A. Capelli

Influence of age, circadian and homeostatic processes on inhibitory motor control: a Go/Nogo task study.

Introduction The contribution of circadian system and sleep pressure influences on executive performance as a function of age has never been studied. The aim of our study was to determine the age-related evolution of inhibitory motor control (i.e., ability to suppress a prepotent motor response) and sustained attention under controlled high or low sleep pressure conditions. Methods 14 healthy young males (mean age  = 23±2.7; 20–29 years) and 11 healthy older males (mean age  = 68±1.4; 66–70 years) were recruited. The volunteers were placed for 40 hours in “constant routine”. In the “Sleep Deprivation SD” condition, the volunteer was kept awake for 40 hours to obtain a high sleep pressure condition interacting with the circadian process. In the “NAP” condition, the volunteer adopted a short wake/sleep cycle (150/75 min) resulting in a low sleep pressure condition to counteract the homeostatic pressure and investigate the circadian process. Performances were evaluated by a simple reaction time task and a Go/Nogo task repeated every 3H45. Results In the SD condition, inhibitory motor control (i.e., ability to inhibit an inappropriate response) was impaired by extended wakefulness equally in both age groups (P<.01). Sustained attention (i.e. ability to respond accurately to appropriate stimuli) on the executive task decreased under sleep deprivation in both groups, and even more in young participants (P<.05). In the NAP condition, age did not influence the time course of inhibitory motor control or sustained attention. In the SD and NAP conditions, older participants had a less fluctuating reaction time performance across time of day than young participants (P<.001). Conclusion Aging could be a protective factor against the effects of extended wakefulness especially on sustained attention failures due to an attenuation of sleep pressure with duration of time awake.

Modafinil Improves Real Driving Performance in Patients with Hypersomnia: A Randomized Double-Blind Placebo-Controlled Crossover Clinical Trial

STUDY OBJECTIVE Patients with excessive daytime sleepiness (EDS) are at high risk for driving accidents, and physicians are concerned by the effect of alerting drugs on driving skills of sleepy patients. No study has up to now investigated the effect of modafinil (a reference drug to treat EDS in patients with hypersomnia) on on-road driving performance of patients suffering from central hypersomnia. The objective is to evaluate in patients with central hypersomnia the effect of a wake-promoting drug on real driving performance and to assess the relationship between objective sleepiness and driving performance. DESIGN AND PARTICIPANTS Randomized, crossover, double-blind placebo-controlled trial conducted among 13 patients with narcolepsy and 14 patients with idiopathic hypersomnia. Patients were randomly assigned to receive modafinil (400 mg) or placebo for 5 days prior to the driving test. Each condition was separated by at least 3 weeks of washout. MEASUREMENTS Mean number of Inappropriate Line Crossings, Standard Deviation of Lateral Position of the vehicle and mean sleep latency in the Maintenance of Wakefulness Test were assessed. RESULTS Modafinil reduced the mean number of Inappropriate Line Crossings and Standard Deviation of Lateral Position of the vehicle compared to placebo (F(1,25) = 4.88, P < 0.05 and F(1,25) = 3.87, P = 0.06 tendency). Mean sleep latency at the Maintenance of Wakefulness Test significantly correlated with the mean number of Inappropriate Line Crossings (r = -0.41, P < 0.001). CONCLUSIONS Modafinil improves driving performance in patients with narcolepsy and idiopathic hypersomnia. The Maintenance of Wakefulness Test is a suitable clinical tool to assess fitness to drive in this population.

Sleep Loss and Accidents--Work Hours, Life Style, and Sleep Pathology

A very important outcome of reduced sleep is accidents. The present chapter will attempt to bring together some of the present knowledge in this area. We will focus on the driving situation, for which the evidence of the link between sleep loss and accidents is quite well established, but we will also bring up working life in general where evidence is more sparse. It should be emphasized that reduced sleep as a cause of accidents implies that the mediating factor is sleepiness (or fatigue). This link is discussed elsewhere in this volume, but here we will bring in sleepiness (subjective or physiological) as an explanatory factor of accidents. Another central observation is that many real life accident studies do not link accidents to reduced sleep, but infer reduced sleep and/or sleepiness from the context, like, for example, from work schedules, life styles, or sleep pathology. Reduced sleep is mainly due to suboptimal work schedules (or to a suboptimal life style) or to sleep pathology. We have divided the present chapter into two areas.

Acute versus chronic partial sleep deprivation in middle-aged people: differential effect on performance and sleepiness.

STUDY OBJECTIVE To evaluate the effects of acute sleep deprivation and chronic sleep restriction on vigilance, performance, and self-perception of sleepiness. DESIGN Habitual night followed by 1 night of total sleep loss (acute sleep deprivation) or 5 consecutive nights of 4 hr of sleep (chronic sleep restriction) and recovery night. PARTICIPANTS Eighteen healthy middle-aged male participants (age [(± standard deviation] = 49.7 ± 2.6 yr, range 46-55 yr). MEASUREMENTS Multiple sleep latency test trials, Karolinska Sleepiness Scale scores, simple reaction time test (lapses and 10% fastest reaction times), and nocturnal polysomnography data were recorded. RESULTS Objective and subjective sleepiness increased immediately in response to sleep restriction. Sleep latencies after the second and third nights of sleep restriction reached levels equivalent to those observed after acute sleep deprivation, whereas Karolinska Sleepiness Scale scores did not reach these levels. Lapse occurrence increased after the second day of sleep restriction and reached levels equivalent to those observed after acute sleep deprivation. A statistical model revealed that sleepiness and lapses did not progressively worsen across days of sleep restriction. Ten percent fastest reaction times (i.e., optimal alertness) were not affected by acute or chronic sleep deprivation. Recovery to baseline levels of alertness and performance occurred after 8-hr recovery night. CONCLUSIONS In middle-aged study participants, sleep restriction induced a high increase in sleep propensity but adaptation to chronic sleep restriction occurred beyond day 3 of restriction. This sleepiness attenuation was underestimated by the participants. One recovery night restores daytime sleepiness and cognitive performance deficits induced by acute or chronic sleep deprivation. CITATION Philip P; Sagaspe P; Prague M; Tassi P; Capelli A; Bioulac B; Commenges D; Taillard J. Acute versus chronic partial sleep deprivation in middle-aged people: differential effect on performance and sleepiness. SLEEP 2012;35(7):997-1002.

In-car nocturnal blue light exposure improves motorway driving: a randomized controlled trial

Prolonged wakefulness greatly decreases nocturnal driving performance. The development of in-car countermeasures is a future challenge to prevent sleep-related accidents. The aim of this study is to determine whether continuous exposure to monochromatic light in the short wavelengths (blue light), placed on the dashboard, improves night-time driving performance. In this randomized, double-blind, placebo-controlled, cross-over study, 48 healthy male participants (aged 20–50 years) drove 400 km (250 miles) on motorway during night-time. They randomly and consecutively received either continuous blue light exposure (GOLite, Philips, 468 nm) during driving or 2*200 mg of caffeine or placebo of caffeine before and during the break. Treatments were separated by at least 1 week. The outcomes were number of inappropriate line crossings (ILC) and mean standard deviation of the lateral position (SDLP). Eight participants (17%) complained about dazzle during blue light exposure and were removed from the analysis. Results from the 40 remaining participants (mean age ± SD: 32.9±11.1) showed that countermeasures reduced the number of inappropriate line crossings (ILC) (F(2,91.11) = 6.64; p<0.05). Indeed, ILC were lower with coffee (12.51 [95% CI, 5.86 to 19.66], p = 0.001) and blue light (14.58 [CI, 8.75 to 22.58], p = 0.003) than with placebo (26.42 [CI, 19.90 to 33.71]). Similar results were found for SDLP. Treatments did not modify the quality, quantity and timing of 3 subsequent nocturnal sleep episodes. Despite a lesser tolerance, a non-inferior efficacy of continuous nocturnal blue light exposure compared with caffeine suggests that this in-car countermeasure, used occasionally, could be used to fight nocturnal sleepiness at the wheel in blue light-tolerant drivers, whatever their age. More studies are needed to determine the reproducibility of data and to verify if it can be generalized to women. Trial Registration ClinicalTrials.gov NCT01070004

Maintenance of Wakefulness Test scores and driving performance in sleep disorder patients and controls

OBJECTIVE Sleepiness at the wheel is a risk factor for traffic accidents. Past studies have demonstrated the validity of the Maintenance of Wakefulness Test (MWT) scores as a predictor of driving impairment in untreated patients with obstructive sleep apnea syndrome (OSAS), but there is limited information on the validity of the maintenance of wakefulness test by MWT in predicting driving impairment in patients with hypersomnias of central origin (narcolepsy or idiopathic hypersomnia). The aim of this study was to compare the MWT scores with driving performance in sleep disorder patients and controls. METHODS 19 patients suffering from hypersomnias of central origin (9 narcoleptics and 10 idiopathic hypersomnia), 17 OSAS patients and 14 healthy controls performed a MWT (4×40-minute trials) and a 40-minute driving session on a real car driving simulator. Participants were divided into 4 groups defined by their MWT sleep latency scores. The groups were pathological (sleep latency 0-19 min), intermediate (20-33 min), alert (34-40 min) and control (>34 min). The main driving performance outcome was the number of inappropriate line crossings (ILCs) during the 40 minute drive test. RESULTS Patients with pathological MWT sleep latency scores (0-19 min) displayed statistically significantly more ILC than patients from the intermediate, alert and control groups (F (3, 46)=7.47, p<0.001). INTERPRETATION Pathological sleep latencies on the MWT predicted driving impairment in patients suffering from hypersomnias of central origin as well as in OSAS patients. MWT is an objective measure of daytime sleepiness that appears to be useful in estimating the driving performance in sleepy patients.

Time Course of Neurobehavioral Alertness During Extended Wakefulness in Morning- and Evening-Type Healthy Sleepers

The aim of the study was to evaluate the influence of chronotype (morning-type versus evening-type) living in a fixed sleep-wake schedule different from ones preferred sleep schedules on the time course of neurobehavioral performance during controlled extended wakefulness. The authors studied 9 morning-type and 9 evening-type healthy male subjects (21.4 ± 1.9 yrs). Before the experiment, all participants underwent a fixed sleep-wake schedule mimicking a regular working day (bedtime: 23:30 h; wake time: 07:30 h). Then, following two nights in the laboratory, both chronotypes underwent a 36-h constant routine, performing a cognitive test of sustained attention every hour. Core body temperature, salivary melatonin secretion, objective alertness (maintenance of wakefulness test), and subjective sleepiness (visual analog scale) were also assessed. Evening-types expressed a higher level of subjective sleepiness than morning types, whereas their objective levels of alertness were not different. Cognitive performance in the lapse domain remained stable during the normal waking day and then declined during the biological night, with a similar time course for both chronotypes. Evening types maintained optimal alertness (i.e., 10% fastest reaction time) throughout the night, whereas morning types did not. For both chronotypes, the circadian performance profile was correlated with the circadian subjective somnolence profile and was slightly phase-delayed with melatonin secretion. Circadian performance was less correlated with circadian core body temperature. Lapse domain was phase-delayed with body temperature (2–4 h), whereas optimal alertness was slightly phase-delayed with body temperature (1 h). These results indicate evening types living in a fixed sleep-wake schedule mimicking a regular working day (different from their preferred sleep schedules) express higher subjective sleepiness but can maintain the same level of objective alertness during a normal waking day as morning types. Furthermore, evening types were found to maintain optimal alertness throughout their nighttime, whereas morning types could not. The authors suggest that evening-type subjects have a higher voluntary engagement of wake-maintenance mechanisms during extended wakefulness due to adaptation of their sleep-wake schedule to social constraints. (Author correspondence: jack.taillard@gmail.com)

Factors Associated With Serious Traffic Crashes: A Prospective Study in Southwest France

understand DMAA’s potential health effects. Supplements containing DMAA have been implicated as potentially contributing agents in multiple serious adverse events, including panic attacks, seizures, stress-induced cardiomyopathy, and 2 deaths. In Europe and New Zealand, DMAA use as a party drug has been implicated in at least 1 hemorrhagic stroke. Causality has yet to be proven, but these adverse effects are consistent with DMAA’s known pharmacologic actions. In The Dispensatory of the United States of America 1950 Edition, DMAA’s systemic toxic effects in animals was described as “greater than that of ephedrine and less than that of amphetamine,” and the authors counseled that if DMAA’s use as a nasal inhaler “produces side effects such as headache, nervousness, mental stimulation, or tremors, the drug should be discontinued.” Small trials have also demonstrated that DMAA-containing supplements increase blood pressure and heart rate. Last summer, Health Canada banned DMAA from all supplements, and last December, the US military removed DMAA-containing supplements from all military exchanges worldwide (Table). In late April 2012, 6 years after DMAA had been introduced as a dietary supplement, the US Food and Drug Administration (FDA) sent warning letters to 10 manufacturers requiring them to provide evidence to support their conclusion that DMAA is a safe supplement ingredient. Given that DMAA is a potentially dangerous ingredient and that manufacturers’ claims that it is naturally derived are unsubstantiated, manufacturers and distributors should immediately recall all DMAA-containing supplements. The extensive mainstream sales of DMAA combined with the FDA’s delayed response expose the potentially serious public health risks entailed when consuming new supplement ingredients. Published Online: May 7, 2012. doi:10.1001 /archinternmed.2012.1677. Corrected May 14, 2012. Author Affiliations: Department of Medicine, Harvard Medical School, Cambridge Health Alliance, Somerville, Massachusetts. Correspondence: Dr Cohen, Harvard Medical School, Cambridge Health Alliance, 236 Highland Ave, Somerville, MA 02143 (pcohen@challiance.org). Financial Disclosure: None reported.

Sleepiness, Sleep Disorders and Attention-Deficit/Hyperactivity Disorder: Pathophysiological Rationale and Future Perspectives

The links between sleep and attention-deficit hyperactivity disorder (ADHD) have been a topic of ongoing research and clinical interest in children over the last three decades and more recently in adults suffering from ADHD. Clinically, psychiatrists are faced with frequent reports of sleep disorders in adults and children with ADHD and conversely, sleep specialists report certain symptoms of ADHD (attention deficits, urge for fidgeting) in patients suffering from primary sleep disorders. Excessive sleepiness is found in ADHD and sleep disorders such as hypersomnia, sleep breathing disorder (SDB), periodic limb movements in sleep (PLMS) and circadian rhythm disorders. This has encouraged authors to suggest a model of ADHD involving a deficit in alertness. The aim of this article is to clarify the pathophysiological rationale for the relationship between sleep/arousal and attention-deficit/hyperactivity disorder and to explore future perspectives in terms of management, treatment and development of research fields.