The overall aim is to clarify the nature or the eye-tracking performance deficit seen in schizophrenia. The proposed work will be performed at a large clinical research center devoted to the study of schizophrenia and affective disorders. Eye movement recordings with high-resolution infrared oculography have already been obtained in reasonably large and well- characterized groups of patients with schizophrenia or affective disorders, and normal controls. Patients with schizophrenia have been studied after withdrawal from medication and after treatment either with typical neuroleptics or the atypical neuroleptic clozapine. Patients with affective disorders have been studied either in the unmedicated condition or during treatment with antidepressants. Smooth pursuit tracking, saccadic tracking and ocular fixation have all been recorded in the same subjects in the same session. Methods for assessment of smooth pursuit, saccadic tracking and ocular fixation are largely in place, although refinements are planned. These methods are based on a neuroophthalmologic approach and offer an improvement over previous global assessments of performance for two reasons. First, these methods will aid in the description of abnormal performance in terms of the systems which control ocular motor function. Also, with this approach, results can eventually be related to brain mechanisms which underly ocular motor function. Two years of support are requested to allow or data analysis and manuscript preparation. The following issues will be addressed: 1) Is the low pursuit gain seen in schizophrenia specific to this disorder vis-a-vis affective disorder? 2) Is the deficit in gain a function of average performance only, or does it extend to optimal performance? 3) Do patients with schizophrenia tolerate more position error during smooth pursuit and ocular fixation? 4) Are there effects of typical and atypical neuroleptics that can be discerned with these improved methods? (Preliminary data is presented which suggests that clozapine improves the consistency of smooth pursuit performance). 5) Do the eye-tracking data provide support for the theory that schizophrenia is a disorder of cerebral laterality? 6) Do patients with schizophrenia perform saccadic tracking tasks abnormality? 7) Do patients with schizophrenia have increased rates of saccadic intrusion during ocular fixation? 8) Which of the three tracking tasks, and which variables, are most useful in the discrimination of patients with schizophrenia from patients with affective disorders or normal controls?
