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.     

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.     

Admixture analysis of smooth pursuit eye movements in probands with schizophrenia and their relatives suggests gain and leading saccades are potential endophenotypes

Abnormalities during a smooth pursuit eye movement task (SPEM) are common in schizophrenic patients and their relatives. This study assessed various components of SPEM performance in first-degree unaffected relatives of schizophrenic patients. One hundred individuals with schizophrenia, 137 unaffected first-degree relatives, and 69 normal controls completed a 16.7 degrees/s SPEM task. Smooth pursuit gain, catch-up saccades (CUS), large anticipatory saccades, and leading saccades (LS) were identified. Groups were compared with parametric and admixture analyses. Schizophrenic patients performed more poorly than unaffected relatives and normals on gain, CUS, and LS. Unaffected relatives were more frequently impaired than normals only on gain and LS. Relatives of childhood-onset and adult-onset probands had similar impairments. Gain and frequency of leading saccades may be genetic endophenotypes in childhood-onset and adult-onset 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.     

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.     

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.     

The effects of dividing attention on smooth pursuit eye tracking

Attentional processes have traditionally been closely linked to the production of saccadic eye movements, but their role in the control of smooth pursuit eye movements remains unclear. In two experiments we used dual task paradigms to vary the attentional resources available for pursuit eye tracking. In both experiments we found that attentionally demanding secondary tasks impaired smooth pursuit performance, resulting in decreased velocity and increased position error. These findings suggest that attention is important for the maintenance of accurate smooth pursuit, and do not support the hypothesis that pursuit is a relatively automatic function that proceeds optimally in the absence of attentional control. These results add weight to the suggestion that a similar functional architecture underlies both pursuit and saccadic eye movements.     

Differential effects of blinks on horizontal saccade and smooth pursuit initiation in humans

Blinks executed during eye movements affect kinetic eye movement parameters, e.g., peak velocity of saccades is decreased, their duration is increased, but their amplitude is not altered. This effect is mainly explained by the decreased activity of premotor neurons in the brainstem: omni-pause neurons (OPN) in the nucleus raphe interpositus. Previous studies examined the immediate effect of blinks directly on eye movements but not their effect when they are elicited several hundred milliseconds before the eye movements. In order to address this question we tested blinks elicited before the target onset of saccades and pursuit and compared the results to the gap effect: if a fixation light is extinguished for several hundred milliseconds, the reaction time (latency) for subsequent saccades or smooth pursuit eye movements is decreased. Monocular eye and lid movements were recorded in nine healthy subjects using the scleral search-coil system. Laser stimuli were front-projected onto a tangent screen in front of the subjects. Horizontal step-ramp smooth pursuit of 20 deg/s was elicited in one session, or 5 deg horizontal visually guided saccades in another experimental session. In one-third of the trials (smooth pursuit or saccades) the fixation light was extinguished for 200 ms before stimulus onset (gap condition), and in another third of the trials reflexive blinks were elicited by a short airpuff before the stimulus onset (blink condition). The last third of the trials served as controls (control condition). Stimulus direction and the three conditions were randomized for saccades and smooth pursuit separately. The latency of the step-ramp smooth pursuit in the blink condition was found to be decreased by 10 ms, which was less than in the gap condition (38 ms). However, the initial acceleration and steady-state velocity of smooth pursuit did not differ in the three conditions. In contrast, the latency of the saccades in the gap condition was decreased by 39 ms, but not in the blink condition. Saccade amplitude, peak velocity, and duration were not different in the three conditions. There was also no difference in blink amplitude and duration of pupil occlusion in the blink condition, neither in saccades nor in smooth pursuit. The latency reduction of smooth pursuit, but not of saccades, may neither be explained by the brief pupil occlusion nor by visual suppression, warning signals, or the startle response. Whether the effects are caused by the influence of blinks on OPNs or other premotor structures remains to be tested.     

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.     

Target selection for predictive smooth pursuit eye movements

Previous work has indicated that after exposure to a moving stimulus, people are able to produce predictive smooth eye movements prior to reappearance of the stimulus. Here, we investigated whether subjects are able to extract relevant velocity information from two simultaneously presented targets and use this information to produce a subsequent predictive response. A trial consisted of a series of two or five presentations of moving stimuli, preceded 500 ms earlier by an audio warning cue. In the first one or four presentations, subjects fixated during the presentation of two moving targets and in the final presentation they tracked a single moving target. During fixation, two moving targets were presented concurrently, originating from the fixation point and moving horizontally to the right at differing velocities (10, 20, 30 or 40°/s), with each target being presented at the same velocity throughout a trial. In the tracking presentation, the fixation cross was extinguished and only a single target was presented, which the subjects were required to track with their eyes. To cue which of the two targets would be presented, the appropriate target was presented statically at the same time as the audio warning cue. A significant relationship was found between eye velocity 100 ms after the start of the tracking target (i.e. prior to visual feedback) and the cued target velocity. Thus, subjects were able to make predictive eye movements that were of appropriate velocity for the cued target, despite fixating and being uncertain which target was relevant, during previous exposure.     

Low frequency rTMS over posterior parietal cortex impairs smooth pursuit eye tracking

The role of the posterior parietal cortex in smooth pursuit eye movements remains unclear. We used low frequency repetitive transcranial magnetic stimulation (rTMS) to study the cognitive and neural systems involved in the control of smooth pursuit eye movements. Eighteen participants were tested on two separate occasions. On each occasion we measured smooth pursuit eye tracking before and after 6 min of 1 Hz rTMS delivered at 90% of motor threshold. Low frequency rTMS over the posterior parietal cortex led to a significant reduction in smooth pursuit velocity gain, whereas rTMS over the motor cortex had no effect on gain. We conclude that low frequency offline rTMS is a potentially useful tool with which to explore the cortical systems involved in oculomotor control.     

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.     

Smooth pursuit in schizophrenia: Abnormalities of open- and closed-loop responses

A sample of 29 schizophrenia patients and 27 nonpsychiatric subjects were tested on measures of open- and closed-loop smooth-pursuit performance. Rashbass step-ramps were used to measure pursuit latency and open-loop gain. Regular ramps were used to calculate frequency and amplitude of both catch-up saccades and square-wave jerks, frequency of anticipatory saccades, and steady-state gain. Schizophrenia patients demonstrated lower open-loop gain than did nonpsychiatric subjects, an effect that was accentuated at faster target velocities. They also showed reduced steady-state gain, but only to 30%s right-moving targets. There was no evidence of saccadic abnormalities during smooth pursuit among the schizophrenia patients. These patients generated fewer square-wave jerks than did nonpsychiatric subjects for 10% left-moving targets. These results suggest an abnormality of smooth-pursuit initiation among patients with schizophrenia.     

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.     

The association between lithium carbonate and smooth pursuit eye tracking among first-episode patients with psychotic affective disorders

The association between treatment with lithium carbonate and smooth pursuit eye tracking performance was investigated in first-episode patients with psychotic affective disorders. The horizontal pursuit performance of patients with major depression and bipolar disorder who were receiving lithium carbonate was contrasted with that of patients not receiving lithium carbonate. In addition, the accuracy and quality of pursuit eye tracking was examined in bipolar patients whose lithium status changed from the time of initial testing to the time of retest 10 months later. For the combined group of depressed and bipolar patients, treatment with lithium carbonate was not associated with worse pursuit performance. Bipolar disordered patients on lithium did not differ in tracking proficiency from those not on lithium; bipolar patients whose lithium status changed from intake to retest also did not display a significant change in pursuit performance.     

Blink effects on ongoing smooth pursuit eye movements in humans

Blinks are known to affect eye movements, e.g., saccades, slow and fast vergence, and saccade-vergence interaction, in two ways: by superimposition of blink-associated eye movements and changes of the central premotor activity in the brainstem. The goal of this study was to determine, for the first time, the effects of trigeminal evoked blinks on ongoing smooth pursuit eye movements which could be related to visual sensory or premotor neuronal changes. This was compared to the effect of a target disappearing for 100–300 ms duration during ongoing smooth pursuit (blank paradigm) in order to control for the visual sensory effects of a blink. Eye and blink movements were recorded in eight healthy subjects with the scleral search coil technique. Blink-associated eye movements during the first 50% of the blink duration were non-linearly superimposed on the smooth pursuit eye movements. Immediately after the blink-associated eye movements, the pursuit velocity slowly decreased by an average of 3.2±2.1°/s. This decrease was not dependent on the stimulus direction. The pursuit velocity decrease caused by blinks which occluded the pupil more than 50% could be explained mostly by blanking the visual target. However, small blinks that did not occlude the pupil (<10% of lid closure) also decreased smooth pursuit velocity. Thus, this blink effect on pursuit velocity cannot be explained by blink-associated eye movements or by the blink having blanked the visual input. We propose that part of this effect might either be caused by incomplete visual suppression during blinks and/or a change in the activity of omnipause neurons.     

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.     

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.