Oculomotor abnormalities parallel cerebellar
histopathology in autism
Y Takarae, N J Minshew, B Luna, J A Sweeney
J Neurol Neurosurg Psychiatry 2004;75:1359–1361. doi: 10.1136/jnnp.2003.022491
Objective: To investigate cerebellar function in autism by
measuring visually guided saccades.
Methods: A visually guided saccade task was performed by
46 high-functioning individuals with autism with and without
delayed language acquisition, and 104 age and IQ matched
Results: Individuals with autism had increased variability in
saccade accuracy, and only those without delayed language
development showed a mild saccadic hypometria. Neither
autistic group showed a disturbance in peak saccade velocity
Conclusions: The observed saccadic abnormalities suggest a
functional disturbance in the cerebellar vermis or its output
through the fastigial nuclei, consistent with reported cere-
bellar histopathology in autism. The pattern of mild
hypometria and variable saccade accuracy is consistent with
chronic rather than acute effects of cerebellar vermis lesions
reported in clinical and non-human primate studies, as might
be expected in a neurodevelopmental disorder. The different
patterns of oculomotor deficits in individuals with autism with
and without delayed language development suggest that
pathophysiology at the level of the cerebellum may differ
depending on an individual’s history of language develop-
the posterolateral cerebellar hemispheres and adjacent
archicerebellar cortex.1Abnormalities in the inferior olive
and fastigial nuclei have been reported, which are input and
output structures of the oculomotor vermis (lobules VI and
VII).1–3Some magnetic resonance imaging (MRI) studies
have reported altered volumes of vermal lobules VI and VII.4 5
The cerebellum is crucial for eye movement control.6 7
Purkinje cells in the hemispheres and vermis optimise
saccade accuracy by influencing the onset and offset of
saccades.8–10Markedly hypometric and hypermetric saccades
are seen immediately after cerebellar lesions.11 12While
overall saccade accuracy typically improves gradually after
cerebellar lesions, increased variability in saccade accuracy
often persists after posterior vermis lesions.12 13
increased variability of saccade accuracy may provide a
useful index for neurodevelopmental abnormalities of the
cerebellum associated with autism.
The current study examined saccade dynamics and
accuracy in high-functioning individuals with autism who
did not have mental retardation. Recent genetic studies
suggest that language delay may be an endophenotypic
marker for a subgroup of individuals with pervasive devel-
opmental disorders (PDD).14 15For this reason, and because
europathological abnormalities of the cerebellum have
been a consistent histopathological finding in autism.
Reduced Purkinje cell counts are most prominent in
Asperger’s disorder, which is differentiated from autism
primarily by the absence of delayed language development,
has traditionally been described as having more prominent
motor abnormalities,16we examined oculomotor parameters
in relation to each individual’s history of delayed language
A total of 46 individuals meeting DSM-IV17criteria for autism
based on the Autism Diagnostic Interview-Revised and the
Autism Diagnostic Observation Schedule18–20participated in the
study. DSM-IV allows diagnoses of autistic disorder with or
without a history of early language delay. Of these individuals
with autism, 28 had a history of delayed language acquisition
and 18 did not. Language delay was defined as the absence of
single word utterances by 24 months and/or spoken phrases by
3 years of age. Individuals with autism were excluded if they
had an associated infectious, genetic, or metabolic disorder
such as fragile X syndrome or tuberous sclerosis.
All participants had Verbal and Full Scale IQ scores of 70 or
higher based on the age appropriate Wechsler Intelligence
Scale (table 1), and thus no participant met the DSM-IV
criteria for mental retardation. All participants were at least 8
years old (by which time the ability to make visually guided
saccades typically reaches adult levels).21
A total of 104 healthy individuals—who had no current or
past history of psychiatric or neurological disorder, birth or
developmental abnormalities, or family history of psychiatric
and neurological disorders thought to have a genetic
component—were recruited from the community through
None of the participants was taking medications known to
affect cognitive or oculomotor abilities at the time of testing,
and none had a history of head injury, birth injury, or seizure
disorder. Far acuity was normal or corrected to at least 20/40.
All participants and their guardians provided informed
Eye movement tasks
Participants were tested alone in a dark room, and instruc-
tions were provided via an intercom. Stationary visual targets
were presented in the horizontal plane on a circular arc (1 m
radius) at eye level with red light emitting diodes, each
subtending 0.2˚of visual angle. Participants were seated at
the centre of the arc with a chin rest. Eye movements were
measured using infrared reflection sensors mounted on spec-
tacle frames (Model 210; Applied Science Laboratories,
Bedford, MA). Blinks were identified using electrodes placed
immediately above and below the left eye.
Visually guided saccade task
Each trial started with a half second tone and a central target
with variable duration of 1.5–2.5 seconds. At the offset of the
central target, a peripheral target appeared 10˚to the left or
right (15 trials at each location, pseudorandomly assigned).
Peak velocity, peak acceleration and deceleration, gain (ratio
of saccade amplitude over target distance), and latency were
measured for each primary saccade.
Eye movement measurement procedure
Eye movement recordings were digitised at 500 Hz with a
14 bit A/D converter (DI-210; Dataq Instruments, Akron, OH)
and smoothed using a custom finite impulse response filter
after differentiating the position trace to calculate velocity
and acceleration. The filter had a gradual transition band
(from pass to no pass) between 20 Hz and 65 Hz for velocity
and position data, and 30 Hz and 65 Hz for acceleration data.
Trials were excluded from the analysis if blinks occurred
between 100 msec before and 70 msec after the onset of a
peripheral target. Saccades were identified when eye accel-
eration exceeded 1000˚/sec2until 25% of peak deceleration.
There was a significant group difference in saccade gain,
F2,147=3.53, p,0.05. Individuals with autism without
language delay had significantly lower saccade gain than
healthy participants, t120=2.25, p,0.05. The autistic group
with language delay did not differ from the other groups.
Analysis of absolute saccade error yielded similar results.
Peak saccade velocity
Because the hypometric saccades of some individuals with
autism would likely have lower peak velocities, we computed
the ratio of peak velocity over amplitude for each saccade
before testing for differences in peak saccade velocities across
groups. No group differences were detected.
There was no overall group difference in saccade latencies,
indicating that the individuals with autism shifted attention
and initiated eye movements toward peripheral targets as
rapidly as healthy individuals.
Acceleration and deceleration of saccades
When peak saccade acceleration and deceleration were
adjusted for saccade amplitude, there were no significant
group differences in either of these measures.
Consistency of saccade accuracy
To evaluate variability in saccade accuracy, we computed the
standard deviation of saccade gain over all trials separately
for each individual subject. There were significant group
differences in this measurement, F2,147=10.13, p,0.001.
Both, the group without language delay, t120=2.28, p,0.05,
and the group with language delay, t130=4.22, p,0.001, had
more variable saccade accuracies than healthy individuals.
The two autistic groups were not significantly different from
each other (fig 1).
We examined visually guided saccades in high functioning
individuals with autism and observed a subtle motor deficit
attributable to cerebellar dysfunction. The observation of
reduced saccade accuracy in the context of normal saccade
Demographic characteristics of the participants and eye movement measurements
No. of participants
Age (mean (SD))
Verbal IQ (mean (SD))
Performance IQ (mean (SD))
Full Scale IQ (mean (SD))
Handedness (% right)
Peak velocity in deg/sec (mean (SD))
NS when corrected for saccade
NS when corrected for saccade
NS when corrected for saccade
Latency in msec (mean (SD))
Peak acceleration in deg/sec2(mean (SD))
Peak deceleration in deg/sec2(mean (SD))17035 (3995)15711 (3552)14927 (3010)
Standard deviation of individual subjects’ saccade gain 0.090 (0.031)
0.947 (0.047)0.927 (0.056)
*Significant difference from the healthy group at p,0.05.
NS, not significant.
of the increased ‘‘within-individual’’ variability in saccade landing
positions seen in an individual with autism who had language delay, an
individual without early language delay and a healthy individual. Each
point in the figure represents the landing position of one saccade. The X
axis in the graph is organized from first (leftmost) to last (rightmost)
eccentric saccade for each of the three subjects. The solid line indicates
the 10˚ target step amplitude.
Variability in saccade landing positions. Illustrative examples
1360Takarae, Minshew, Luna, et al
latencies suggests a deficit in motor function rather than in Download full-text
Reduction in saccade accuracy has been reported in
autism,22but the sample in that study was small and
included individuals with mental retardation. Further, this
deficit was not examined in relation to clinical characteristics
such as early language development. In the present study,
individuals without language delay demonstrated mildly
hypometric (undershooting) saccades and reduced consis-
tency of saccade accuracy over trials. In contrast, individuals
with early language delay did not show a reduction in
average saccade accuracy, consistent with our previous
report.23However, this group had increased variability in
saccade accuracy caused by a mixture of hypometric and
hypermetric saccades. Normal peak saccade velocity or
acceleration suggests that the abnormalities in saccade
accuracy do not arise at the level of pontine burst neurones.
However, characterisation of saccade dynamics across larger
saccade amplitudes and using higher resolution measure-
ments is needed to rule out deficits we could not detect.
Further, the absence of prolonged saccade latencies suggests
that basal ganglia dysfunction is not the cause of the saccade
abnormalities we observed. Rather, the observed increase in
saccade variability implicates the cerebellum, which plays a
primary role in determining the accuracy of saccades.8 9This
interpretation is consistent with histopathological and
neuroimaging evidence of cerebellar abnormalities in aut-
Dysmetria of saccades is commonly seen after cerebellar
lesions. Acute lesions and inactivation of the cerebellar
vermis and caudal fastigial nuclei result in gross hypometria
and hypermetria, respectively.11 12 24However, because cere-
bellar pathology in autism is neurodevelopmental rather than
the result of an acute event, the expected pattern of
oculomotor deficits is likely to parallel chronic effects of
cerebellar lesions. Adult monkeys with experimental cere-
bellar vermis lesions show recovery over a period of months
in the ability to make accurate saccades but increased
variability in saccade accuracy remains an enduring defi-
cit.12 13This is understood to result from the absence of the
dynamic adaptive modulation of saccades by the cerebellar
vermis, which leaves the subject unable to adapt saccade
commands to compensate for ongoing subtle biomechanical
variability within the oculomotor system resulting from
factors such as muscle fatigue.7 25
The relatively subtle hypometria and increased variability
in saccade accuracy are modest relative to abnormalities
observed immediately after lesions. However, they are
clinically important in documenting abnormal cerebellar
functioning in autism because the compensatory capacity of
cerebellar sensorimotor systems is typically very robust.
Though subtle, patterns of performance were different
between the two autism groups. While those with and
without language delay showed increased variability in
saccade accuracy, only those without language delay showed
a pattern of hypometric saccades. This raises the possibility
that oculomotor control in these two groups of individuals
with autism may be fundamentally different at the level of
the cerebellum, which warrants further investigation.
Y Takarae, J A Sweeney, University of Illinois at Chicago, Chicago, IL,
N J Minshew, B Luna, University of Pittsburgh, Pittsburgh, PA, USA
This study was supported by the NICHD Collaborative Program of
Excellence in Autism HD35469, NIH grants NS33355and MH01433,
and the National Alliance for Autism Research.
Competing interests: none declared
Correspondence to: J A Sweeney, PhD, Center for Cognitive Medicine,
Department of Psychiatry (MC 913), University of Illinois at Chicago,
912 S. Wood St, Suite 235, Chicago, IL 60612-7327, USA;
Received 7 July 2003
In revised form 9 December 2003
Accepted 14 December 2003
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