Abnormalities in visually guided saccades suggest corticofugal dysregulation in never-treated schizophrenia

Article (PDF Available)inBiological Psychiatry 57(2):145-54 · February 2005with37 Reads
DOI: 10.1016/j.biopsych.2004.10.024 · Source: PubMed
Abstract
Previous studies have reported intact visually guided saccades in schizophrenia, but these are limited by potential acute and long-term pharmacological treatment effects, small sample sizes, and a failure to follow patients over time. Visually guided saccades were examined in 44 antipsychotic-naive patients experiencing their first episode of schizophrenia prior to treatment and again after 6, 26, and 52 weeks of antipsychotic treatment. Thirty-nine matched healthy individuals were followed over the same period. Before treatment, patients showed faster saccade latencies to unpredictable visual targets, suggesting reduced inhibitory regulation of brainstem saccade generators by neocortical attentional systems. Risperidone treatment reduced this deficit, suggesting a facilitation of attentional function, but haloperidol treatment did not. However, there was also a modest decline in saccade accuracy after risperidone treatment. The ability to sustain fixation of static central and peripheral targets was unimpaired before and after treatment. These findings provide evidence for impairments in neocortical attentional systems that cause reduced corticofugal regulation of brainstem systems in schizophrenia. This dysfunction appears to be minimized by the atypical antipsychotic risperidone but at the cost of a subtle reduction in saccade accuracy, possibly mediated via adverse effects on cerebellar vermis function.

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Available from: John A Sweeney, Jan 02, 2014
    • "Although no eye movement recordings were carried out in the present study, their contribution to the results can be considered through the available literature. As regards schizophrenia , it is generally agreed that pro-saccades and fixation are not impaired (Hutton, Joyce, Barnes, & Kennard, 2002; Reilly, Harris, Keshavan, & Sweeney, 2005). However, oculomotor disturbances have been evidenced in more complex tasks requiring scanning of visual scenes (Delerue, Hayhoe, & Boucart, 2013; Sprenger et al., 2013) or during left-to-right scanning, like in reading (Whitford et al., 2013). "
    Full-text · Article · Dec 2015 · Frontiers in Neuroscience
    • "Studies of oculomotor control may be highly informative regarding cerebellar function in ASD owing to their well-defined neurophysiological substrates, quantitative nature, high degree of heritability (Bell et al., 1994), and stability over time (Yee et al., 1998; Reilly et al., 2005; Irving et al., 2006; Lencer et al., 2008). Abnormalities of eye gaze also are part of the diagnostic criteria for ASD, and while these deficits have been well studied during social interactions, it is possible that more fundamental and earlier emerging alterations of oculomotor control could contribute to atypical patterns of eye gaze coordination among affected children (Bryson et al., 2007; Elison et al., 2013). "
    [Show abstract] [Hide abstract] ABSTRACT: The cerebellum has been repeatedly implicated in gene expression, rodent model and post-mortem studies of autism spectrum disorder (ASD). How cellular and molecular anomalies of the cerebellum relate to clinical manifestations of ASD remains unclear. Separate circuits of the cerebellum control different sensorimotor behaviors, such as maintaining balance, walking, making eye movements, reaching and grasping. Each of these behaviors has been found to be impaired in ASD, suggesting that multiple distinct circuits of the cerebellum may be involved in the pathogenesis of patients’ sensorimotor impairments. We will review evidence that the development of these circuits is disrupted in individuals with ASD and that their study may help elucidate the pathophysiology of sensorimotor deficits and core symptoms of the disorder. Preclinical studies of monogenetic conditions associated with ASD also have identified selective defects of the cerebellum and documented behavioral rescues when the cerebellum is targeted. Based on these findings, we propose that cerebellar circuits may prove to be promising targets for therapeutic development aimed at rescuing sensorimotor and other clinical symptoms of different forms of ASD.
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    • "Studies of oculomotor control may be highly informative regarding cerebellar function in 252 ASD owing to their well-defined neurophysiological substrates, quantitative nature, high degree 253 of heritability (Bell et al., 1994), and stability over time (Yee et al., 1998; Reilly et al., 2005; 254 Irving et al., 2006; Lencer et al., 2008). Abnormalities of eye gaze also are part of the diagnostic 255 criteria for ASD, and while these deficits have been well studied during social interactions, it is 256 possible that more fundamental and earlier emerging alterations of oculomotor control could 257 contribute to atypical patterns of eye gaze coordination among affected children (Bryson et al., 258 2007; Elison et al., 2013). "
    [Show abstract] [Hide abstract] ABSTRACT: The cerebellum has been repeatedly implicated in gene expression, rodent model and post-mortem studies of autism spectrum disorder (ASD). How cellular and molecular anomalies of the cerebellum relate to clinical manifestations of ASD remains unclear. Separate circuits of the cerebellum control different sensorimotor behaviors, such as maintaining balance, walking, making eye movements, reaching and grasping. Each of these behaviors has been found to be impaired in ASD, suggesting that multiple distinct circuits of the cerebellum may be involved in the pathogenesis of patients’ sensorimotor impairments. We will review evidence that the development of these circuits is disrupted in individuals with ASD and that their study may help elucidate the pathophysiology of sensorimotor deficits and core symptoms of the disorder. Preclinical studies of monogenetic conditions associated with ASD also have identified selective defects of the cerebellum and documented behavioral rescues when the cerebellum is targeted. Based on these findings, we propose that cerebellar circuits may prove to be promising targets for therapeutic development aimed at rescuing sensorimotor and other clinical symptoms of different forms of ASD.
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