Amplitude criteria and anticipatory saccades during smooth pursuit eye movements in schizophrenia.

Increased frequency of anticipatory saccades during smooth pursuit eye movements is a potential marker of genetic risk for schizophrenia even in the absence of clinical symptomology. The operational definition of anticipatory saccades has often included an amplitude criterion; however, these amplitude criteria have often differed across studies. This study reports on the effect of varying amplitude criteria on the effect size in a comparison of 29 schizophrenic adults and 29 normal subjects during a 16.7 degrees/s constant velocity task. The inclusion of small amplitude anticipatory saccades, with amplitudes of 1-4 degrees, consistently increased effect size (largest effect size = 1.61). The inclusion of large anticipatory saccades, with amplitudes of 4 degrees or greater, had an inconsistent impact on effect size. The separation of anticipatory saccades into leading saccades (anticipatory saccades with amplitude 1-4 degrees) and large anticipatory saccades (amplitude > 4 degrees) deserves further exploration.     

Mixture analysis of smooth pursuit eye movements in schizophrenia

The goal of this study was to replicate and extend previous findings indicating that the eye movement data of schizophrenic patients is best represented by the mixture of two groups, one of which has distinctly poor performance. Forty-nine schizophrenic patients and 32 normal controls had their smooth pursuit eye movements quantified by calculating the root mean square (RMS) deviation between the target and eye waveforms. Based on the finding of mixture in the distribution of RMS error, the patients were divided in to low (better tracking) and high (worse tracking) RMS error subgroups. The high RMS error patient had abnormally decreased gain. Both patient subgroups had abnormally increased frequency of catch-up saccades and increased phase lag. Distinguishing between these two subgroups may be useful in clarifying the pathophysiology of abnormal pursuit and its relationship to heterogeneity in schizophrenia.     

Stimulus characteristics influence the gain of smooth pursuit eye movements in normal subjects

Summary Impaired smooth pursuit eye movements are commonly believed to indicate a lesion of the central nervous system. Smooth pursuit performance, however, is strongly dependent on non-specific variables like cooperation, arousal and attentiveness. Therefore, disturbed smooth pursuit can be attributed either to lesions of the smooth pursuit system per se, or to the influence of non-controlled variables (non-structural disturbances). This renders the evaluation of smooth pursuit uncertain. In the present study we attempted to design a stimulus that yields smooth pursuit eye movements, which are not influenced by uncontrolled variations of state and input, for a better separation of structural lesions of the pursuit system and the effect of nonspecific variables. Our results suggest that a stimulus that leads to a centrally generated representation (percept) of motion is most suitable to elicit high gains of smooth pursuit (sigma pursuit), but only if attentiveness is optimal. Beta-motion (motion elicited by discrete steps of the target) or real target motion are capable to render the smooth pursuit performance optimal, even with low attentiveness, when the fixation point and its wider surroundings or enough discrete points in the neighbourhood move in the same direction in space.     

Judging object velocity during smooth pursuit eye movements

Our tendency to constantly shift our gaze and to pursue moving objects with our eyes introduces obvious problems for judging objects' velocities. The present study examines how we deal with these problems. Specifically, we examined when information on rotations (such as eye movements) is obtained from retinal, and when from extra-retinal sources. Subjects were presented with a target moving across a textured background. Moving the background allowed us to manipulate the retinal information on rotation independently of the extra-retinal information. The subjects were instructed to pursue the target with their eyes. At some time during the presentation the target's velocity could change. We determined how various factors influence a subject's perception of such changes in velocity. Under more or less natural conditions, there was no change in perceived target velocity as long as the relative motion between target and background was maintained. However, experiments using conditions that are less likely to occur outside the laboratory reveal how extra-retinal signals are involved in velocity judgements.     

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

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.     

Smooth pursuit eye movements in children

Smooth pursuit eye movements consists of slow eye movements that approximate the velocity of the eyes to that of a small moving target, so that target image is kept at or near the fovea. Little information on smooth pursuit is available in children. We used an infrared eye tracker to record smooth pursuit in 38 typically developing children, aged 8–19 years. Participants followed a visual target moving sinusoidally at ±10° amplitude, horizontally and vertically at 0.25 or 0.5 Hz. The mean horizontal smooth pursuit gains, the ratio of eye to target velocities, were 0.84 at 0.25 Hz and 0.73 at 0.5 Hz. Mean vertical smooth pursuit gains were 0.68 at 0.25 Hz and 0.45 at 0.5 Hz. Smooth pursuit gains were significantly lower for vertical in comparison to horizontal tracking, and for 0.5 Hz in comparison to 0.25 Hz tracking (P<0.0001). Smooth pursuit gains increased with age (P<0.01, Pearson’s correlation tests), with horizontal gains attaining reported adult values by mid adolescence. Vertical gains had large variability among participants. The median phase, the time interval between eye and target velocities, varied between 39 and 86 ms. Phase was not influenced by age. We conclude that smooth pursuit gains are lower in children than gains reported in adults. Vertical pursuit gain is significantly lower than horizontal pursuit gain. Gains improve with age and approach adult values in mid adolescence. Children have larger phases than reported adults values indicating that prediction in the smooth pursuit system is less mature in children.     

Heritability of different measures of smooth pursuit eye tracking dysfunction: a study of normal twins

Research studies have found that smooth pursuit eye movement dysfunction may serve as an index of genetic liability to develop schizophrenia. The heritability of various measures of smooth pursuit eye tracking proficiency and the saccades that occur during smooth pursuit was examined in 64 monozygotic (MZ) and 48 dizygotic (DZ) twin pairs. Two age cohorts were assessed (11-12 and 17-18 years of age). Intraclass correlations indicated significant similarity in the MZ twins for almost all measures in both age cohorts, whereas few of the DZ twin correlations attained significance. Biometrical modeling indicated that genetic mechanisms influence performance on both global and specific eye tracking measures, accounting for about 40% to 60% of the variance. These findings suggest that the underlying brain systems responsible for smooth pursuit and saccade generation during pursuit are under partial genetic control.     

Perceived motion direction during smooth pursuit eye movements

Although many studies have been devoted to motion perception during smooth pursuit eye movements, relatively little attention has been paid to the question of whether the compensation for the effects of these eye movements is the same across different stimulus directions. The few studies that have addressed this issue provide conflicting conclusions. We measured the perceived motion direction of a stimulus dot during horizontal ocular pursuit for stimulus directions spanning the entire range of 360 degrees. The stimulus moved at either 3 or 8 degrees/s. Constancy of the degree of compensation was assessed by fitting the classical linear model of motion perception during pursuit. According to this model, the perceived velocity is the result of adding an eye movement signal that estimates the eye velocity to the retinal signal that estimates the retinal image velocity for a given stimulus object. The perceived direction depends on the gain ratio of the two signals, which is assumed to be constant across stimulus directions. The model provided a good fit to the data, suggesting that compensation is indeed constant across stimulus direction. Moreover, the gain ratio was lower for the higher stimulus speed, explaining differences in results in the literature.     

Preparatory modulation of the gain of visuo-motor transmission for smooth pursuit in monkeys

Brief movement of a foveated target is known to elicit higher velocity ocular (tracking) responses if the target is in motion rather than stationary. We determined whether similar perturbations of a stationary target would have greater ocular effects if we merely increased the probability that the target might undergo sustained motion. For this, we examined the effect of interleaving trials in which the target was always stationary with trials in which the target underwent sustained motion that required the animal to track. We found that perturbation of the stationary target had a greater effect when there were interleaved trials in which the target moved, as though the gain of the visuo-motor transmission had been increased in anticipation of future tracking. Electronic Publication     

Ocular motor delayed-response task performance among patients with schizophrenia and their biological relatives

Schizophrenia patients and their relatives have saccadic abnormalities characterized by problems inhibiting a response. The dorsolateral prefrontal cortex and its associated circuitry ostensibly mediate inhibition and support correct delayed response performance. In this context, two components of delayed response task performance are of interest: memory saccade metrics and error saccades made during the delay. To evaluate these variables, an ocular motor delayed response task was presented to 23 schizophrenia patients, 25 of their first-degree biological relatives, and 19 normal subjects. The measure that best differentiated groups was an increased frequency of error saccades generated during the delay by schizophrenia subjects and relatives. Decreased memory saccade gain also characterized patients and relatives. The similar pattern of results demonstrated by the patients with schizophrenia and their relatives suggests that performance on ocular motor delayed response tasks, either alone or in combination with other saccadic variables, may provide useful information about neural substrates associated with a liability for developing schizophrenia.     

Eye movement and visual motion perception in schizophrenia I: Apparent motion evoked smooth pursuit eye movement reveals a hidden dysfunction in smooth pursuit eye movement in schizophrenia

To date, smooth pursuit eye movement in schizophrenia has only been investigated using a target stimulus in continuous motion. However, smooth pursuit can also be evoked by an oscillating jumping dot that appears to be in apparent motion and although there is no continuous motion on the retinal surface this apparently moving stimulus can effortlessly elicit smooth-pursuit eye movement. In the first of two experiments smooth pursuit eye movement was evoked by target stimuli in continuous (real) motion at seven target velocities from 5.0 to 35.0 deg/s, and in a second experiment it was measured in response to an oscillating jumping dot in apparent motion at eight target velocities from 5.0 to 25.0 deg/s in a group with mixed-symptoms in schizophrenia and in a control group. The results of Experiment 1 provided no evidence for a dysfunction in continuous motion evoked smooth pursuit eye movement in the group with schizophrenia. However, following the removal of saccadic eye movements in smooth pursuit, the group with schizophrenia showed significantly lower smooth pursuit eye velocity at target velocities from 20.0 to 35.0 deg/s. The results of Experiment 2 revealed that apparent motion evoked smooth pursuit eye velocity in the group with schizophrenia was significantly lower in comparison with normal observers at all target velocities up to 25.0 deg/s with the inclusion or exclusion of saccadic eye movements. The findings demonstrate that overall smooth pursuit eye movement evoked in response to a continuous (real) motion target in the group with schizophrenia may nevertheless contain a hidden temporal resolution and integration dysfunction that is revealed when smooth pursuit eye movement is evoked in response to an oscillating jumping dot in apparent motion. The findings also demonstrate that normal smooth pursuit eye movement in normal observers can be made to resemble the dysfunctional smooth pursuit eye movement that is naturally found in some people with schizophrenia by using a target stimulus in apparent motion.     

Localization and motion perception during smooth pursuit eye movements

We investigated the relationship between compensation for the effects of smooth pursuit eye movements in localization and motion perception. Participants had to indicate the perceived motion direction, the starting point and the end point of a vertically moving stimulus dot presented during horizontal smooth pursuit. The presentation duration of the stimulus was varied. From the indicated starting and end points, the motion direction was predicted and compared with the actual indicated directions. Both the directions predicted from localization and the indicated directions deviated from the physical directions, but the errors in the predicted directions were larger than those in the indicated directions. The results of a control experiment, in which the same tasks were performed during fixation, suggest that this difference reflects different transformations from a retinocentric to a head-centric frame of reference. This difference appears to be mainly due to an asymmetry in the effect of retinal image motion direction on localization during smooth pursuit.     

Abnormality of smooth pursuit eye movement initiation: Specificity to the schizophrenia spectrum?

Schizophrenia patients have a deficiency of smooth pursuit eye movement initiation. We addressed whether this deficit is specifically related to a predisposition for schizophrenia. Thirty-two relatives of schizophrenia patients, eight schizotypals, 13 psychiatric comparison, and 33 nonpsychiatric subjects were assessed on smooth pursuit initiation. The nonpsychiatric subjects had significantly higher eye accelerations than did subjects in the other three groups, who did not significantly differ. The relatives were subdivided into three groups: (a) those with a schizophrenia spectrum disorder ( n = 4) performed similarly to the schizotypals; (b) those with a major depression history ( n = 7) were similar to the psychiatric comparison subjects; and (c) those with no psychiatric history differed from the nonpsychiatric subjects only on 30°/s targets. There was also a significant relationship between offspring and parent eye accelerations to 30°/s targets ( r = .476). These results suggest that pursuit initiation deficits may be associated with a nonspecific, genetically transmitted neurological abnormality among schizophrenia spectrum disorder subjects.     

Characteristics of open- and closed-loop smooth pursuit responses among obsessive-compulsive disorder, schizophrenia, and nonpsychiatric individuals

Twenty obsessive-compulsive disorder patients and comparison samples of 20 schizophrenia and 20 nonpsychiatric individuals were presented with (a) a step-ramp task designed to measure smooth pursuit initiation and (b) a regular ramp task designed to measure steady-stale tracking performance. Obsessive-compulsive disorder and non-psychiatric individuals had statistically similar pursuit reaction time and average eye accelerations during the open-loop interval. They also had similar closed-loop performance. Schizophrenia patients, however, had delayed pursuit reaction times and reduced eye acceleration during the last 60 ms of the open-loop interval. These findings suggest that brain regions supporting smooth pursuit performance are unimpaired among obsessive-compulsive disorder patients. Furthermore, the deficits found in the schizophrenia patients replicate and extend the results of previous smooth pursuit studies.     

Effects of dual task demands on the accuracy of smooth pursuit eye movements

The effect of attention allocation on smooth pursuit eye movements (SPEM) was investigated. Eye movements were electrooculographically recorded in 27 healthy subjects who tracked a visual target that moved horizontally with constant or unpredictably varying velocity. In some trials, subjects performed additional auditory discrimination tasks varying in difficulty. Pursuit error decreased when attention was divided between both tasks. The pattern of results is incompatible with the assumption made in previous research that attention enhancement improves SPEM accuracy. Rather, ocular smooth pursuit appears to be executed in the automatic mode, although intentional and selective processes must contribute. Moreover, controlled attention directed to the tracking task interfered with smooth pursuit. A reinterpretation of earlier studies in which visual monitoring tasks were used to improve eye tracking is needed.     

Anticipatory smooth eye movements and predictive pursuit after unilateral lesions in human brain

Anticipatory smooth eye movements precede expected changes in target motion. It has been questioned whether anticipatory smooth eye movements are a component of the smooth pursuit system. Five subjects with unilateral brain lesions and five control subjects were tested with predictable double-ramp stimuli to determine whether these lesions have a similar effect on horizontal, visually guided smooth pursuit, anticipatory smooth eye movements, and the predictive component of smooth pursuit. All four subjects with a brain lesion involving the parietal or parietal-frontal lobe had parallel velocity asymmetries in all three forms of smooth eye movements, with lowest velocities toward the side of the lesion. A similar uniformity and magnitude of smooth eye movement directional asymmetries were not found in control subjects. Unidirectional attenuation of these three forms of smooth eye movements provides evidence that they are part of a unified smooth eye movement system.     

Scaling of smooth anticipatory eye velocity in response to sequences of discrete target movements in humans

We investigated the ability to generate anticipatory smooth pursuit to sequences of constant velocity (ramp) stimuli of increasing complexity. Previously, it was shown that repeated presentation of sequences composed of four ramps with two speeds in two directions, evoked anticipatory smooth pursuit after only one or two presentations. Here, sequences of four or six ramps, each having a choice of four speeds and either one or two directions (uni- or bi-directional) were examined. The components of each sequence were presented as discrete ramps (duration: 400 ms; randomised velocity: 10–40°/s), each starting from the centre with 1,200 ms periods of central fixation between ramps, allowing anticipatory activity to be segregated from prior eye movement. Auditory warning cues occurred 600 ms prior to each target presentation. Anticipatory smooth eye velocity was assessed by calculating eye velocity 50 ms after target onset (V ₅₀), prior to the availability of visual feedback. Despite being required to re-fixate centre during inter-ramp gaps, subjects could still generate anticipatory smooth pursuit with V ₅₀ comparable to single speed control sequences, but with less accuracy. In the steady state V ₅₀ was appropriately scaled in proportion to upcoming target velocity for each ramp component and thus truly predictive. Only one to two repetitions were required to attain a steady-state for unidirectional sequences (four or six ramps), but three or four repeats were required for bi-directional sequences. Results suggest working memory can be used to acquire multiple levels of velocity information for prediction, but its use in rapid prediction is compromised when direction as well as speed must be retained.