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Tyson, Terence L.

Publications and source records attributed to Tyson, Terence L..

Novel Classifier of Neural Impairment

The proposed research aligns with Ames Core Competency within the area of Intelligent/Adaptive Systems under Human Systems Integration. This will serve as a robust, efficient, and user-friendly human performance assessment tool that could provide immediate neural status of crewmembers in low-orbit and deep space missions. The human operator is a critical element of crew safety and should be evaluated consistently to mitigate potential off-nominal situations propagated from human error. Flagged deficits in oculomotor performance could act as an alert signal for crewmembers to opt out of cognitively demanding tasks or to prevent irreversible compromise in crewmember health.

impairment↗

Distinct Pattern of Oculomotor Impairment Associated with Acute Sleep Loss and Circadian Misalignment

Sleep loss and circadianmisalignment have long been known to impair human cognitive and motor performance with significant societal and health consequences. It is well known that human reaction time to a visual cue is impaired following sleep loss and circadian misalignment, but it has remained unclear how more complex visuomotor control behaviour is altered under these conditions. In this study, we measured 14 parameters of the voluntary ocular tracking response of 12 human participants (six females) to systematically examine the effects of sleep loss and circadianmisalignment using a constant routine 24 h acute sleep-deprivation paradigm. The combination of state-of-the-art oculometric and sleep-research methodologies allowed us to document, for the first time, large changes in many components of pursuit, saccades and visual motion processing as a function of time awake and circadian phase. Further, we observed a pattern of impairment across our set of oculometric measures that is qualitatively different from that observed previously with other mild neural impairments. We conclude that dynamic vision and visuomotor control exhibit a distinct pattern of impairment linked with time awake and circadian phase. Therefore, a sufficiently broad set of oculometric measures could provide a sensitive and specific behavioural biomarker of acute sleep loss and circadian misalignment. We foresee potential applications of such oculometric biomarkers assisting in the assessment of readiness-to-perform higher risk tasks and in the characterization of sub-clinical neural impairment in the face of a multiplicity of potential risk factors, including disrupted sleep and circadian rhythms.

Stone, Leland S.↗

Low-Dose Caffeine Administration During Acute Sleep Deprivation Eliminates Visual Motion Processing Impairment, but Does Not Improve Saccadic Rate

Oculomotor tracking performance changes according to time awake. A constant routine (CR) study demonstrated that increasing time awake 1) reduces the precision of visual motion processing, 2) decreases steady-state closed-loop pursuit performance and 3) decreases peak saccadic velocity. We aimed to determine the contribution of homeostatic sleep pressure on these oculometric changes by administering low-dose caffeine over one night of sleep deprivation. Participants completed two weeks of at-home 8.5 hours sleep per day, followed by an approximately 24-hour laboratory CR in semi-recumbent posture under less than 4 lux of light. The visual tracking task was performed every two hours after waking and hourly overnight. Low-dose caffeine of 0.3 milligrams per kilogram was administered hourly during the biological night. Nine participants (5F) completed the study. Caffeine dosing: 1) prevented the impairment of visual motion processing, 2) reduced by approximately half the impairment of closed-loop pursuit performance (gain, minus 0.47 percent per hour, significance of slope change: p (probability) less than 0.006; proportion smooth, minus 0.35 percent per hour, p less than 0.005), and 3) had an insignificant (p less than 0.39) effect on the impairment of saccadic peak velocity (slope, minus 1.13 percent per hour; intercept, minus 0.62 percent per hour). These results suggest that visual motion processing and some proportion of closed-loop pursuit performance are impaired due to homeostatic mechanisms during sleep deprivation.

Sleep↗

Increased Dependence on Saccades for Ocular Tracking with Low Dose Alcohol

Previous studies have shown that certain features of oculomotor performance are impaired at or slightly below the legal limit for driving in most U.S. States (0.08% Blood Alcohol Concentration or BAC). Specifically, alcohol impairs saccadic velocity and steady-state tracking at levels between 0.04% and 0.1% BAC. Here we used a suite of standardized oculometric measures to examine the effect of ultra-low levels of alcohol (down to 0.01% BAC) on steady-state tracking. Our high-uncertainty tracking task reveals that the smooth pursuit system is highly sensitive to BAC, with impairmentextrapolating back to BAC levels at or below 0.01%. BAC generates a dose dependent increase in reliance on the saccadic system that maintains overall steady-state tracking effectiveness at least up to 0.08% BAC, albeit with a significant decrease in smoothness.

Tyson, Terence L.↗

Impairment of Human Ocular Tracking with Low-Dose Alcohol

Previous studies have documented adverse effects of alcohol on oculomotor performance. For example, moderate-dose alcohol (yielding a Blood Alcohol Concentration or BAC of 0.04-0.1%) has been shown to decrease steady-state pursuit gain (Fransson et al., 2010, Clin Neurophysiol, 121(12): 2134; Moser et al., 1998, J Neurol, 245(8): 542; Roche & King, 2010, Psychopharmacology, 212(1): 33), to increase saccade latency (Moser et al., 1998, J Neurol, 245(8): 542; Roche & King, 2010, Psychopharmacology, 212(1): 33), to decrease peak saccadic velocity (Fransson et al., 2010, Clin Neurophysiol, 121(12): 2134; Roche & King, 2010, Psychopharmacology, 212(1): 33), and to increase the frequency of catch-up saccades (Moser et al., 1998, J Neurol, 245(8): 542). Here, we administered two doses of ethanol on different days, yielding moderate (0.06%) and low (0.02%) levels of initial BAC, to examine the effects on human ocular tracking over BACs ranging from 0.00 to 0.07%. Twelve subjects (8 females) participated in a 5-day study. Three days of at-home measurements of daily activity and sleep were monitored, followed by two laboratory days where, ~5 hours after awakening, we administered one of the two possible single doses of alcohol. Using a previously published paradigm (Liston & Stone, 2014, J Vis, 14(14): 12), we measured oculomotor performance multiple times throughout the day with three pre-dosing baseline runs and bi-hourly post-dosing test runs until the subject recorded a BAC of 0.00% for two hours. BAC was measured before each run using an Alco-Sensor IV breathalyzer (Intoximeters, Inc., St. Louis, MO). For each of the oculometric measures, for each subject, we computed the within-subject % deviation for each test run from their baseline averaged across their three pre-dosing runs. We then averaged the data across subjects in 0.01% BAC bins. Finally, we used linear regression to compute the slope and x-intercept (threshold) of the mean binned % deviation as a function of BAC. We found that pursuit initiation was impaired at very low BAC levels, with significant (p < 0.002) linear trends in latency (+1.3%/0.01%BAC) and initial acceleration (-4.6%/0.01%BAC) with extrapolated absolute thresholds at or below 0.01% BAC. We also found that steady-state tracking was impaired showing significant (p < 0.002) linear trends in gain (- 3.8%/0.01%BAC) and catch-up saccade amplitude (+9.1%/0.01%BAC), again with extrapolated absolute thresholds around 0.01% BAC. We also found a significant (p < 0.02) increase in pursuit direction noise (+9.8%/0.01%BAC) with an extrapolated absolute threshold below 0.01% BAC. Many aspects of ocular tracking are impaired in a dose-dependent manner beginning at a BAC level around 0.01%, with significant effects at levels lower than previously reported and up to 8-times lower than the legal limit for driving in most states.

human performance↗

Oculomotor Behavior Metrics Change According to Circadian Phase and Time Awake

There is a need for non-invasive, objective measures to forecast performance impairment arising from sleep loss and circadian misalignment, particularly in safety-sensitive occupations. Eye-tracking devices have been used in some operational scenarios, but such devices typically focus on eyelid closures and slow rolling eye movements and are susceptible to the intrusion of head movement artifacts. We hypothesized that an expanded suite of oculomotor behavior metrics, collected during a visual tracking task, would change according to circadian phase and time awake, and could be used as a marker of performance impairment.

sleep deprivation↗

Circadian and Fatigue Effects on the Dynamics of the Pupillary Light Reflex

The pupillary light reflex (PLR) is known to be driven by the photo-entrainment of intrinsically-photosensitive retinal ganglion cells. These ganglion cells are known to have retino-hypothalamic projections to the suprachiasmatic nuclei (SCN), which regulates circadian rhythms, and bilateral retinal projections to the pretectal area, which mediates the PLR (Dacey et al., 2005; Hattar et al., 2002, 2006). The magnitude of the PLR has previously been shown to show circadian variation (Mnch et al., 2012). In this study, we used a constant routine protocol (Mills et al., 1978) to examine circadian and fatigue effects on the dynamics of the PLR. We characterized the PLR (pupil size as a function of time) in response to a square-wave change in the luminance of a white display background, at ten different times over a single circadian cycle. Twelve subjects participated in three daytime baseline runs followed by 7 nighttime runs each separated by an hour (17 23 hours after awakening). The constriction and dilation phases of the PLR waveform were fit separately with a single exponential model (Longtin Milton, 1988; Milton Longtin, 1990) with time constants estimated using a least-squares method. The dilation time constant exhibited a distinct sinusoidal modulation across the circadian cycle and, after 23 hours of wakefulness, decreased on average by 82 ms (paired t-test, p 0.05) relative to baseline (mean: 543 ms). The constriction time constant however, did not show an overall decrease with increased wakefulness. We conclude that the dynamics of the PLR show circadian variation and that, in addition, the briskness of the dilation response to a step-decrease in luminance shows a homeostatic enhancement with increased wakefulness.

human performance↗

Correlated Changes in Retinal Thickness and Visuomotor Function in Asymptomatic Plaquenil Toxicity Patients

We have previously shown that a 5-minute eye-movement test can capture a number of largely independent “oculometric” parameters of human visual/visuomotor function (Liston & Stone, 2014). This test has been successfully used to characterize mild neural impairment due to traumatic brain injury, sleep and circadian disruption, and alcohol consumption (Liston et al., 2017; Stone et al, 2019; Tyson et al, 2021). Here, we extend this approach to study patients at risk of progressive posterior-segment illness to see how oculometrics relate to standard clinical ophthalmological measures. Five female patients (<20:40 BCVA, 34-60 years old) undergoing hydroxychloroquine treatment (2-7mg/kg/day for 10-23 years for rheumatologic illness) have participated thus far. Under monocular viewing conditions in randomized order, they tracked a moving spot undergoing radial step-ramp motion in one of 90 randomized directions, at one of 5 randomized speeds, starting at random times (for details, see Stone et al, 2019). We computed nine independent oculometrics (latency, initial acceleration, steady-state gain, proportion smooth, saccadic rate, saccadic amplitude, direction noise, speed responsiveness, and speed noise). Spectral-domain optical coherence tomography (Zeiss, Dublin, CA) was used to measure the average thickness of the nine Early Treatment Diabetic Retinopathy Study macular sectors from the internal limiting membrane to the retinal pigmented epithelium. We used Pearson’s correlation between retinal thickness and our oculometrics with t-statistics to test separate one-sided hypotheses across 10 retinae. Our preliminary analysis found significant changes in several different aspects of visuomotor performance. Most notably, latency increased, initial acceleration decreased, and steady-state pursuit gain decreased as retinal thickness decreased (r2 = 0.364, 0.579, and 0.692; one-tailed P = 0.032, 0.005, and 0.001, respectively). Speed responsiveness appeared to decrease, but this effect was marginal for our current sample (r2 = 0.253, P = 0.069). Lastly, direction discrimination and saccadic behavior appeared unchanged. We conclude that oculometrics may provide sensitive measures of changes in retinal thickness. More importantly, oculometrics have the potential to detect impairment before it becomes evident with standard clinical imaging tools, while also providing insight into the behavioral implications of any resulting deficits in visual/visuomotor function.

eye movements↗