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  • Addiction, Drugs
  • Information from Lay-Language Summaries is Embargoed Until the Conclusion of the Scientific Presentation

    049—Human Biomarkers of Autism

    Saturday, November 09, 2013, 1:00 pm - 5:00 pm

    49.09: Eye movement abnormalities in autism spectrum disorder implicate sensorimotor and cognitive control brain systems

    Location: Halls B-H

    *L. M. SCHMITT, M. W. MOSCONI, J. A. SWEENEY;
    Psychiatry, UT Southwestern Med. Ctr., Dallas, TX

    Abstract Body: Background
    Eye movement abnormalities, including reduced saccade accuracy and impaired top-down control of prepotent responses, have been identified in individuals with autism spectrum disorder (ASD). Here, we conducted a detailed analysis of saccade metrics in individuals with ASD. We utilized ‘gap’ and ‘overlap’ tasks to investigate attentional control of saccade latencies in PRO and ANTI saccade tasks.
    Methods
    Sixty-eight individuals with ASD and 50 healthy controls, matched on age (6-44 years), gender and nonverbal IQ performed PRO and ANTI saccade tasks. Each task trials with a 200 ms delay between center fixation offset and peripheral target onset (GAP), or a 200 ms OVERLAP between these cues. We examined the accuracy, latency, velocity, duration, acceleration, and deceleration of saccades, as well as their variability across trials during the PRO task. The rate of inhibition errors and saccade latencies were examined during the ANTI task.
    Results
    During the PRO task, individuals with ASD showed increased variability across trials in the accuracy, latency, velocity, and peak deceleration of their saccades. In addition, subjects with ASD made saccades with skewed waveforms characterized by a disproportionate amount of time accelerating compared to decelerating their movements. During the ANTI task, individuals with ASD made more inhibition errors, and their increased rate of errors was associated with shorter saccade latencies during OVERLAP trials.
    Conclusions
    Evidence of increased trial-to-trial variability in saccade accuracy and velocity and altered saccade acceleration in ASD indicate alterations in cerebellar-brainstem systems. Findings of increased ANTI error rates associated with shorter saccade latencies in ASD implicates dysfunctions within fronto-striatal-collicular systems involved in strategically delaying responses. Thus, these findings indicate disruptions in both subcortical sensorimotor systems and higher order cognitive control systems in ASD.

    Lay Language Summary: Lay Summary: Eye movement abnormalities in autism spectrum disorder implicate sensorimotor and executive brain systems
    Eye gaze abnormalities during social interactions are a defining feature of autism spectrum disorder (ASD). Our research indicates, however, that deficits in controlling eye movements are not restricted to social exchanges, suggesting that individuals with ASD also exhibit fundamental impairments in sensorimotor control. Specifically, we found that eye movements in ASD were characterized by reduced accuracy, slower velocities, and longer durations. Individuals with ASD also showed difficulty suppressing unwanted eye movements indicating compromised executive control of behavior.
    Prevalence rates of ASD have risen exponentially in the past 10 years, but our understanding of the brain mechanisms responsible for this disorder is limited. Impaired social-communication abilities and restricted, repetitive behaviors are the core features of ASD, but the majority of individuals with ASD also show movement abnormalities that may underlie some of individuals’ social-communication deficits. Because the neurophysiological bases of sensorimotor processes are well defined via non-human primate studies, examinations of sensorimotor deficits in ASD are uniquely promising for identifying brain mechanisms in this disorder.
    In the present study, we examined 65 individuals with ASD and 43 healthy control individuals performing visually guided prosaccade (PRO) and antisaccade (ANTI) tasks. In the PRO task, individuals were instructed to rapidly shift their eye gaze (i.e., make a saccade) from a central target to a target of variable location on the left or right side. Controlling saccades, including ensuring their accuracy and monitoring the speed with which they are performed, involves dynamic changes in brain circuitry within the cerebellum and brainstem nuclei. The ANTI task was performed to determine how well individuals could inhibit, or suppress a saccade when instructed to look in the opposite direction of a peripheral target. This task involves top-down control from prefrontal and striatal brain circuits, and thus engages brain networks independent from those supporting the saccades elicited during the PRO task. Each task included conditions that differed in the relative timing of central target disappearance and peripheral target appearance. This manipulation allowed us to examine the relative influence of attentional factors on saccade performance in ASD.
    We found that saccade accuracy was both reduced and more variable across trials in individuals with ASD. Individuals with ASD also made saccades with reduced velocity, and it took them longer to complete their movements. The rate at which individuals with ASD accelerated their saccades was reduced as well, implicating dysfunction within cerebellar-brainstem circuits supporting rapid and accurate shifts in eye gaze in ASD. Reduced rates of eye movement acceleration were associated with handwriting impairments suggesting that eye movement deficits may disrupt everyday tasks requiring precise hand-eye coordination. In addition to these fundamental deficits in motor control, we found that individuals with ASD made more inhibition errors during the ANTI task. These findings indicate that higher-order brain systems involved in behavioral control also may be affected in ASD. For subjects with ASD, reduced ability to inhibit unwanted eye movements was related to failures in strategically delaying the initiation of saccades in order to improve performance. In contrast, healthy controls consistently delayed the onset of their eye movements during the ANTI task indicating a strategic re-prioritization of accuracy over speed.
    Our findings provide novel evidence that dysfunction of cerebellar-brainstem and frontostriatal brain systems supporting sensorimotor processes may play a fundamental role in the development of ASD. Each of these brain systems has been implicated previously in post-mortem brain and MRI anatomical studies. Future studies of the development of these dysfunctions, and their relationship to the dysmaturation of core social-communication features in this disorder are needed.