Abnormal Vestibulo-Ocular Reflexes and Possible Link to Cerebellar Deficits in Autism

Background: Early identification and intervention have been shown to have a significant effect on the prognosis for children with autism spectrum disorders (ASD). It is also clear that the abnormal neurobiological processes resulting in ASD occur during fetal development and/or infancy long before the onset of the classic behavioral symptoms. Thus, identification of a bio-behavioral marker that occurs early in development and is related to the neurobiology of ASD would be particularly useful. Differences in sensory processing and motor coordination have been observed in children with ASD as early as 2 to 3 years of age. Motor control differences include decreased postural stability, decreased muscle tone, delayed motor milestones and altered vestibulo-ocular reflexes. Such motor deficits may share a common dependence upon appropriate processing of vestibular sensory input. The rotational vestibulo-ocular reflex (rVOR) functions to maintain stable vision by generating oculomotor responses to angular rotation head movements. The rVOR is useful for studying vestibular related sensory motor processing in this population as it involves a relatively simple reflex system, amenable to study in children with ASD.

Objectives:  To determine whether vestibular sensory processing and related oculomotor control is compromised in ASD by testing rVOR function in ASD and typically developing (TD) children.

Methods: Fifteen children diagnosed with ASD and 16 TD children ages 6-12 participated in two types of whole body rVOR tests, performed on a computer controlled rotary chair: (1) velocity step tests (100º/second peak velocity) performed in 3 conditions (light, dark, and fixation suppression) and (2) sinusoidal harmonic acceleration tests (conducted at 0.05, 0.1 and 0.5 Hz frequencies with a peak velocity of 60º/second) performed in 2 conditions (dark and fixation suppression).  For velocity step tests we assessed post rotary nystagmus gain, time constant of decay, and symmetry.  For sinusoidal harmonic acceleration tests we assessed gain and phase lag.

Results:  We observed three main differences in rVOR metrics including: (1) Participants with ASD exhibited greater time constant of decay of post-rotary nystagmus during velocity step tests in the dark and fixation suppression conditions, compared to TD controls; (2) Participants with ASD exhibited greater per-rotary nystagmus gain during velocity step tests in the dark condition, compared to TD controls;(3) Participants with ASD greater gain during sinusoidal harmonic acceleration (SHA) tests in the dark as well as fixation suppression conditions, compared to TD controls.

Conclusions:  The current findings of greater gain and time constant of decay in participants with ASD indicate a lack of inhibition from the cerebellum to the brainstem velocity storage mechanisms in ASD. In particular, these findings indicate possible decreased Purkinje cell output to vestibular nuclei. Thus, rVOR may serve as a functional measure of pre- and post-natal neuropathological processes suspected in the cerebellum in ASD involving Purkinje cell loss and warrant further study. Furthermore, rVOR abnormalities could serve as a bio-behavioral marker if further study indicates they are reliably observed and specific to the ASD population.