Eye tracking: empirical foundations for a minimal reporting guideline.

In this paper, we present a review of how the various aspects of any study using an eye tracker (such as the instrument, methodology, environment, participant, etc.) affect the quality of the recorded eye-tracking data and the obtained eye-movement and gaze measures. We take this review to represent the empirical foundation for reporting guidelines of any study involving an eye tracker. We compare this empirical foundation to five existing reporting guidelines and to a database of 207 published eye-tracking studies. We find that reporting guidelines vary substantially and do not match with actual reporting practices. We end by deriving a minimal, flexible reporting guideline based on empirical research (Section "An empirically based minimal reporting guideline").

Oculomotor atypicalities in Developmental Coordination Disorder.

Children with Developmental Coordination Disorder (DCD) fail to acquire adequate motor skill, yet surprisingly little is known about the oculomotor system in DCD. Successful completion of motor tasks is supported by accurate visual feedback. The purpose of this study was to determine whether any oculomotor differences can distinguish between children with and without a motor impairment. Using eye tracking technology, visual fixation, smooth pursuit, and pro- and anti-saccade performance were assessed in 77 children that formed three groups: children with DCD (aged 7-10), chronologically age (CA) matched peers, and a motor-match (MM) group (aged 4-7). Pursuit gain and response preparation in the pro- and anti-saccade tasks were comparable across groups. Compared to age controls, children with DCD had deficits in maintaining engagement in the fixation and pursuit tasks, and made more anti-saccade errors. The two typically developing groups performed similarly, except on the fast speed smooth pursuit and antisaccade tasks, where the CA group outperformed the younger MM group. The findings suggest that children with DCD have problems with saccadic inhibition and maintaining attention on a visual target. Developmental patterns were evident in the typically developing groups, suggesting that the pursuit system and cognitive control develop with age. This study adds to the literature by being the first to systematically identify specific oculomotor differences between children with and without a motor impairment. Further examination of oculomotor control may help to identify underlying processes contributing to DCD. A video abstract of this article can be viewed at: https://youtu.be/NinXa2KlB4M. [Correction added on 27 January 2017, after first online publication: The video abstract link was added.].

The influence of hallucination proneness and social threat on time perception.

INTRODUCTION: Individuals with schizophrenia frequently report disturbances in time perception, but the precise nature of such deficits and their relation to specific symptoms of the disorder is unclear. We sought to determine the relationship between hallucination proneness and time perception in healthy individuals, and whether this relationship is moderated by hypervigilance to threat-related stimuli. METHODS: 206 participants completed the Revised Launay-Slade Hallucination Scale (LSHS-R) and a time reproduction task in which, on each trial, participants viewed a face (happy, angry, neutral, or fearful) for between 1 and 5 s and then reproduced the time period with a spacebar press. RESULTS: High LSHS-R scores were associated with longer time estimates, but only during exposure to angry faces. A factor analysis of LSHS-R scores identified a factor comprising items related to reality monitoring, and this factor was most associated with the longer time estimates. CONCLUSIONS: During exposure to potential threat in the environment, duration estimates increase with hallucination proneness. The experience of feeling exposed to threat for longer may serve to maintain a state of hypervigilance which has been shown previously to be associated with positive symptoms of schizophrenia.

Misperceiving facial affect: effects of laterality and individual differences in susceptibility to visual hallucinations.

It has been suggested that certain types of auditory hallucinations may be the by-product of a perceptual system that has evolved to be oversensitive to threat-related stimuli. People with schizophrenia and high schizotypes experience visual as well as auditory hallucinations, and have deficits in processing facial emotions. We sought to determine the relationship between visual hallucination proneness and the tendency to misattribute threat and non-threat related emotions to neutral faces. Participants completed a questionnaire assessing visual hallucination proneness (the Revised Visual Hallucination Scale - RVHS). High scoring individuals (N=64) were compared to low scoring individuals (N=72) on a novel emotion detection task. The high RVHS group made more false positive errors (ascribing emotions to neutral faces) than the low RVHS group, particularly when detecting threat-related emotions. All participants made more false positives when neutral faces were presented to the right visual field than to the left visual field. Our results support continuum models of visual hallucinatory experience in which tolerance for false positives is highest for potentially threatening emotional stimuli and suggest that lateral asymmetries in face processing extend to the misperception of facial emotion.

Antisaccade task performance in obsessive-compulsive disorder and its clinical correlates.

OBJECTIVE: Obsessive-Compulsive Disorder (OCD) is characterized by abnormalities in the cortico-striato-thalamo-cortical (CSTC) circuitry of the brain. Antisaccade eye movement tasks measure aspects of the voluntary control of behaviour that are sensitive to CSTC circuitry dysfunction. METHOD: In this study, we examined antisaccade eye movement parameters of OCD patients in comparison with healthy controls (HC). In addition, we also examined the relationship between the antisaccade eye movement parameters and the severity of OCD. Antisaccade performance among right handed OCD patients (N = 65) was compared to matched right handed HC (N = 57). Eye tracking data during the task performance were collected using an Eye-Link eye-tracker at 1000-Hz sampling rate. OCD symptom severity was evaluated using Yale-Brown obsessive compulsive scale. RESULTS: The antisaccade error percentage was significantly greater in OCD patients than HC (p < 0.001). In addition, OCD patients had less accurate final eye position compared to HC (p < 0.001). There were no significant correlation between antisaccade parameters and OCD severity measures. CONCLUSION: Deficient performance in antisaccade task supports CSTC abnormality in OCD and this appears to be independent of the illness severity. Examining this in remitted participants with OCD and in unaffected first degree relatives could help ascertaining their endophenotype validity.

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.

Characterization of the Frmd7 Knock-Out Mice Generated by the EUCOMM/COMP Repository as a Model for Idiopathic Infantile Nystagmus (IIN).

In this study, we seek to exclude other pathophysiological mechanisms by which Frmd7 knock-down may cause Idiopathic Infantile Nystagmus (IIN) using the Frmd7.tm1a and Frmd7.tm1b murine models. We used a combination of genetic, histological and visual function techniques to characterize the role of Frmd7 gene in IIN using a novel murine model for the disease. We demonstrate that the Frmd7.tm1b allele represents a more robust model of Frmd7 knock-out at the mRNA level. The expression of Frmd7 was investigated using both antibody staining and X-gal staining confirming previous reports that Frmd7 expression in the retina is restricted to starburst amacrine cells and demonstrating that X-gal staining recapitulates the expression pattern in this model. Thus, it offers a useful tool for further expression studies. We also show that gross retinal morphology and electrophysiology are unchanged in these Frmd7 mutant models when compared with wild-type mice. High-speed eye-tracking recordings of Frmd7 mutant mice confirm a specific horizontal optokinetic reflex defect. In summary, our study confirms the likely role for Frmd7 in the optokinetic reflex in mice mediated by starburst amacrine cells. We show that the Frmd7.tm1b model provides a more robust knock-out than the Frmd7.tm1a model at the mRNA level, although the functional consequence is unchanged. Finally, we establish a robust eye-tracking technique in mice that can be used in a variety of future studies using this model and others. Although our data highlight a deficit in the optiokinetic reflex as a result of the starburst amacrine cells in the retina, this does not rule out the involvement of other cells, in the brain or the retina where Frmd7 is expressed, in the pathophysiology of IIN.

Using event-related fMRI to examine sustained attention processes and effects of APOE ε4 in young adults.

In this study we investigated effects of the APOE ε4 allele (which confers an enhanced risk of poorer cognitive ageing, and Alzheimer's Disease) on sustained attention (vigilance) performance in young adults using the Rapid Visual Information Processing (RVIP) task and event-related fMRI. Previous fMRI work with this task has used block designs: this study is the first to image an extended (6-minute) RVIP task. Participants were 26 carriers of the APOE ε4 allele, and 26 non carriers (aged 18-28). Pupil diameter was measured throughout, as an index of cognitive effort. We compared activity to RVIP task hits to hits on a control task (with similar visual parameters and response requirements but no working memory load): this contrast showed activity in medial frontal, inferior and superior parietal, temporal and visual cortices, consistent with previous work, demonstrating that meaningful neural data can be extracted from the RVIP task over an extended interval and using an event-related design. Behavioural performance was not affected by genotype; however, a genotype by condition (experimental task/control task) interaction on pupil diameter suggested that ε4 carriers deployed more effort to the experimental compared to the control task. fMRI results showed a condition by genotype interaction in the right hippocampal formation: only ε4 carriers showed downregulation of this region to experimental task hits versus control task hits. Experimental task beta values were correlated against hit rate: parietal correlations were seen in ε4 carriers only, frontal correlations in non-carriers only. The data indicate that, in the absence of behavioural differences, young adult ε4 carriers already show a different linkage between functional brain activity and behaviour, as well as aberrant hippocampal recruitment patterns. This may have relevance for genotype differences in cognitive ageing trajectories.

Clinical correlates of saccadic eye movement in antipsychotic-naïve schizophrenia.

Some aspects of saccadic performance have been found to be abnormal in chronic schizophrenia. The majority of this research has, however, been performed on patients treated with long-term antipsychotic medication. Very few studies have examined saccadic performance in antipsychotic-naïve/free patients. There are also very few studies describing the relationship between saccadic performance and clinical symptoms, particularly in antipsychotic free patients. In this study, we compared pro and antisaccade performance in a large sample of antipsychotic-naïve/free schizophrenia patients (N = 45) with healthy controls (N = 57). Clinical symptoms were assessed using Scale for Assessment of Positive Symptoms (SAPS) and Negative Symptoms (SANS). In the antisaccade task, patients made significantly more errors, and their correct antisaccades had smaller amplitudes in comparison to healthy controls. Higher error rates were associated with increased severity of hallucinations. In the prosaccade task, patients had less accurate final eye positions, and made saccades with slower latency and reduced amplitude compared to the healthy controls. These observations in schizophrenia patients without the potential confounds of antipsychotic treatment suggest intrinsic link between saccadic deficits and schizophrenia pathogenesis. The relationship between antisaccade errors and hallucination severity supports the potential link between hallucinations and deficits in inhibitory control.

Disrupted neural activity patterns to novelty and effort in young adult APOE-e4 carriers performing a subsequent memory task.

INTRODUCTION: The APOE e4 allele has been linked to poorer cognitive aging and enhanced dementia risk. Previous imaging studies have used subsequent memory paradigms to probe hippocampal function in e4 carriers across the age range, and evidence suggests a pattern of hippocampal overactivation in young adult e4 carriers. METHODS: In this study, we employed a word-based subsequent memory task under fMRI; pupillometry data were also acquired as an index of cognitive effort. Participants (26 non-e4 carriers and 28 e4 carriers) performed an incidental encoding task (presented as word categorization), followed by a surprise old/new recognition task after a 40 minute delay. RESULTS: In e4 carriers only, subsequently remembered words were linked to increased hippocampal activity. Across all participants, increased pupil diameter differentiated subsequently remembered from forgotten words, and neural activity covaried with pupil diameter in cuneus and precuneus. These effects were weaker in e4 carriers, and e4 carriers did not show greater pupil diameter to remembered words. In the recognition phase, genotype status also modulated hippocampal activity: here, however, e4 carriers failed to show the conventional pattern of greater hippocampal activity to novel words. CONCLUSIONS: Overall, neural activity changes were unstable in e4 carriers, failed to respond to novelty, and did not link strongly to cognitive effort, as indexed by pupil diameter. This provides further evidence of abnormal hippocampal recruitment in young adult e4 carriers, manifesting as both up and downregulation of neural activity, in the absence of behavioral performance differences.

The antisaccade task as an index of sustained goal activation in working memory: modulation by nicotine.

INTRODUCTION: The antisaccade task provides a laboratory analogue of situations in which execution of the correct behavioural response requires the suppression of a more prepotent or habitual response. Errors (failures to inhibit a reflexive prosaccade towards a sudden onset target) are significantly increased in patients with damage to the dorsolateral prefrontal cortex and patients with schizophrenia. Recent models of antisaccade performance suggest that errors are more likely to occur when the intention to initiate an antisaccade is insufficiently activated within working memory. Nicotine has been shown to enhance specific working memory processes in healthy adults. MATERIALS AND METHODS: We explored the effect of nicotine on antisaccade performance in a large sample (N = 44) of young adult smokers. Minimally abstinent participants attended two test sessions and were asked to smoke one of their own cigarettes between baseline and retest during one session only. RESULTS AND CONCLUSION: Nicotine reduced antisaccade errors and correct antisaccade latencies if delivered before optimum performance levels are achieved, suggesting that nicotine supports the activation of intentions in working memory during task performance. The implications of this research for current theoretical accounts of antisaccade performance, and for interpreting the increased rate of antisaccade errors found in some psychiatric patient groups are discussed.

Acute effects of nicotine on visual search tasks in young adult smokers.

RATIONALE: Nicotine is known to improve performance on tests involving sustained attention and recent research suggests that nicotine may also improve performance on tests involving the strategic allocation of attention and working memory. OBJECTIVES: We used measures of accuracy and response latency combined with eye-tracking techniques to examine the effects of nicotine on visual search tasks. METHODS: In experiment 1 smokers and non-smokers performed pop-out and serial search tasks. In experiment 2, we used a within-subject design and a more demanding search task for multiple targets. In both studies, 2-h abstinent smokers were asked to smoke one of their own cigarettes between baseline and tests. RESULTS: In experiment 1, pop-out search times were faster after nicotine, without a loss in accuracy. Similar effects were observed for serial searches, but these were significant only at a trend level. In experiment 2, nicotine facilitated a strategic change in eye movements resulting in a higher proportion of fixations on target letters. If the cigarette was smoked on the first trial (when the task was novel), nicotine additionally reduced the total number of fixations and re-fixations on all letters in the display. CONCLUSIONS: Nicotine improves visual search performance by speeding up search time and enabling a better focus of attention on task relevant items. This appears to reflect more efficient inhibition of eye movements towards task irrelevant stimuli, and better active maintenance of task goals. When the task is novel, and therefore more difficult, nicotine lessens the need to re-fixate previously seen letters, suggesting an improvement in working memory.

Structural neural networks subserving oculomotor function in first-episode schizophrenia.

BACKGROUND: Smooth pursuit and antisaccade abnormalities are well documented in schizophrenia, but their neuropathological correlates remain unclear. METHODS: In this study, we used statistical parametric mapping to investigate the relationship between oculomotor abnormalities and brain structure in a sample of first-episode schizophrenia patients (n = 27). In addition to conventional volumetric magnetic resonance imaging, we also used magnetization transfer ratio, a technique that allows more precise tissue characterization. RESULTS: We found that smooth pursuit abnormalities were associated with reduced magnetization transfer ratio in several regions, predominantly in the right prefrontal cortex. Antisaccade errors correlated with gray matter volume in the right medial superior frontal cortex as measured by conventional magnetic resonance imaging but not with magnetization transfer ratio. CONCLUSIONS: These preliminary results demonstrate that specific structural abnormalities are associated with abnormal eye movements in schizophrenia.

The relationship between antisaccades, smooth pursuit, and executive dysfunction in first-episode schizophrenia.

BACKGROUND: Both oculomotor and neuropsychologic deficits have been used to support the hypothesis that schizophrenia is associated with prefrontal cortex dysfunction, but studies that have specifically investigated the relationships between these deficits have produced inconsistent findings. METHODS: We measured both smooth pursuit and antisaccade performance in a large group (n = 109) of patients with first-episode schizophrenia and a group of matched control subjects (n = 59) and investigated the relationship between performance on these tasks and performance on a range of executive tasks. We additionally explored the relationship between these variables and measures of psychopathology at presentation and duration of untreated psychosis. RESULTS: Antisaccade errors were significantly correlated with spatial working memory performance. Smooth pursuit gain did not correlate with any neuropsychologic measure. There were no reliable correlations between either oculomotor variables and measures of psychopathology and duration of untreated psychosis. CONCLUSIONS: These findings suggest that in schizophrenia working memory and antisaccade performance reflect the same abnormal prefrontal substrates and that smooth pursuit is mediated by a separate neural abnormality.

Lateral asymmetry in saccadic eye movements during face processing: the role of individual differences in schizotypy.

Healthy individuals with high as compared to low levels of schizotypal personality traits make more first saccades to the left side of faces, suggesting increased right hemisphere (RH) dominance for face processing. Patients with schizophrenia, however, show attenuated or reversed RH dominance for face processing. It is unclear whether the increased RH dominance found in high schizotypes is specific to face processing or whether it is also observable for other stimuli matched in terms of low-level visual properties. We measured gaze to faces and symmetrical fractal patterns and found higher Magical Ideation (MI) is associated with an increased left-side bias for initial saccade landing points and dwell times when free-viewing faces. These laterality biases were unaffected by facial emotion. Schizotypy scores were not related to laterality biases when viewing fractals. Our results provide further evidence that high schizotypy is associated with an increase in RH dominance for face processing.

The effects of self-report cognitive failures and cognitive load on antisaccade performance.

Individuals reporting high levels of distractibility in everyday life show impaired performance in standard laboratory tasks measuring selective attention and inhibitory processes. Similarly, increasing cognitive load leads to more errors/distraction in a variety of cognitive tasks. How these two factors interact is currently unclear; highly distractible individuals may be affected more when their cognitive resources are taxed, or load may linearly affect performance for all individuals. We investigated the relationship between self-reported levels of cognitive failures (CF) in daily life and performance in the antisaccade task, a widely used tool examining attentional control. Levels of concurrent cognitive demand were manipulated using a secondary auditory discrimination task. We found that both levels of self-reported CF and task load increased antisaccade latencies while having no effect on prosaccade eye-movements. However individuals rating themselves as suffering few daily life distractions showed a comparable load cost to those who experience many. These findings suggest that the likelihood of distraction is governed by the addition of both internal susceptibility and the external current load placed on working memory.

Pupil size changes during recognition memory.

Pupils dilate to a greater extent when participants view old compared to new items during recognition memory tests. We report three experiments investigating the cognitive processes associated with this pupil old/new effect. Using a remember/know procedure, we found that the effect occurred for old items that were both remembered and known at recognition, although it was attenuated for known compared to remembered items. In Experiment 2, the pupil old/new effect was observed when items were presented acoustically, suggesting the effect does not depend on low-level visual processes. The pupil old/new effect was also greater for items encoded under deep compared to shallow orienting instructions, suggesting it may reflect the strength of the underlying memory trace. Finally, the pupil old/new effect was also found when participants falsely recognized items as being old. We propose that pupils respond to a strength-of-memory signal and suggest that pupillometry provides a useful technique for exploring the underlying mechanisms of recognition memory.

Discrimination learning, reversal, and set-shifting in first-episode schizophrenia: stability over six years and specific associations with medication type and disorganization syndrome.

BACKGROUND: The intradimensional/extradimensional (IDED) task assesses different forms of learning from feedback. Limited evidence suggests that attentional set-shifting deteriorates over time in schizophrenia. We tested this hypothesis and examined the specificity of learning impairments identified by this task. METHOD: Two hundred sixty-two first-episode patients and 76 healthy control subjects, matched for age and premorbid IQ, were tested; 104 patients and 25 control subjects were reassessed 1 and 3 years later, and 31 patients were reassessed additionally 6 years later. RESULTS: Patients showed impaired set-shifting that correlated with current IQ and working memory, but there were no impairments when subgroups were matched on current IQ. In contrast, patients showed marked impairments in rule reversal learning that survived correction for IQ, were present in the context of intact rule abstraction, and correlated with disorganization symptoms. Patients prescribed second-generation antipsychotics were worse on set-shifting compared with first-generation, a finding not explained by demographic data, illness characteristics, or IQ. Patients and control subjects showed stable IDED performance over the first 6 years of illness, although set-shifting was inconsistent over the first year. Those with residual negative symptoms were more likely to fail the set-shifting stage at follow-up. CONCLUSIONS: First-episode schizophrenia patients can learn and generalize rules but are inflexible when rules change, reflecting reduced responsiveness to negative feedback and difficulty in switching attention. Rule-reversal is a promising target for translational studies, because it is specific, clinically relevant, and might reflect orbitofrontal dysfunction. Set-shifting is related to poor function more generally but might be sensitive to medication effects and valuable for clinical trials.

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.