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.

IntroductionNumerous studies have shown that adults with depression have distinct oculomotor alterations during saccade tasks, but whether similar alterations occur in adolescents is largely unknown. The purpose of the present study was to test if eye-tracking during a structured saccade task could distinguish a group of adolescents with depression from healthy controls. We hypothesized that, due to overlapping circuitry between depression pathology and the oculomotor system, adolescents with depression would show alterations in fixation, saccade, and pupil behaviour.Methods51 adolescents with depression and 66 age-matched healthy controls completed the Interleaved Pro- and Anti-Saccade Task (IPAST) and several self-reported questionnaires for psychiatric symptoms. Oculomotor outcomes included fixatioy -40n acquisition, fixation breaks, correct rate, saccadic reaction time, rate of correct express-latency pro-saccades, rate of express- and regular-latency anti-saccade errors, baseline pupil size, as well as pupil constriction and dilation sizes following task instruction.ResultsIn comparison to healthy controls, adolescents with depression displayed impairments acquiring fixation, made more fixation breaks in pro- and anti-saccade trials, more anti-saccade errors, more express-latency saccades overall, had a smaller pupil constriction in pro-saccade trials and had a smaller pupil dilation in pro- and anti-saccade trials. No differences were found for saccadic reaction time, rate of correct pro-saccades, rate of regular-latency anti-saccade errors, pupil constriction size during anti-saccade trials, or baseline pupil size.LimitationsPatients had psychiatric comorbidities and were using psychotropic medication. While this reflected clinical reality, these factors may have influenced oculomotor behaviour.ConclusionsAdolescents with depression had altered fixation, saccade, and pupil behaviour during IPAST. Given that many cases of adolescent depression remain undetected, accessible and objective screening approaches are highly needed. This oculomotor phenotype may be used in the development of such a screening tool to detect those at risk.

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.

Psychiatry lacks objective biomarkers for assessing depression, relying instead on subjective measures, such as the Hamilton Depression Rating Scale (HAMD-17). This study examined whether speech features could serve as objective markers of depressive symptoms and its associated cognitive difficulties. Sixty-six individuals with major depressive disorder (MDD) and 54 non-depressed control participants completed a speech assessment, responding to the prompt: “Please tell me how you are feeling today.” Linguistic (valence, emotional intensity, agency) and acoustic (pitch, pitch variance, speech rate, time spent pausing) features were derived from natural language processing. These speech features were analyzed individually and collectively as a composite score representing overall speech disturbance. A subset of participants (40 with MDD, 38 controls) also completed a validated executive function task. ANCOVA models compared speech features between groups. Linear regression models examined associations between speech features, depression severity (HAMD-17), and performance on an executive function task. Compared to controls, individuals with MDD used language that was more negatively valenced, emotionally intense, and less agentic. They also demonstrated lower pitch, slower speech rate, and more time spent pausing. The composite speech score also differed between groups. Speech features and executive function were not associated with depression severity, as measured by the HAMD-17. However, several speech features were associated with executive function. Taken together, these findings suggest that speech features may provide a scalable, objective method for detecting depressive symptoms and associated executive difficulties.

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.

Demyelination disrupts the transmission of electrical signals in the brain and affects neurodevelopment in children with disorders such as multiple sclerosis and myelin oligodendrocyte glycoprotein-associated disorders. Although cognitive impairments are prevalent in these conditions, some children maintain cognitive function despite substantial structural injury. These findings raise an important question: in addition to the degenerative process, do compensatory neural mechanisms exist to mitigate the effects of myelin loss? We propose that a multi-dimensional approach integrating multiple neuroimaging modalities, including diffusion tensor imaging, magnetoencephalography and eye-tracking, is key to investigating this question. We examine the structural and functional connectivity of the default mode and executive control networks due to their significant roles in supporting higher-order cognitive processes. As cognitive proxies, we examine saccade reaction times and direction errors during an interleaved pro- (eye movement towards a target) and anti-saccade (eye movement away from a target) task. 28 typically developing children, 18 children with multiple sclerosis and 14 children with myelin oligodendrocyte glycoprotein-associated disorders between 5 and 18.9 years old were scanned at the Hospital for Sick Children. Tractography of diffusion MRI data examined structural connectivity. Intracellular and extracellular microstructural parameters were extracted using a white matter tract integrity model to provide specific inferences on myelin and axon structure. Magnetoencephalography scanning was conducted to examine functional connectivity. Within groups, participants had longer saccade reaction times and greater direction errors on the anti- versus pro-saccade task; there were no group differences on either task. Despite similar behavioural performance, children with demyelinating disorders had significant structural compromise and lower bilateral high gamma, higher left-hemisphere theta and higher right-hemisphere alpha synchrony relative to typically developing children. Children diagnosed with multiple sclerosis had greater structural compromise relative to children with myelin oligodendrocyte glycoprotein-associated disorders; there were no group differences in neural synchrony. For both patient groups, increased disease disability predicted greater structural compromise, which predicted longer saccade reaction times and greater direction errors on both tasks. Structural compromise also predicted increased functional connectivity, highlighting potential adaptive functional reorganisation in response to structural compromise. In turn, increased functional connectivity predicted faster saccade reaction times and fewer direction errors. These findings suggest that increased functional connectivity, indicated by increased alpha and theta synchrony, may be necessary to compensate for structural compromise and preserve cognitive abilities. Further understanding these compensatory neural mechanisms could pave the way for the development of targeted therapeutic interventions aimed at enhancing these mechanisms, ultimately improving cognitive outcomes for affected individuals.

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.

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.

BACKGROUND: Borderline personality disorder (BPD) is associated with heightened impulsivity, evidenced by increased substance abuse, self-harm, and suicide attempts. Addressing impulsivity in individuals with BPD is a therapeutic objective, but its underlying neural basis in this clinical population remains unclear, partly due to its frequent comorbidity with attention-deficit/hyperactivity disorder (ADHD). METHODS: We used a response inhibition paradigm-the interleaved pro-/antisaccade task-among adolescents diagnosed with BPD with and without comorbid ADHD (n = 25 and n = 24, respectively) during concomitant video-based eye tracking. We quantified various eye movement response parameters reflective of impulsive action during the task, including delay to fixation acquisition, fixation breaks, anticipatory saccades, and direction errors with express saccade (saccade reaction time: 90-140 ms) and regular saccade latencies (saccade reaction time RESULTS: Individuals with BPD exhibited deficient response preparation, as evidenced by reduced visual fixation on task cues and greater variability of saccade responses (i.e., saccade reaction time and peak velocity). The ADHD/BPD group shared these traits and made more anticipatory responses and direction errors with express saccade latencies and reduced error correction. CONCLUSIONS: Saccadic deficits in BPD and ADHD/BPD stemmed not from an inability to execute antisaccades but rather from inadequate preparation for the upcoming task set. These distinctions may arise due to abnormal signaling in cortical areas like the frontal eye fields, posterior parietal cortex, and anterior cingulate cortex. Understanding these mechanisms could provide insights into targeted interventions focusing on task set preparation to manage response inhibition deficits in BPD and ADHD/BPD.

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.

Abstract Oculomotor tasks generate a potential wealth of behavioural biomarkers for neurodegenerative diseases. Overlap between oculomotor and disease-impaired circuitry reveals the location and severity of disease processes via saccade parameters measured from eye movement tasks such as prosaccade and antisaccade. Existing studies typically examine few saccade parameters in single diseases, using multiple separate neuropsychological test scores to relate oculomotor behaviour to cognition; however, this approach produces inconsistent, ungeneralizable results and fails to consider the cognitive heterogeneity of these diseases. Comprehensive cognitive assessment and direct inter-disease comparison are crucial to accurately reveal potential saccade biomarkers. We remediate these issues by characterizing 12 behavioural parameters, selected to robustly describe saccade behaviour, derived from an interleaved prosaccade and antisaccade task in a large cross-sectional data set comprising five disease cohorts (Alzheimer’s disease/mild cognitive impairment, amyotrophic lateral sclerosis, frontotemporal dementia, Parkinson’s disease, and cerebrovascular disease; n = 391, age 40–87) and healthy controls (n = 149, age 42–87). These participants additionally completed an extensive neuropsychological test battery. We further subdivided each cohort by diagnostic subgroup (for Alzheimer’s disease/mild cognitive impairment and frontotemporal dementia) or degree of cognitive impairment based on neuropsychological testing (all other cohorts). We sought to understand links between oculomotor parameters, their relationships to robust cognitive measures, and their alterations in disease. We performed a factor analysis evaluating interrelationships among the 12 oculomotor parameters and examined correlations of the four resultant factors to five neuropsychology-based cognitive domain scores. We then compared behaviour between the abovementioned disease subgroups and controls at the individual parameter level. We theorized that each underlying factor measured the integrity of a distinct task-relevant brain process. Notably, Factor 3 (voluntary saccade generation) and Factor 1 (task disengagements) significantly correlated with attention/working memory and executive function scores. Factor 3 also correlated with memory and visuospatial function scores. Factor 2 (pre-emptive global inhibition) correlated only with attention/working memory scores, and Factor 4 (saccade metrics) correlated with no cognitive domain scores. Impairment on several mostly antisaccade-related individual parameters scaled with cognitive impairment across disease cohorts, while few subgroups differed from controls on prosaccade parameters. The interleaved prosaccade and antisaccade task detects cognitive impairment, and subsets of parameters likely index disparate underlying processes related to different cognitive domains. This suggests that the task represents a sensitive paradigm that can simultaneously evaluate a variety of clinically relevant cognitive constructs in neurodegenerative and cerebrovascular diseases and could be developed into a screening tool applicable to multiple diagnoses.