Smooth pursuit eye movements allow primates to keep gaze pointed at small objects moving across stationary surroundings. In monkeys trained to track a small moving target, we have injected brief perturbations of target motion under different initial conditions as probes to read out the state of the visuo-motor pathways that guide pursuit. A large eye movement response was evoked if the perturbation was applied to a moving target the monkey was tracking. A small response was evoked if the same perturbation was applied to a stationary target the monkey was fixating. The gain of the response to the perturbation increased as a function of the initial speed of target motion and as a function of the interval from the onset of target motion to the time of the perturbation. The response to the perturbation also was direction selective. Gain was largest if the perturbation was along the axis of ongoing target motion and smallest if the perturbation was orthogonal to the axis of target motion. We suggest that two parallel sets of visual motion pathways through the extrastriate visual cortex may mediate, respectively, the visuo-motor processing for pursuit and the modulation of the gain of transmission through those pathways.

The ocular-following responses elicited by brief unexpected movements of the visual scene were studied in human subjects. Response latencies varied with the type of stimulus and decreased systematically with increasing stimulus speed but, unlike those of monkeys, were not solely determined by the temporal frequency generated by sine-wave stimuli. Minimum latencies (70–75 ms) were considerably shorter than those reported for other visually driven eye movements. The magnitude of the responses to sine-wave stimuli changed markedly with stimulus speed and only slightly with spatial frequency over the ranges used. When normalized with respect to spatial frequency, all responses shared the same dependence on temporal frequency (band-pass characteristics with a peak at 16 Hz), indicating that temporal frequency, rather than speed per se, was the limiting factor over the entire range examined. This suggests that the underlying motion detectors respond to the local changes in luminance associated with the motion of the scene. Movements of the scene in the immediate wake of a saccadic eye movement were on average twice as effective as movements 600 ms later: post-saccadic enhancement. Less enhancement was seen in the wake of saccade-like shifts of the scene, which themselves elicited weak ocular following, something not seen in the wake of real saccades. We suggest that there are central mechanisms that, on the one hand, prevent the ocular-following system from tracking the visual disturbances created by saccades but, on the other, promote tracking of any subsequent disturbance and thereby help to suppress post-saccadic drift. Partitioning the visual scene into central and peripheral regions revealed that motion in the periphery can exert a weak modulatory influence on ocular-following responses resulting from motion at the center. We suggest that this may help the moving observer to stabilize his/her eyes on nearby stationary objects.

Inferior frontal eye field (FEF) projections to the dorsolateral pontine nucleus (DLPN), and corticocortical connections with the superior temporal sulcal (STS) cortex, were studied in five macaque monkeys which had received horseradish peroxidase (HRP) gel implants into the inferior prearcuate cortex (including area 45 of Walker, 1940). These connections were contrasted with those from the dorsal FEF (area 8a) in another macaque monkey. Findings of heavy inferior FEF projections to the ipsilateral DLPN (light to the contralateral DLPN) and reciprocal connections with the deep caudal bank and fundus of the superior temporal sulcus (STS), presumed to be the middle temporal (MT) visual area (Maunsell & Van Essen, 1983a), appeared to go hand in hand with more pronounced projections to the stratum superficialis of the superior colliculus (SC). In contrast, the HRP gel implant in the dorsal prearcuate cortex (area 8a of Walker, 1940) resulted in only very light projections to the ipsilateral DLPN, more pronounced projections to the dorsomedial pontine nucleus (DMPN), almost no projection to the stratum superficialis (SS), and more pronounced reciprocal connections with the upper bank of the STS, presumed to be the medial superior temporal (MST) area (Maunsell & Van Essen, 1983a). Both the inferior and dorsal FEF also had extensive reciprocal connections with the ventral intraparietal area (VIP; Maunsell & Van Essen, 1983a) in the caudal bank of the intraparietal sulcus. The correlated projections of the inferior FEF to the DLPN, MT area, and SS may explain its reported role in smooth pursuit (Lynch, 1987), in addition to its well-established role in the production of voluntary purposeful saccadic eye movements (Bruce et al., 1985).

As a step toward understanding the mechanism by which targets are selected for smooth-pursuit eye movements, we examined the behavior of the pursuit system when monkeys were presented with two discrete moving visual targets. Two rhesus monkeys were trained to select a small moving target identified by its color in the presence of a moving distractor of another color. Smooth-pursuit eye movements were quantified in terms of the latency of the eye movement and the initial eye acceleration profile. We have previously shown that the latency of smooth pursuit, which is normally around 100 ms, can be extended to 150 ms or shortened to 85 ms depending on whether there is a distractor moving in the opposite or same direction, respectively, relative to the direction of the target. We have now measured this effect for a 360 deg range of distractor directions, and distractor speeds of 5–45 deg/s. We have also examined the effect of varying the spatial separation and temporal asynchrony between target and distractor. The results indicate that the effect of the distractor on the latency of pursuit depends on its direction of motion, and its spatial and temporal proximity to the target, but depends very little on the speed of the distractor. Furthermore, under the conditions of these experiments, the direction of the eye movement that is emitted in response to two competing moving stimuli is not a vectorial combination of the stimulus motions, but is solely determined by the direction of the target. The results are consistent with a competitive model for smooth-pursuit target selection and suggest that the competition takes place at a stage of the pursuit pathway that is between visual-motion processing and motor-response preparation.

Objectives: It is increasingly important to develop predictors of treatment response and outcome in schizophrenia. Neuropsychological impairments, particularly those reflecting frontal lobe function, appear to predict poor outcome. Eye movement abnormalities probably also reflect frontal lobe deficits. We wished to see if these two aspects of schizophrenia were correlated and whether they could distinguish a treatment resistant from a treatment responsive group.

Methods: Ten treatment resistant schizophrenic patients were compared with ten treatment responsive patients on three eye movement paradigms (reflexive saccades, antisaccades and smooth pursuit), clinical psychopathology (BPRS, SANS and CGI) and a neuropsychological test battery designed to detect frontal lobe dysfunction. Ten aged-matched controls also carried out the eye movement tasks.

Results: Both treatment responsive (p = 0.038) and treatment resistant (p = 0.007) patients differed significantly from controls on the antisaccade task. The treatment resistant group had a higher error rate than the treatment responsive group, but the difference was not statistically significant. Similar poor neuropsychological test performance was found in both groups.

Conclusions: To demonstrate the biological differences characteristic of treatment resistance, larger sample sizes and wider differences in outcome between the two groups are necessary.

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°/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.

Increased frequency of anticipatory saccades during smooth pursuit eye movements is a potential marker of genetic risk for schizophrenia. Postsaccadic slowing criteria are used to separate anticipatory from other types of saccades. However, the necessary duration of slowed pursuit required to identify an anticipatory saccade remains undetermined. We explored the effect of various postsaccadic slowing duration criteria on effect size in a comparison of younger and older schizophrenic and normal adults. For large anticipatory saccades, varying the duration of postsaccadic slowing criteria did not notably change effect size. For smaller leading saccades, a limited 50-ms duration postsaccadic slowing criterion produced the largest effect size (1.54), and maintained a similar effect size across a broad age range. Leading saccades with a limited duration postsaccadic slowing criteria are a possible marker of genetic risk for schizophrenia.

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.

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°/s constant velocity task. The inclusion of small amplitude anticipatory saccades, with amplitudes of 1–4°, consistently increased effect size (largest effect size = 1.61). The inclusion of large anticipatory saccades, with amplitudes of 4° or greater, had an inconsistent impact on effect size. The separation of anticipatory saccades into leading saccades (anticipatory saccades with amplitude 1–4°) and large anticipatory saccades (amplitude >4°) deserves further exploration.

Two psychophysiological measures, poor suppression of midlatency auditory-evoked responses in a paired stimulus paradigm and ocular motor abnormalities, may index genetic liability for schizophrenia. An important feature of these measures is that both patients and their nonpsychotic relatives exhibit basically the same performance. These measures may be successful endophenotypes for schizophrenia because they assess poor response inhibition associated with dysfunction of dorsolateral prefrontal cortex circuitry. Data bearing on this hypothesis are reviewed, and it is posited that assessment of the auditory-evoked gamma band response and saccade measures of inhibitory abilities are the most valid behavioral measures of schizophrenia's neuropathological correlates. The extant data suggest that psychophysiological studies of schizophrenia can provide consistent and theoretically meaningful information for localizing neuropathology and for assessing the genetics of this complex disorder.