An explorative approach to understanding individual differences in driving performance and neurocognition in long-term benzodiazepine users

Objective: Previous research reported cognitive and psychomotor impairments in long‐term users of benzodiazepine receptor agonists (BZRAs). This article explores the role of acute intoxication and clinical complaints. Methods: Neurocognitive and on‐road driving performance of 19 long‐term (≥6 months) regular (≥twice weekly) BZRA users with estimated plasma concentrations, based on self‐reported use, exceeding the therapeutic threshold (CBZRA+), and 31 long‐term regular BZRA users below (CBZRA−), was compared to that of 76 controls. Results: BZRA users performed worse on tasks of response speed, processing speed, and sustained attention. Age, but not CBZRA or self‐reported clinical complaints, was a significant covariate. Road‐tracking performance was explained by CBZRA only. The CBZRA + group exhibited increased mean standard deviation of lateral position comparable to that at blood‐alcohol concentrations of 0.5 g/L. Conclusions: Functional impairments in long‐term BZRA users are not attributable to self‐reported clinical complaints or estimated BZRA concentrations, except for road‐tracking, which was impaired in CBZRA + users. Limitations to address are the lack of assessment of objective clinical complaints, acute task related stress, and actual BZRA plasma concentrations. In conclusion, the results confirm previous findings that demonstrate inferior performance across several psychomotor and neurocognitive domains in long‐term BZRA users

Single- and dual-task performance during on-the-road driving at a low and moderate dose of alcohol: A comparison between young novice and more experienced drivers

Driving experience and alcohol are two factors associated with a higher risk of crash involvement in young novice drivers. Driving a car is a complex task involving multiple tasks leading to dividing attention. The aim of this study was to compare the single and combined effects of a low and moderate dose of alcohol on single- and dual-task performance between young novice and more experienced young drivers during actual driving. Nine healthy novice drivers were compared with 9 more experienced drivers in a three-way, placebo-controlled, cross-over study design. Driving performance was measured in actual traffic, with standard deviation of lateral position as the primary outcome variable. Secondary task performance was measured with an auditory word learning test during driving. Results showed that standard deviation of lateral position increased dose-dependently at a blood alcohol concentration (BAC) of 0.2 and 0.5 g/L in both novice and experienced drivers. Secondary task performance was impaired in both groups at a BAC of 0.5 g/L. Furthermore, it was found that driving performance in novice drivers was already impaired at a BAC of 0.2 g/L during dual-task performance. The findings suggest that young inexperienced drivers are especially vulnerable to increased mental load while under the influence of alcohol

Nicotine deprivation elevates neural representation of smoking-related cues in object-sensitive visual cortex: a proof of concept study

OBJECTIVE: In the current study, we use functional magnetic resonance imaging (fMRI) and multi-voxel pattern analysis (MVPA) to investigate whether tobacco addiction biases basic visual processing in favour of smoking-related images. We hypothesize that the neural representation of smoking-related stimuli in the lateral occipital complex (LOC) is elevated after a period of nicotine deprivation compared to a satiated state, but that this is not the case for object categories unrelated to smoking. METHODS: Current smokers (≥10 cigarettes a day) underwent two fMRI scanning sessions: one after 10 h of nicotine abstinence and the other one after smoking ad libitum. Regional blood oxygenated level-dependent (BOLD) response was measured while participants were presented with 24 blocks of 8 colour-matched pictures of cigarettes, pencils or chairs. The functional data of 10 participants were analysed through a pattern classification approach. RESULTS: In bilateral LOC clusters, the classifier was able to discriminate between patterns of activity elicited by visually similar smoking-related (cigarettes) and neutral objects (pencils) above empirically estimated chance levels only during deprivation (mean = 61.0%, chance (permutations) = 50.0%, p = .01) but not during satiation (mean = 53.5%, chance (permutations) = 49.9%, ns.). For all other stimulus contrasts, there was no difference in discriminability between the deprived and satiated conditions. CONCLUSION: The discriminability between smoking and non-smoking visual objects was elevated in object-selective brain region LOC after a period of nicotine abstinence. This indicates that attention bias likely affects basic visual object processing

On-the-road driving performance the morning after bedtime use of suvorexant 15 and 30 mg in healthy elderly

Suvorexant is a first-in-class orexin receptor antagonist for treating insomnia. There is a general concern that hypnotics may impair next-morning driving ability. The objective of this study was to evaluate next-morning driving performance in older adults after single and repeated doses of suvorexant. Double-blind, randomized, placebo-controlled, 4-period crossover study in 24 healthy volunteers (10 females), aged 65-80 years. Subjects were treated with suvorexant (15 and 30 mg) for eight consecutive nights, zopiclone 7.5 mg nightly on days 1 and 8, and placebo. Driving performance was assessed on days 2 and 9 (9 h after dosing) using a 1-h standardized highway driving test in normal traffic, measuring standard deviation of lateral position (SDLP). Drug-placebo differences in SDLP > 2.4 cm were considered to reflect clinically meaningful driving impairment. Driving performance as measured by SDLP was not impaired following suvorexant. Mean drug-placebo differences in SDLP following suvorexant 15 and 30 mg on day 2 and 9 were 0.6 cm or less. Their 90 % CIs were all below the threshold of 2.4 cm for clinical relevance and included zero, indicating effects were not clinically meaningful or statistically significant. Symmetry analysis showed no significant differences between the number of participants who had SDLP differences > 2.4 cm and those who had SDLP differences There was no clinically meaningful residual effect of suvorexant 15 and 30 mg on next-morning driving (9 h after bedtime dosing) in healthy older adults, as assessed by mean changes in SDLP and by the number of participants on drug versus placebo that exceeded a predetermined threshold for clinically meaningful impairment

On-the-road driving performance the morning after bedtime administration of lemborexant in healthy adult and elderly volunteers

Study Objectives: To assess potential effects of lemborexant on next-morning driving performance in adult and elderly healthy volunteers. Methods: Randomized, double-blind, double-dummy, placebo and active-controlled, four period incomplete crossover study in 48 healthy volunteers (22 females), 23-78 years old. Participants were treated at bedtime for 8 consecutive nights with 2 of 3 dose levels of lemborexant (2.5, 5, or 10 mg), zopiclone 7.5 mg (on the first and last night with placebo on intervening nights), or placebo. Driving performance was assessed in the morning on day 2 and 9 using a standardized highway driving test in normal traffic, measuring standard deviation of lateral position (SDLP). Drug-placebo differences in SDLP > 2.4 cm were considered to reflect clinically meaningful driving impairment. Results: Mean drug-placebo differences in SDLP following lemborexant 2.5, 5, and 10 mg on day 2 and 9 were 0.74 cm or less. The upper bound of the 95% confidence intervals (CIs) for lemborexant treatment groups were all below 2.4 cm and the 95% CIs included zero, indicating that the effects were neither clinically meaningful nor statistically significant. Symmetry analysis further supported the lack of clinically meaningful impairment with lemborexant. Conclusions: When assessed starting ~9 h after lemborexant administration at bedtime the previous night, there was no statistically significant or clinically meaningful effect on driving performance in healthy adults and elderly, as assessed by either mean differences in SDLP relative to placebo or symmetry analysis. In this study, lemborexant at doses up to 10 mg was well-tolerated

On-the-Road Driving Performance the Morning after Bedtime Use of Suvorexant 20 and 40 mg: A Study in Non-Elderly Healthy Volunteers

Study Objective: To evaluate next-morning driving performance in adults younger than 65 years, after single and repeated doses of suvorexant 20 and 40 mg. Design: Double-blind, placebo-controlled, 4-period crossover study. Setting: Maastricht University, The Netherlands. Participants: 28 healthy volunteers (15 females), aged 23 to 64 years. Interventions: Suvorexant (20 and 40 mg) for 8 consecutive nights; zopiclone 7.5 mg nightly on day 1 and 8; placebo. Measurements: Performance on day 2 and 9 (9 h after dosing) using a one-hour standardized highway driving test in normal traffic, measuring standard deviation of lateral position (SDLP). Drug-placebo changes in SDLP > 2.4 cm were considered to reflect meaningful driving impairment. Results: Mean drug-placebo changes in SDLP following suvorexant 20 and 40 mg were 1.01 and 1.66 cm on day 2, and 0.48 and 1.31 cm on Day 9, respectively. The 90% CIs of these changes were all below 2.4 cm. Symmetry analysis showed that more subjects had SDLP changes > 2.4 cm than < -2.4 cm following suvorexant 20 and 40 mg on day 2, and following suvorexant 40 mg on day 9. Four female subjects requested that a total of 5 driving tests-all following suvorexant-stop prematurely due to self-reported somnolence. Conclusions: As assessed by mean changes in standard deviation of lateral position (SDLP), there was no clinically meaningful residual effect of suvorexant in doses of 20 and 40 mg on next-morning driving (9 h after bedtime dosing) in healthy subjects < 65 years old. There may be some individuals who experience next-day effects, as suggested by individual changes in SDLP and prematurely stopped tests