A model of smooth pursuit eye movement deficit associated with the schizophrenia phenotype

Abstract

Smooth pursuit eye movement (SPEM) abnormalities in schizophrenia, although well described, are poorly understood. SPEMs are initiated by motion of an object image on the retina. During initiation, the eyes accelerate until they approximate target velocity and a state of minimal retinal motion is achieved. Pursuit is maintained through predictive eye movements based on extraretinal signals and corrections based on deviations from the fovea. Here, initiation and predictive pursuit responses were used to estimate the contributions of retinal and extraretinal signals to pursuit maintenance in schizophrenia patients' relatives. Relatives exhibited normal initiation, but had lower predictive pursuit gain compared with controls. Relatives had normal gain during pursuit maintenance, presumably by greater reliance on retinal error. This was confirmed by group differences in regression coefficients for retinal and extraretinal measures, and suggests that schizophrenia SPEM deficits involve reduced ability to maintain or integrate extraretinal signals, and that retinal error may be used to compensate. DescriptorsSmooth pursuit eye movements; Schizophrenia; Predictive pursuit; Extra-retinal processing; Smooth pursuit initiation A wealth of evidence, including a recent preliminary report citing linkage of pursuit abnormality to chromosome 6p21 in relatives of schizophrenic patients, suggests that the smooth pursuit deficit marks the genetic liability to schizophrenia (Arolt et al., 1996;Clementz & Sweeney, 1990;Levy, Holzman, Matthysse, & Mendell, 1994). Although many aspects of the smooth pursuit deficit associated with the schizophrenia phenotype(s) have been well described, only recently have investigators focused on understanding the underlying neuronal mechanisms of these eye movement abnormalities (Clementz & McDowell, 1994;Ross et al., 1995;Sweeney et al., 1998). The smooth pursuit function is a highly developed and complex system served by a widely distributed neuronal network (Leigh & Zee, 1991). In recent years, many of the normal functions of the component processes of the smooth pursuit system in humans, and the underlying neurophysiological substrates in monkeys, have become known (Assad & Maunsell, 1995;Barnes, Barnes, & Chakraborti, 2000;Barton et al., 1996;Komatsu & Wurtz, 1989;Krauzlis, 2001; MacAvoy, Gottlib, & Bruce, 1991; Newsome, Wurtz, Dersteler, & Mikami, 1985;Newsome, Wurtz, & Komatsu, 1988;Schmid, Rees, Frith, & Barnes, 2001;Suh, Leung, & Kettner, 2000). Examination of smooth pursuit in schizophrenia within a neurophysiology-based framework has an advantage over traditional methods, in that it is likely to identify specific brain regions that are associated with observed deficits. In addition, the identification of a functionally specific deficit is likely to be more sensitive and specific in identifying the phenotype compared with traditional global measures.Normally, the pursuit system needs motion information to generate smooth pursuit eye movements. During initiation of smooth pursuit, ...

Smooth Pursuit Eye Movement, Prepulse Inhibition, and Auditory Paired Stimuli Processing Endophenotypes Across the Schizophrenia-Bipolar Disorder Psychosis Dimension

“…Our results support predictive pursuit gain as a putative endophenotype of psychosis thought to reflect a selective deficit in processing and/or utilizing extraretinal motion signals during SPEM. 20 The time-frequency effects in auditory ERPs observed here replicate well-established findings in the literature.…”

“…SZR, especially those with schizotypy, have been found to differ from HC on the contributions from these 2 components toward maintaining SPEM such that maintenance pursuit in SZR is dependent more on the retinal and less on extraretinal processing. 20 Such increased dependence on the retinal motion information may be due to compensation for impaired extraretinal processing (as found here in both SZR and BDR). It is possible that relatives are able to normally pursue the moving target (which is reflected in normal maintenance gain) using this compensatory mechanism.…”

“…Although prior studies suggested maintenance (closed-loop) gain as one of the SPEM components distinguishing SZR from HC (see Calkins et al 32 for review and meta-analysis), we found normal maintenance gain but selectively impaired predictive pursuit gain in both SZR and BDR. This finding may be interpreted in the light of Thaker's et al 20 model of differential contributions of pursuit initiation (driven by retinal motion) and predictive pursuit (driven by extraretinal motion processing) to maintenance pursuit. SZR, especially those with schizotypy, have been found to differ from HC on the contributions from these 2 components toward maintaining SPEM such that maintenance pursuit in SZR is dependent more on the retinal and less on extraretinal processing.…”

“…It is possible that relatives are able to normally pursue the moving target (which is reflected in normal maintenance gain) using this compensatory mechanism. 20 Furthermore, Avila et al 27 reported higher sensitivity/predictive accuracy of predictive pursuit compared with traditional maintenance gain in SZP and SZR that may also contribute to our differential SPEM findings in relatives. These findings point out at high complexity of the SPEM system and suggest that there may be more than 1 abnormality within this system associated with schizophrenia liability.…”

Trait vs. State Markers for Schizophrenia: Identification and Characterization Through Visual Processes

“…It has also been demonstrated that eye tracking dysfunction is present in bipolar patients [14][15][16] but not, or to a much lesser extent, in relatives of bipolar patients [17]. The combination of these results provides unequivocal evidence that eye tracking dysfunction is a trait characteristic in schizophrenia [18][19][20]. Genetic linkage studies suggest that eye tracking dysfunction is a susceptibility marker for schizophrenia [21,22].…”