Saccadic eye movement abnormalities in autism spectrum disorder indicate dysfunctions in cerebellum and brainstem

Abstract

Background: Individuals with autism spectrum disorder (ASD) show atypical scan paths during social interaction and when viewing faces, and recent evidence suggests that they also show abnormal saccadic eye movement dynamics and accuracy when viewing less complex and non-social stimuli. Eye movements are a uniquely promising target for studies of ASD as their spatial and temporal characteristics can be measured precisely and the brain circuits supporting them are well-defined. Control of saccade metrics is supported by discrete circuits within the cerebellum and brainstem - two brain regions implicated in magnetic resonance (MR) morphometry and histopathological studies of ASD. The functional integrity of these distinct brain systems can be examined by evaluating different parameters of visually-guided saccades.

Methods: A total of 65 participants with ASD and 43 healthy controls, matched on age (between 6 and 44-years-old), gender and nonverbal IQ made saccades to peripheral targets. To examine the influence of attentional processes, blocked gap and overlap trials were presented. We examined saccade latency, accuracy and dynamics, as well as the trial-to-trial variability of participants' performance.

Results: Saccades of individuals with ASD were characterized by reduced accuracy, elevated variability in accuracy across trials, and reduced peak velocity and prolonged duration. In addition, their saccades took longer to accelerate to peak velocity, with no alteration in the duration of saccade deceleration. Gap/overlap effects on saccade latencies were similar across groups, suggesting that visual orienting and attention systems are relatively spared in ASD. Age-related changes did not differ across groups.

Conclusions: Deficits precisely and consistently directing eye movements suggest impairment in the error-reducing function of the cerebellum in ASD. Atypical increases in the duration of movement acceleration combined with lower peak saccade velocities implicate pontine nuclei, specifically suggesting reduced excitatory activity in burst cells that drive saccades relative to inhibitory activity in omnipause cells that maintain stable fixation. Thus, our findings suggest that both cerebellar and brainstem abnormalities contribute to altered sensorimotor control in ASD.

Keywords: Autism spectrum disorder (ASD); Brainstem; Cerebellum; Eye movement; Saccade; Sensorimotor.

Figure 1

A representative sample of position (bottom), velocity (middle) and acceleration/deceleration (top) traces of a single visually-guided saccade. Parameters used to define the dynamics of each saccade, including the peak velocity and duration of the movement, and the acceleration and deceleration phases of the movement are shown in the velocity trace. Deg, degrees; s, seconds.

Figure 2

Cumulative frequency plot of gap and overlap saccade latencies for participants with ASD and healthy controls. Saccade latencies for overlap trials were significantly greater across participants. The extent to which latencies increased did not differ between groups, but latency variability was increased in ASD. ASD, autism spectrum disorder; Con, control.

Figure 3

Individuals with ASD showed reduced accuracy of saccades compared to healthy controls. Absolute error of saccades in degrees of visual angle was increased in individuals with ASD (top). Individuals with ASD also demonstrated increased trial-to-trial variability of saccade accuracy compared to controls (bottom). Both abnormalities were greater for larger saccades at 20 and 30 degrees compared to 10 degrees. *P <0.05; **P <0.01; ***P <0.001. ASD, autism spectrum disorder; Con, control; Deg, degrees.

Figure 4

Individuals with ASD showed reduced peak saccade velocities and increased saccade durations. Individuals with ASD had reduced peak saccade velocities compared to healthy controls (top). The duration of their movements was increased compared to controls (bottom). *P <0.05; **P <0.01. ASD, autism spectrum disorder; Con, control; Deg, degrees.

Figure 5

Individuals with ASD took longer to reach peak velocity than healthy controls. The time spent accelerating saccades was increased in ASD compared to healthy controls (top). Individuals with ASD showed similar durations of the deceleration phase of their saccades (bottom). * P <0.05; **P <0.01. ASD, autism spectrum disorder; Con, control; Deg, degrees.