Oculomotor abnormalities parallel cerebellar histopathology in autism. Neurology, Neurosurgery, and Psychiatry, 75, 1359-1361

University of Pittsburgh, Pittsburgh, Pennsylvania, United States
Journal of Neurology Neurosurgery & Psychiatry (Impact Factor: 6.81). 10/2004; 75(9):1359-61. DOI: 10.1136/jnnp.2003.022491
Source: PubMed


To investigate cerebellar function in autism by measuring visually guided saccades.
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 healthy individuals.
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 or latency.
The observed saccadic abnormalities suggest a functional disturbance in the cerebellar vermis or its output through the fastigial nuclei, consistent with reported cerebellar 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 development.

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    • "Many eye movement studies in autism have addressed the way in which social information affects eye movement and have not examined the characteristics of saccades . For those studies that do test the timing, quality and accuracy of saccades in autism, many have found eye movements to be slow to initiate, inaccurate and highly variable in amplitude [29] [30] [31] [32] [33] [34] [35] but some others have found no differences in latency of saccade initiation or saccade accuracy [36] [37]. "
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    ABSTRACT: This project assessed dyspraxia in high-functioning school aged children with autism with a focus on Ideational Praxis. We examined the association of specific underlying motor function including eye movement with ideational dyspraxia (sequences of skilled movements) as well as the possible role of visual-motor integration in dyspraxia. We found that compared to IQ-, sex- and age-matched typically developing children, the children with autism performed significantly worse on: Ideational and Buccofacial praxis; a broad range of motor tests, including measures of simple motor skill, timing and accuracy of saccadic eye movements and motor coordination; and tests of visual-motor integration. Impairments in individual children with autism were heterogeneous in nature, although when we examined the praxis data as a function of a qualitative measure representing motor timing, we found that children with poor motor timing performed worse on all praxis categories and had slower and less accurate eye movements while those with regular timing performed as well as typical children on those same tasks. Our data provide evidence that both motor function and visual-motor integration contribute to dyspraxia. We suggest that dyspraxia in autism involves cerebellar mechanisms of movement control and the integration of these mechanisms with cortical networks implicated in praxis.
    Behavioural brain research 04/2014; 269. DOI:10.1016/j.bbr.2014.04.011 · 3.03 Impact Factor
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    • "In recent years a number of studies have provided evidence for common generators of saccades and microsaccades (Martinez-Conde et al., 2013). The observed higher variability of eye position during fixation in the ASD participants might therefore mirror studies that reported problems in oculomotor control for saccadic eye movements (Goldberg et al., 2002; Takarae et al., 2004; Stanley-Cary et al., 2011), with higher variability of landing positions in ASD participants. "
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    ABSTRACT: A key feature of early visual cortical regions is that they contain discretely organized retinotopic maps. Titration of these maps must occur through experience, and the fidelity of their spatial tuning will depend on the consistency and accuracy of the eye movement system. Anomalies in fixation patterns and the ballistics of eye movements are well documented in autism spectrum disorder (ASD), with off-center fixations a hallmark of the phenotype. We hypothesized that these atypicalities might affect the development of visuo-spatial maps and specifically that peripheral inputs might receive altered processing in ASD. Using high-density recordings of visual evoked potentials (VEPs) and a novel system-identification approach known as VESPA (visual evoked spread spectrum analysis), we assessed sensory responses to centrally and peripherally presented stimuli. Additionally, input luminance was varied to bias responsiveness to the magnocellular system, given previous suggestions of magnocellular-specific deficits in ASD. Participants were 22 ASD children (7-17 years of age) and 31 age- and performance-IQ-matched neurotypical controls. Both VEP and VESPA responses to central presentations were indistinguishable between groups. In contrast, peripheral presentations resulted in significantly greater early VEP and VESPA amplitudes in the ASD cohort. We found no evidence that anomalous enhancement was restricted to magnocellular-biased responses. The extent of peripheral response enhancement was related to the severity of stereotyped behaviors and restricted interests, cardinal symptoms of ASD. The current results point to differential visuo-spatial cortical mapping in ASD, shedding light on the consequences of peculiarities in gaze and stereotyped visual behaviors often reported by clinicians working with this population.
    European Journal of Neuroscience 05/2013; 38(1). DOI:10.1111/ejn.12243 · 3.18 Impact Factor
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    • "Ocular motor impairment associated neurodevelopmental abnormalities of the cerebellum are often more subtle than the symptoms classically associated with cerebellar damage (Salman et al., 2006; Tavano et al., 2007; Stanley-Cary et al., 2011), such as ataxia or lesioning (Barash et al., 1999; Fielding et al., 2010; Federighi et al., 2011). Our findings support a growing body of evidence implicating greater functional disturbance of the cerebellum in HFA than AD (Takarae et al., 2004; Nayate et al., 2005; Nowinski et al., 2005; Rinehart et al., 2006a,b; Stanley-Cary et al., 2011), consistent with current understanding of the neuropathology of these disorders (Abell et al., 1999; Bauman and Kemper, 2005; McAlonan et al., 2008, 2009; Yu et al., 2011). Our findings distinguish HFA from AD on the basis of ocular motor performance, which raises the concern that combining groups on the autism spectrum with different language and cognitive development histories may obscure important motor control features. "
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    ABSTRACT: Motor impairments have been found to be a significant clinical feature associated with autism and Asperger's disorder (AD) in addition to core symptoms of communication and social cognition deficits. Motor deficits in high-functioning autism (HFA) and AD may differentiate these disorders, particularly with respect to the role of the cerebellum in motor functioning. Current neuroimaging and behavioral evidence suggests greater disruption of the cerebellum in HFA than AD. Investigations of ocular motor functioning have previously been used in clinical populations to assess the integrity of the cerebellar networks, through examination of saccade accuracy and the integrity of saccade dynamics. Previous investigations of visually guided saccades in HFA and AD have only assessed basic saccade metrics, such as latency, amplitude, and gain, as well as peak velocity. We used a simple visually guided saccade paradigm to further characterize the profile of visually guided saccade metrics and dynamics in HFA and AD. It was found that children with HFA, but not AD, were more inaccurate across both small (5°) and large (10°) target amplitudes, and final eye position was hypometric at 10°. These findings suggest greater functional disturbance of the cerebellum in HFA than AD, and suggest fundamental difficulties with visual error monitoring in HFA.
    Frontiers in Integrative Neuroscience 11/2012; 6:99. DOI:10.3389/fnint.2012.00099
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