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

Center for Cognitive Medicine, University of Illinois at Chicago, Chicago, Illinois 60612, USA.
Biological Psychiatry (Impact Factor: 10.26). 02/2005; 57(2):145-54. DOI: 10.1016/j.biopsych.2004.10.024
Source: PubMed


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
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    • "However, such work has been limited by the difficulty in identifying measures that are sensitive to these factors . One approach that has been successful in this regard has been the use of eye movement tasks assessing cognitive and sensorimotor functions, as these have been shown to be sensitive to changes pre-topost treatment in first-episode schizophrenia (Reilly et al., 2005; Keedy et al., 2006; Reilly et al., 2006; Harris et al., 2009) and are further advantaged by the neural system physiology being well characterized in animal and human literature (Stahl, 2004; Schiller and Tehovnik, 2005; Sweeney et al., 2007; Hutton, 2008). A key observation of change pre-to-post treatment has been reported for the predictive saccade task, a motor learning paradigm requiring shifts of gaze (saccades) to track a visual target as it alternates between two locations at a constant interval. "
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    ABSTRACT: Neurocognitive deficits are associated with most psychotic disorders, but may differ across diagnosis and by treatment status. This ambiguity is partly addressed in longitudinal pre/post treatment studies with first episode patients. Antipsychotic-naïve first-episode schizophrenia patients have shown intact performance on a predictive saccade task that assesses simple motor learning, spatial abilities, and response planning. After antipsychotic treatment, however, schizophrenia patients performing this task show a selective impairment in the accuracy of anticipatory responses, generated from learned internal representations of the task stimulus. This finding is in line with other observations of antipsychotic medication effects on frontostriatal systems, particularly dorsolateral prefrontal cortex. We sought to replicate this provocative finding with an independent sample of antipsychotic-naïve first-episode schizophrenia patients and extend it by including a group of patients with first episode bipolar disorder with psychosis (BDP). Matched healthy controls were also studied in parallel. Schizophrenia patients demonstrated intact performance pretreatment followed by impairment post-treatment for accuracy of anticipatory responses, and worse accuracy was associated with higher antipsychotic dose. BDP patients displayed saccade accuracy deficits before and after treatment and had no correlation of performance and antipsychotic dose. The findings suggest different neural alterations early in the course of each psychotic disorder, and different vulnerabilities to antipsychotic treatment effects between schizophrenia and BDP.
    Schizophrenia Research 08/2014; 159(1). DOI:10.1016/j.schres.2014.07.028 · 3.92 Impact Factor
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    • "Thus, there were no differences in the speed with which participant groups shifted attention and gaze to unpredictable visual targets (see Figure 1B). In contrast, results of a previous study on a subset of schizophrenia patients included in these analyses who were followed longitudinally (35 of the current 59 patients; Reilly et al., 2005) showed shorter visually-guided saccade latencies in the schizophrenia group compared to healthy individuals. The differences in these results are due to two patient participants in the current sample (not included in the previous study) who showed particularly long visually-guided saccade latencies, increasing the group mean by 4 msec and the standard deviation by over 10.5 msec compared to the previous investigation. "
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    ABSTRACT: Recent evidence indicates common genetic, neurobiological, and psychopharmacological aspects of schizophrenia and psychotic affective disorders. Some similarities in neurocognitive deficits associated with these disorders have also been reported. We investigated performance on antisaccade and visually-guided saccade tasks in treatment-naïve first-episode psychosis patients (schizophrenia n=59, major depression n=15, bipolar disorder n=9), matched non-psychotic major depression patients (n=40), and matched healthy individuals (n=106). All psychosis groups displayed elevated antisaccade error rates relative to healthy individuals. Antisaccade latencies were elevated in schizophrenia, but no significant error rate or latency differences were observed among psychosis groups. For schizophrenia only, shorter visually guided saccade latencies were associated with higher antisaccade error rates. Schizophrenia was also the only group without a significant relationship between visually guided and antisaccade latencies. Reflexive saccades were unimpaired except in psychotic unipolar depression, where saccades were hypometric. As in schizophrenia, antisaccade abnormalities are present in affective psychoses, even early in the course of illness and prior to treatment. Disturbances in frontostriatal systems are believed to occur in both affective psychoses and schizophrenia, potentially causing some similar cognitive abnormalities across psychotic disorders. However, the distinct pattern of dysfunction in schizophrenia across oculomotor paradigms suggests possible unique causes of their observed oculomotor performance deficits.
    Psychiatry Research 11/2009; 170(2-3):150-6. DOI:10.1016/j.psychres.2008.10.031 · 2.47 Impact Factor
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    • "Previous studies have examined RT of visually triggered saccades in patients with schizophrenia, and most of these studies have reported that the mean RT of patients is not different from that of controls (Iacono et al., 1981; Levin et al., 1982; Gale and Holzman, 2000). In a recent study Reilly et al. (2005) reported that RT in visually triggered saccades were faster for patients with schizophrenia that were drug naïve and this difference then disappeared when these patients were treated with antipsychotics. Examination of their data do not reveal differences in the variability of RT between patients and controls that were especially present for large target eccentricities even at baseline. "
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    ABSTRACT: Slower mean reaction time (RT), known as psychomotor slowing, is well documented in patients with schizophrenia. Fewer studies have shown increased variability of RT in these patients suggesting a basic difference in the distribution of RT. In this study median RT and its variability were measured for visually guided saccades performed by 53 patients and 1089 control subjects. Then average cumulative RT distributions were derived for each group and the RT distribution for each group was modeled using a decision signal rising linearly to a threshold signaling the beginning of the visually guided saccade. There was a small increase in the median RT for patients while their RTs were much more variable from trial to trial leading to a difference in the average RT distribution of the patient group. The model application led to the conclusion that this difference in the distribution of RT for patients could be attributed to a basic difference in information processing leading to the decision to move the eyes to the visually presented target. This information-processing difference could be the result of a difference in the build-up of neuronal activity involved in the generation of visually guided saccades in the frontal cortex.
    Psychiatry Research 08/2009; 168(2):129-36. DOI:10.1016/j.psychres.2008.04.015 · 2.47 Impact Factor
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