Search

Background Smooth pursuit deficits are an intermediate phenotype for schizophrenia that may result from disturbances in visual motion perception, sensorimotor transformation, predictive mechanisms, or alterations in basic oculomotor control. Which of these components are the primary causes of smooth pursuit impairments and whether they are impaired similarly across psychotic disorders remain to be established. Methods First-episode psychotic patients with bipolar disorder ( n = 34), unipolar depression ( n = 24), or schizophrenia ( n = 77) and matched healthy participants ( n = 130) performed three smooth pursuit tasks designed to evaluate different components of pursuit tracking. Results On ramp tasks, maintenance pursuit velocity was reduced in all three patients groups with psychotic bipolar patients exhibiting the most severe impairments. Open loop pursuit velocity was reduced in psychotic bipolar and schizophrenia patients. Motion perception during pursuit initiation, as indicated by the accuracy of saccades to moving targets, was not impaired in any patient group. Analyses in 138 participants followed for 6 weeks, during which patients were treated and psychotic symptom severity decreased, and no significant change in performance in any group was revealed. Conclusions Sensorimotor transformation deficits in all patient groups suggest a common alteration in frontostriatal networks that dynamically regulate gain control of pursuit responses using sensory input and feedback about performance. Predictive mechanisms appear to be sufficiently intact to compensate for this deficit across psychotic disorders. The absence of significant changes after acute treatment and symptom reduction suggests that these deficits appear to be stable over time.

Background Problems with the voluntary control of behavior, such as those leading to increased antisaccade errors, are accepted as evidence of prefrontal dysfunction in schizophrenia. We previously reported that speeded prosaccade responses, i.e., shorter response latencies for automatic shifts of attention to visual targets, were associated with higher antisaccade error rates in schizophrenia. This suggests that dysregulation of automatic attentional processes may contribute to disturbances in prefrontally mediated control of voluntary behavior. Methods Twenty-four antipsychotic-naive schizophrenia patients and 30 healthy individuals completed three tasks: a no-gap prosaccade task in which subjects shifted gaze toward a peripheral target that appeared coincident with the disappearance of a central fixation target and separate prosaccade and antisaccade tasks in which a temporal gap or overlap of the central target offset and peripheral target onset occurred. Sixteen patients were retested after 6 weeks of antipsychotic treatment. Results Patients’ prosaccade latencies in the no-gap task were speeded compared with healthy individuals. While patients were not atypical in the degree to which response latencies were speeded or slowed by the gap and overlap manipulations, those patients with diminished attentional engagement on the prosaccade task (i.e., reduced overlap effect) had significantly elevated antisaccade error rates. This effect persisted in patients evaluated after antipsychotic treatment. Conclusions This study provides evidence that a reduced ability to engage attention may render patients more distracted by sensory inputs, thereby further compromising impaired executive control during antisaccade tasks. Thus, alterations in attentional and executive control functions can synergistically disrupt voluntary behavioral responses in schizophrenia.

Background This study sought to replicate previous findings of worsened performance on a translational spatial working memory task among antipsychotic-naive first-episode schizophrenia patients after antipsychotic treatment and to extend these findings by examining whether changes in the allocation of covert attention contribute to this effect. Methods Fourteen antipsychotic-naive schizophrenia patients performed an oculomotor delayed response task before and 6 weeks after antipsychotic treatment (risperidone n = 11; olanzapine n = 3). Fifteen matched healthy individuals were studied in parallel. Results Patients’ pretreatment deficit in accurately remembering spatial locations was exacerbated by antipsychotic treatment, consistent with previous findings; however, this occurred only when covert attention was directed away from remembered locations during delay periods. Conclusions Disruption in the allocation of covert attention might contribute to patients’ decline in spatial working memory after antipsychotic treatment. Alterations in prefrontal dopaminergic systems or reduced thalamocortical drive might account for this apparent adverse cognitive effect of antipsychotic treatment.

Background 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. Methods 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. Results 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. Conclusions 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.