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

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

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

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

Dose-dependent sensorimotor impairment in human ocular tracking after acute low-dose alcohol administration

Key points: Oculomotor behaviours are commonly used to evaluate sensorimotor disruption due to ethanol (EtOH). The current study demonstrates the dose-dependent impairment in oculomotor and ocular behaviours across a range of ultra-low BACs (\u3c0.035%). Processing of target speed and direction, as well as pursuit eye movements, are significantly impaired at 0.015% BAC, suggesting impaired neural activity within brain regions associated with the visual processing of motion. Catch-up saccades during steady visual tracking of the moving target compensate for the reduced vigour of smooth eye movements that occurs with the ingestion of low-dose alcohol. Saccade dynamics start to become ‘sluggish’ at as low as 0.035% BAC. Pupillary light responses appear unaffected at BAC levels up to 0.065%. Abstract: 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

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

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

Pupil diameter reflects uncertainty in attentional selection during visual search

Pupil diameter has long been used as a metric of cognitive processing. However, recent advances suggest that the cognitive sources of change in pupil size may reflect LC-NE function and the calculation of unexpected uncertainty in decision processes (Aston-Jones & Cohen, 2005b; Yu & Dayan, 2005). In the current experiments, we explored the role of uncertainty in attentional selection on task-evoked changes in pupil diameter during visual search. We found that task-evoked changes in pupil diameter were related to uncertainty during attentional selection as measured by reaction time and performance accuracy (Experiments 1-2). Control analyses demonstrated that the results are unlikely to be due to error monitoring or response uncertainty. Our results suggest that pupil diameter can be used as an implicit metric of uncertainty in ongoing attentional selection requiring effortful control processes