CURRENT PROGRESS IN SCHIZOPHRENIA RESEARCH: EYE MOVEMENT ABNORMALITIES IN SCHIZOPHRENIA: WHAT IS THE NATURE OF THE DEFICIT?

The presence of smooth pursuit eye movement (SPEM) abnormalities among patients with schizophrenia and their relatives has been consistently reported in the schizophrenia literature. Interest in these abnormalities is twofold. First, familial aggregation of SPEM deficits suggests that they may be useful in searching for genes related to schizophrenia by providing a neurophysiological marker of genetic vulnerability—one that can be used to identify the phenotype independent of the presence or absence of overt clinical signs and symptoms (Arolt et al., 1996). Second, localization and description of the smooth pursuit deficit in schizophrenia is likely to provide insight into the pathological changes in neuronal functioning that characterize individuals who carry the genetic liability for schizophrenia. However, to use the presence of SPEM abnormalities to search for genes and to study pathophysiology, we need to understand what is the specific nature of the deficit. SPEM is a complex behavioral response served by a widely distributed neuronal network including the occipital cortex, the medial and medial superior temporal and posterior parietal regions of the cortex, the frontal eye fields, the cerebellum, the basal ganglia, and the brain stem areas. This is shown in Figure 1. SPEMs are generated in response to the movement of a target image on the retina (i.e., retinal motion). This initial response, in combination with saccadic eye movements, allows us to capture the image of a moving object onto the fovea, where visual acuity is greatest. This phase of the response is often referred to as initiation and is primarily based on the processing of retinal motion by the medial temporal region of the cortex (Lisberger and Movshon, 1999). When the eyes have reached and are moving with the target, there is limited retinal motion; the brain uses internal representations of the motor command and previous retinal motion information (i.e., extraretinal signals) to help maintain pursuit (Barnes and Asselman, 1992). This component of the response is referred to as predictive pursuit, and is thought to involve neurons in medial superior temporal and posterior parietal regions of the cortex and in the cerebellum (Assad and Maunsell, 1995; Komatsu and Wurtz, 1989; Suh et al., 2000). Several studies of SPEM performance in schizophrenia have found that patients exhibit decreased eye acceleration during initiation (Clementz et al., 1995). Because the initiation of pursuit is based primarily on retinal motion signals, these findings suggest that SPEM abnormalities in schizophrenia reflect a deficit in retinal motion processing. This would appear consistent with psychophysical studies of motion perception, which report higher perceptual thresholds for velocity discrimination in patients with schizophrenia and their relatives (Chen et al., 1999). Alternatively, it has been shown that healthy subjects improve during initiation when targets are repeated—presumably by predicting target motion based on the motor and sensory memory of previous targets (Barnes et al., 2000). This raises the possibility that abnormal initiation in schizophrenia is related to a deficit in extraretinal signal processing. Additionally, recent studies by Turano et al. have shown that both retinal and extraretinal signals can play a role in the perception of motion (Turano and Massof, 2001), providing an alternative explanation for the findings of previous psychophysical studies of motion perception in schizophrenia. Target masking, a procedure in which the target is briefly extinguished or masked along its trajectory, has been used to study the extraretinal component of the SPEM response. During target masking, the 1 Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Box 21247, Baltimore, Maryland 21228. Send reprint requests to Dr. Thaker. Supported by NIH Grants MH49826 and MH40279. 0022-3018/02/1907–479 Vol. 190, No. 7 THE JOURNAL OF NERVOUS AND MENTAL DISEASE Printed in U.S.A. Copyright © 2002 by Lippincott Williams & Wilkins