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Smooth pursuit eye movement dysfunction is considered to be a valid schizophrenia endophenotype. Recent studies have tried to refine the phenotype in order to identify the specific neurophysiological deficits associated with schizophrenia. We used a variation of the smooth eye pursuit paradigm, during which the moving target is occluded for a short period of time and subjects are asked to continue tracking. This is designed to isolate the predictive processes that drive the extraretinal signal, a process previously reported to be defective in schizophrenia patients as well as their healthy relatives. In the current study, we investigated the relationship between predictive pursuit performance indices and age, education, non-verbal IQ, schizotypy and state anxiety, depression in 795 young Greek military conscripts. State anxiety was related to better predictive pursuit performance (increase in residual pursuit gain), while disorganized schizotypy was related to deficient predictive pursuit performance (decreased residual gain). This effect was independent of the effect of disorganized schizotypy on other oculomotor functions supporting the hypothesis that predictive pursuit might be specifically affected in schizophrenia spectrum disorders and could be considered as a distinct oculomotor endophenotype.

Conscious monitoring of behavior is an essential control function for adaptation and learning. Antisaccade performance was investigated in a large sample of young healthy men in two tasks, one that required conscious error monitoring and one that did not. Conscious error monitoring did not lead to changes in error rate between the two tasks, while other antisaccade parameters were significantly modulated. Application of signal detection theory showed a large inter-individual variability in error detection sensitivity: the majority of individuals were unable to monitor antisaccade errors (chance error detection group), while a minority that successfully monitored their errors (non-chance error detection group) were worse in antisaccade performance in both tasks. These results were explained by the hypothesis of two modes of antisaccade processing favored by each one of the two groups: a mode of conscious cortical cognitive control leading to error monitoring, worse performance and no post-error adaptation and a mode of non-conscious subcortical control leading to chance error monitoring, post-error slowing and better performance of the antisaccade task. This hypothesis was corroborated by the results of the genotype analysis. Error-monitoring sensitivity in the non-chance error detection group was modulated by COMT genotype variations that in turn did not have an effect on error rate. On the other hand, DRD4 genotype variations were related to differences in antisaccade error rate while not affecting error-monitoring sensitivity.

Individuals with schizotypal personality disorder or high scores in questionnaires measuring schizotypy are at high risk for the development of schizophrenia and they also share some of the same phenotypic characteristics such as eye-tracking dysfunction (ETD). The question arises whether these individuals form a distinct high-risk group in the general population or whether schizotypy and ETD co-vary in the general population with no distinct cutoff point for a high-risk group. A large sample of military conscripts aged 18-25 were screened using oculomotor, cognitive and psychometric tools for the purposes of a prospective study on predisposing factors for the development of psychosis. Schizotypy measured using the perceptual aberration scale (PAS) and the schizotypal personality questionnaire (SPQ), anxiety and depression, measured using the Symptom Checklist 90-R, had no effect on pursuit performance in the total sample. Small groups of individuals with very high scores in schizotypy questionnaires were then identified. These groups were not mutually exclusive. The high PAS group had higher root-mean-square error scores (a quantitative measure for pursuit quality) than the total sample, and the high disorganized factor of SPQ group had lower gain and higher saccade frequencies in pursuit than the total sample. The presence of significant differences in pursuit performance only for predefined high schizotypy groups favors the hypothesis that individuals with high schizotypy might present one or more high-risk groups, distinct from the general population, that are prone to ETD as that observed in schizophrenia.

Smooth eye pursuit is believed to involve the integration of an extraretinal signal formed by an internal representation of the moving target and a retinal signal using the visual feedback to evaluate performance. A variation of the smooth eye pursuit paradigm (in which the moving target is occluded for a short period of time and subjects are asked to continue tracking) designed to isolate the predictive processes that drive the extraretinal signal was performed by 1,187 young men. The latency to the onset of change in pursuit speed, the time of decelerating eye-movement speed and the steady state residual gain were measured for each subject and correlated with measures of other oculomotor (closed-loop smooth eye pursuit, saccade, antisaccade, active fixation) and cognitive tasks (measuring sustained attention and working memory). Deceleration time increased with increasing age, while education, general IQ and cognitive variables had no effect on predictive pursuit performance. Predictive pursuit indices were correlated to those of closed-loop pursuit and antisaccade performance, but these correlations were very weak except for a positive correlation of residual gain to saccade frequency in the fixation task with distracters. This correlation suggested that the maintenance of active fixation is negatively correlated with the ability to maintain predictive pursuit speed. In conclusion, this study presents predictive pursuit performance in a large sample of apparently healthy individuals. Surprisingly, predictive pursuit was weakly if at all related to closed-loop pursuit or other oculomotor and cognitive tasks, supporting the usefulness of this phenotype in the study of frontal lobe integrity in normal and patient populations.

The facilitation of response known as the “gap effect” (a decrease of response latency), observed for saccades and antisaccades when attention is modulated prior to such eye movements, was studied in patients with schizophrenia and in controls. The hypothesis tested was whether patients would show a deficient attentional facilitation in response latency. Fifteen patients with schizophrenia and 17 healthy controls performed blocks of saccades and antisaccades in a “gap” condition and an “overlap” condition. Saccade and antisaccade response latencies as well as the error rate for antisaccades were measured for each subject. A similar gap effect (decrease in latency for the gap compared to the overlap condition) was present in the saccade task for patients and controls. In contrast the gap effect in the antisaccade task was absent in 50% of patients compared to none of the controls. This finding was interpreted as indicative of deficient preprocessing in antisaccade-specific cortical areas in schizophrenia (such as the prefrontal cortex), while visually guided saccade processing remained intact. Our results, in addition to many other recent findings, could lead to specific hypotheses on cortical dysfunction in schizophrenia.

A total of 940 young men performed a task in which they actively maintained fixation for 50 s in three conditions: a). on a visual target, b). on a visual target while distracting targets appeared briefly on the periphery and c). with no visual target present. The same individuals completed psychometric evaluation tests measuring IQ, schizotypy and current state-dependent psychopathology. The proportion of fixation time decreased and saccade frequency increased in condition b compared wih condition a, and sequentially in condition c compared with condition b. A trend towards a decrease in proportion of fixation time and increase in saccade frequency was found as the subjects maintained fixation during the task and this time-dependent deterioration of performance was again most pronounced in condition c, less so in condition b and absent in condition a. Psychometric test scores were significantly correlated with fixation performance in the population. Worse performance in all three fixation conditions was observed for individuals with lower IQ scores. A deterioration of fixation performance with time in condition b was correlated with disorganization characteristics of schizotypy, suggesting that these individuals had difficulty maintaining active fixation in the presence of increased inhibitory load. A connection of such a difficulty with the frontal lobes and their role in the control of voluntary inhibitory functions is discussed.