Engineering topics

Leland S Stone

Publications and source records attributed to Leland S Stone.

7 records

NASA NTRS2024

Oculometric Biomarkers of Visuomotor Deficits in Clinically Asymptomatic Patients With Systemic Lupus Erythematosus Undergoing Long-Term Hydroxychloroquine Treatment

Introduction: This study examines a set of oculomotor measurements, or “oculometric” biomarkers, as potential early indicators of visual and visuomotor deficits due to retinal toxicity in asymptomatic Systemic Lupus Erythematosus (SLE) patients on long-term hydroxychloroquine (HCQ) treatment. The aim is to identify subclinical functional impairments that are otherwise undetectable by standard clinical tests and to link them to structural retinal changes. Methods: We measured oculomotor responses in a cohort of SLE patients on chronic HCQ therapy using a previously established behavioral task and analysis technique. We also examined the relationship between oculometrics, OCT measures of retinal thickness, and standard clinical perimetry measures of visual function in our patient group using Bivariate Pearson Correlation and a Linear Mixed-Effects Model (LMM). Results: Significant visual and visuomotor deficits were found in 12 asymptomatic SLE patients on long-term HCQ therapy compared to a cohort of 17 age-matched healthy controls. Notably, six oculometrics were significantly different. The median initial pursuit acceleration was 22%, steady-state pursuit gain 16%, proportion smooth 7%, and target speed responsiveness 31% lower, while catch-up saccade amplitude was 46% and fixation error 46% larger. Excluding the two patients with diagnosed mild toxicity, four oculometrics, all but fixation error and proportion smooth, remained significantly impaired compared to controls. Across our population of 12 patients (24 retinae), we found that pursuit latency, initial acceleration, steady-state gain, and fixation error were linearly related to retinal thickness even when age was accounted for, while standard measures of clinical function (Mean Deviation and Pattern Standard Deviation) were not. Discussion: Our data show that specific oculometrics are sensitive early biomarkers of functional deficits in SLE patients on HCQ that could be harnessed to assist in the early detection of HCQ-induced retinal toxicity and other visual pathologies, potentially providing early diagnostic value beyond standard visual field and OCT evaluations.

eye movements↗

NASA NTRS2023

Differential Saccade-Pursuit Coordination Under Sleep Loss and Low-Dose Alcohol

Introduction: Ocular tracking of a moving object requires tight coordination between smooth pursuit and saccadic eye movements. Normally, pursuit drives gaze velocity to closely match target velocity, with residual position offsets corrected by catch-up saccades. However, how/if common stressors affect this coordination is largely unknown. This study seeks to elucidate the effects of acute and chronic sleep loss, and low-dose alcohol, on saccade-pursuit coordination, as well as that of caffeine. Methods: We used an ocular tracking paradigm to assess three metrics of tracking (pursuit gain, saccade rate, saccade amplitude) and to compute “ground lost” (from reductions in steady-state pursuit gain) and “ground recouped” (from increases in steady-state saccade rate and/or amplitude). We emphasize that these are measures of relative changes in positional offsets, and not absolute offset from the fovea. Results: Under low-dose alcohol and acute sleep loss, ground lost was similarly large. However, under the former, it was nearly completely recouped by saccades, whereas under the latter, compensation was at best partial. Under chronic sleep restriction and acute sleep loss with a caffeine countermeasure, the pursuit deficit was dramatically smaller, yet saccadic behavior remained altered from baseline. In particular, saccadic rate remained significantly elevated, despite the fact that ground lost was minimal. Discussion: This constellation of findings demonstrates differential impacts on saccade-pursuit coordination with low-dose alcohol impacting only pursuit, likely through extrastriate cortical pathways, while acute sleep loss not only disrupts pursuit but also undermines saccadic compensation, likely through midbrain/brainstem pathways. Furthermore, while chronic sleep loss and caffeine-mitigated acute sleep loss show little residual pursuit deficit, consistent with uncompromised cortical visual processing, they nonetheless show an elevated saccade rate, suggesting residual midbrain and/or brainstem impacts.

smooth pursuit↗

NASA NTRS2020

Dose-Dependent Sensorimotor Impairment in Human Ocular Tracking After Acute Low-Dose Alcohol Administration

Changes in oculomotor behaviours are often used as metrics of sensorimotor disruption due to ethanol (EtOH); however, previous studies have focused on deficits at blood-alcohol concentrations (BACs) above about 0.04%.We investigated the dose dependence of the impairment in oculomotor and ocular behaviours caused by EtOH administration across a range of ultra-low BACs (≤0.035%).We took repeated measures of oculomotor and ocular performance from sixteen participants, both pre- and post-EtOH administration. To assess the neurological impacts across a wide range of brain areas and pathways, our protocol measured 21 largely independent performance metrics extracted from a range of behavioural responses ranging from ocular tracking of radial step-ramp stimuli, to eccentric gaze holding, to pupillary responses evoked by light flashes. Our results show significant impairment of pursuit and visual motion processing at 0.015% BAC, reflecting degraded neural processing within extrastriate cortical pathways. However, catch-up saccades largely compensate for the tracking displacement shortfall caused by low pursuit gain, although there still is significant residual retinal slip and thus degraded dynamic acuity. Furthermore, although saccades are more frequent, their dynamics are more sluggish (i.e. show lower peak velocities) starting at BAC levels as low as 0.035%. Small effects in eccentric gaze holding and no effect in pupillary response dynamics were observed at levels below 0.07%, showing the higher sensitivity of the pursuit response to very low levels of blood alcohol, under the conditions of our study.

visual motion processing↗

NASA NTRSDate not supplied

Oculometric Analysis of Saccadic Compensation for Visual Motion Processing Impairment due to Alcohol and Sleep Disruption

The Visuomotor Control Laboratory at Ames Research Center has developed a 5-minute ocular tracking test that computes 21 largely independent metrics of visuomotor performance, reflecting neural signal processing along a number of distinct pathways through cortex, brainstem, and cerebellum. Human sensorimotor performance is resilient to the challenges and stressors of many operational environments, in part, because overall performance is achieved through multiple parallel systems. Our multidimensional oculometrics allow us to examine impacts on these sub-components separately. To illustrate this, we contrasted the effects of two mild neural stressors, acute sleep-deprivation and low-dose alcohol. We have previously shown that, in both cases, oculometric analysis is a highly sensitive indicator of impairment. Here we quantified not only the observed impact on the performance of one sub-system, smooth pursuit, which uses high-level cortical processing of visual motion to track a moving object, but also the observed (partial) compensation by an evolutionarily older mid-brain and brainstem subsystem, saccades, which generates jumps in eye position to catch up with the target when smooth pursuit is inadequate. Specifically, we examined the dose-response (effect size vs. dose size) of the ground lost (pursuit deficit) and the ground recouped (saccadic compensation) across three separate studies – acute low-dose alcohol administration (16 subjects), acute sleep loss (12 subjects), and acute sleep loss with caffeine intervention (9 subjects). We computed the dose-response slopes using linear regression. The figure below shows that, in the case of acute sleep deprivation, the resulting slopes for ground lost and ground recouped (mean ± SE across subjects) were significantly different (paired t-test, t(11) = 5.17, p < 0.001), indicating poor saccadic compensation. However, when sleep loss was coupled with caffeine ingestion, ground lost was decreased and ground recouped increased such that the slopes were no longer different (t(8) = -0.05, p = 0.965). With alcohol, the two slopes were large albeit not significantly different (t(15) = 0.96, p = 0.351), indicating significant pursuit impairment but effective saccadic compensation. Our findings show that sleep deprivation and alcohol affect oculomotor performance differently. Low-dose alcohol effects appear predominantly cortical, with effective brainstem compensation. Sleep loss and circadian disruption however appears to affect both cortical and brainstem pathways with caffeine providing an effective countermeasure to both effects. Beyond the mere detection of impairment, our oculometric assessment allows us to characterize the nature of the deficit, to provide insight into the neural substrate, and to assess the effectiveness of countermeasures.

pursuit↗

NASA NTRSDate not supplied

The Effects of Chronic Sleep Restriction on Multiple Object Tracking

The ability to simultaneously track numerous moving objects in the presence of irrelevant stimuli is essential for carrying out a variety of tasks. Sleep loss has been found to impair neurocognitive functioning and, as a result, attentional processing capacity is reduced. A common form of sleep loss is chronic sleep restriction (CSR), in which an inadequate amount of sleep is obtained over consecutive days. The objective of the current study was to determine if performance on the multiple object tracking (MOT) task was adversely impacted by a week of CSR. Twelve healthy participants (6 males, 6 females) kept a fixed sleep-wake schedule, with a constant waketime, at home for four weeks (activity monitors worn on the participant’s nondominant wrist were used to confirm compliance). Weeks one and three were deemed washout weeks, during which participants maintained a 9-hour sleep-wake schedule. Weeks two and four were deemed experimental weeks, during which participants were randomly assigned a 5-hour (CSR) and 9-hour (sleep satiation) sleep-wake schedule. Following night seven of each experimental week, participants completed a 13-hour laboratory visit under dim light (less than 15 lux) where they maintained a constant posture and were provided with hourly isocaloric snacks. MOT was presented at approximately 6 and 8 hours after waking. Participants were required to track four, five, or six moving targets in the presence of identical distractors (always 12 total objects). It was found that participants slept significantly less during the week of CSR compared to the week of sleep satiation. There was no difference in the overall proportion of correct MOT responses following the CSR and sleep satiation weeks. However, an additional analysis examining only the 6 target condition found that the proportion of correct responses was significantly lower following the week of CSR. These findings suggest that CSR has an adverse impact on tracking performance when the cognitive demand was higher. This has implications for individuals, such as air traffic controllers and truck drivers, who must visually track multiple moving objects under high workload situations, often while chronically sleep deprived.

sleep restriction↗

NASA NTRSDate not supplied

Normative Baseline Oculomotor Performance

Future missions to the moon or Mars will require the crew to monitor and assess their health and performance more autonomously, necessitating approaches that are easily useable and interpretable by non-clinicians. The eye-movement-based performance metrics (oculometrics) obtained from NASA-patented technology developed at the Visuomotor Control Laboratory can reliably detect and discriminate the source of mild neural impairment relative to an individual’s baseline visual and sensorimotor performance and can predict performance in manual control tasks. This study aims to develop a database of normative performance that can be used to enable the detection of impairment without a within-subject baseline and to facilitate power analyses for the design of future studies.

eye movements↗

NASA NTRSDate not supplied

Oculometric Surveillance of Neuro-Ocular Function

Future missions to the moon or Mars will require the crew to monitor and assess their health and performance more autonomously, with approaches easily useable and interpretable by non-clinicians. If an autonomous oculometric diagnostic-support system proves to be a reliable predictor of impending impairment of visual function in the case of primary ocular pathology on Earth, then it could also be applied in the future to the surveillance of crew to detect the potential progression of sensorimotor and neuro-ocular compromises during extended spaceflight missions, e.g., SANS, and thus guide earlier and more effective countermeasure intervention. Towards that goal, we intend to determine if a set of largely independent eye-movement metrics, called oculometrics, measured using a simple voluntary eye-tracking task that can be completed in just 5 minutes per eye, could provide clinically valid biomarkers of functional visual deficits due to primary ocular pathology. The premise is that oculometrics could be used to monitor slowly evolving ocular pathologies, potentially detecting them even before structural evidence appears in ocular imaging or other current state-of-the-art clinical measures. This study investigates how NASA’s patented oculometric assessment of visual and visuomotor function, shown to correlate with performance in a manual control task, will correlate with standard ophthalmological tests to confirm clinical and thus operational, validity.

eye movements↗