation of the earth-vertical (24,25). Lesions affecting
these structures may cause a skew deviation or OTR, pre-
sumably by disrupting the symmetry of the otolithic path-
ways (24,26). Generally, uvulonodular and dentate nuclear
lesions result in a contraversive OTR, while lesions affecting
the biventral or inferior semilunar lobule cause an ipsiver-
sive OTR (1,24).
SACCADES
Saccades are rapid eye movements that redirect the fovea
from one object of interest to another and must be fast and
accurate to ensure visual clarity. Human saccades jump to
a target within w250 milliseconds are fast (w600°/s), brief
(w30–100 milliseconds), accurate, and stop abruptly (with
little subsequent ocular drift) (27). Saccades are generated
by a pulse-step command. To ensure accuracy, the pulse
Beh et al: J Neuro-Ophthalmol 2017; 37: 87-98
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State-of-the-Art Review
command must be of the correct magnitude; to keep the eye
still following the saccade, the step command must match
that of the pulse and be sustained for the duration of the
fixation (17).
Cortical eye fields (frontal, parietal, and supplementary)
predominantly project to the superior colliculi, the vital
nodal point that integrates and relays commands from the
cortical eye fields and basal ganglia to the brainstem saccade-
generator, as well as to the OMV and CFN by way of the
NRTP and the dorsolateral pontine nuclei (1,5,6,22,27–
31). The cerebellum also receives input from the cortical
eye fields, NPH, and premotor burst-neurons in the brain-
stem reticular formation (1). The cerebellum in turn proj-
ects efferents back to these structures, including projections
to the cortical eye fields (via the thalamus) and superior
colliculi (1).
The cerebellum is essential to saccadic sensorimotor
adaptation and accuracy. Its immediate responsibility is
propelling and accelerating the eyes to a target of interest,
monitoring the progress of the saccade, and ensuring that
the saccade lands on target by choking the pulse drive off at
the precise time; its long-term role is to assure accuracy by
adapting for persistent end-point errors (4,32). Total cere-
bellectomy abolishes saccadic adaptation for both pulse-size
and pulse-step match (33). The OMV and CFN play a cru-
cial role in saccadic adaptation and accuracy. Stimulation
studies show that OMV stimulation produces ipsiversive
saccades, and that it is organized topographically; lobule
V produces upward and horizontal saccades, while lobules
VI and VII elicit horizontal and downward saccades (1).
The CFN and OMV show significant changes in electrical
activity related to saccadic adaptation; furthermore, brain-
stem structures (especially the NRTP) that are intimately
linked by afferent and efferent projections with the CFN
and OMV also demonstrate changes in neuronal activity
during adaptation (34). Inactivation of the CFN abrogates
saccadic adaptation (34–36); however, there is evidence that
saccadic adaptation can occur during the period of CFN
inactivation but cannot be expressed until this output path-
way regains function, suggesting that the OMV is the crit-
ical cerebellar structure required for saccadic adaptation,
rather than the CFN (34,35). Lesion studies suggest that
while OMV-CFN lesions impair the pulse-size adaptation
(resulting in pulse-size dysmetria), pulse-step match is con-
trolled by the flocculus-paraflocculus (1,37). Apart from
these structures, there is evidence that the lateral cerebellar
hemispheres also participate in saccade adaptation (38).
Conjugate saccade pulse dysmetria is a classic sign of
cerebellar disease (1,17,18,39). Bilateral OMV lesions that
spare the CFN cause hypometric saccades; on the other
hand, unilateral CFN lesions result in hypometric contra-
versive and hypermetric ipsiversive saccades (35,40–49).
Total cerebellectomy and bilateral CFN inactivation causes
saccadic hypermetria (33,48,50). As such, we can infer that
the CFN overcomes the inherent hypermetric tendency of
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the brainstem saccade pulse-generator (41), presumably by
balancing the activity between omnipanuse neurons and
excitatory and inhibitory burst-neurons (51–55).
To guarantee the eyes land on target, the OMV
monitors saccade performance and adjusts its inhibition of
the CFN (4) to ensure that saccade-related CFN neurons
fire just before the onset of contraversive saccades and
toward the end of ipsiversive saccades (36,51,56–58); this
discharge pattern suggests that the CFN provides the
“push” for contraversive saccades to propel the eyes toward
a target and applies the “brakes” for ipsiversive saccades to
stop on target. Therefore, in unilateral CFN lesions, con-
tralesional saccades are hypometric due to insufficient
“push,” and ipsilesional saccades are hypermetric as a result
of damaged “brakes.” On the other hand, unilateral OMV
lesions cause hypermetric contraversive and hypometric ip-
siversive saccades, and bilateral OMV damage results in
bilateral hypometric saccades because their inhibitory effect
on the CFN is lost (thereby “disinhibiting the inhibitors”)
(59).
Ocular lateropulsion refers to horizontal conjugate gaze
deviation during eye closure, either toward (ipsipulsion) or
away from (contrapulsion) the side of the lesion, that is,
corrected by a saccade when the eyes are opened. Ocular
lateropulsion is typically accompanied by saccadic latero-
pulsion and horizontal misdirection of vertical saccades. In
ipsipulsion, damage to the inhibitory climbing fibers from
the contralateral ION (travelling in the inferior cerebellar
peduncle) to OMV Purkinje cells leads to increased
inhibition of the ipsilateral CFN (mimicking the effects of
an ipsilateral CFN lesion) (60,61). This results in hypomet-
ric contraversive and hypermetric ipsiversive saccades. On
the other hand, contrapulsion results from damage to fibers
traveling in the uncinate fasciculus from the contralateral
CFN to the ipsilateral PPRF (62,63), leading to hypometric
ipsilesional and hypermetric contralesional saccades (Fig. 2).
CFN damage also affects vertical saccades and gaze
position, since both CFNs are active during vertical saccades
(36,55,56). In unilateral lesions, the unopposed “push”
from the unaffected CFN results in ipsilesional horizontal

FIG. 2. Pathways for ocular and saccadic lateropulsion. Inhibitory climbing fibers travel from the inferior olivary nucleus (ION)
to the contralateral ocular motor vermis (OMV) and pass through the inferior cerebellar peduncle. The OMV then projects to
and exerts inhibitory control over the ipsilateral caudal fastigial nuclei (CFN). Efferents from the CFN project to the fellow CFN
and subsequently travel via the uncinate fasciculus (in the superior cerebellar peduncle) to the contralateral paramedian
pontine reticular formation (PPRF), an integral part of the brainstem saccade brainstem generator. The CFN also send
efferent projections to the superior colliculi, thalamus, rostral interstitial nucleus of the medial longitudinal fasciculus, and
mesencephalic reticular formation. In ipsipulsion, damage to the inhibitory climbing fibers from the contralateral ION to OMV
Purkinje cells leads to increased inhibition of the ipsilateral CFN, resulting in hypometric contraversive and hypermetric
ipsiversive saccades. Vertical saccades demonstrate an ipsilesional horizontal bias in saccadic ipsipulsion. Contraversive
pursuit may also be impaired in this disorder. On the other hand, contrapulsion results from damage to fibers traveling in the
uncinate fasciculus from the contralateral CFN (efferents originating from the fellow CFN), to the ipsilateral PPRF, leading to
hypometric ipsilesional and hypermetric contralesional saccades. Vertical saccades demonstrate a contralesional horizontal
bias in this condition.

90 Beh et al: J Neuro-Ophthalmol 2017; 37: 87-98

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deviation of vertical saccades. Additionally, the eyes are
often slightly deviated ipsilesionally during fixation
(48,55). In saccadic lateropulsion, vertical saccades exhibit
a curved trajectory due to cross-coupling of horizontal bias
into vertical eye movements. The horizontal bias is directed
contralesionally in contrapulsion and vice versa (1,63,64).
Further, the amplitude of horizontal misdirection may be
greater in upward compared to downward saccades (65).
The posterior inposed nuclei (PIN) fire for every saccade
(66) and receive projections from saccade-related pontine
nuclei via the paraflocculus (67,68). Each PIN, in turn,
conveys efferent projections to the contralateral superior
colliculi and interstitial nucleus of Cajal (69). In primates,
PIN inactivation results in hypermetric upward saccades
and hypometric downward saccades, as well as upward
deviation of horizontally directed saccades (70). The
cross-coupling of inappropriate vertical components into
horizontal saccades has also been observed with pontine
lesions (71), perhaps reflecting damage to the brainstem-
PIN circuitry.
Saccadic intrusions are a feature of certain disorders that
affect the cerebellum and/or brainstem. Square-wave jerks
are prominent sign in certain cerebellar disorders (e.g.,
Friedreich ataxia, spinocerebellar ataxia 8); while the precise
etiopathological basis is unclear, some have suggested that
a dysfunctional inhibitory system (which includes the
cerebellum) is to blame (1,72). Macrosaccadic oscillations
(thought to be an extreme form of saccadic hypermetria)
have been recognized in midline cerebellar lesions affecting
the CFN and are hypothesized to be due to CFN output
dysfunction (72). Ocular flutter and opsoclonus are believed
to arise in cerebellar disorders that impair Purkinje cell
inhibition of the CFN, resulting in premotor burst neuron
oscillations (1,72).
PURSUIT
The cerebellum plays a crucial role in the smooth eye
tracking of a moving target, either when the head is still
(i.e., smooth pursuit), or when the head is passively moving
with the target (i.e., VOR cancelation). Complete cerebel-
lectomy abolishes smooth pursuit in humans and monkeys
(19,73,74). The main cerebellar structures involved in pur-
suit eye movements are the flocculus-paraflocculus, OMV,
CFN, and ansiform lobule (hemisphere lobule VII). The
nodulus, uvula, and lateral cerebellar hemispheres also con-
tribute to pursuit (7,75–83).
In monkeys, bilateral flocculus and paraflocculus abla-
tion completely impairs smooth pursuit (75,80), while uni-
lateral inactivation impairs ipsilateral pursuit (84). In
humans, the paraflocculus plays a greater role in smooth
pursuit compared to the flocculus, which is predominantly
concerned with the VOR (16, 80). As part of the network
that controls smooth pursuit, the paraflocculus receives af-
ferents from the dorsolateral pontine nuclei and mossy fiber
Beh et al: J Neuro-Ophthalmol 2017; 37: 87-98
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State-of-the-Art Review
input from the vestibular nuclei, NPH, PMT, as well as
climbing fibers from the contralateral ION (16,67,85).
The OMV (which receives pursuit input from the
NRTP) is also important in pursuit tracking. In addition
to encoding gaze velocity during pursuit tracking, the OMV
Purkinje cells also respond to retinal slip velocity and hence
encode target velocity in space (1,76,86). OMV lesions
affect the initiation of smooth pursuit (reducing initial
acceleration by over 50%) and affect pursuit adaptation
to novel stimuli (87). In contradistinction, uvulonodular
lesions impair sustained pursuit without affecting pursuit
initiation (81).
CFN neurons fire most vigorously during contraversive
pursuit and just before the end of ipsiversive pursuit
(88,89). As such, their role in pursuit is similar to their role
in saccades—to accelerate contraversive pursuit and to slow
down ipsiversive pursuit so that the eyes accurately match
the target’s velocity (89). Unilateral CFN lesions impair
contralateral pursuit, while unilateral OMV damage affects
ipsilateral pursuit (87,89). Interestingly, while bilateral
OMV lesions cause bilateral pursuit deficits (87), bilateral
CFN damage leaves pursuit relatively intact (89), suggesting
that pursuit deficits from CFN lesions are the result of
asymmetry between the 2 CFN (4). In vertical pursuit,
the CFN, nodulus, and ventral uvula are more active during
downward pursuit and as such, lesions of these structures
may cause decreased downward pursuit gain (87–89).
The ansiform lobule receives input from the frontal
cortical areas (via the pontine nuclei) and from the
nucleus of the optic tract (via climbing fibers from the
ION); it is hypothesized that the ansiform lobule
may help suppress background motion induced by
smooth pursuit of a small target on the foreground
(1,90,91).
An unusual, but highly conspicuous manifestation of
cavernous angiomas of the middle cerebellar peduncle
(MCP) is cross-coupling of torsional into vertical eye
movements, resulting in direction-changing torsional
nystagmus during vertical pursuit (64). It is hypothesized
that the smooth pursuit neural network is based on a ves-
tibular labyrinthine coordinate system; vertical VOR and
pursuit signals encoded in “anterior canal coordinates” are
conveyed to the vestibulocerebellum via the MCP (92–
94). Therefore, unilateral MCP lesions would cause an
imbalance in the torsional components during vertical
pursuit, resulting in a contralesional-beating torsional nys-
tagmus during upward tracking (due to the unopposed
anterior canal signals) and a ipsilesional-beating torsional
component during downward tracking (due to the unop-
posed posterior canal signals) (64).
GAZE-HOLDING
The neural integrator is inherently “leaky” and the eye
position signal is a decaying exponential resulting in slow
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centripetal drifting of the eyes until corrective saccadic
quick-phases move the eye back to target. This is the basis
for gaze-evoked nystagmus (GEN) (1).
The flocculus-paraflocculus is tasked with improving
the performance of this inherently leaky neural integrator
(75,95). Positive feedback loops between the cerebellum
and brainstem, via connections from the NPH and
MVN, to the vestibulocerebellum and PMT, optimize
the performance of the neural integrator to maintain
eccentric gaze stability (1,96). Floccular-parafloccular le-
sions result in GEN (since the output of the neural inte-
grator cannot be maintained) and postsaccadic drifts
(because the step is not correctly matched to the pulse
command) (1). Furthermore, since the flocculus is crucial
for adaptive control of the time constant of the neural
integrator, the GEN from cerebellar disease is often
persistent (1,97). Postsaccadic drifts are another manifes-
tation of the pulse-step mismatch arising from flocculus-
paraflocculus lesions (1,75).
DOWNBEAT NYSTAGMUS
Downbeat nystagmus (DBN) is a prominent and
common manifestation of floccular-parafloccular lesions
(75,98–102). Less frequently, DBN is caused by lesions
affecting the uvula/nodulus (103), OMV (104), or
PMT (105).
Hypothetically, the upward drift consists of 2 compo-
nents—a gaze-evoked drift and an upward bias (106). The
gaze-evoked drift results from a leaky gaze-holding neural
integrator (106,107). The upward bias is hypothesized to
consist of gravity-dependent and gravity-independent com-
ponents (98,99,106). The gravity-dependent component
may be the consequence of otolith-ocular reflex hyperactiv-
ity (98) and explain the effect of position on DBN. The
pathophysiologic basis of the gravity-independent compo-
nent is less clear; the most-favored hypothesis (108) is that
the geometric configuration of the canals predisposes to an
upward ocular drift (due to relative predominance of the
anterior canal pathways), that is, normally suppressed by the
flocculus-paraflocculus. Cerebellar disease unmasks this
upward vestibular bias, resulting in DBN (108–113).
Others have proposed that neural integrator dysfunction
results in an upward shift of Listing’s plane for static eye
positions (104,106). Alternately, based on the observation
that downward pursuit is more impaired than upward pur-
suit in cerebellar disease, it is possible that floccular damage
causes an asymmetry of vertical smooth-pursuit signals,
where a preponderance of upward velocity results in spon-
taneous upward drifts (1,99,102,114,115).
VESTIBULO-OCULAR REFLEX
By detecting head motion and position and generating
compensatory eye movements, the VOR ensures that the
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angle of gaze remains on target during head motion (1,116).
The 3-neuron VOR reflex path consists of vestibular gan-
glion cells, inhibitory and excitatory oculomotor relay neu-
rons in the medial and superior vestibular nuclei and
Y-group, and the motor neurons of the ocular motor nuclei
(85). The angular VOR (AVOR) stabilizes the eyes in space
during angular head acceleration (1,117). On the other
hand, the translational VOR (TVOR), which relies on the
otolithic organs to transform linear head acceleration into
angular eye rotation, stabilizes eye position to compensate
for translational head movements (118–121).
VOR performance needs to be continuously adjusted and
optimized to correct for any change in visual circumstance
(e.g., changes in spectacle lenses, disease states that affect
balance) (1). VOR adaptation (changes in gain, direction,
and phase) is driven by error signals from retinal slip. While
vestibulocerebellar lesions do not abolish the VOR, such
lesions impair VOR adaptation (80,97,116,117,122–128).
The flocculus is essential to VOR adaptation. It receives
bilateral mossy fiber input primarily from the vestibular nuclei,
PMT, NPH, and NRTP, as well as climbing fibers from the
contralateral ION (1). The flocculus, in turn, projects to the
ipsilateral SVN, MVN, Y-group, and basal interstitial nucleus
of the cerebellum (1,129,130). Floccular Purkinje cells trans-
form vestibular and nonvestibular (efference copies, head
velocity, and retinal image slip) input into compensatory ocu-
lar motor signals that ultimately produce accurate and precise
VOR responses (1,96,121,122,125,131–136). Additionally,
the flocculus modifies VOR gain, inhibiting the horizontal
VOR during low-frequency stimulation, but facilitating it
at high-frequency stimulation (137). Following floccular dam-
age, VOR gain exceeds 1 with low frequency stimulation
(75,116,117,123,138), but is diminished at high frequencies
(75,123,137,139). Furthermore, floccular lesions may cause
VOR misdirection, as evidenced by cross-coupling of upward
bias into horizontal VOR, most likely due to disinhibition of
anterior canal pathways (116,117,140).
The nodulus and ventral uvula receive afferent signals
from the canals and otolith organs, secondary projections
from the vestibular nuclei, and tertiary input from the
ION (141–163). Uvulonodular efferent fibers project in
a topographic fashion back to the Y-group and the mag-
nocellular layer of the MVN (1,164). The nodulus and
ventral uvula are responsible for generating the TVOR
(by integrating linear head acceleration signals from oto-
lithic organs to head velocity) and controlling the velocity-
storage mechanism (which enhances the low frequency
performance of the AVOR) (1,162). Nodular lesions in
monkeys impair the sustained component of TVOR,
impair downward pursuit, and cause DBN when fixation
is eliminated (80,162). Clinically, uvulonodular lesions
cause DBN in the dark, positional horizontal nystagmus,
abnormal ocular counter-roll, and variants of the skew
deviation (1). In some cerebellar diseases, the TVOR can
be severely impaired despite relative preservation of AVOR
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 State-of-the-Art Review

(93,165), suggesting that preferential uvulonodular dam-
age occurs in certain pathologies.
The velocity-storage mechanism maintains the spatial
orientation of the AVOR by realigning the eye velocity-
vector toward the gravito-inertial acceleration vector. Since
movement in a terrestrial environment activates the canals
and otolith organs, these signals are processed in a head-based
canal-coordinate frame (rotated relative to the cardinal axes of
the head). On the other hand, velocity storage processes
information in a spatially linked coordinate frame, the yaw
axis of which is a combination of the head-vertical and
gravito-inertial acceleration vector. In other words, the
velocity-storage mechanism transforms sensory signals from
a head-fixed reference frame into a spatially linked reference
frame (1,166–174). The nodulus and ventral uvula (with
their GABAergic Purkinje projections to the ipsilateral ves-
tibular nuclei) are critical components of the velocity-storage
mechanism (171,175–179). Stimulation of the nodulus re-
duces the VOR time-constant, while stimulation of the uvula
produces nystagmus without altering the VOR time-constant
(180). Lesions of these structures prolong the velocity-storage
effect for horizontal AVOR and negate the effect of maneu-
vers that typically shorten the duration of postrotational nys-
tagmus (e.g., pitching the head forwards—“tilt-suppression

TABLE 1. Summary of the function of the 3 principal cerebellar regions involved in ocular motor control and
clinical findings arising from lesions affecting these structures
Structure Functions and Effect of Lesions of These Structures

Flocculus and paraflocculus Controls:

! Saccade adaptation
! Pursuit adaptation
! Gaze-holding
! Vestibulo-ocular reflex (VOR) adaptation, gain, up/down asymmetry and
direction
Effect of Lesions:
! Saccadic pursuit
! Gaze-evoked nystagmus, and rebound nystagmus
! Downbeat nystagmus
! Impaired VOR adaptation
! Postsaccadic drifts
Nodulus and ventral uvula Controls:
! Pursuit gain
! Integrating linear head acceleration signals from otoliths to head velocity
! Velocity storage
Effect of Lesions:
! Downbeat nystagmus in the dark
! Impaired velocity storage (leading to prolonged postrotatory nystagmus,
impaired tilt-suppression of postrotatory nystagmus, perverted head-
shaking nystagmus, and/or periodic alternating nystagmus)
! Positional nystagmus
Ocular motor vermis (OMV) and caudal Controls:
fastigial nucleus (CFN)
! Saccade adaptation and accuracy
! Smooth pursuit initiation and adaptation
! Vergence
Bilateral OMV lesions:
! Bilateral hypometric saccades, saccadic pursuit
Bilateral CFN lesions:
! Bilateral hypermetric saccades, saccadic pursuit
Unilateral OMV lesions:
! Ocular contrapulsion
! Saccadic contrapulsion
! Ipsiversive saccadic pursuit
Unilateral CFN lesions:
! Ocular ipsipulsion
! Saccadic ipsipulsion (hypometric contralateral, and hypermetric
ipsilateral saccades)
! Contraversive saccadic pursuit
Adapted from Refs. 1 and 59.

Beh et al: J Neuro-Ophthalmol 2017; 37: 87-98 93

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 State-of-the-Art Review
nystagmus”) (1,138,175,181–184). Velocity-storage dys-
function from uvulonodular damage may also account for
the cross-coupling of upward bias into horizontal eye move-
ments with low-frequency head rotation around an earth-
vertical axis, with sustained optokinetic stimulation with
the head upright, and following horizontal head-shaking
(4,116,174).
PERIODIC ALTERNATING NYSTAGMUS
Acquired periodic alternating nystagmus (PAN) is a sponta-
neous horizontal nystagmus that reverses direction at
predictable intervals (approximately 90–120 seconds);
during the brief transition period, vertical nystagmus or
square-wave jerks may occur (1). Some patients learn to
use Alexander law to partially or completely null the nys-
tagmus by using periodic head turns in the direction of
the quick phases (185,186). Smooth pursuit and optoki-
netic responses are usually impaired in PAN; convergence
is typically spared and may sometimes suppress PAN
(187,188). Uvulonodular lesions have been shown to
result in PAN in both experimental studies and in humans
(173,175). Since the nodulus and uvula normally inhibits
velocity storage, uvulonodular damage results in excessive
prolongation of rotationally induced nystagmus; normal
vestibular adaptive mechanisms are activated to correct
this abnormality but instead produce the alternating
oscillations that characterize PAN (1,187,189). Visual fix-
ation usually suppresses these oscillations; however, dis-
eases that cause PAN often affect the flocculus and
paraflocculus and impair this process (1). The ability of
baclofen to successfully abolish PAN provides pharmaco-
logical evidence that the nodulus and uvula maintain
inhibitory control over the velocity-storage mechanism
using gamma-aminobutyric acid (GABA) (1,190).
CONCLUSION
The cerebellum ensures the precision of ocular movements
and occupies a central role in all classes of eye movements,
both in real-time control and in long-term calibration and
learning (i.e., adaptation). The flocculus-paraflocculus are
crucial to VOR gain and direction, pulse-step matching for
saccades, pursuit gain, and gaze-holding. The OMV-CFN
are essential in saccadic accuracy and pursuit gain. The
nodulus and ventral uvula are involved in the low-frequency
VOR responses (Table 1). The most important, intriguing,
and impressive role of the cerebellum in eye movement
control is its ability to constantly monitor the brain’s
performance, detect errors, readjust, and recalibrate its
responses to guarantee optimal visual acuity.
STATEMENT OF AUTHORSHIP
Category 1: a. Conception and design: S. C. Beh, T. C. Frohman,
E. M. Frohman; b. Acquisition of data: S. C. Beh; c. Analysis and
94
Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.
interpretation of data: S. C. Beh. Category 2: a. Drafting the manuscript:
S. C. Beh; b. Revising it for intellectual content: S. C. Beh,
T. C. Frohman, E. M. Frohman. Category 3: a. Final approval of the
completed manuscript: S. C. Beh, T. C. Frohman, E. M. Frohman.
ACKNOWLEDGMENTS
The authors thank Jason Thean Kit Ooi for his help in
preparing the figures herein.
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