A biomarker and endophenotype for anorexia nervosa?

OBJECTIVE: Recent research has suggested that a type of atypical eye movement, called square wave jerks, together with anxiety, may distinguish individuals with anorexia nervosa from those without anorexia nervosa and may represent a biomarker and endophenotype for the illness. The aim of this study was to identify the presence of this proposed marker in individuals currently with anorexia nervosa relative to healthy controls, and to identify the state independence and heritability of this putative marker by exploring whether it also exists in individuals who are weight-restored from anorexia nervosa and first-degree relatives (i.e. sisters of people with anorexia nervosa). METHODS: Data from 80 female participants (20/group: current anorexia nervosa, weight-restored from anorexia nervosa, sisters of people with anorexia nervosa and healthy controls) were analysed. Square wave jerk rate was acquired during a fixation task, and anxiety was measured with the State Trait Anxiety Inventory. RESULTS: Current anorexia nervosa, weight-restored from anorexia nervosa and sisters of people with anorexia nervosa groups made significantly more square wave jerks than healthy controls, but did not differ from one another. Square wave jerk rate and anxiety were found to discriminate groups with exceptionally high accuracy (current anorexia nervosa vs healthy control = 92.5%; weight-restored from anorexia nervosa vs healthy control = 77.5%; sisters of people with anorexia nervosa vs healthy control = 77.5%; p < .001). CONCLUSION: The combination of square wave jerk rate and anxiety was found to be a promising two-element marker for anorexia nervosa, and has the potential to be used as a biomarker or endophenotype to identify people at risk of anorexia nervosa and inform future treatments.

Effects of tracker location on the accuracy and precision of the Gazepoint GP3 HD for spectacle wearers.

Remote view eye-tracking systems are prone to errors when used on spectacle wearers due to reflections from the lenses and frame that result in inaccurate tracking. Traditionally, these trackers are situated below a computer monitor and the viewer's eye moments are recorded while they view the screen. Reflections may be influenced by the pantoscopic tilt of the spectacles, whereby the tilt angle causes incident light to be reflected to the camera. To overcome this problem, we propose mounting the tracker above the monitor to avoid these reflections and test the accuracy and precision of subjects with single vision spectacles, multifocals, and no correction, using both mounting positions. Experimental results showed that this alternate position had overall worse accuracy (4.06° ± 0.13) and precision (0.67° ± 0.05) compared to the standard configuration (2.15° ± 0.06 vs. 0.50° ± 0.03), with more invalid readings (5.91 vs. 19.19%) for single vision lens wearers. Multifocals performed better for the top-mounting position for the top portion of the monitor, suggesting higher-order aberrations from the bottom portion of the lens negatively impact data quality. Higher pantoscopic tilt angles displayed an improved accuracy for this alternate position (r(9) = - 0.69, p = 0.02), with superior accuracy for tilt angles greater than 14° compared to the standard configuration. This study quantifies the impact of spectacle wear on eye-tracking performance and suggests other alternate mounting positions may be viable in certain situations.

Surgical interventions for infantile nystagmus syndrome.

BACKGROUND: Infantile nystagmus syndrome (INS) is a type of eye movement disorder that can negatively impact vision. Currently, INS cannot be cured, but its effects can potentially be treated pharmacologically, optically, or surgically. This review focuses on the surgical interventions for INS. Despite the range of surgical interventions available, and currently applied in practice for the management of INS, there is no clear consensus, and no accepted clinical guidelines regarding the relative efficacy and safety of the various treatment options. A better understanding of these surgical options, along with their associated side effects, will assist clinicians in evidence-based decision-making in relation to the management of INS. OBJECTIVES: To assess the efficacy and safety of surgical interventions for INS. SEARCH METHODS: We searched CENTRAL, MEDLINE Ovid, Embase Ovid, ISRCTN registry, ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) to 3 July 2020, with no language restrictions. SELECTION CRITERIA: We included randomised controlled trials (RCTs) studying the efficacy and safety of surgical options for treating INS. DATA COLLECTION AND ANALYSIS: Our prespecified outcome measures were the change from baseline in: binocular best-corrected distance visual acuity; head posture; amplitude, frequency, intensity, and foveation period durations of the nystagmus waveform; visual recognition times; quality of life and self-reported outcome measures; incidence of adverse effects with a probable causal link to treatment; and permanent adverse effects after surgery. Two review authors independently screened titles and abstracts and full-text articles, extracted data from eligible RCTs, and judged the risk of bias using the Cochrane tool. We reached consensus on any disagreements by discussion. We summarised the overall certainty of the evidence using the GRADE approach. MAIN RESULTS: We only identified one eligible RCT (N = 10 participants), undertaken in India. This trial randomised participants to receive either a large retro-equatorial recession of the horizontal rectus muscle of 9 mm on the medial rectus and 12 mm on the lateral rectus, or a simple tenotomy and resuturing of the four horizontal rectus muscles. We did not identify any RCTs comparing a surgical intervention for INS relative to no treatment. In the single eligible RCT, both eyes of each participant received the same intervention. The participants' age and gender were not reported, nor was information on whether participants were idiopathic or had sensory disorders. The study only included participants with null in primary position and did not explicitly exclude those with congenital periodic alternating nystagmus. The study did not report funding source(s) or author declaration of interests. The evaluation period was six months. We judged this study at low risk for sequence generation and other sources of bias, but at high risk of bias for performance and detection bias. The risk of bias was unclear for selection bias, attrition bias, and reporting bias. There is very uncertain evidence about the effect of the interventions on visual acuity and change in amplitude, frequency, and intensity of the nystagmus waveform. We were unable to calculate relative effects due to lack of data. None of the participants in either intervention group reported adverse effects at six-month follow-up (very low-certainty evidence). There was no quantitative data reported for quality of life, although the study reported an improvement in quality of life after surgery in both intervention groups (very low-certainty evidence). Change in head posture, foveation period durations of the nystagmus waveform, visual recognition times, and permanent adverse effects after surgery were not reported in the included study. We judged the certainty of the evidence, for both the primary and secondary efficacy outcomes, to be very low. Due to a lack of comprehensive reporting of adverse events, there was also very low-certainty of the safety profile of the evaluated surgical interventions in this population. As such, we are very uncertain about the relative efficacy and safety of these interventions for the surgical management of INS. AUTHORS' CONCLUSIONS: This systematic review identified minimal high-quality evidence relating to the efficacy and safety of surgical interventions for INS. The limited availability of evidence must be considered by clinicians when treating INS, particularly given these procedures are irreversible and often performed on children. More high-quality RCTs are needed to better understand the efficacy and safety profile of surgical interventions for INS. This will assist clinicians, people with INS, and their parents or caregivers to make evidence-based treatment decisions.

Eye movements in anorexia nervosa: State or trait markers?

OBJECTIVE: Differences in saccadic eye movements are widely reported in mental illnesses, and can indirectly inform our understanding of neurobiological and cognitive underpinnings of psychiatric conditions, including anorexia nervosa (AN). Preliminary research has suggested that individuals with AN may show specific eye movement abnormalities; whether these deficits are representative of state or trait effects is, however, unclear. The aim of this study was to identify whether there are demonstrable differences in performance on saccadic eye movement tasks in individuals with current AN (c-AN), those who are weight-restored from AN (wr-AN), biological sisters of individuals with AN (AN-sis), and healthy controls (HC). METHODS: Eighty participants took part in the study (n = 20/group). A set of saccadic eye movement tasks was administered, including prosaccade, antisaccade, memory-guided saccade, and visual scanpath tasks. RESULTS: The c-AN group showed an increased rate of inhibitory errors to 10° targets on the memory-guided saccade task. DISCUSSION: The results are discussed in terms of the potential role of the superior colliculus in AN, and that the findings may reflect a state measure of AN.

Effects of age and visual attention demands on optokinetic nystagmus suppression.

INTRODUCTION: The utility of optokinetic nystagmus suppression as an index of visual attention has been demonstrated; however, a gap exists in our understanding of the effects of aging on attentional division. The purpose of this study was to explore the effect of a subject's age upon their ability to allocate visual attention among multiple salient elements which varied in location and complexity. METHOD: Large-field optokinetic nystagmus (OKN)-inducing animations were presented along with a central flashing fixation point to 27 subjects: 15 younger adults (range 19-23, mean age 21.4); and 12 older adults (range 65-89, mean age 74). Subjects were instructed to fixate on a central point while attending to either moving features of the background or solely to the fixation target. Failure of subjects to accurately divide their attention was quantified by optokinetic gain (eye velocity/background velocity). Gain was analysed in two separate 3-way ANOVAs: one at the central location with the between-subjects variable of age and within-subjects variables of complexity and dynamism; and one using only the dynamic tasks, including a between-subjects variable of age and within-subjects variables of complexity and location. RESULTS: A strong effect of age was found between subjects during the more attentionally demanding dynamic tasks, but there was only a marginal effect during the static tasks. All within-subjects variables were highly significant, and there were several significant 2- and 3-way interactions. CONCLUSION: This study provides strong evidence for the compounding effects of senescence and stimulus characteristics on an adult's ability to accurately allocate visual attention. These findings show that OKN suppression may be a useful framework for quantification of attentional resources in older subjects.

High-definition transcranial direct current stimulation in anorexia nervosa: A pilot study.

OBJECTIVE: Anorexia nervosa (AN) is a serious psychiatric condition often associated with poor outcomes. Biologically informed treatments for AN, such as brain stimulation, are lacking, in part due to the unclear nature of the neurobiological contributions to the illness. However, recent research has suggested a specific neurobiological target for the treatment of AN, namely stimulation of the inferior parietal lobe (IPL). The aim of this study was to stimulate-noninvasively-the left IPL in individuals with AN using high-definition transcranial direct current stimulation (HD-tDCS). METHOD: Twenty participants will be randomized to receive 10 daily sessions of HD-tDCS or sham HD-tDCS (placebo). Assessments will be carried out at baseline and end point, as well as 4- and 12-week follow-ups. DISCUSSION: This pilot investigation will primarily determine the feasibility and acceptability of this intervention.

White matter microstructure in anorexia nervosa.

The neurobiological underpinnings of anorexia nervosa (AN) are unclear. White matter deficits have been described in the illness, but findings are inconsistent between studies. The aim of this study was to investigate differences in white matter microstructure in AN using diffusion-weighted imaging (DWI). It was hypothesised that people with AN, relative to a healthy control (HC) group, would show decreased functional anisotropy (FA) and increased mean diffusivity (MD) in the fornix and superior longitudinal fasciculus, consistent with previous literature. Analyses were conducted on 23 females with AN and 26 age- and gender-matched HCs using tract-based spatial statistics (TBSS). The results revealed widespread FA decreases and MD increases in the AN group. Our hypothesis was largely supported, although FA differences were not specifically found in the fornix. The findings suggest extensive differences in white matter structure in AN, which may contribute to AN pathophysiology.

Cerebellar volume correlates with saccadic gain and ataxia in adult Niemann-Pick type C.

BACKGROUND AND PURPOSE: Cerebellar Purkinje cells are known to be highly vulnerable to neuronal pathology in Niemann-Pick type C (NPC), a disease where widespread white matter changes have also been reported. We sought to determine the relationship between white and grey matter cerebellar changes and clinical variables in NPC. MATERIALS AND METHODS: Ten adult patients with NPC were matched to control subjects (n=27) on age and gender. Patients were rated for symptom duration and severity, degree of ataxia, and were assessed for saccadic eye measures. Cerebellar white and grey matter volumes were automatically segmented using the Freesurfer software package. RESULTS: NPC patients had a significant reduction in both grey and white matter volumes. Volume did not correlate with symptom duration or severity, but did correlate with saccadic gain and ataxia measures. CONCLUSIONS: Both cerebellar grey and white matter volume decreases in adult NPC, and these changes are associated with impairments in saccadic gain and in motor control.

A guide to optometrists for appraising and using artificial intelligence in clinical practice.

Artificial intelligence systems are becoming increasingly available as diagnostic aids for optometric practice. These perform well but are often 'black-box' systems offering little or no insight into how a decision was reached. While there is potential for artificial intelligence to improve patient outcomes, clinicians without training in computer science may find it difficult to ascertain whether these technologies are suitable for their practice, or how they should be used. This review provides an overview of how artificial intelligence systems work in optometry, their strengths, weaknesses, and regulatory considerations. A checklist is provided for appraising a system, covering regulatory approvals, ascertaining what the system can and cannot do, how it can be used in practice, whether it is suitable for the clinical population, and whether the outputs can be explained. Artificial intelligence has the potential to improve accuracy and efficiency in many areas of optometry if used correctly, and should be embraced by clinicians as an assistive tool.

Video game training in traumatic brain injury patients: an exploratory case report study using eye tracking.

Remediation of attentional impairments is an essential component of cognitive rehabilitation after traumatic brain injury (TBI). Evidence from healthy participants has demonstrated attentional improvement following playing an action video game. This exploratory study investigated its application in TBI participants in a multiple baselines single case experimental design (SCED). Saccadic eye movements, recognized as the visible indicators of visual attention, were assessed to evaluate the effectiveness of the game training. Three severe TBI participants were trained in an action game for 10 hours. Saccadic eye movements during a self-paced saccade and an abstract visual search task were investigated during baseline, mid training and post-training. Using Percentage of Non-overlapping Data (PND), analysis showed consistent increase in the rate of the self-paced saccades in participants 1 (PND=80%) and 2 (PND=70%). In abstract search, fixation duration showed a minimally effective decrease for participant 2 (PND= 60%) and a moderately effective reduction in participant 3 (PND= 80%). Search time showed a highly effective reduction in participant 2 (PND = 100%) and moderately effective decrease in participant 3 (PND=70%). Overall, video game training might modify allocation of attention in eye movements. More evidence is required to validate the usefulness of this novel method of the cognitive training.

Developmental eye movement test: what is it really measuring?

PURPOSE: The Developmental Eye Movement (DEM) test is commonly used as a clinical visual-verbal ocular motor assessment tool. However, while the DEM test ratio has been reported to correlate with horizontal saccadic eye movements, there have been no published comparative studies of the DEM test and objective eye movement measures. The aim of this study was to compare DEM test performance with explicit quantification of saccadic eye movements, reading performance, symptomatology and visual processing speed, to assess the validity of the DEM test in clinical practice. METHODS: One hundred fifty-eight children aged 8 to 11 years completed the DEM test and a battery of eye movement tasks, recorded by a Microguide 1000 infrared eye tracker. All subjects completed a symptomatology survey. Reading performance and visual processing data was collected for 77 and 75 children, respectively. RESULTS: One hundred twenty-nine of the 158 subjects (81.65%) passed the DEM test. There was no significant correlation between any component of DEM test performance and quantitative eye movement parameters (gain, latency, asymptotic peak velocity, and number of corrective saccades) or symptomatology. There were significant correlations between DEM test outcome and reading performance, and with visual processing speed. CONCLUSIONS: DEM test performance does not correlate with saccadic eye movement skills or symptomatology. However, it is related to reading performance and visual processing speed. This study suggests that although DEM test times may not correlate directly with eye movement parameters, they do correlate with aspects of reading performance and thus may serve a diagnostic role in clinical practice.

Extraversion degrades performance on the antisaccade task.

Previous studies have suggested that baseline and task-related activity within the prefrontal cortex varies with the degree of extraversion; we examined whether this trait influenced performance on the antisaccade task, a measure commonly used in psychiatric and neurological disorders. Extraversion was assessed in young normal subjects using the Eysenck Personality Questionnaire-Revised Short-scale. Highly extraverted and highly introverted subjects' antisaccade errors and latencies were evaluated. Extraversion was associated with significantly more errors but did not influence the latency of either correct or erroneous responses. This effect on error rate but not latency is similar to that seen in schizotypal personality disorder, whereas normal ageing, as well as schizophrenia and attention deficit-hyperactivity disorder, increase errors and also delay saccade onset. This is the first study in a young, non-clinical population to show an influence of a normal personality dimension on an ocular motor measure.

Is experience in multi-genre video game playing accompanied by impulsivity?

Developing impulsivity has been one of the main concerns thought to arise from the increasing popularity of video gaming. Most of the relevant literature has treated gamers as pure-genre players (i.e. those who play only a specific genre of game). However, it is not clear how impulsivity is associated with different genres of games in multi-genre gamers, given that there is increasing diversity in the games played by individuals. In this study, we compared 33 gamers to 23 non-gamers in a go/no-go task: the Continuous Performance Test (CPT). To evaluate whether or not impulsivity occurs as a trade-off between speed and accuracy, we emphasised fast performance to all participants. Then, to examine the ability to predict impulsivity from game genre-hours, we fitted separate multiple regression models to several dependent variables. As an additional measure, we also compared groups in an antisaccade task. In the CPT, gamers showed a trend towards significantly faster reaction time (RT), accompanied by higher false alarm rate (FAR) and more risk-taking response bias (ß), suggesting impulsive responses. Interestingly, there was a significant negative correlation between RT and FAR across all participants, suggesting an overall speed-accuracy trade-off strategy, perhaps driven by the emphasis on speed during task instruction. Moreover, time spent on role playing games (RPG) and real-time strategy (RTS) games better predicted FAR and ß than did time spent on action and puzzle games. In the antisaccade task; however, gamers showed a shorter antisaccade latency but a comparable error rate in comparison with non-gamers. There was no specific game genre which could predict performance in the antisaccade task. Altogether, there was no evidence of oculomotor impulsivity in gamers; however, the CPT results suggested the presence of impulsive responses in gamers, which might be the result of a speed-accuracy trade-off. Furthermore, there was a difference in game genres, with time spent on RPG and RTS games being accompanied by greater probability of impulsive responses. Training studies are required to investigate the causality of different video game genres on the development of impulsivity.

The influence of action video game playing on eye movement behaviour during visual search in abstract, in-game and natural scenes.

Action game playing has been associated with several improvements in visual attention tasks. However, it is not clear how such changes might influence the way we overtly select information from our visual world (i.e. eye movements). We examined whether action-video-game training changed eye movement behaviour in a series of visual search tasks including conjunctive search (relatively abstracted from natural behaviour), game-related search, and more naturalistic scene search. Forty nongamers were trained in either an action first-person shooter game or a card game (control) for 10 hours. As a further control, we recorded eye movements of 20 experienced action gamers on the same tasks. The results did not show any change in duration of fixations or saccade amplitude either from before to after the training or between all nongamers (pretraining) and experienced action gamers. However, we observed a change in search strategy, reflected by a reduction in the vertical distribution of fixations for the game-related search task in the action-game-trained group. This might suggest learning the likely distribution of targets. In other words, game training only skilled participants to search game images for targets important to the game, with no indication of transfer to the more natural scene search. Taken together, these results suggest no modification in overt allocation of attention. Either the skills that can be trained with action gaming are not powerful enough to influence information selection through eye movements, or action-game-learned skills are not used when deciding where to move the eyes.

Infantile nystagmus: current concepts in diagnosis and management.

This review examines current approaches to the diagnosis and management of congenital forms of nystagmus. Emphasis is placed on diagnostic features that are amenable to clinical identification but those issues that can be addressed only with more detailed investigations, such as eye movement recording, are indicated. Non-surgical management, including prism spectacles, contact lenses and vision therapy, is discussed, as are surgical approaches. Because many aspects of congenital forms of nystagmus, particularly as experienced by patients with the condition in their normal lives, are poorly addressed in both the clinical and research literature, these limitations are also highlighted.

Divided visual attention: A comparison of patients with multiple sclerosis and controls, assessed with an optokinetic nystagmus suppression task.

Multiple sclerosis (MS) frequently causes impairment of cognitive function. We compared patients with MS with controls on divided visual attention tasks. The MS patients' and controls' stare optokinetic nystagmus (OKN) was recorded in response to a 24°/s full field stimulus. Suppression of the OKN response, judged by the gain, was measured during tasks dividing visual attention between the fixation target and a second stimulus, central or peripheral, static or dynamic. All participants completed the Audio Recorded Cognitive Screen. MS patients had lower gain on the baseline stare OKN. OKN suppression in divided attention tasks was the same in MS patients as in controls but in both groups was better maintained in static than in dynamic tasks. In only dynamic tasks, older age was associated with less effective OKN suppression. MS patients had lower scores on a timed attention task and on memory. There was no significant correlation between attention or memory and eye movement parameters. Attention, a complex multifaceted construct, has different neural combinations for each task. Despite impairments on some measures of attention, MS patients completed the divided visual attention tasks normally.

The effects of increased visual task demand on foveation in congenital nystagmus.

Commonly, when an individual with congenital nystagmus (CN) performs a visually demanding task their nystagmus intensifies and their visual acuity decreases, probably due to poorer foveation. However, the relationship between fixation attempt and nystagmus waveform has never been quantified. In this study 14 CN subjects viewed a Landolt C of varying orientation and size. They indicated its orientation via a button array whilst eye movements were recorded. Foveation was uncorrelated with optotype size. These results suggest that CN is not exacerbated by visual demand per se rather the need to do something visually demanding of importance to the individual.

Longitudinal assessment of reflexive and volitional saccades in Niemann-Pick Type C disease during treatment with miglustat.

BACKGROUND: Niemann-Pick Type C disease (NPC), is an autosomal recessive neurovisceral disorder of lipid metabolism. One characteristic feature of NPC is a vertical supranuclear gaze palsy particularly affecting saccades. However, horizontal saccades are also impaired and as a consequence a parameter related to horizontal peak saccadic velocity was used as an outcome measure in the clinical trial of miglustat, the first drug approved in several jurisdictions for the treatment of NPC. As NPC-related neuropathology is widespread in the brain we examined a wider range of horizontal saccade parameters and to determine whether these showed treatment-related improvement and, if so, if this was maintained over time. METHODS: Nine adult NPC patients participated in the study; 8 were treated with miglustat for periods between 33 and 61 months. Data were available for 2 patients before their treatment commenced and 1 patient was untreated. Tasks included reflexive saccades, antisaccades and self-paced saccades, with eye movements recorded by an infrared reflectance eye tracker. Parameters analysed were reflexive saccade gain and latency, asymptotic peak saccadic velocity, HSEM-α (the slope of the peak duration-amplitude regression line), antisaccade error percentage, self-paced saccade count and time between refixations on the self-paced task. Data were analysed by plotting the change from baseline as a proportion of the baseline value at each test time and, where multiple data values were available at each session, by linear mixed effects (LME) analysis. RESULTS: Examination of change plots suggested some modest sustained improvement in gain, no consistent changes in asymptotic peak velocity or HSEM-α, deterioration in the already poor antisaccade error rate and sustained improvement in self-paced saccade rate. LME analysis showed statistically significant improvement in gain and the interval between self-paced saccades, with differences over time between treated and untreated patients. CONCLUSIONS: Both qualitative examination of change scores and statistical evaluation with LME analysis support the idea that some saccadic parameters are robust indicators of efficacy, and that the variability observed across measures may indicate locally different effects of neurodegeneration and of drug actions.

Self perception and facial emotion perception of others in anorexia nervosa.

BACKGROUND: Whether individuals with anorexia nervosa (AN) are able to accurately perceive emotions from faces of others is unclear. Furthermore, whether individuals with AN process images of their own face differently to healthy individuals has thus far not been investigated. Therefore, the aim of this study was to investigate facial affect processing and the processing of one's own face through measures of emotion identification, functional magnetic resonance imaging (fMRI) and eyetracking. METHODS: Twenty-four females with AN and 25 matched healthy control participants were presented with an implicit emotion processing task during fMRI and eyetracking, followed by an explicit emotion identification task. RESULTS: The AN group were found to 'hyperscan' stimuli and avoided visually attending to salient features of their own face images. RESULTS of the fMRI revealed increased activity to own face stimuli in AN in the right inferior and middle temporal gyri, and right lingual gyrus. AN participants were not found to display emotion identification deficits to the standard emotional face stimuli. DISCUSSION: The findings are discussed in terms of increased anxiety to disorder-relevant stimuli in AN. Potential clinical implications are discussed in relation to the use of eyetracking techniques to improve the perception of self in AN.