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

Abstract

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 (<0.035%). 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.

Keywords: alcohol; saccades; smooth pursuit; visual motion processing.

Figure 1. Time course of BACs during the 2‐day lab procedure for a single participant

The diagram shows the first and second days with the higher and lower initial doses, respectively. Sleep (in green) was defined by the data collected from actigraphy. The inverted black triangles represent repeated BAC measurements from an individual participant across the two sequential days of testing.

Figure 2. Example stimulus data set from a single participant

Data set of randomly selected spatial and temporal parameters for a given 90‐trial test run of the step‐ramp ocular tracking task for a single participant. A, the timeline of trial events for the step‐ramp ocular tracking task. B, the histogram of the pre‐motion fixation durations, randomly sampled from an exponential probability density function ranging from 200 to 5000 ms. C, the histogram of the target motion durations, randomly sampled from a uniform probability density function ranging from 700 to 1000 ms. D, a polar plot showing the 90 radial trajectories of target motion in blue. The randomly chosen target speed (16, 18, 20, 22, or 24 deg/s) is reflected in the trajectory length of the radial lines.

Figure 3. Dose effect on subjective drunkenness

Control data from all participants associated with BACs below 0.025% showing a systematic vertical shift in the subjective experience of drunkenness between the two initial dose conditions. The figure plots scores using a slider scale ranging from 0 to 100, with 0 indicating ‘sober’ and 100 indicating ‘extremely drunk’.

Figure 4. Dose effect on objective oculometrics

Objective oculometric data from all participants associated with BACs below 0.025% generally shows a lack of clear differences in performance between dose conditions. Only four of the 21 oculometrics showed a significant difference (P < 0.05) between the dose conditions and only two (latency not shown) were in the same direction as in the subjective data in Fig. 3.

Figure 5. Example response data from an individual participant

A, an example trial from a pre‐dosing run. The blue trace shows the smooth eye velocity over the entire trial. The green horizontal line indicates the constant target speed (16 deg/s in this trial). Our steady‐state analysis interval spans from 400 to 700 ms. The initial 150 ms (sloped yellow line) of tracking, after an initial fixation baseline (red horizontal line) marking the latency (131 ms), represents the open‐loop acceleration (88.1 deg/s²) of smooth pursuit (Lisberger & Westbrook, 1985; Tychsen & Lisberger, 1986). Note the single initial saccade (in red) and high steady‐state pursuit gain with no catch‐up saccades during near‐perfect steady‐state tracking (gain of 1.02). B, an example post‐dosing trial at a measured BAC of 0.0325% for the same participant. Note the longer latency (152 ms), lower open‐loop acceleration (43.7 deg/s²), and multiple catch‐up saccades during steady‐state tracking to compensate for the attenuated pursuit gain (0.43), with no indication of a smooth corrective acceleration associated with the sustained steady‐state retinal slip. C, the oculometric summary chart of the computed oculometrics before dose administration for the same participant. D, the oculometric summary chart after dose administration for the same participant. Note the systematic impairment of visual and sensorimotor performance with gaze‐holding and saccade dynamics mildly compromised and with the PLR largely unaffected.

Figure 6. Pursuit behaviour

Dose‐response curves of pursuit behaviour as a function of BAC. Panels show plots of median percentage change from within‐subject baseline (error bars representing interquartile range across subjects) across both dose conditions for latency (A), acceleration (B), gain (C) and proportion smooth (D) as a function of BAC. Points in red are significantly different than baseline as indicated by the horizontal dotted line (Wilcoxon signed‐rank, Bonferroni‐Holm corrected, one‐tailed, P < 0.05). On average, steady‐state gain was reduced by ∼16% and ∼22% at 0.035% and 0.055% BAC, respectively, resulting in an ∼69% and ∼91% increase, respectively, in the average ground lost due to inadequate pursuit during the steady‐state tracking interval compared to that during baseline performance. Note the scale difference in A.

Figure 7. Saccade behaviour

Dose‐response curves of saccadic behaviour as a function of BAC. Panels show plots of the median percentage change from within‐subject baseline (error bars representing interquartile range across subjects) across both dose conditions for rate (A), amplitude (C), peak velocity: slope (B) and intercept (D) as a function of BAC. Points in red are significantly different than baseline as indicated by the horizontal dotted line (Wilcoxon signed‐rank, Bonferroni‐Holm corrected, one‐tailed, P < 0.05). On average, saccadic amplitude and rate were both increased at 0.035% BAC, by 37% and 24% respectively, resulting in a ∼70% mean increase in the amount of ground recouped by saccades above that during baseline performance (i.e. complete compensation for the 69% decrease in ground lost from impaired pursuit). At 0.055% BAC, on average, the ground recouped was ∼94% in response to the ∼91% lost.

Figure 8. Visual motion processing

Dose‐response curves of visual motion processing as a function of BAC. Panels show plots of the median percentage change from within‐subject baseline (error bars representing interquartile range across subjects) across both dose conditions for direction noise (A) and asymmetry (B), and speed noise (C) and slope (D) as a function of BAC. Points in red are significantly different than baseline as indicated by the horizontal dotted line (Wilcoxon signed‐rank, Bonferroni‐Holm corrected, one‐tailed, P < 0.05).

Figure 9. Eccentric gaze holding

Dose‐response curves of gaze holding behaviour as a function of BAC. Panels show plots of the median percentage change from within‐subject baseline (error bars representing interquartile range across subjects) across both dose conditions for centripetal (A) and lateral (B) drift. Although there was a significant linear increase in centripetal drift with increasing BAC, no individual points were found to be significantly different than baseline as indicated by the horizontal dotted line (Wilcoxon signed‐rank, Bonferroni‐Holm corrected, one‐tailed, P > 0.14).

Figure 10. Pupillary light reflex

Dose‐response curves of the pupillary light reflex as a function of BAC. Panels show plots of the median percentage change from within‐subject baseline (error bars representing interquartile range across subjects) across both dose conditions of the constriction (A) and dilatation (B) time constants as well as of the average pupil size (C).