Humans blink their eyes 16-20 times each minute to spread tear film on the cornea, representing a substantial amount of waking time when one's eyes are closed. These spontaneous blinks are strategically timed to prioritize the processing of important visual input, balancing both stimulus characteristics and personal goals. Until now, the learning process underlying blink timing has not been investigated in detail. Here, we present video-based eye-tracking data from 703 healthy participants (aged 5-91 years, 470 female) performing a structured interleaved prosaccade/antisaccade task, in which we previously found that blinks are suppressed in anticipation of visual stimulus appearance. Our goals are to understand (1) how participants modify their blink timing according to the temporal contingencies of the task, (2) whether the capacity to do so impacts performance, and (3) whether this pattern varies with age. We found evidence that participants quickly adapted their blink timing to minimize co-occurrence with task-relevant stimuli. Blink probability decreased in periods that would compromise antisaccade execution and increased when visual input was less critical. We also found significant differences in blink timing and in the rate of blink adaptation across the task for participants with low versus high error rates. Furthermore, the rate of blink adaptation increased gradually from childhood to early adulthood and then decreased with advanced age. This work supports a possible link between the regulation of blink behavior and lifespan changes in learning capacity and inhibitory control.

Background: Functional motor disorder (FMD) is a common and disabling condition with incompletely understood pathophysiology. Eye-tracking offers a method to objectively examine cognitive and motor control processes and their underlying neural pathways. We aimed to quantify saccade, blink and pupil responses in FMD and healthy controls performing an interleaved pro-/anti-saccade task, and to investigate the relationships between oculomotor measures and motor and non-motor symptom severity. Methods: We conducted video-based eye-tracking in 104 patients with clinically definite FMD and 115 age- and sex-matched healthy controls performing the saccade task. Patients completed questionnaires on depressive, pain-related, dissociative, non-motor somatic symptoms. Clinician-rated motor severity and centrally acting medication was recorded in FMD patients. Results: Compared to controls, FMD patients showed increased anti-saccade error rates (p < 0.001), anticipatory saccades (p ≤ 0.003), altered blink distribution (p < 0.001), and reduced pupil dilation velocity (p < 0.001). However, reduced pupil dilation velocity was not significant in subsample of unmedicated patients. Higher anti-saccade error rates were significantly associated with depressive symptoms, pain severity, dissociative symptoms, non-motor somatic symptom burden, and motor severity (all p < 0.05). Conclusions: We hypothesize that the altered saccade and blink responses result from altered processing in the frontal cortex and basal ganglia which provide critical input to brainstem oculomotor control areas in FMD. These results support neurobiological models proposing altered predictive and attentional processing underlying FMD. Association between oculomotor measures and symptom severity suggests that specific cognitive abnormalities may play a role in the pathophysiology of these symptoms in FMD. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was supported by the Czech Ministry of Health (NW24-04-00456 and MH CZ-DRO-VFN00064165) and by the Czech Ministry of Education, Youth and Sports /EU ERDF-Project Brain Dynamics, No. CZ.02.01.01/00/22_008/0004643. Funding support also came from the Canadian Institutes of Health Research (MOP-FDN-148418 and PJT-190028 to DPM). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics committee of the General University Hospital in Prague (approval no. 37/19), gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors.

BACKGROUND:Eye tracking may be a useful tool to screen for abnormalities in children with opsoclonus-myoclonus-ataxia syndrome (OMAS). Our objectives were to (1) evaluate differences in cognitive metrics and free-viewing eye tracking metrics between children with a diagnosis of OMAS and age- and sex-matched healthy controls; and (2) investigate correlations between both metrics. METHODS:Participants (2-16 years old) with a diagnosis of OMAS (n = 9) and healthy controls (n = 14) completed a free-viewing eye-tracking task (EyeLink 1000 Plus) and cognitive testing (5 cognitive domains; NIH Toolbox). We quantified saccades and ran correlational analyses with corrected cognitive testing scores. RESULTS:Children with a diagnosis of OMAS demonstrated suppressed saccade rates and longer fixation durations. Higher mean saccade rates were positively associated with better performance on the Dimensional Change Card Sort task (P = 0.011) and the List Sorting Working Memory Test (P = 0.001), while longer fixation durations were negatively associated with performance on both the Dimensional Change Card Sort task (P = 0.001) and the List Sorting Working Memory Test (P = 0.014). CONCLUSIONS:Reduced saccade rates and longer fixation durations in the free-viewing eye-tracking task were associated with worse cognitive functioning related to set-shifting and working memory. The study introduces a potential new screening tool to increase accessibility for younger patients with OMAS to some proxy for formal cognitive testing.

Freezing of gait is a debilitating motor symptom in Parkinson's disease that significantly increases fall risk and impairs quality of life. The poorly understood pathophysiology of freezing of gait presents challenges for early prediction and therapeutic intervention. This prospective study investigated whether eye movement abnormalities, specifically in the anti-saccade paradigm, could predict freezing of gait onset in Parkinson's disease patients over a two-year follow-up period. We analysed longitudinal data from the Ontario Neurodegenerative Disease Research Initiative, focusing on Parkinson's disease patients without freezing of gait at baseline who underwent comprehensive clinical evaluations and eye movement recordings. Anti-saccade reaction time and error ratio, combined with clinical measures including right upper extremity rigidity, demonstrated significant predictive value for freezing of gait development within two years. These findings suggest that eye movement deficits and upper limb rigidity emerge years before freezing of gait onset, indicating a prodromal phase in freezing of gait pathogenesis. The predictive relationship between these measures supports the hypothesis of shared neural substrates, potentially involving the mesencephalic locomotor region, in the development of both oculomotor dysfunction and gait freezing episodes.

Canada and the United States are both aging and becoming increasingly diverse. Despite this demographic shift, non-White racial/ethnic groups remain underrepresented in research on cognitive impairment and dementia. A major barrier to inclusivity is the lack of cognitive assessments that are valid in individuals with diverse language and cultural backgrounds. Eye tracking tasks can potentially overcome this barrier since they do not require verbal responses and use culturally neutral stimuli. Here, we tested this hypothesis by comparing performance on standard neuropsychological tests and eye tracking tasks across individuals from White and underrepresented ethnic groups (UEG). Participants were cognitively unimpaired adults enrolled in the Canadian Multi-Ethnic Research on Aging (CAMERA) study. Participants completed a battery of standard neuropsychological tests and two well-characterized eye tracking tasks: the interleaved pro/anti-saccade task (IPAST), which assesses executive function, and the visual paired comparison task (VPCT), which assesses visual memory. We included 54 participants (mean age=68.68±6.91, 70% female) with a Clinical Dementia Rating global score of 0. Among them, 22% of participants self-identified as White (n=12) and the remaining participants identified as being from an UEG (n=42; 37% East Asian, 37% South Asian, 4% Other). Linear regression models assessed whether ethnic background (White vs. UEG) was associated with task performance after adjusting for age, sex, and years of education. We found that ethnic background influenced performance on several standard neuropsychological tests, including the MoCA (β=0.26, p=0.03), phonemic fluency (β=0.29, p=0.02), category fluency (β=0.38, p=0.003), and Benson Complex Figure delay (β=0.23, p=0.08), such that the UEG group had lower scores. There were no group differences on Trails A and B or the Symbol Digit Modalities Test (p-values>0.1). Importantly, ethnic background did not influence performance on either eye tracking task (IPAST: β=-0.17, p=0.17; VPCT: β=0.02, p=0.83). Our preliminary results suggest that ethnic background influences performance on several standard neuropsychological tests, but not performance on the IPAST or VPCT. With further validation in larger samples, these eye tracking tasks may provide a brief and language-free way to screen and monitor cognitive impairment in diverse samples currently underrepresented in dementia research.

In Parkinson’s Disease, key brain regions involved in generating saccades and producing adaptive anticipatory behaviour are impacted, however the intersection of these deficits is not well characterized. Effective Parkinson’s Disease biomarkers are lacking, and video-based eye tracking provides a low-cost, non-invasive means to quantify eye-movement behaviour and address this knowledge gap. In a preliminary study, we analyzed predictive saccade behaviour in eight Parkinson’s patients (ON and OFF medication) and twenty controls aged 51-80 years. Participants performed a visual metronome task, moving their eyes in synchrony with a visual target jumping at a fixed rate on a computer screen. This was contrasted with a random task where the timing of target jumps was not predictable. Saccades made in anticipation of target appearance were classified as predictive, while those made significantly after were classified as reactive. There were no significant differences in saccadic metrics (i.e., reaction time, peak velocity, and amplitude) between groups. Parkinson’s Disease’s impact on saccade reaction time and predictive saccade generation was subtle, however these patients generated multi-stepping, hypometric saccades with reduced velocity compared to controls. The effects of dopaminergic medication on saccade metrics were inconsistent, with some improvement of saccade amplitude. Weak to moderate correlations were obtained between saccade metrics and disease severity and duration. This pilot study contributes to the understanding of saccade performance in evaluating the neural underpinnings of motor impairments in Parkinson’s Disease. Further investigation with more participant recruitment will be necessary to identify which saccade features are sensitive and specific to Parkinson’s Disease.

Background Saccade, pupil, and blink control are impaired in patients with α-synucleinopathies (αSYN): Parkinson's disease (PD) and multiple system atrophy (MSA). Isolated REM (rapid eye movement) Sleep Behavior Disorder (iRBD) is a prodromal stage of PD and MSA and a prime candidate for investigating early oculo-pupillo-motor abnormalities that may precede or predict conversion to clinically manifest αSYN. Objective Determine whether saccade, pupil, and blink responses in iRBD are normal or similar to those identified in PD and MSA. Methods Video-based eye-tracking was conducted with 68 patients with iRBD, 49 with PD, 17 with MSA, and 95 healthy controls (CTRL) performing an interleaved pro-/anti-saccade task that probed sensory, motor, and cognitive processes involved in eye movement control. Results Horizontal saccade and blink behavior was intact in iRBD, but abnormal in PD and MSA. iRBD patients, however, demonstrated reduced pupil dilation size, which closely resembled the changes found in PD and MSA. In the iRBD group, the extent of these pupillary changes appeared to correlate with the degree of hyposmia and reduction in dopamine transporter imaging signal. Conclusions Pupil abnormalities were present in iRBD, but blink and horizontal saccade responses were intact. Future longitudinal studies are required to determine which prodromal pupil abnormalities predict conversion from iRBD to PD or MSA and to identify the time window, in relation to conversion, when horizontal saccade responses become abnormal.

Oculomotor behaviour changes in patients with Parkinson’s disease (PD) are a promising source of prodromal disease markers. Capitalizing on this phenomenon to facilitate early diagnosis requires oculomotor assessment in prodromal cohorts. We examined oculomotor behaviour in non-manifesting LRRK2 G2019S mutation carriers (LRRK2-NM), who have heightened PD risk. Seventeen LRRK2-NM participants, 47 patients with idiopathic PD, and 63 healthy age-matched control participants completed an interleaved pro- and antisaccade task while undergoing video-based eye-tracking. We analyzed between-group differences in saccade, pupil, blink, and fixation acquisition behaviour. Patients with PD showed previously demonstrated abnormalities (saccade hypometria, antisaccade errors). Relative to controls, LRRK2-NM participants and patients with PD both displayed increased short-latency prosaccades and reduced pupil velocity, plus altered fixation acquisition—less preemptive returning of gaze to the future fixation point location. Interestingly, the effect on blink probability was opposite—higher than controls in LRRK2-NM participants but lower in patients with PD. Future longitudinal studies must confirm the viability of these features as prodromal PD markers.

The pupil is modulated by luminance, arousal, bottom-up sensory, and top-down cognitive signals, and has increasingly been used to assess these aspects of brain functioning in health and disease. However, changes in pupil dynamics across the lifespan have not been extensively examined, hindering our ability to fully utilize the pupil in probing these underlying neural processes in development and aging in healthy and clinical cohorts. Here, we examined pupil responses during the interleaved pro-/anti-saccade task (IPAST) in healthy participants across the lifespan (n = 567, 5-93 years of age). Based on the extracted measurements of pupil dynamics, we demonstrated age-related changes in pupil measures and task modulation. Moreover, we characterized the underlying factors and age-related effects in components of pupil responses that may be attributed to developmental and aging changes in the associated brain regions. Finally, correlations between factors of pupil dynamics and saccade behaviors revealed evidence of shared neural processes in the pupil and saccade control circuitries. Together, these results demonstrate changes in pupil dynamics as a result of development and aging, providing a baseline with which altered pupil responses due to neurological deficits at different ages can be studied.

Objective Video-based eye tracking was used to investigate saccade, pupil, and blink abnormalities among patients with Huntington’s disease (HD) who watched sequences of short videos. HD, an autosomal dominant neurodegenerative disorder resulting from a CAG mutation on chromosome 4, produces motor and cognitive impairments including slow or irregular eye movements, which have been studied using structured tasks. Methods To explore how HD affects eye movements under instruction free conditions, we assessed 22 HD patients and their age matched controls in a 10-minute video-based free viewing task. Results Patients with HD experienced a significant reduction in saccade exploration rate following video clip transitions, an increase in pupil reactions to luminance changes after clip transitions, and a significant higher blink rate throughout the task compared to the control group. Conclusions These results show that HD has a significant impact on how patients visually explore and respond to their environment under unconstrained and ecologically natural conditions. Significance Eye tracking in HD patients revealed saccadic, pupil, and blink abnormalities in early HD patients, suggestive of brain circuitry abnormalities that probably involve brain stem deficits. Further research should explore the impact of these changes on the quality of life of the patients affected by the disease.

Introduction Epilepsy is a common neurological disorder characterised by recurrent seizures. Almost half of patients who have an unprovoked first seizure (UFS) have additional seizures and develop epilepsy. No current predictive models exist to determine who has a higher risk of recurrence to guide treatment. Emerging evidence suggests alterations in cognition, mood and brain connectivity exist in the population with UFS. Baseline evaluations of these factors following a UFS will enable the development of the first multimodal biomarker-based predictive model of seizure recurrence in adults with UFS.Methods and analysis 200 patients and 75 matched healthy controls (aged 18–65) from the Kingston and Halifax First Seizure Clinics will undergo neuropsychological assessments, structural and functional MRI, and electroencephalography. Seizure recurrence will be assessed prospectively. Regular follow-ups will occur at 3, 6, 9 and 12 months to monitor recurrence. Comparisons will be made between patients with UFS and healthy control groups, as well as between patients with and without seizure recurrence at follow-up. A multimodal machine-learning model will be trained to predict seizure recurrence at 12 months.Ethics and dissemination This study was approved by the Health Sciences and Affiliated Teaching Hospitals Research Ethics Board at Queen’s University (DMED-2681-22) and the Nova Scotia Research Ethics Board (1028519). It is supported by the Canadian Institutes of Health Research (PJT-183906). Findings will be presented at national and international conferences, published in peer-reviewed journals and presented to the public via patient support organisation newsletters and talks.Trial registration number NCT05724719.

Spontaneous eye blinking is gaining popularity as a proxy for higher cognitive functions, as it is readily modulated by both environmental demands and internal processes. Prior studies were impoverished in sample size, sex representation, and age distribution, making it difficult to establish a complete picture of the behavior. Here we present eye-tracking data from a large cohort of normative participants (n = 604; 393 F; aged 5-93 years) performing two tasks: one with structured, discrete trials (interleaved pro-/anti-saccade task, IPAST) and one with a less structured, continuous organization in which participants watch movies (free-viewing; FV). Sex- and age-based analyses revealed that females had higher blink rates between the ages of 22 and 58 years in the IPAST and 22 and 34 years in FV. We derived a continuous measure of blink probability to reveal behavioral changes driven by stimulus appearance in both paradigms. In the IPAST, blinks were suppressed near stimulus appearance, particularly on correct anti-saccade trials, which we attribute to the stronger inhibitory control required for anti-saccades compared with pro-saccades. In FV, blink suppression occurred immediately after scene changes, and the effect was sustained on scenes where gaze clustered among participants (indicating engagement of attention). Females were more likely than males to blink during appearance of novel stimuli in both tasks, but only within the age bin of 18-44 years. The consistency of blink patterns in each paradigm endorses blinking as a sensitive index for changes in visual processing and attention, while sex and age differences drive interindividual variability.

AbstractObjectiveThis study measured eye movements in children with a history of opsoclonus‐myoclonus ataxia syndrome in order to identify abnormalities in saccade and pupil behavior that map onto specific alterations in brainstem pathways.MethodsWe used video‐based eye tracking while participants freely viewed 10 min of short (2–4 s) video clips without instructions. Clip transitions represented a large visual perturbation and we quantified multiple characteristics of saccade and pupil responses following these transitions in 13 children recovering from opsoclonus‐myoclonus and 13 healthy, age‐matched control participants.ResultsThe frequency of saccades and distribution of fixation durations differed between the groups. Following the clip transitions, children recovering from opsoclonus‐myoclonus ataxia syndrome exhibited longer time to initiate saccades, leading to a delay in harvesting visual information. Clip transitions to lighter clips produced similar pupil constriction responses in the two groups. However, clip transitions to darker clips produced dilation responses that were initiated earlier and of greater magnitude in opsoclonus‐myoclonus ataxia syndrome, suggesting removal or suppression of a signal that delays dilation.InterpretationChildren with a history of opsoclonus‐myoclonus ataxia syndrome demonstrated key abnormalities in saccade and pupil metrics. We propose a novel hypothesis in which dysfunction in the pathway from the superior colliculus to the mesencephalic and pontine reticular formation that houses the saccade and pupil premotor circuits could produce these results.

ABSTRACT: Background/Objective: Identifying a patient’s dominant language hemisphere is an important evaluation performed prior to epilepsy surgery and is commonly assessed using functional magnetic resonance imaging (fMRI). However, the lack of standardization and resultant heterogeneity of fMRI paradigms used in clinical practice limits the ability of cross-center comparisons to be made regarding language laterality results. Methods: Through surveying Canadian Epilepsy Centres in combination with reviewing supporting literature, current fMRI language lateralization practices for the clinical evaluation of patients with epilepsy were assessed. To encourage standardization of this practice, we outlined a two-part paradigm series that demonstrates widespread acceptance, reliability and accessibility in lateralizing various aspects of language functioning in individuals with average or near-average IQ and normal literacy skills. Results: The collected data confirm a lack of standardization in fMRI laterality assessments leading to clinical heterogeneity in stimulation and control tasks, paradigm design and timing, laterality index calculations, thresholding values and analysis software and technique. We suggest a Sentence Completion (SC) and Word Generation (WG) paradigm series as it was most commonly employed across Canada, demonstrated reliability in lateralizing both receptive and expressive language areas in supporting literature, and could be readily intelligible to an inclusive population. Conclusion: Through providing recommendations for a two-part paradigm series, we hope to contribute to the standardization of this practice across Canada to reduce clinical heterogeneity, encourage communicability between institutions, and enhance methodologies for the surgical treatment of epilepsy for the benefit of all individuals living with epilepsy in Canada.

Abstract Background The oculomotor circuit spans many cortical and subcortical areas that have been implicated in psychiatric disease. This, combined with previous findings, suggests that eye tracking may be a useful method to investigate eating disorders. Therefore, this study aimed to assess oculomotor behaviors in youth with and without an eating disorder. Methods Female youth with and without an eating disorder completed a structured task involving randomly interleaved pro-saccade (toward at a stimulus) and anti-saccade (away from stimulus) trials with video-based eye tracking. Differences in saccades (rapid eye movements between two points), eye blinks and pupil were examined. Results Youth with an eating disorder (n = 65, M age = 17.16 ± 3.5 years) were compared to healthy controls (HC; n = 65, M age = 17.88 ± 4.3 years). The eating disorder group was composed of individuals with anorexia nervosa (n = 49), bulimia nervosa (n = 7) and other specified feeding or eating disorder (n = 9). The eating disorder group was further divided into two subgroups: individuals with a restrictive spectrum eating disorder (ED-R; n = 43) or a bulimic spectrum eating disorder (ED-BP; n = 22). In pro-saccade trials, the eating disorder group made significantly more fixation breaks than HCs (F(1,128) = 5.33, p = 0.023). The ED-BP group made the most anticipatory pro-saccades, followed by ED-R, then HCs (F(2,127) = 3.38, p = 0.037). Groups did not differ on rate of correct express or regular latency pro-saccades. In anti-saccade trials, groups only significantly differed on percentage of direction errors corrected (F(2, 127) = 4.554, p = 0.012). The eating disorder group had a significantly smaller baseline pupil size (F(2,127) = 3.60, p = 0.030) and slower pro-saccade dilation velocity (F(2,127) = 3.30, p = 0.040) compared to HCs. The ED-R group had the lowest blink probability during the intertrial interval (ITI), followed by ED-BP, with HCs having the highest ITI blink probability (F(2,125) = 3.63, p = 0.029). Conclusions These results suggest that youth with an eating disorder may have different oculomotor behaviors during a structured eye tracking task. The oculomotor behavioral differences observed in this study presents an important step towards identifying neurobiological and cognitive contributions towards eating disorders.

The tremendous increase in the use of video-based eye tracking has made it possible to collect eye tracking data from thousands of participants. The traditional procedures for the manual detection and classification of saccades and for trial categorization (e.g., correct vs. incorrect) are not viable for the large datasets being collected. Additionally, video-based eye trackers allow for the analysis of pupil responses and blink behaviors. Here, we present a detailed description of our pipeline for collecting, storing, and cleaning data, as well as for organizing participant codes, which are fairly lab-specific but nonetheless, are important precursory steps in establishing standardized pipelines. More importantly, we also include descriptions of the automated detection and classification of saccades, blinks, “blincades” (blinks occurring during saccades), and boomerang saccades (two nearly simultaneous saccades in opposite directions where speed-based algorithms fail to split them), This is almost entirely task-agnostic and can be used on a wide variety of data. We additionally describe novel findings regarding post-saccadic oscillations and provide a method to achieve more accurate estimates for saccade end points. Lastly, we describe the automated behavior classification for the interleaved pro/anti-saccade task (IPAST), a task that probes voluntary and inhibitory control. This pipeline was evaluated using data collected from 592 human participants between 5 and 93 years of age, making it robust enough to handle large clinical patient datasets. In summary, this pipeline has been optimized to consistently handle large datasets obtained from diverse study cohorts (i.e., developmental, aging, clinical) and collected across multiple laboratory sites.