Acute administration of alprazolam, alcohol and their combination on cognitive performance and mood: A randomised, double-blind, placebo-controlled study.

BACKGROUND: Recreational co-consumption of benzodiazepines and alcohol is a common practise; yet, the cognitive effects of this combination remain poorly understood. This study aimed to investigate the acute cognitive effects of combining a 1 mg dose of alprazolam with a moderate dose of alcohol (target 0.04% blood alcohol concentration (BAC)) in a non-clinical population. METHODS: In this randomised, double-blind, placebo-controlled, crossover trial, participants completed computerised cognitive assessments and the brief biphasic alcohol effects scale (B-BAES) after consuming 1 mg of alprazolam, both with and without a moderate dose of alcohol (target 0.04% BAC). RESULTS: Among 20 healthy participants (mean age = 28.6, SD ± 4.0 years, 60% female), we found that a peak BAC of 0.03% had no significant impact on cognitive performance. Both the individual use of alprazolam and its combination with alcohol resulted in impaired reaction time, digit vigilance, and verbal, spatial and numeric working memory tasks, although an additive effect when alcohol and alprazolam were consumed together was not evident. The most pronounced cognitive effects occurred at 100 min after dosing, coinciding with increased alprazolam concentrations. Sedative effects were heightened with alcohol, alprazolam and their combination while no stimulative effects were reported. CONCLUSIONS: Our findings highlight the significant implications of a therapeutic dose of alprazolam on impairing cognitive performance. This is particularly relevant considering the frequency of non-medical alprazolam use. Future studies should explore different dosages, administration timings and long-term effects to inform the development of public health policies and guidelines regarding the combined use of alcohol and benzodiazepines.

Driving impairment and altered ocular activity under the effects of alprazolam and alcohol: A randomized, double-blind, placebo-controlled study.

BACKGROUND: Alprazolam, also known by trade-name Xanax, is regularly detected along with alcohol in blood samples of drivers injured or killed in traffic collisions. While their co-consumption is principally legal, policy guidelines concerning fitness-to-drive are lacking and methods to index impairment are underdeveloped. METHODS: In this randomized, double-blind, placebo-controlled, crossover trial, we examined whether legally permissible levels of alcohol [target 0.04% blood alcohol concentration (BAC)], alprazolam (1mg), and their combination impacts driving performance, and whether driving impairment can be indexed by ocular activity. Participants completed a test battery consisting of a 40-minute simulated highway drive with ocular parameters assessed simultaneously, the Karolinska Sleepiness Scale, and a confidence to drive assessment following four separate treatment combinations. The predictive efficacy of ocular parameters to identify alcohol and alprazolam-related driving impairment was also examined. RESULTS: Among 21 healthy, fully licensed drivers (37% female, mean age 28.43, SD ± 3.96), driving performance was significantly impacted by alprazolam, alcohol, and their combination. Linear regression models revealed that the odds of an out-of-lane event occurring increased five-fold under the influence alprazolam alone and when combined with alcohol. An increase in gaze transition entropy (GTE) demonstrated the strongest association with the odds of an out-of-lane event occurring in the same minute, with both microsleeps and fixation rate achieving moderate accuracy across treatments. CONCLUSIONS: Alprazolam and alcohol, alone and in combination, impaired select aspects of vehicle control over time. GTE, microsleeps, and fixation rate show potential as real-time indicators of driving impairment and crash risk associated with alcohol and alprazolam consumption.

Acute neurocognitive and subjective effects of oral methamphetamine with low doses of alcohol: A randomised controlled trial.

BACKGROUND: Methamphetamine is often recreationally co-consumed with alcohol due to desirable off-target effects; however, the acute neurocognitive and subjective consequences of combined use are unclear. METHODS: In a randomised, placebo-controlled, counterbalanced, cross-over study design, the effects of acute oral methamphetamine (0.42 mg/kg) were assessed with and without low doses of alcohol (target 0.04% blood-alcohol concentration, BAC) on subjective intoxication, alertness, physiological outcomes and neurocognition during the ascending and descending phases of the BAC curve. Sixteen healthy adults (mean age = 30.4 years, SD ± 4.4, 67% male) completed four experimental sessions over 4 weeks involving a one-week washout period. RESULTS: Cardiovascular measures [heart rate (beats/minute), blood pressure (mmHg)] were predictably elevated following methamphetamine, but unaffected by combined alcohol use. Methamphetamine and alcohol produce divergent effects on subjective alertness and sedation across time, yet their combination produced predominantly sustained stimulative effects independent of the biphasic alcohol curve. At a peak BAC of 0.029%, alcohol alone impaired performance across most functional neurocognitive domains relative to placebo and methamphetamine only, and the addition of methamphetamine attenuated these effects. Methamphetamine alone produced isolated improvement in psychomotor speed consistent with peak drug effects. CONCLUSION: Methamphetamine combined with alcohol does not substantially alter the physiological or metabolic profile compared to either drug alone. Strong stimulative effects of methamphetamine appear to mask the biphasic sedative and performance effects of low doses of alcohol, which may underlie motivations for co-consumption in recreational settings and increase propensity for harm.

Effect of CannEpil® on simulated driving performance and co-monitoring of ocular activity: A randomised controlled trial.

BACKGROUND: Medicinal cannabis products containing Δ9-tetrahydrocannabinol (THC) are increasingly accessible. Yet, policy guidelines regarding fitness to drive are lacking, and cannabinoid-specific indexations of impairment are underdeveloped. AIMS: To determine the impact of a standardised 1 mL sublingual dose of CannEpil®, a medicinal cannabis oil containing 100 mg cannabidiol (CBD) and 5 mg THC on simulated driving performance, relative to placebo and whether variations in vehicle control can be indexed by ocular activity. METHODS: A double-blind, within-subjects, randomised, placebo-controlled, crossover trial assessed 31 healthy fully licensed drivers (15 male, 16 female) aged between 21 and 58 years (M = 38.0, SD = 10.78). Standard deviation of lateral position (SDLP), standard deviation of speed (SDS) and steering variability were assessed over time and as a function of treatment during a 40 min simulated drive, with oculomotor parameters assessed simultaneously. Oral fluid and plasma were collected at 30 min and 2.5 h. RESULTS: CannEpil did not significantly alter SDLP across the full drive, although increased SDLP was observed between 20 and 30 min (p < 0.05). CannEpil increased SDS across the full drive (p < 0.05), with variance greatest at 20-30 min (p < 0.001). CannEpil increased fixation duration (p < 0.05), blink rate (trend p = 0.051) and decreased blink duration (p < 0.001) during driving. No significant correlations were observed between biological matrices and performance outcomes. CONCLUSIONS: CannEpil impairs select aspects of vehicle control (speed and weaving) over time. Alterations to ocular behaviour suggest that eye tracking may assist in determining cannabis-related driver impairment or intoxication. Australian and New Zealand Clinician Trials Registry, https://anzctr.org.au(ACTRN12619000932167).

The impact of break duration, time of break onset, and prior shift duration on the amount of sleep between shifts in heavy vehicle drivers.

This study aimed to examine the impact of break duration between consecutive shifts, time of break onset, and prior shift duration on total sleep time (TST) between shifts in heavy vehicle drivers (HVDs), and to assess the interaction between break duration and time of break onset. The sleep (actigraphy and sleep diaries) and work shifts (work diaries) of 27 HVDs were monitored during their usual work schedule for up to 9 weeks. Differences in TST between consecutive shifts and days off were assessed. Linear mixed models (followed by pairwise comparisons) assessed whether break duration, prior shift duration, time of break onset, and the interaction between break duration and break onset were related to TST between shifts. Investigators found TST between consecutive shifts (mean [SD] 6.38 [1.38] h) was significantly less than on days off (mean [SD] 7.63 [1.93] h; p < 0.001). Breaks starting between 12:01 and 8:00 a.m. led to shorter sleep (p < 0.05) compared to breaks starting between 4:01 and 8:00 p.m. Break durations up to 7, 9, and 11 h (Australian and European minimum break durations) resulted in a mean (SD) of 4.76 (1.06), 5.66 (0.77), and 6.41 (1.06) h of sleep, respectively. The impact of shift duration prior to the break and the interaction between break duration and time of break were not significant. HVDs' sleep between workdays is influenced independently by break duration and time of break onset. This naturalistic study provides evidence that current break regulations prevent sufficient sleep duration in this industry. Work regulations should evaluate appropriate break durations and break onset times to allow longer sleep opportunities for HVDs.

Effects of alcohol intoxication on driving performance, confidence in driving ability, and psychomotor function: a randomized, double-blind, placebo-controlled study.

RATIONALE: Alcohol-induced driving impairment can occur with any departure from a zero-blood alcohol concentration (BAC). Because intoxication is characterised by impaired judgement, drivers under the influence of alcohol may overestimate their capacity to safely operate a vehicle. OBJECTIVES: This study examined the effects of alcohol on driving performance, four-choice reaction time (FCRT), and self-rated confidence in driving ability. It specifically focused on alcohol doses equal to commonly enforced legal BAC limits (i.e. 0.05% and 0.08%). METHODS: A randomized, double-blind, placebo-controlled design was utilised. Seventeen participants were tested in three conditions: placebo and two alcohol conditions aiming for BACs of 0.05% and 0.08%. Participants underwent a baseline FCRT task and a 1-h simulated highway driving task before completing another FCRT task and rated their confidence in their driving ability. RESULTS: The high and low alcohol dose conditions resulted in a mean BAC of 0.07%, and 0.04%, respectively (n = 17). The high BAC treatment significantly increased standard deviation of lateral position (SDLP) by 4.06 ± 5.21 cm and standard deviation of speed (SDS) by 0.69 ± 0.17 km/h relative to placebo, while confidence in driving ability remained unchanged across treatments. FCRT performance was impaired by the high BAC treatment (all < 0.01), but there we no significant differences between placebo and low BAC conditions. CONCLUSIONS: The findings of this study show that driving performance and associated psychomotor functioning become significantly impaired below legally permissible driving limits in some jurisdictions. We identified a dissociation between driving performance and subjective awareness of impairment. Despite a significantly diminished driving ability at 0.07% BAC, drivers were unaware of their impairment.

Effects of psychotropic drugs on ocular parameters relevant to traffic safety: A systematic review.

Driving is a complex neurobehavioural task necessitating the rapid selection, uptake, and processing of visual information. Eye movements that are critical for the execution of visually guided behaviour such as driving are also sensitive to the effects of psychotropic substances. The Embase (via Ovid), EBSCOHost, Psynet, Pubmed, Scopus and Web of Science databases were examined from January 01st, 2000 to December 31st, 2021. Study selection, data extraction and Cochrane Risk of Bias (RoB2) assessments were conducted according to PRISMA guidelines. The review was prospectively registered (CRD42021267554). In total, 36 full-text articles examined the effects of six principal psychotropic drug classes on measures of oculomotor parameters relevant to driving. Centrally depressing substances affect oculomotor responses in a dose-dependent manner. Psychostimulants improve maximal speed, but not accuracy, of visual search behaviours. Inhaled Δ-9-tetrahydrocannabinol (THC) increases inattention (saccadic inaccuracy) but does not consistently affect other oculomotor parameters. Alterations to composite ocular parameters due to psychoactive substance usage likely differently compromises performance precision during driving through impaired ability to select and process dynamic visual information.

On-road driving impairment following sleep deprivation differs according to age.

Impaired driving performance due to sleep loss is a major contributor to motor-vehicle crashes, fatalities, and serious injuries. As on-road, fully-instrumented studies of drowsy driving have largely focused on young drivers, we examined the impact of sleep loss on driving performance and physiological drowsiness in both younger and older drivers of working age. Sixteen 'younger' adults (M = 24.3 ± 3.1 years [21-33 years], 9 males) and seventeen 'older' adults (M = 57.3 ± 5.2, [50-65 years], 9 males) undertook two 2 h drives on a closed-loop track in an instrumented vehicle with a qualified instructor following (i) 8 h sleep opportunity the night prior (well-rested), and (ii) after 29-h of total sleep deprivation (TSD). Following TSD, both age groups displayed increased subjective sleepiness and lane departures (p < 0.05), with younger drivers exhibiting 7.37 × more lane departures, and 11 × greater risk of near crash events following sleep loss. While older drivers exhibited a 3.5 × more lane departures following sleep loss (p = 0.008), they did not have a significant increase in near-crash events (3/34 drives). Compared to older adults, younger adults had 3.1 × more lane departures (p = < 0.001), and more near crash events (79% versus 21%, p = 0.007). Ocular measures of drowsiness, including blink duration, number of long eye closures and PERCLOS increased following sleep loss for younger adults only (p < 0.05). These results suggest that for older working-aged adults, driving impairments observed following sleep loss may not be due to falling asleep. Future work should examine whether this is attributed to other consequences of sleep loss, such as inattention or distraction from the road.

The Combined Effects of Alcohol and Benzodiazepines on Driving-Related Neurocognitive Skills: A Systematic Review.

OBJECTIVE: Research concerning the combined effects of alcohol and benzodiazepines on driving-related skills is largely inconsistent. Because as many as 88% of benzodiazepine users report the additional consumption of alcohol, this review aims to provide an updated and concise synthesis of the available high-quality research. METHOD: We searched EBSCOhost, PubMed, Scopus, and Web of Science until April 1, 2020, for double-blind, placebo-controlled, repeated-measures intervention trials that examined the effects of alcohol (any dose provided as blood alcohol concentration [BAC]) in combination with oral benzodiazepines on neurocognitive tasks related to driving. RESULTS: We identified evidence of a substance and timing-dependent interaction for measures of reaction time, tracking, divided attention, and visual functioning. Administering alcohol in conjunction with or shortly after a benzodiazepine resulted in a stronger interactive effect than when administration occurred further apart. An additive and/or synergistic effect often occurred when a therapeutic dose of benzodiazepine was combined with alcohol at a BAC below .05%. CONCLUSIONS: Combined alcohol and benzodiazepine use was associated with significant impairments in driving-related neurocognitive skills. There is a clear need for more high-quality research in this area to better elucidate the mechanisms of alcohol and benzodiazepine interactions. Drivers may be unaware of impairments following the combination of these drugs at legal driving limits. Thus, drivers should be warned to take caution when consuming even small amounts of alcohol while under treatment with benzodiazepines.

The impact of 7-hour and 11-hour rest breaks between shifts on heavy vehicle truck drivers' sleep, alertness and naturalistic driving performance.

BACKGROUND: An inadequate rest break between shifts may contribute to driver sleepiness. This study assessed whether extending the major rest break between shifts from 7-hours (Australian industry standard) to 11-hours, improved drivers' sleep, alertness and naturalistic driving performance. METHODS: 17 heavy vehicle drivers (16 male) were recruited to complete two conditions. Each condition comprised two 13-hour shifts, separated by either a 7- or 11-hour rest break. The initial 13-hour shift was the drivers' regular work. The rest break and following 13-hour shift were simulated. The simulated shift included 5-hours of naturalistic driving with measures of subjective sleepiness, physiological alertness (ocular and electroencephalogram) and performance (steering and lane departures). RESULTS: 13 drivers provided useable data. Total sleep during the rest break was greater in the 11-hour than the 7-hour condition (median hours [25th to 75th percentile] 6.59 [6.23, 7.23] vs. 5.07 [4.46, 5.38], p = 0.008). During the simulated shift subjective sleepiness was marginally better for the 11-hour condition (mean Karolinska Sleepiness Scale [95th CI] = 4.52 [3.98, 5.07] vs. 5.12 [4.56, 5.68], p = 0.009). During the drive, ocular and vehicle metrics were improved for the 11-hour condition (p<0.05). Contrary to expectations, mean lane departures p/hour were increased during the 11-hour condition (1.34 [-0.38,3.07] vs. 0.63 [-0.2,1.47], p = 0.027). CONCLUSIONS: Extending the major rest between shifts substantially increases sleep duration and has a modest positive impact on driver alertness and performance. Future work should replicate the study in a larger sample size to improve generalisability and assess the impact of consecutive 7-hour major rest breaks.

Alexithymia explains atypical spatiotemporal dynamics of eye gaze in autism.

Recognition of emotional facial expressions is considered to be atypical in autism. This difficulty is thought to be due to the way that facial expressions are visually explored. Evidence for atypical visual exploration of emotional faces in autism is, however, equivocal. We propose that, where observed, atypical visual exploration of emotional facial expressions is due to alexithymia, a distinct but frequently co-occurring condition. In this eye-tracking study we tested the alexithymia hypothesis using a number of recent methodological advances to study eye gaze during several emotion processing tasks (emotion recognition, intensity judgements, free gaze), in 25 adults with, and 45 without, autism. A multilevel polynomial modelling strategy was used to describe the spatiotemporal dynamics of eye gaze to emotional facial expressions. Converging evidence from traditional and novel analysis methods revealed that atypical gaze to the eyes is best predicted by alexithymia in both autistic and non-autistic individuals. Information theoretic analyses also revealed differential effects of task on gaze patterns as a function of alexithymia, but not autism. These findings highlight factors underlying atypical emotion processing in autistic individuals, with wide-ranging implications for emotion research.

Driver monitoring systems (DMS): The future of impaired driving management?

OBJECTIVE: Driver monitoring systems (DMS) are the next generation of vehicle safety technology. Broadly, these refer to the embedded, aftermarket wearable or vehicle-mounted devices that collect observable information about the operator to make real-time assessment of their capacity to perform the driving task. Integrating biobehavioral monitoring (primarily ocular metrics) with driving performance assessments, these systems function to infer driver state in real time to identify operator conditions that negatively affect driving (such as fatigue, inattention, or distraction). METHOD: We review available methods used to infer driver state, as referenced against accepted models for optimal performance. Modeling our observations on deviation from predetermined performance thresholds used to trigger graded safety alerts, we suggest that many psychoactive substances produce alterations to biobehavioral processes including attentional and motor control, which affect performance indices in a manner already arguably captured by these technologies. RESULTS: Using these existing frameworks, there is considerable potential to similarly catalogue the effect of many common intoxicants known to negatively affect driving ability. This will provide safety-relevant and practical biological models for the development of next-generation multimodal DMS that integrate ocular and physiological variables sensitive to the effects of common and emergent psychoactive substances. CONCLUSION: These devices have tangible potential application across all areas of transportation, including aviation, rail, and all commercial and private vehicle systems.

Amphetamine-induced alteration to gaze parameters: A novel conceptual pathway and implications for naturalistic behavior.

Amphetamine produces a multiplicity of well-documented end-order biochemical, pharmacological and biobehavioural effects. Mechanistically, amphetamine downregulates presynaptic and postsynaptic striatal monoamine (primarily dopaminergic) systems, producing alterations to key brain regions which manifest as stereotyped ridged behaviour which occurs under both acute and chronic dosing schedules and persists beyond detoxification. Despite evidence of amphetamine-induced visual attentional dysfunction, no conceptual synthesis has yet captured how characteristic pharmaco-behavioural processes are critically implicated via these pathways, nor described the potential implications for safety-sensitive behaviours. Drawing on known pathomechanisms, we propose a cross-disciplinary, novel conceptual functional system framework for delineating the biobehavioural consequences of amphetamine use on visual attentional capacity and discuss the implications for functional and behavioural outcomes. Specifically, we highlight the manifest implications for behaviours that are conceptually driven and highly dependent on visual information processing for timely execution of visually-guided movements. Following this, we highlight the potential impact on safety-sensitive, but common behaviours, such as driving a motor vehicle. The close pathophysiological relationship between oculomotor control and higher-order cognitive processes further suggests that dynamic measurement of movement related to the motion of the eye (gaze behaviour) may be a simple, effective and direct measure of behavioural performance capabilities in naturalistic settings. Consequently, we discuss the potential efficacy of ocular monitoring for the detection and monitoring of driver states for this drug user group, and potential wider application. Significance statement: We propose a novel biochemical-physiological-behavioural pathway which delineates how amphetamine use critically alters oculomotor function, visual-attentional performance and information processing capabilities. Given the manifest implications for behaviours that are conceptually driven and highly dependent on these processes, we recommend oculography as a novel means of detecting and monitoring gaze behaviours during naturalistic tasks such as driving. Real-word examination of gaze behaviour therefore present as an effective means to detect driver impairment and prevent performance degradation due to these drugs.

Eye-Blink Parameters Detect On-Road Track-Driving Impairment Following Severe Sleep Deprivation.

STUDY OBJECTIVES: Drowsiness leads to 20% of fatal road crashes, while inability to assess drowsiness has hampered drowsiness interventions. This study examined the accuracy of eye-blink parameters for detecting drowsiness related driving impairment in real time. METHODS: Twelve participants undertook two sessions of 2-hour track-driving in an instrumented vehicle following a normal night's sleep or 32 to 34 hours of extended wake in a randomized crossover design. Eye-blink parameters and lane excursion events were monitored continuously. RESULTS: Sleep deprivation increased the rates of out-of-lane driving events and early drive terminations. Episodes of prolonged eyelid closures, blink duration, the ratio of amplitude to velocity of eyelid closure, and John's Drowsiness Score (JDS, a composite score) were also increased following sleep deprivation. A time-on-task (drive duration) effect was evident for out-of-lane events rate and most eye-blink parameters after sleep deprivation. The JDS demonstrated the strongest association with the odds of out-of-lane events in the same minute, whereas measures of blink duration and prolonged eye closure were stronger indicators of risk for out-of-lane events over longer periods of 5 minutes and 15 minutes, respectively. Eye-blink parameters also achieved moderate accuracies (specificities from 70.12% to 84.15% at a sensitivity of 50%) for detecting out-of-lane events in the same minute, with stronger associations over longer timeframes of 5 minutes to 15 minutes. CONCLUSIONS: Eyelid closure parameters are useful tools for monitoring and predicting drowsiness-related driving impairment (out-of-lane events) that could be utilized for monitoring drowsiness and assessing the efficacy of drowsiness interventions. CLINICAL TRIAL REGISTRATION: This study is registered with the Australian New Zealand Clinical Trial Registry (ANCTR), http://www.anzctr.org.au/TrialSearch.aspx ACTRN12612000102875. CITATION: Shekari Soleimanloo S, Wilkinson VE, Cori JM,Westlake J, Stevens B, Downey LA, Shiferaw BA, Rajaratnam SMW, Howard ME. Eye-blink parameters detect on-road track-driving impairment following severe sleep deprivation. J Clin Sleep Med. 2019;15(9):1271-1284.

Gaze entropy measures detect alcohol-induced driver impairment.

Driving under the influence of alcohol is an ongoing cause of road traffic accidents. The biphasic nature of alcohol effects on subjective experience appears to contribute to the prevalence of drink-driving, as people perceive the declining phase of the BAC curve as recovery from intoxication and are more willing to drive despite significant impairments in objectively measured functions. The present study investigates whether alcohol-induced changes in gaze behaviour can be detected during engagement in a simulated driving task. In a repeated-measures and placebo-controlled design, this study examines the biphasic influence of moderate alcohol intake (0.6 g/kg) on measures of gaze behaviour and simulated driving performance. Twenty-two healthy young adults completed three driving sessions (baseline, ascending and descending) under two conditions (placebo, alcohol) while their eye movements were simultaneously recorded. The results revealed that gaze behaviour as measured by gaze transition entropy (GTE) and stationary gaze entropy (SGE) and driving performance measured by the standard deviation of lateral position (SDLP) of the vehicle, were significantly affected by alcohol across the ascending and descending sessions. The alcohol-induced reduction in GTE with an increase in SGE is discussed as alcohol's impact on top-down modulation of gaze resulting in more dispersed and erratic pattern of visual scanning. The observed changes in gaze behaviour also mediated the influence of alcohol upon driving performance. These results have significant implications for the development of driver monitoring systems that can detect alcohol-induced impairment.

Driving Simulator Performance After Administration of Analgesic Doses of Ketamine With Dexmedetomidine or Fentanyl.

PURPOSE/BACKGROUND: As a sole agent, ketamine acutely compromises driving ability; however, performance after coadministration with the adjuvant sedating agents dexmedetomidine or fentanyl is unclear. METHODS/PROCEDURES: Using a randomized within-subject design, 39 participants (mean ± SD age, 28.4 ± 5.8 years) received 0.3 mg/kg bolus followed by 0.15 mg kg h infusion of ketamine (3-hour duration), in addition to either (i) 0.7 µg kg h infusion of dexmedetomidine for 1.5 hours (n = 19; KET/DEX) or (ii) three 25 µg fentanyl injections for 1.5 hours (n = 20; KET/FENT). Whole blood drug concentrations were determined during ketamine only, at coadministration (KET/DEX or KET/FENT) and at 2 hours after treatment. Subjective effects were determined using a standardized visual analog scale. Driving performance was assessed at baseline and at posttreatment using a validated computerized driving simulator. Primary outcomes included SD of lateral position (SDLP) and steering variability (SV). FINDINGS/RESULTS: Administration of ketamine with dexmedetomidine but not fentanyl significantly increased SDLP (F1,18 = 22.60, P < 0.001) and reduced SV (F1,18 = 164.42, P < 0.001) 2 hours after treatment. These deficits were comparatively greater for the KET/DEX group than for the KET/FENT group (t37 = -5.21 [P < 0.001] and t37 = 5.22 [P < 0.001], (respectively). For the KET/DEX group, vehicle control (SV) and self-rated performance (visual analog scale), but not SDLP, was inversely associated with ketamine and norketamine blood concentrations (in nanograms per milliliter). Greater subjective effects were moderately associated with driving deficits. IMPLICATIONS/CONCLUSIONS: Driving simulator performance is significantly compromised after coadministration of analgesic range doses of ketamine with dexmedetomidine but not fentanyl. An extended period of supervised driver abstinence is recommended after treatment, with completion of additional assessments to evaluate home readiness.

Gaze Entropy Measures Reveal Alcohol-Induced Visual Scanning Impairment During Ascending and Descending Phases of Intoxication.

OBJECTIVE: Visuospatial awareness is critical for everyday activities like driving. Higher order processes, such as visuospatial working memory (VSWM) and top-down modulation of gaze control, enable goal-driven visual scanning. Although available evidence suggests that alcohol differentially affects VSWM during the ascending and descending phases of the blood alcohol concentration (BAC) curve, it remains unclear whether such impact extends to a systemic disruption of visual scanning behavior. METHOD: In a placebo-controlled and repeated-measures design, the present study investigated the influence of moderate alcohol intake (0.6 g/kg) on VSWM and gaze behavior by using gaze entropy measures to quantify visual scanning efficiency. Thirty-eight (18 female, 20 male) healthy participants completed a VSWM task across three consecutive sessions (baseline, ascending, descending) while their eye movements were simultaneously recorded. RESULTS: Performance in VSWM was affected during the descending session, where response accuracy declined significantly. Stationary gaze entropy (SGE) and gaze transition entropy (GTE) measures significantly reduced during both ascending and descending sessions. Fixation rate and duration were also affected by alcohol, but only during the ascending session. CONCLUSIONS: Reduction in SGE suggests a less explorative distribution of gaze, whereas low GTE is indicative of reduced visual scanning efficiency. These findings reflect the detrimental effects of alcohol on top-down control of gaze behavior, which may limit visual scanning efficiency. Deficits in visual scanning efficiency across the blood alcohol concentration curve may reduce visuospatial awareness and contribute to unintentional injuries during periods of intoxication.

A review of gaze entropy as a measure of visual scanning efficiency.

While the concept of entropy has been applied to gaze analysis, it is unclear what aspects of visual scanning it measures. In this review, we first outline gaze control as a complex system of spatial prediction. Second, we provide a brief introduction to the concept of entropy within the context of information theory as the foundation for gaze entropy measures; with a specific focus on equations for Shannon's entropy and conditional entropy. The application of these equations to gaze data is described as stationary gaze entropy (SGE) and gaze transition entropy (GTE) respectively. Third, we present an updated model of gaze orientation and propose an adaptable definition of GTE as a measure of visual scanning efficiency that underlies overall gaze dispersion measured by SGE. Finally, we review studies that have utilised GTE and SGE to assess visual scanning and discuss their results in relation to our proposed definitions and associated hypotheses. Methodological limitations in gaze entropy measures are discussed and suggestions provided to improve interpretability and generalisability of future studies.

The acute and residual effects of escalating, analgesic-range doses of ketamine on driving performance: A simulator study.

Ketamine hydrochloride elicits potent psychotomimetic and neurobehavioural effects which make it incompatible with driving; however, the direct effect on driving performance is yet to be assessed. Using an open label, within-subjects protocol, 15 males and 5 females (mean age = 30.8 years) were administered three fixed, stepwise increasing sub-anaesthetic doses of intravenous (IV) ketamine solution [(i) 8 mg/h IV infusion plus 30 mg bolus, (ii) 12 mg/h IV infusion and (iii) 20 mg/h infusion]. Whole blood ketamine and norketamine concentrations were determined at each treatment step and at 2 h post-infusion. Driving performance was assessed at baseline, at each treatment step and at 2 h post-treatment using a validated computerised driving simulator. Standard Deviation of Lateral Position (SDLP) and Steering Variability (SV) were assessed. Linear Fixed Effect Modelling indicated a main effect for time (dose) for SDLP (F[4,72] = 33.22, p < 0.0001) and SV (F[4,72] = 4.65, p < 0.002). Post-hoc analyses revealed significant differences from baseline at each treatment step for SDLP (all p < 0.001), and for 12 mg/h treatment step for SV (p = 0.049). Post-treatment driving performance returned to baseline levels. Weak positive linear associations were observed between SDLP and whole blood ketamine concentrations (R2 = 0.11, ß = 29.96, p = 0.001) and norketamine (R2 = 0.09, ß = 28.87, p = 0.003). These findings suggest that even under highly controlled conditions, ketamine intoxication significantly alters simulated driving performance. At the highest dose, ketamine produced changes to SDLP considered incompatible with safe driving, highlighting how ketamine consumption may translate to an increased risk of road trauma.

Stationary gaze entropy predicts lane departure events in sleep-deprived drivers.

Performance decrement associated with sleep deprivation is a leading contributor to traffic accidents and fatalities. While current research has focused on eye blink parameters as physiological indicators of driver drowsiness, little is understood of how gaze behaviour alters as a result of sleep deprivation. In particular, the effect of sleep deprivation on gaze entropy has not been previously examined. In this randomised, repeated measures study, 9 (4 male, 5 female) healthy participants completed two driving sessions in a fully instrumented vehicle (1 after a night of sleep deprivation and 1 after normal sleep) on a closed track, during which eye movement activity and lane departure events were recorded. Following sleep deprivation, the rate of fixations reduced while blink rate and duration as well as saccade amplitude increased. In addition, stationary and transition entropy of gaze also increased following sleep deprivation as well as with amount of time driven. An increase in stationary gaze entropy in particular was associated with higher odds of a lane departure event occurrence. These results highlight how fatigue induced by sleep deprivation and time-on-task effects can impair drivers' visual awareness through disruption of gaze distribution and scanning patterns.