Smooth Pursuit Eye Movement Task Research Articles

Oculomotor atypicalities in motor neurone disease: a systematic review.

Cognitive dysfunction is commonplace in Motor Neurone Disease (MND). However, due to the prominent motor symptoms in MND, assessing patients' cognitive function through traditional cognitive assessments, which oftentimes require motoric responses, may become increasingly challenging as the disease progresses. Oculomotor pathways are apparently resistant to pathological degeneration in MND. As such, abnormalities in oculomotor functions, largely driven by cognitive processes such as saccades and smooth pursuit eye movement, may be reflective of frontotemporal cognitive deficits in MND. Thus, saccadic and smooth pursuit eye movements may prove to be ideal mechanistic markers of cognitive function in MND. To ascertain the utility of saccadic and smooth pursuit eye movements as markers of cognitive function in MND, this review summarizes the literature concerning saccadic and smooth pursuit eye movement task performance in people with MND. Of the 22 studies identified, noticeable patterns suggest that people with MND can be differentiated from controls based on antisaccade and smooth pursuit task performance, and thus the antisaccade task and smooth pursuit task may be potential candidates for markers of cognition in MND. However, further studies which ascertain the concordance between eye tracking measures and traditional measures of cognition are required before this assumption is extrapolated, and clinical recommendations are made. https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=376620, identifier CRD42023376620.

The effect of temporal expectation on the correlations of frontal neural activity with alpha oscillation and sensory-motor latency

In a dynamic environment, we seek to enhance behavioral responses by anticipating future events. Previous studies have shown that the probability distribution of the timing of future events could shape our expectation of event timing; furthermore, the modulation of alpha oscillation is known to be a critical neural factor. However, a link between the modulation of alpha oscillation by temporal expectation and single neural activity is missing. In this study, we investigated how temporal expectation modulated frontal neural activities and behavioral reaction time by recording neural activity from the frontal eye field smooth pursuit eye movement region of monkeys while they performed a smooth pursuit eye movement task. We found that the temporal expectation reduced the coherence between the neural spiking and alpha frequency of the local field potential, along with the trial-by-trial correlation between the neural spiking activity and pursuit latency. This result suggests that the desynchronization of alpha oscillation by temporal expectation would be related to the decorrelation of population neural activity, which could be the neural source of reaction time enhancement by temporal expectation.

Multivariate EEG activity reflects the Bayesian integration and the integrated Galilean relative velocity of sensory motion during sensorimotor behavior

Humans integrate multiple sources of information for action-taking, using the reliability of each source to allocate weight to the data. This reliability-weighted information integration is a crucial property of Bayesian inference. In this study, participants were asked to perform a smooth pursuit eye movement task in which we independently manipulated the reliability of pursuit target motion and the direction-of-motion cue. Through an analysis of pursuit initiation and multivariate electroencephalography activity, we found neural and behavioral evidence of Bayesian information integration: more attraction toward the cue direction was generated when the target motion was weak and unreliable. Furthermore, using mathematical modeling, we found that the neural signature of Bayesian information integration had extra-retinal origins, although most of the multivariate electroencephalography activity patterns during pursuit were best correlated with the retinal velocity errors accumulated over time. Our results demonstrated neural implementation of Bayesian inference in human oculomotor behavior.

Neural mechanisms of background and velocity effects in smooth pursuit eye movements.

Smooth pursuit eye movements (SPEM) are essential to guide behaviour in complex visual environments. SPEM accuracy is known to be degraded by the presence of a structured visual background and at higher target velocities. The aim of this preregistered study was to investigate the neural mechanisms of these robust behavioural effects. N=33 participants performed a SPEM task with two background conditions (present and absent) at two target velocities (0.4 and 0.6Hz). Eye movement and BOLD data were collected simultaneously. Both the presence of a structured background and faster target velocity decreased pursuit gain and increased catch-up saccade rate. Faster targets additionally increased position error. Higher BOLD response with background was found in extensive clusters in visual, parietal, and frontal areas (including the medial frontal eye fields; FEF) partially overlapping with the known SPEM network. Faster targets were associated with higher BOLD response in visual cortex and left lateral FEF. Task-based functional connectivity analyses (psychophysiological interactions; PPI) largely replicated previous results in the basic SPEM network but did not yield additional information regarding the neural underpinnings of the background and velocity effects. The results show that the presentation of visual background stimuli during SPEM induces activity in a widespread visuo-parieto-frontal network including areas contributing to cognitive aspects of oculomotor control such as medial FEF, whereas the response to higher target velocity involves visual and motor areas such as lateral FEF. Therefore, we were able to propose for the first time different functions of the medial and lateral FEF during SPEM.

The influence of neck torsion and sequence of cycles on intra-trial reliability of smooth pursuit eye movement test in patients with neck pain disorders.

The sensory mismatch commonly observed in patients with neck pain disorders could alter intra-trial reliability in simple implicit smooth pursuit eye movement tasks. This could be more pronounced when neck is in torsioned position (SPNT). The aim of this study was to explore the effects of neck torsion, target movement velocity and amplitude on intra-trial reliability of smooth pursuit eye movements in patients with neck pain disorders and healthy individuals. SPNT test was evaluated in 32 chronic neck pain patients and 32 healthy controls. Ten cycles were performed using video-oculography at three different velocities (20°s-1, 30°s-1 and 40°s-1) and at three different amplitudes (30°, 40° and 50°) of target movement. Intra-trial reliability and differences between average gain and SPNT difference from the second to fifth cycle and from the sixth to ninth cycle were assessed using ICC3.1 and factorial analysis of variance, respectively. Intra-trial reliability for gain and SPNT difference at all target movement amplitudes and velocities proved to be good to excellent in both observed groups. Patients with neck pain disorders presented with a trend of inferior gain performance between the sixth and ninth cycle at 30°s-1 of target movement as compared to healthy individuals which was only evident when neck was in torsioned position. Although intra-trial reliability of smooth pursuit neck torsion test is good to excellent, the effects of learning are not as pronounced in patients with neck pain disorders.

Sensory gating is related to positive and disorganised schizotypy in contrast to smooth pursuit eye movements and latent inhibition

Since the characteristics and symptoms of both schizophrenia and schizotypy are manifested heterogeneously, it is possible that different endophenotypes and neurophysiological measures (sensory gating and smooth pursuit eye movement errors) represent different clusters of symptoms. Participants (N = 205) underwent a standard conditioned-pairing paradigm to establish their sensory gating ratio, a smooth-pursuit eye-movement task, a latent inhibition task, and completed the Schizotypal Personality Questionnaire. A Multidimensional Scaling analysis revealed that sensory gating was related to positive and disorganised dimensions of schizotypy. Latent inhibition and prepulse inhibition were not related to any dimension of schizotypy. Smooth pursuit eye movement error was unrelated to sensory gating and latent inhibition, but was related to negative dimensions of schizotypy. Our findings suggest that the symptom clusters associated with two main endophenotypes are largely independent. To fully understand symptomology and outcomes of schizotypal traits, the different subtypes of schizotypy (and potentially, schizophrenia) ought to be considered separately rather than together.

Encoding of eye movements explains reward-related activity in cerebellar simple spikes.

The cerebellum exhibits both motor and reward-related signals. However, it remains unclear whether reward is processed independently from the motor command or might reflect the motor consequences of the reward drive. To test how reward-related signals interact with sensorimotor processing in the cerebellum, we recorded Purkinje cell simple spike activity in the cerebellar floccular complex while monkeys were engaged in smooth pursuit eye movement tasks. The color of the target signaled the size of the reward the monkeys would receive at the end of the target motion. When the tracking task presented a single target, both pursuit and neural activity were only slightly modulated by the reward size. The reward modulations in single cells were rarely large enough to be detected. These modulations were only significant in the population analysis when we averaged across many neurons. In two-target tasks where the monkey learned to select based on the size of the reward outcome, both behavior and neural activity adapted rapidly. In both the single- and two-target tasks, the size of the reward-related modulation matched the size of the effect of reward on behavior. Thus, unlike cortical activity in eye movement structures, the reward-related signals could not be dissociated from the motor command. These results suggest that reward information is integrated with the eye movement command upstream of the Purkinje cells in the floccular complex. Thus reward-related modulations of the simple spikes are akin to modulations found in motor behavior and not to the central processing of the reward value.NEW & NOTEWORTHY Disentangling sensorimotor and reward signals is only possible if these signals do not completely overlap. We recorded activity in the floccular complex of the cerebellum while monkeys performed tasks designed to separate representations of reward from those of movement. Activity modulation by reward could be accounted for by the coding of eye movement parameters, suggesting that reward information is already integrated into motor commands upstream of the floccular complex.

Mechanisms of smooth pursuit eye movements in schizotypy

Several studies suggest that highly schizotypal individuals display a deficit in smooth pursuit eye movements (SPEM), which are considered an important biomarker of schizophrenia. In schizophrenia, abnormal SPEM is thought to be driven by impairments in motion perception. In schizotypy, the processes underlying reduced SPEM performance have not been examined so far, and there are no studies on motion perception deficits in schizotypy. Thus, in this registered report, we aimed to investigate whether motion perception is impaired in highly schizotypal individuals, and how it contributes to SPEM performance. On an exploratory basis, we were interested in the association between schizotypy and prediction, another mechanism underlying SPEM. To address this issue, participants with high total scores of the Oxford–Liverpool Inventory of Feelings and Experiences (O-LIFE short form) and control participants with low scores (N = 86 in each group) performed a standard sinusoidal SPEM task, random dot kinematograms to measure motion perception, and a blanking SPEM task to assess prediction abilities. Group comparisons as well as mediator analyses were carried out to identify whether motion perception or prediction are responsible for SPEM performance in schizotypy. We found reduced blanking SPEM performance in schizotypes compared to controls, but no group differences regarding sinusoidal SPEM and motion perception. Although no significant mediators were identified for SPEM performance in schizotypes, an exploratory analysis revealed an association between motion perception and SPEM gain in high, but not in low schizotypy. Our findings imply that despite the schizotypy-related impairment in prediction, motion perception seems to be a more important predictor of SPEM performance in schizotypes. A deficit in prediction that does not relate to SPEM performance suggests that protective factors (e.g., other cognitive processes) might operate in schizotypal individuals to maintain SPEM performance on a healthy level.

Predicting Trial-by-Trial Variation in Oculomotor Behavior Using Multivariate Electroencephalography Theta Phase

When we interact with our environment, there is often a significant amount of variations in our behavioral responses to incoming sensory input even when inputs are identical. Variations in sensory-motor behavior can be caused by several factors, including changes in cognitive status and intrinsic neural variations in the brain. The correct identification of neural sources of behavioral variations is important for understanding the underlying neural mechanisms of sensory-motor behavior and for practical applications (e.g., the development of a precise brain-computer interface). However, studies on humans that investigate the neural sources of the trial-by-trial variation of the sensory-motor behavior are scarce. In this study, we explored the neural correlates of behavioral variations in smooth pursuit eye movements. We collected electroencephalography (EEG) activity from 15 participants while they performed a smooth pursuit eye movement task, wherein they tracked randomly selected visual motion targets that moved radially from the center of the screen. We isolated neural components that are specific to the trial-by-trial variation of smooth pursuit latency, speed, and direction using a novel multivariate pattern-analysis technique. We found that the phase of the spatially distributed multivariate theta oscillation was correlated with the trial-by-trial variation of pursuit latency and direction. This suggests that the changing patterns of the theta phase across EEG sensors can predict upcoming behavioral variations.

Effects of nicotine on smooth pursuit eye movements in healthy non-smokers.

The non-selective nicotinic acetylcholine receptor (nAChR) agonist nicotine has been argued to improve attention via enhanced filtering of irrelevant stimuli. Here, we tested this hypothesis in the context of smooth pursuit eye movements (SPEMs), an oculomotor function previously shown to improve with nicotine in some but not all studies. In order to test whether nicotine improves performance particularly when the inhibition of distracting stimuli is required, SPEM was elicited in conditions with or without peripheral distractors. Additionally, different target frequencies were employed in order to parametrically vary general processing demands on the SPEM system. Healthy adult non-smokers (N= 18 females, N= 13 males) completed a horizontal sinusoidal SPEM task at different target frequencies (0.2Hz, 0.4Hz, 0.6Hz) in the presence or absence of peripheral distractors in a double-blind, placebo-controlled, cross-over design using a 2mg nicotine gum. Nicotine increased peak pursuit gain relative to placebo (p< .001), but an interaction with distractor condition (p= .001) indicated that this effect was most pronounced in the presence of distractors. Catch-up saccade frequency was reduced by nicotine (p= .01), particularly at higher target frequencies (two-way interaction, p= .04). However, a three-way interaction (p= .006) indicated that the reduction with nicotine was strongest at the highest target frequency (0.6Hz) only without distractors, whereas in the presence of distractors, it was strongest at 0.4-Hz target frequency. There were no effects of nicotine on subjective state measures. Together, these findings support a role of both distractor inhibition and general processing load in the effects of nicotine on smooth pursuit.

Schizotypy and smooth pursuit eye movements as potential endophenotypes of obsessive-compulsive disorder.

Patients with obsessive-compulsive disorder (OCD) show dysfunctions of the fronto-striatal circuitry, which imply corresponding oculomotor deficits including smooth pursuit eye movements (SPEM). However, evidence for a deficit in SPEM is inconclusive, with some studies reporting reduced velocity gain while others did not find any SPEM dysfunctions in OCD patients. Interestingly, psychosis-like traits have repeatedly been linked to both OCD and impaired SPEM. Here, we examined a large sample of n = 168 patients with OCD, n = 93 unaffected first-degree relatives and n = 171 healthy control subjects to investigate whether elevated levels of schizotypy and SPEM deficits represent potential endophenotypes of OCD. We applied a SPEM task with high demands on predictive pursuit that is more sensitive to assess executive dysfunctions than a standard task with continuous visual feedback, as episodes of target blanking put increased demands on basal ganglia and prefrontal involvement. Additionally, we examined the relation between schizotypy and SPEM performance in OCD patients and their relatives. Results indicate that OCD patients and unaffected relatives do not show deficient performance in either standard or predictive SPEM. Yet, both patients and relatives exhibited elevated levels of schizotypy, and schizotypy was significantly correlated with velocity gain during standard trials in unmedicated and depression-free OCD patients. These findings highlight the role of schizotypy as a candidate endophenotype of OCD and add to the growing evidence for predisposing personality traits in OCD. Furthermore, intact gain may represent a key characteristic that distinguishes the OCD and schizophrenia patient populations.

Smooth pursuit eye movements in psychiatric inpatients

IntroductionEye movements are used in several studies as a biomarker in order to evaluate cortical alterations in psychiatric disorders. Pursuit eye movements’ deficits were found both in schizophrenia and in affective disorder patients. Nevertheless, these findings are still controversial.ObjectivesSet up a system to record and evaluate the eye movements in psychiatric patients.AimsTo verify the applicability of a smooth pursuit task in a sample of psychiatric inpatients and to prove its efficiency in discriminating patient and control group performance.MethodsA sample of psychiatric inpatients was tested at psychiatric service of diagnosis and care of AUSL Romagna-Cesena. Eye movement measures were collected at a sampling rate of 60 Hz using the eye tribe tracker, a bar plugged into a PC, placed below the screen and containing both webcam and infrared illumination. Subjects underwent to a smooth pursuit eye movement task. They had to visually follow a white dot target moving horizontally on a black background with a sinusoidal velocity. At the end of the task, a chart of the eye movements done is shown on the screen. Data are off-line analyzed to calculate several eye movement parameters: gain, eye movement delay with respect to the movement of the target, maximum speed and number of saccades exhibited during pursuit.ResultsPatients compared to controls showed higher delay and lower gain values.ConclusionsFindings confirm the adequacy of this method in order to detect eye movement differences between psychiatric patients and controls in a smooth pursuit task.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Effects of ketamine on brain function during smooth pursuit eye movements.

The uncompetitive NMDA receptor antagonist ketamine has been proposed to model symptoms of psychosis. Smooth pursuit eye movements (SPEM) are an established biomarker of schizophrenia. SPEM performance has been shown to be impaired in the schizophrenia spectrum and during ketamine administration in healthy volunteers. However, the neural mechanisms mediating SPEM impairments during ketamine administration are unknown. In a counter-balanced, placebo-controlled, double-blind, within-subjects design, 27 healthy participants received intravenous racemic ketamine (100 ng/mL target plasma concentration) on one of two assessment days and placebo (intravenous saline) on the other. Participants performed a block-design SPEM task during functional magnetic resonance imaging (fMRI) at 3 Tesla field strength. Self-ratings of psychosis-like experiences were obtained using the Psychotomimetic States Inventory (PSI). Ketamine administration induced psychosis-like symptoms, during ketamine infusion, participants showed increased ratings on the PSI dimensions cognitive disorganization, delusional thinking, perceptual distortion and mania. Ketamine led to robust deficits in SPEM performance, which were accompanied by reduced blood oxygen level dependent (BOLD) signal in the SPEM network including primary visual cortex, area V5 and the right frontal eye field (FEF), compared to placebo. A measure of connectivity with V5 and FEF as seed regions, however, was not significantly affected by ketamine. These results are similar to the deviations found in schizophrenia patients. Our findings support the role of glutamate dysfunction in impaired smooth pursuit performance and the use of ketamine as a pharmacological model of psychosis, especially when combined with oculomotor biomarkers. Hum Brain Mapp 37:4047-4060, 2016. © 2016 Wiley Periodicals, Inc.

Neural effects of methylphenidate and nicotine during smooth pursuit eye movements

IntroductionNicotine and methylphenidate are putative cognitive enhancers in healthy and patient populations. Although they stimulate different neurotransmitter systems, they have been shown to enhance performance on overlapping measures of attention. So far, there has been no direct comparison of the effects of these two stimulants on behavioural performance or brain function in healthy humans. Here, we directly compare the two compounds using a well-established oculomotor biomarker in order to explore common and distinct behavioural and neural effects. MethodsEighty-two healthy male non-smokers performed a smooth pursuit eye movement task while lying in an fMRI scanner. In a between-subjects, double-blind design, subjects either received placebo (placebo patch and capsule), nicotine (7mg nicotine patch and placebo capsule), or methylphenidate (placebo patch and 40mg methylphenidate capsule). ResultsThere were no significant drug effects on behavioural measures. At the neural level, methylphenidate elicited higher activation in left frontal eye field compared to nicotine, with an intermediate response under placebo. DiscussionThe reduced activation of task-related regions under nicotine could be associated with more efficient neural processing, while increased hemodynamic response under methylphenidate is interpretable as enhanced processing of task-relevant networks. Together, these findings suggest dissociable neural effects of these putative cognitive enhancers.

Neural mechanisms of smooth pursuit eye movements in schizotypy.

Patients with schizophrenia as well as individuals with high levels of schizotypy are known to have deficits in smooth pursuit eye movements (SPEM). Here, we investigated, for the first time, the neural mechanisms underlying SPEM performance in high schizotypy. Thirty-one healthy participants [N = 19 low schizotypes, N = 12 high schizotypes (HS)] underwent functional magnetic resonance imaging at 3T with concurrent oculographic recording while performing a SPEM task with sinusoidal stimuli at two velocities (0.2 and 0.4 Hz). Behaviorally, a significant interaction between schizotypy group and velocity was found for frequency of saccades during SPEM, indicating impairments in HS in the slow but not the fast condition. On the neural level, HS demonstrated lower brain activation in different regions of the occipital lobe known to be associated with early sensory and attentional processing and motion perception (V3A, middle occipital gyrus, and fusiform gyrus). This group difference in neural activation was independent of target velocity. Together, these findings replicate the observation of altered pursuit performance in highly schizotypal individuals and, for the first time, identify brain activation patterns accompanying these performance changes. These posterior activation differences are compatible with evidence of motion processing deficits from the schizophrenia literature and, therefore, suggest overlap between schizotypy and schizophrenia both on cognitive-perceptual and neurophysiological levels. However, deficits in frontal motor areas observed during pursuit in schizophrenia were not seen here, suggesting the operation of additional genetic and/or illness-related influences in the clinical disorder.

In Six-month-old Infants, Prenatal Exposure to Maternal Anxiety is Associated with Less Developed Smooth Pursuit Eye Movements: An Initial Study.

There are an increasing number of reports suggesting an association between maternal anxiety experienced during pregnancy and adverse outcomes of the offspring. However, exploration of the biological changes in the brain that mediate that relationship has been hampered by the lack of appropriate biomarkers. This report represents an initial step exploring whether a potential infant biomarker, smooth pursuit eye movements, may be associated with prenatal exposure to maternal anxiety. Blinded cross-sectional study. Department of Psychiatry, University of Colorado School of Medicine. Data collected from July 2011 to May 2012. Forty-three infants including 34 whose prenatal maternal anxiety status was identified (12 with a known maternal prenatal anxiety diagnosis and 22 without) had eye movements recorded during a smooth pursuit eye movement task at four and/or six months of age. At 6 months of age, infants with prenatal exposure to maternal anxiety, compared to infants without such exposure, spent a higher percentage of time utilizing smooth pursuit (t=2.7, df=24, P=.013), had longer duration of smooth pursuit uninterrupted by saccades (t=2.5, df=24, P=.019), and had decreased frequency of forward saccades (t=3.8, df=24, P=.001). No differences between groups were identified at 4 months of age. Smooth pursuit abnormalities may, at six months of age, be a potential biomarker for prenatal maternal anxiety exposure.

Cerebellar hyperactivity during smooth pursuit eye movements in bipolar disorder

Introduction Smooth pursuit eye movements (SPEM) are abnormal in individuals with schizophrenia and individuals with bipolar disorder. Functional imaging methods have revealed greater hippocampal activity and less frontotemporal, visual, and posterior cerebellar activity in individuals with schizophrenia when performing a SPEM task. The underlying neurobiology of SPEM deficits in bipolar disorder is unknown. Methods Functional magnetic resonance imaging at 3T was performed on fourteen subjects with bipolar disorder and 14 subjects without psychiatric illness during a block design SPEM task. Clinical measures were assessed on the day of testing and related to imaging measures. Results Subjects with bipolar disorder had greater hemodynamic response than control subjects in cerebellar vermis. Responses were associated with levels of depressive symptoms on the day of study. Discussion Increased cerebellar vermis activity during the smooth pursuit eye movement task in individuals with bipolar disorder further implicates cerebellar involvement in bipolar disorder. Increased hemodynamic response within the hippocampus was not seen in these individuals and may be a finding specific to schizophrenia.

Functional Magnetic Resonance Imaging of Effects of a Nicotinic Agonist in Schizophrenia

3-(2,4-Dimethoxybenzylidene)-anabaseine (DMXB-A) is a partial agonist at alpha7-nicotinic acetylcholine receptors and is now in early clinical development for treatment of deficits in neurocognition and sensory gating in schizophrenia. During its initial phase 2 test, functional magnetic resonance imaging (fMRI) studies were conducted to determine whether the drug had its intended effect on hippocampal inhibitory interneurons. Increased hemodynamic activity in the hippocampus in schizophrenia is found during many tasks, including smooth pursuit eye movements, and may reflect inhibitory dysfunction. Placebo and two doses of drug were administered in a random, double-blind crossover design. After the morning drug/placebo ingestion, subjects underwent fMRI while performing a smooth pursuit eye movement task. Data were analyzed from 16 nonsmoking patients, including 7 women and 9 men. The 150-mg dose of DMXB-A, compared with placebo, diminished the activity of the hippocampus during pursuit eye movements, but the 75-mg dose was ineffective. The effect at the 150-mg dose was negatively correlated with plasma drug levels. The findings are consistent with the previously established function of alpha7-nicotinic receptors on inhibitory interneurons in the hippocampus and with genetic evidence for deficits in these receptors in schizophrenia. Imaging of drug response is useful in planning future clinical tests of this compound and other nicotinic agonists for schizophrenia.

Neuregulin-1 genotypes and eye movements in schizophrenia

Neuregulin-1 (NRG-1) is a putative susceptibility gene for schizophrenia but the neurocognitive processes that may involve NRG-1 in schizophrenia are unknown. Deficits in antisaccade (AS) and smooth pursuit eye movements (SPEM) are promising endophenotypes, which may be associated with brain dysfunctions underlying the pathophysiology of schizophrenia. The aim of this study was to investigate the associations of NRG-1 genotypes with AS and SPEM in schizophrenia patients and healthy controls. Patients (N = 113) and controls (N = 106) were genotyped for two NRG-1 single nucleotide polymorphisms (SNPs); SNP8NRG222662, a surrogate marker for the originally described Icelandic NRG-1 risk haplotype, and SNP8NRG243177, which has recently been associated with individual differences in brain function. Subjects underwent infrared oculographic assessment of AS and SPEM. The study replicates previous findings of impaired AS and SPEM performance in schizophrenia patients (all P < 0.005; all d = 0.5-1.5). SNP8NRG243177 risk allele carriers had marginally increased variability of AS spatial error (P = 0.050, d = 0.3), but there were no significant genotype effects on other eye movement variables and no significant diagnosis-by-genotype interactions. Generally, risk allele carriers (G allele for SNP8NRG222662 and T allele for SNP8NRG243177) had numerically worse performance than non-carriers on most AS and SPEM variables. The results do not suggest that NRG-1 genotype significantly affects AS and SPEM task performance. However, the power of the sample to identify small effects is limited and the possibility of a type II error must be kept in mind. Larger samples may be needed to reliably investigate such gene effects on oculomotor endophenotypes.

Eye movement deficits in schizophrenia

Deficits in antisaccade (AS) and smooth pursuit eye movements (SPEM) are promising endophenotypes in genetic studies of schizophrenia. The Icelandic population lends itself ideally to genetic studies due to its ethnic homogeneity and well-documented genealogy. The primary aim of this study was to assess AS and SPEM performance in a large Icelandic sample. Additional aims were to investigate the relationship between AS and SPEM task performance and to assess internal consistency, within-session performance changes and effects of SPEM target velocity on performance. Patients with schizophrenia (N = 118) and healthy controls (N = 109) matched for age and gender underwent infrared oculographic assessment of AS and SPEM (at target velocities of 12 degrees , 24 degrees and 36 degrees /s). On the AS task patients displayed significantly more reflexive errors, longer latency, increased intra-individual latency variability, and reduced amplitude gain compared to controls. On the SPEM task, patients had significantly lower velocity gain and more frequent saccades during pursuit at all velocities, but group differences in velocity gain increased with increasing target velocity. Internal consistency of performance was high for all variables in both groups (Cronbach's alpha >0.77 for AS and >0.85 for SPEM) except for AS spatial error in patients (alpha = 0.38). A moderate association was found between AS and SPEM performance. By and large, patients and controls showed similar patterns of systematic within-session performance changes. Our findings confirm the existence of robust eye movement deficits in schizophrenia in a large sample. These measures may be studied as endophenotypes in future studies of potential schizophrenia risk genotypes in the genetically homogenous Icelandic population.