Antisaccade Responses Research Articles

Anti-saccades reveal impaired attention control over negative social evaluation in individuals with depressive symptoms

Depressed individuals are excessively sensitive to negative information but blunt to positive information, which has been considered as vulnerability to depression. Here, we focused on inhibitory control over attentional bias on social evaluation in individuals with depression. We engaged individuals with and without depressive symptoms (categorized by Beck Depression Inventory-II) in a novel attention control task using positive and negative evaluative adjectives as self-referential feedback given by social others. Participants were instructed to look at sudden onset feedback targets (pro-saccade) or the mirror location of the targets (anti-saccade) when correct saccade latencies and saccade errors were collected. The two indices showed that while both groups displayed longer latencies and more errors for anti-saccade relative to pro-saccade responses depressed individuals spent more time reacting correctly and made more errors than non-depressed individuals in the anti-saccade trials and such group differences were not observed in the pro-saccade trials. Although group differences in correct anti-saccade latencies were found for both positive and negative stimuli, depressed individuals spent more time making correct anti-saccade responses to negative social feedback than to positive ones whereas non-depressed individuals featured longer correct anti-saccade latencies for positive relative to negative evaluations. Our results suggest that depressed individuals feature an impaired ability in attention control for self-referential evaluations, notably those of negative valence, shedding new light on depression-distorted self-schema and corresponding social dysfunctions.

Uncorrected errors and correct saccades in the antisaccade task distinguish between early-stage Alzheimer’s disease dementia, amnestic mild cognitive impairment, and normal aging

ABSTRACT Alzheimer’s disease (AD) dementia is a degenerative illness that is characterized by a gradual decline in cognitive abilities. Amnestic mild cognitive impairment (aMCI) is seen as a precursor to AD. The changes in antisaccade performance that can be seen in MCI may provide important clues in the early detection of AD. Therefore, the antisaccade deficits in AD and aMCI remain a research question. This study aimed to examine antisaccade responses and the relationship between antisaccade and cognitive function in AD, aMCI, and healthy controls (HC). This study included 30 patients with early-stage AD, 34 with aMCI, and 32 HC. Patients with AD showed higher rates of uncorrected error, anticipatory saccades and corrected errors, as well as decreased correct saccade rates, and shortened saccade latency compared to aMCI and HC in this study. Patients with aMCI exhibited increased rates of express saccades relative to HC. The antisaccade task and cognitive domains were found to be significantly related. Our study showed that the rate of correct saccades has the capacity to distinguish AD from HC with 87% sensitivity and 86% specificity (AUC = 0.93, p < 0.001). In addition, the rate of uncorrected errors was found to be capable of distinguishing AD from HC with 84% sensitivity and 83% specificity (AUC = 0.91, p < 0.001). This study presented promising findings that these parameters can be used clinically to differentiate AD and aMCI from healthy older individuals.

Pubertal development underlies optimization of inhibitory control through specialization of ventrolateral prefrontal cortex

Inhibitory control improves into young adulthood after specialization of relevant brain systems during adolescence. However, the biological mechanisms supporting this unique transition are not well understood. Given that adolescence is defined by puberty, we examined relative contributions of chronological age and pubertal maturation to inhibitory control development. 105 8–19-year-olds completed 1–5 longitudinal visits (227 visits total) in which pubertal development was assessed via self-reported Tanner stage and inhibitory control was assessed with an in-scanner antisaccade task. As expected, percentage and latency of correct antisaccade responses improved with age and pubertal stage. When controlling for pubertal stage, chronological age was distinctly associated with correct response rate. In contrast, pubertal stage was uniquely associated with antisaccade latency even when controlling for age. Chronological age was associated with fMRI task activation in several regions including the right dorsolateral prefrontal cortex, while puberty was associated with right ventrolateral prefrontal cortex (VLPFC) activation. Furthermore, task-related connectivity between VLPFC and cingulate was associated with both pubertal stage and response latency. These results suggest that while age-related developmental processes may support maturation of brain systems underlying the ability to inhibit a response, puberty may play a larger role in the effectiveness of generating cognitive control responses.

Deficits in saccadic eye movements differ between subtypes of patients with mild cognitive impairment

ABSTRACT Introduction: Mild cognitive impairment (MCI) is known to be heterogeneous in its cognitive features and course of progression. Whilst memory impairment is characteristic of amnestic MCI (aMCI), cognitive deficits other than memory can occur in both aMCI and non-amnestic MCI (naMCI) and accurate assessment of the subtypes of MCI is difficult for clinicians without the application of extensive neuropsychological testing. In this study, we examine metrics derived from recording of reflexive and voluntary saccadic eye movements as a potential alternative method for discriminating between subtypes and assessing cognitive functions in MCI. Method: A total of 29 MCI patients and 29 age- and education-matched healthy controls (HCs) participated in the cross-sectional study. We recorded horizonta l and vertical pro-saccades and anti-saccade responses. All the participants also completed a comprehensive neuropsychological tests battery. Results: Significant differences in saccadic eye movement were found between the subtypes of MCI and HCs. Patients with aMCI had a higher percentage of short latency “express” saccades than HCs. We found strong associations between saccadic reaction times and cognitive domains, including executive functions and attention. The mini-mental state examination (MMSE) was also found to correlate with uncorrected errors in the anti-saccade task. Conclusions: The increased proportion of saccades in the express latency range in aMCI may be indicative of problems with cognitive inhibitory control in these patients. A focus on this and other saccade metrics in the preclinical and prodromal stages of dementia may help to predict the clinical progression of the disease and direct interventions for the management of MCI. The clinical significance of saccadic eye movement impairments in MCI is not yet fully understood and should be investigated in further studies using larger samples.

A novel variation of the Stroop task reveals reflexive supremacy of peripheral over gaze stimuli in pro and anti saccades.

A long-standing controversy in social attention debates whether gaze-of-another induces reflexive shifts of one's own attention. In attempting to resolve this controversy, we utilized a novel Stroop task, the PAT Stroop, in which pro- and anti-saccade (PAT) responses are made to competing gaze and peripheral stimuli. The first experiment demonstrated a "Stroop effect" for peripheral stimuli, i.e. peripheral distractors interfered with gaze triggers, but gaze distractors did not interfere with peripheral triggers. These results were replicated in the second experiment, which also negated the possibility that the mere display and practice of the "clean PAT" influenced the results. Thus, the use a new PAT Stroop task demonstrated reflexive supremacy of peripheral stimuli over gaze stimuli. This novel variant of the Stroop task demonstrated similar characteristics to the classic color naming Stroop - i.e. an asymmetrical pattern, and again showed the utility and versatility of stoop-like tasks in probing mental tasks.

A preliminary analysis of biomechanics and saccadic responses for concussion

Background Concussion is an injury that occurs in non-sporting and sporting environments. To determine improved clinical methods for identifying this injury, it is important to develop and understand how the impact event results in quantifiable differences in brain functioning—functioning that has been quantified in the past using saccadic measures. The purpose of this research was to examine the relationships between oculomotor deficits, specifically antisaccade responses, and the biomechanics of impact for a concussion. Methods Participants underwent a diffusion tensor imaging protocol as well as saccadic testing to determine differences in brain functioning in comparison to controls. The injury event was then reconstructed in laboratory using physical and finite element models to determine the biomechanics of the impact and brain tissue strain. Relationships between the biomechanical variables and antisaccade responses were then examined. Results The diffusion tensor imaging analyses found that there was a decrease in radial diffusivity and axial diffusivity found in the cerebral peduncle (p &lt; 0.05) and cingulum hippocampus (p &lt; 0.05), respectively. There was an increase in the axial diffusivity for the corona radiata (p &lt; 0.05). The saccadic testing found an increase in mean latency for the concussed group (p &lt; 0.05). The results indicated no significant relationship between mean latency, duration, amplitude and peak velocity antisaccade measures and the biomechanical variables. This may have been influenced not only by a lack of sensitivity in biomechanical variable to antisaccade responses, but also to these responses being affected by factors other than injury such as attentiveness and wakefulness. Conclusion While the sample of this research was small, this research suggests that to improve the understanding of the relationship between impact biomechanics and concussion, methods that can quantify the damage to brain structures through imaging, such as diffusion tensor imaging, may be more appropriate.

Conflict Resolution as Near-Threshold Decision-Making: A Spiking Neural Circuit Model with Two-Stage Competition for Antisaccadic Task.

Automatic responses enable us to react quickly and effortlessly, but they often need to be inhibited so that an alternative, voluntary action can take place. To investigate the brain mechanism of controlled behavior, we investigated a biologically-based network model of spiking neurons for inhibitory control. In contrast to a simple race between pro- versus anti-response, our model incorporates a sensorimotor remapping module, and an action-selection module endowed with a “Stop” process through tonic inhibition. Both are under the modulation of rule-dependent control. We tested the model by applying it to the well known antisaccade task in which one must suppress the urge to look toward a visual target that suddenly appears, and shift the gaze diametrically away from the target instead. We found that the two-stage competition is crucial for reproducing the complex behavior and neuronal activity observed in the antisaccade task across multiple brain regions. Notably, our model demonstrates two types of errors: fast and slow. Fast errors result from failing to inhibit the quick automatic responses and therefore exhibit very short response times. Slow errors, in contrast, are due to incorrect decisions in the remapping process and exhibit long response times comparable to those of correct antisaccade responses. The model thus reveals a circuit mechanism for the empirically observed slow errors and broad distributions of erroneous response times in antisaccade. Our work suggests that selecting between competing automatic and voluntary actions in behavioral control can be understood in terms of near-threshold decision-making, sharing a common recurrent (attractor) neural circuit mechanism with discrimination in perception.

Looking away: distractor influences on saccadic trajectory and endpoint in prosaccade and antisaccade tasks

Successful target selection often occurs concurrently with distractor inhibition. A better understanding of the former thus requires a thorough study of the competition that arises between target and distractor representations. In the present study, we explore whether the presence of a distractor influences saccade processing via interfering with visual target and/or saccade goal representations. To do this, we asked participants to make either pro- or antisaccade eye movements to a target and measured the change in their saccade trajectory and landing position (collectively referred to as deviation) in response to distractors placed near or far from the saccade goal. The use of an antisaccade paradigm may help to distinguish between stimulus- and goal-related distractor interference, as unlike with prosaccades, these two features are dissociated in space when making a goal-directed antisaccade response away from a visual target stimulus. The present results demonstrate that for both pro- and antisaccades, distractors near the saccade goal elicited the strongest competition, as indicated by greater saccade trajectory deviation and landing position error. Though distractors far from the saccade goal elicited, on average, greater deviation away in antisaccades than in prosaccades, a time-course analysis revealed a significant effect of far-from-goal distractors in prosaccades as well. Considered together, the present findings support the view that goal-related representations most strongly influence the saccade metrics tested, though stimulus-related representations may play a smaller role in determining distractor-based interference effects on saccade execution under certain circumstances. Further, the results highlight the advantage of considering temporal changes in distractor-based interference.

Potential effects of reward and loss avoidance in overweight adolescents.

Reward system and inhibitory control are brain functions that exert an influence on eating behavior regulation. We studied the differences in inhibitory control and sensitivity to reward and loss avoidance between overweight/obese and normal-weight adolescents. We assessed 51 overweight/obese and 52 normal-weight 15-y-old Chilean adolescents. The groups were similar regarding sex and intelligence quotient. Using Antisaccade and Incentive tasks, we evaluated inhibitory control and the effect of incentive trials (neutral, loss avoidance, and reward) on generating correct and incorrect responses (latency and error rate). Compared to normal-weight group participants, overweight/obese adolescents showed shorter latency for incorrect antisaccade responses (186.0 (95% CI: 176.8-195.2) vs. 201.3 ms (95% CI: 191.2-211.5), P < 0.05) and better performance reflected by lower error rate in incentive trials (43.6 (95% CI: 37.8-49.4) vs. 53.4% (95% CI: 46.8-60.0), P < 0.05). Overweight/obese adolescents were more accurate on loss avoidance (40.9 (95% CI: 33.5-47.7) vs. 49.8% (95% CI: 43.0-55.1), P < 0.05) and reward (41.0 (95% CI: 34.5-47.5) vs. 49.8% (95% CI: 43.0-55.1), P < 0.05) compared to neutral trials. Overweight/obese adolescents showed shorter latency for incorrect responses and greater accuracy in reward and loss avoidance trials. These findings could suggest that an imbalance of inhibition and reward systems influence their eating behavior.

Heritability and molecular genetic basis of antisaccade eye tracking error rate: a genome-wide association study.

Antisaccade deficits reflect abnormalities in executive function linked to various disorders including schizophrenia, externalizing psychopathology, and neurological conditions. We examined the genetic bases of antisaccade error in a sample of community-based twins and parents (N = 4,469). Biometric models showed that about half of the variance in the antisaccade response was due to genetic factors and half due to nonshared environmental factors. Molecular genetic analyses supported these results, showing that the heritability accounted for by common molecular genetic variants approximated biometric estimates. Genome-wide analyses revealed several SNPs as well as two genes-B3GNT7 and NCL-on Chromosome 2 associated with antisaccade error. SNPs and genes hypothesized to be associated with antisaccade error based on prior work, although generating some suggestive findings for MIR137, GRM8, and CACNG2, could not be confirmed.

Response selection in prosaccades, antisaccades, and other volitional saccades

Saccades made to the opposite side of a visual stimulus (antisaccades) and to central cues (simple volitional saccades) both require active response selection but whether the mechanisms of response selection differ between these tasks is unclear. Response selection can be assessed by increasing the number of response alternatives: this leads to increased reaction times when response selection is more demanding. We compared the reaction times of prosaccades, antisaccades, saccades cued by a central arrow, and saccades cued by a central number, in blocks of either two or six possible responses. In the two-response blocks, reaction times were fastest for prosaccades and antisaccades, and slowest for arrow-cued and number-cued saccades. Increasing response alternatives from two to six caused a paradoxical reduction in reaction times of prosaccades, had no effect on arrow-cued saccades, and led to a large increase in reaction times of number-cued saccades. For antisaccade reaction times, the effect of increasing response alternatives was intermediate, greater than that for arrow-cued saccades but less than that for number-cued saccades. We suggest that this pattern of results may reflect two components of saccadic processing: (a) response triggering, which is more rapid with a peripheral stimulus as in the prosaccade and antisaccade tasks and (b) response selection, which is more demanding for the antisaccade and number-cued saccade tasks, and more automatic when there is direct stimulus-response mapping as with prosaccades, or over-learned symbols as with arrow-cued saccades.

Consider the context: Blocked versus interleaved presentation of antisaccade trials

Conclusions about the cognitive and neural requirements of saccade control may differ as a result of stimulus presentation method. This issue was examined in the current study by evaluating behavioral differences in pro- and antisaccade responses among 12 healthy young adults as a function of task presentation method, length of cue-to-target interval, and previous trial type. A 1-s cue-to-target interval fostered goal neglect, indicated by an increase in uncorrected errors and reaction times for "error" saccades. There was also a strong relationship between speed of visual orienting (prosaccade latencies) and failed inhibition (antisaccade errors) for the simultaneous condition. Interestingly, only the simultaneous condition produced task switch costs (on saccade latencies and error response percentages). The saccadic task presentation method, therefore, can influence conclusions about the cognitive operations supporting successful performance.

ERP indices of persisting and current inhibitory control: A study of saccadic task switching

Previous studies have found that inhibition of a biologically dominant prepotent response tendency is required during the execution of a less familiar, non-prepotent response. However, the lasting impact of this inhibition and the cognitive mechanisms to flexibly switch between prepotent and non-prepotent responses are poorly understood. We examined the neurophysiological (ERP) correlates of switching between prosaccade and antisaccade responses in 22 healthy volunteers. The behavioural data showed significant switch costs in terms of response latency for the prosaccade task only. These costs occurred exclusively in trials when preparation for the switch was limited to 300 ms, suggesting that inhibition of the prepotent prosaccade task either passively dissipated or was actively overcome during the longer 1000 ms preparation interval. In the neurophysiological data, a late frontal negativity (LFN) was visible during preparation for a switch to the prosaccade task that was absent when switching to the antisaccade task, which may reflect the overcoming of persisting inhibition. During task implementation both saccade types were associated with a late parietal positivity (LPP) for switch relative to repetition trials, possibly indicating attentional reorienting to the switched-to task, and visible only with short preparation intervals. When the prosaccade and antisaccade task were contrasted directly during task implementation, the antisaccade task exhibited increased stimulus-locked N2 and decreased P3 amplitudes indicative of active inhibition. The present findings indicate that neurophysiological markers of persisting and current inhibition can be revealed using a prosaccade/antisaccade-switching task.

Frontoparietal Activation With Preparation for Antisaccades

Several current models hold that frontoparietal areas exert cognitive control by biasing task-relevant processing in other brain areas. Previous event-related functional magnetic resonance imaging (fMRI) studies have compared prosaccades and antisaccades, which require subjects to look toward or away from a flashed peripheral stimulus, respectively. These studies found greater activation for antisaccades in frontal and parietal regions at the ends of long (>or=6 s) preparatory periods preceding peripheral stimulus presentation. Event-related fMRI studies using short preparatory periods (<or=4 s) have not found such activation differences except in the frontal eye field. Here, we identified activation differences associated with short (1-s) preparatory periods by interleaving half trials among regular whole trials in a rapid fMRI design. On whole trials, a colored fixation dot instructed human subjects to make either a prosaccade toward or an antisaccade away from a peripheral visual stimulus. Half trials included only the instruction and not peripheral stimulus presentation or saccade generation. Nonetheless, half trials evoked stronger activation on antisaccades than on prosaccades in the frontal eye field (FEF), supplementary eye field (SEF), left dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC), intraparietal sulcus (IPS), and precuneus. Greater antisaccade response-related activation was found in FEF, SEF, IPS, and precuneus but not in DLPFC or ACC. These results demonstrate greater preparatory activation for antisaccades versus prosaccades in frontoparietal areas and suggest that prefrontal cortex and anterior cingulate cortex are more involved in presetting the saccade network for the antisaccade task than generating the actual antisaccade response.

Enhanced cognitive control in Tourette Syndrome during task uncertainty

Tourette Syndrome (TS) is a developmental neurological condition that is characterised by the presence of multiple motor and one or more vocal tics. Tics are highly stereotyped repetitive behaviours that fluctuate in type, complexity and severity. TS has been linked to impaired cognitive control processes, however, a recent study (Mueller et al. in Curr Biol 16:570-573, 2006) demonstrated that young people with TS, although exhibiting chronic motor and vocal tics, nevertheless performed significantly better than a group of age-matched controls on a task that required extremely high levels of cognitive control (i.e., predictably shifting between executing pro-saccade and anti-saccade responses to a visual stimulus). As predictable task sequences allow task-related cognitive processes to commence prior to the presentation of target stimuli we examined whether the superior performance of the TS group could be replicated when task sequences were varied unpredictably. Our results confirmed that both the TS group and an age-matched control group benefited, by the same extent, when the saccade task (pro-saccade vs. anti-saccade) was pre-cued. In contrast, while the control group showed a significant decrease in performance on task switch trials relative to task repetition trials-the TS group exhibited no significant 'costs' of switching task. While task performance was modulated by response and target location shifts in the control group, these factors had less impact on the TS group's performance on task switch trials. These results confirm and extend the previous demonstration that individuals with TS exhibit paradoxically greater levels of cognitive control than healthy controls.

Differential effects of reward and punishment on conscious and unconscious eye movements

Very little is known about how human movements are influenced by abstract rewards and punishments relevant for human behaviour. The purpose of this study was to expand our knowledge of the behavioural effects of monetary reward and punishment. We introduced a high and low reward and punishment scheme into an antisaccade task where trials were either rewarded for a correct response (+1 or +25p) or punished for an incorrect response (-1 or -25p). The monetary value of the trial was indicated by the go signal, so subjects had to both program the location of the movement and determine the valence in the short interval before the eye movement was executed. We analysed both correct antisaccade responses and prosaccade errors. Importantly, the errors in this task can be either conscious (recognised) or unconscious (unrecognised). Saccades in both high-reward and high-punishment trials were slowed compared to saccades in low-reward and low-punishment trials, respectively. Therefore, unlike moderate rewards only (Blaukopf and DiGirolamo in Exp Brain Res 167:654-659, 2005), combining rewards and punishments and increasing motivation levels leads to a delay in movement execution during high valence trials where all actions are slowed, even errors. However, unconscious errors were differentially affected as they were speeded when punishment was high. We conclude that reward and punishment similarly influence the programming of conscious movements, but the strong saliency for punishment affords unconscious errors immunity from this delay.

Inhibition and generation of saccades: Rapid event-related fMRI of prosaccades, antisaccades, and nogo trials

Flexible, adaptive behavior often requires the inhibition of automatic responses in favor of voluntary response generation. The antisaccade task requires active inhibition of the automatic saccade to a peripheral stimulus followed by generation of a voluntary antisaccade to the opposite location. Previous studies demonstrated greater functional magnetic resonance imaging (fMRI) activation for antisaccades than prosaccades in cortical saccade areas but did not distinguish the relative contributions of saccadic inhibition and generation. To address this question, we compared prosaccades, antisaccades, and nogo trials in a rapid event-related fMRI experiment with ten human subjects (6 female, 4 male). Trials were compound, containing a colored fixation point to cue trial type, followed by a 200-ms gap and then peripheral stimulus presentation and response. Required responses for prosaccade, antisaccade, and nogo trials, respectively, were to generate a saccade to the stimulus, look away from it, and inhibit the automatic saccade while maintaining central fixation. Frontal and supplementary eye fields, anterior cingulate cortex, intraparietal sulcus, and precuneus, exhibited surprisingly similar activation patterns for prosaccade and nogo responses, suggesting that BOLD signal in cortical saccade regions might predominantly reflect visual detection and attention processes rather than saccade generation or inhibition. These regions displayed greater activation for antisaccade responses versus prosaccade or nogo responses, possibly due to visuospatial remapping or increased attention levels in the antisaccade task. In right superior frontal sulcus, right supramarginal gyrus, and posterior cingulate sulcus, activation was greater for nogo compared to prosaccade responses, suggesting a role in active saccadic inhibition.

Electroencephalography/magnetoencephalography study of cortical activities preceding prosaccades and antisaccades

The temporal and spatial characteristics of brain activity preceding prosaccades and antisaccades were investigated using source reconstructions of 64-channel electroencephalography and 148-channel magnetoencephalography data. Stimulus-locked data showed early cuneus activity was stronger during antisaccades, and later occipital gyrus activity was stronger preceding prosaccades, which suggests a top-down influence on early visual processing. Response-locked data showed that supplementary eye field, prefrontal cortex, and medial frontal eye field activity was greater for antisaccades than for prosaccades prior to saccade generation. Lateral frontal eye field activity appeared to be inhibited prior to antisaccade response generation. The spatial and temporal resolution of combined electroencephalography/magnetoencephalography data allows the evaluation of specific cortical activities preceding saccades and for demonstration of how activities differ as a function of response contingencies.

Lack of association between prepulse inhibition and antisaccadic deficits in chronic schizophrenia: implications for identification of schizophrenia endophenotypes

Individuals with schizophrenia, compared to healthy individuals, are known to exhibit deficient prepulse inhibition (PPI) of the startle response as well as reduced performance on the antisaccade task. There is evidence for genetic transmission of both PPI and antisaccadic abnormalities in schizophrenia. It has been suggested that PPI and antisaccade measures identify separate endophenotypes, on the basis of a lack of relationship between PPI and antisaccade deficits in patients with schizotypal personality disorder. However, given that patients with schizotypal personality disorder are unlikely to manifest all the abnormalities associated with schizophrenia, it is important to determine that there is no relationship present between these two abnormalities in people affected with schizophrenia. The main objective of this investigation therefore was to establish the lack of the association between PPI and antisaccade deficits in schizophrenia in two independent studies. Study 1 involved 39 patients with schizophrenia and 14 healthy controls and study 2 involved 35 patients with schizophrenia and 22 healthy controls. PPI (uninstructed paradigm) of the acoustically elicited startle (eye blink) was measured electromyographically. Antisaccadic eye movements (standard, non-overlap version) were measured using infrared oculography. Patients displayed reduced PPI and a lower percentage of correct antisaccades relative to healthy controls in both studies. As expected, no relationship occurred between PPI and the percentage of correct antisaccade responses in either group. It is concluded that PPI and antisaccade abnormalities in schizophrenia represent separate endophenotypes, reflecting the functions of different genetic aetiologies and different or only partially overlapping neural systems.

Smooth pursuit and antisaccade performance evidence trait stability in schizophrenia patients and their relatives

Several forms of eye movement dysfunction (EMD) have been widely regarded as candidate endophenotypes of schizophrenia, ultimately capable of identifying individuals carrying schizophrenia susceptibility genes and elucidating the pathophysiology of schizophrenia. As an indication of their trait-like status, candidate endophenotypes optimally evidence stability over time. However, there have been few published reports of test–retest reliability of several forms of EMD in schizophrenia patients and their relatives. In the current investigation, schizophrenia patients and the first-degree biological relatives of schizophrenia patients ( n=15) were administered by an eye movement battery including smooth pursuit, antisaccade and prosaccade tasks, and re-tested after an average of 1.82 years (range=14–24 months). Adequate test–retest reliabilities of smooth pursuit closed-loop gain (Pearson r=0.72), antisaccade error rate ( r=0.73), saccade reaction time to correct antisaccade responses ( r=0.73), and prosaccade hypometria ( r=0.72) were observed. Lower reliabilities were obtained for smooth pursuit open-loop gain ( r=0.52) and prosaccade reaction time ( r=0.43). The results are supportive of the trait-like characteristics of particular forms of EMD in schizophrenia families and of the candidacy of EMD as an endophenotypic marker of schizophrenia.