Jennifer R. Redman

Time of day variations in driving performance

Numerous factors may contribute to the 24-hour pattern of automobile accidents. One factor may be a time of day variation in driving ability. In the present study, 11 male subjects operated a driving simulator for 30 minutes at six times of day. Subjects were instructed to maintain a stable position in the left-hand lane and to drive at a constant speed of 80 km/hour. In addition subjects performed a secondary reaction time task. Subjective mood was measured at the beginning and end of each session. Driving performance was measured in terms of the mean and standard deviation of lateral position and speed. The mean and standard deviation of speed varied significantly across the day for both curved and straight segments. Reaction time was also affected by time of day. Performance was more impaired at 0600 and 0200 hours, with improvements in driving performance between 1000 and 2200 hours and an early afternoon dip. These results suggest that driving performance is subject to diurnal variations. Of particular importance is the result that impairments in driving performance in the early afternoon are of a similar magnitude to those occurring in the late evening and early morning.

Sleep disturbance and melatonin levels following traumatic brain injury

Objectives: Sleep disturbances commonly follow traumatic brain injury (TBI) and contribute to ongoing disability. However, there are no conclusive findings regarding specific changes to sleep quality and sleep architecture measured using polysomnography. Possible causes of the sleep disturbances include disruption of circadian regulation of sleep-wakefulness, psychological distress, and a neuronal response to injury. We investigated sleep-wake disturbances and their underlying mechanisms in a TBI patient sample. Methods: This was an observational study comparing 23 patients with TBI (429.7 ± 287.6 days post injury) and 23 age- and gender-matched healthy volunteers on polysomnographic sleep measures, salivary dim light melatonin onset (DLMO) time, and self-reported sleep quality, anxiety, and depression. Results: Patients with TBI reported higher anxiety and depressive symptoms and sleep disturbance than controls. Patients with TBI showed decreased sleep efficiency (SE) and increased wake after sleep onset (WASO). Although no significant group differences were found in sleep architecture, when anxiety and depression scores were controlled, patients with TBI showed higher amount of slow wave sleep. No differences in self-reported sleep timing or salivary DLMO time were found. However, patients with TBI showed significantly lower levels of evening melatonin production. Melatonin level was significantly correlated with REM sleep but not SE or WASO. Conclusions: Reduced evening melatonin production may indicate disruption to circadian regulation of melatonin synthesis. The results suggest that there are at least 2 factors contributing to sleep disturbances in patients with traumatic brain injury. We propose that elevated depression is associated with reduced sleep quality, and increased slow wave sleep is attributed to the effects of mechanical brain damage.

Fatigue and sleep disturbance following traumatic brain injury--their nature, causes, and potential treatments.

Background:Although fatigue and sleep disturbance are commonly reported following traumatic brain injury (TBI), understanding of their nature and treatment remains limited. Objectives:This article reviews a series of investigations of the nature and causes of fatigue and sleep disturbance following TBI. Methods:A large cohort of community-based patients with TBI, recruited from a TBI rehabilitation program, completed measures of subjective fatigue and sleep disturbances, as well as attentional measures. A subgroup of participants completed polysomnography and assessment of dim light melatonin onset. Results:Fatigue and sleep disturbance are common. Both are associated with anxiety, depression, and pain. However, fatigue is also associated with slowed information processing and the need for increased effort in performing tasks. Sleep disturbances contribute to fatigue. Objective sleep studies show reduced sleep efficiency, increased sleep onset latency, and increased time awake after sleep onset. Depression and pain exacerbate but cannot entirely account for these problems. There is increased slow-wave sleep. Individuals with TBI show lower levels of evening melatonin production, associated with less rapid-eye movement sleep. Conclusions:These findings suggest potential treatments including cognitive behavior therapy supporting lifestyle modifications, pharmacologic treatments with modafinil and melatonin, and light therapy to enhance alertness, vigilance, and mood. Controlled trials of these interventions are needed.

Successful use of S20098 and melatonin in an animal model of delayed sleep-phase syndrome (DSPS)

In human delayed sleep-phase syndrome (DSPS), sleep onset and wake times occur far later than normal. In the population, DSPS may be an important contributor to complaints of sleep onset insomnia. We previously reported an animal model of DSPS in laboratory rats in which the onset of nocturnal activity is delayed by several hours [negative phase angle difference (PAD)]. The effect of melatonin 1 mg/kg SC and S20098 (Servier) 1 and 3 mg/kg on the negative PAD was investigated over 22 days of injections. In comparison to control injections of dimethylsulfoxide (DMSO), both melatonin and S20098 over approximately 9 days phase advanced the onset of activity toward the onset of darkness. At cessation of injections, activity onset delayed over approximately 11 days back toward, but as a group did not reach the original PAD. This effect of melatonin on the phase angle of entrained rats is consistent with its effects on delayed sleep in humans. It is likely, therefore, that S20098 may be of use to ameliorate DSPS in humans.

Dose dependent effects of S-20098, a melatonin agonist, on direction of re-entrainment of rat circadian activity rhythms.

The chronobiotic properties of melatonin are well documented. For example, following an 8-h phase advance of the light-dark cycle daily injections of melatonin administered at the pre-shift dark onset alter the direction of re-entrainment of rat activity rhythms. Using this 8-h phase advance paradigm, the effects of the melatonin agonist S-20098 (1 mg/kg and 3 mg/kg) on the rat circadian system were compared with those of melatonin. S-20098 altered the direction of reentrainment in the same manner as melatonin. A study using lower doses of S-20098 showed that the effect on direction of re-entrainment was dose-dependent, with 100% of rats responding at a dose of 100 µg/kg. S-20098 may, therefore, have therapeutic potential as a chronobiotic in the treatment of circadian disorders in humans.

The effects of cannabis and alcohol on simulated arterial driving: Influences of driving experience and task demand

This study compared the effects of three doses of cannabis and alcohol (placebo, low and high doses), both alone and in combination, on the driving performance of young, novice drivers and more experienced drivers. Alcohol was administered as ethanol (95%) mixed with orange juice in doses of approximately 0, 0.4 and 0.6g/kg. Cannabis was administered by inhalation of smoke from pre-rolled cannabis cigarettes (supplied by the National Institute of Drug Abuse, USA). Active cigarettes contained 19 mg delta-9-THC. Using a counterbalanced design, the simulated driving performance of 25 experienced and 22 inexperienced drivers was tested under the nine different drug conditions in an arterial driving environment during which workload was varied through the drive characteristics as well as through the inclusion of a secondary task. High levels of cannabis generally induced greater impairment than lower levels, while alcohol at the doses used had few effects and did not produce synergistic effects when combined with cannabis. Both cannabis and alcohol were associated with increases in speed and lateral position variability, high dose cannabis was associated with decreased mean speed, increased mean and variability in headways, and longer reaction time, while in contrast alcohol was associated with a slight increase in mean speed. Given the limitations of the study, it is of great interest to further explore the qualitative impairments in driving performance associated with cannabis and alcohol separately and how these impairments may manifest in terms of crash characteristics.

Poor Sleep Quality and Changes in Objectively Recorded Sleep After Traumatic Brain Injury: A Preliminary Study

OBJECTIVES To evaluate changes in sleep quality and objectively assessed sleep parameters after traumatic brain injury (TBI) and to investigate the relationship between such changes and mood state and injury characteristics. DESIGN Survey and laboratory-based nocturnal polysomnography. SETTING Sleep laboratory. PARTICIPANTS Ten community-based subjects with moderate to very severe TBI and 10 age- and sex-matched controls from the general community. INTERVENTIONS Not applicable. MAIN OUTCOME MEASURES Pittsburgh Sleep Quality Index for self-report sleep quality, nocturnal polysomnography for objective sleep recording, and Hospital Anxiety and Depression Scales. RESULTS Compared with controls, TBI patients reported significantly poorer sleep quality and higher levels of anxiety and depression. Objective sleep recording showed that TBI patients showed an increase in deep (slow wave) sleep, a reduction in rapid eye movement sleep, and more frequent nighttime awakenings. No significant relationship was observed between these changes in sleep and injury severity or time since injury. Anxiety and depression covaried with the observed changes in sleep. CONCLUSIONS The findings contribute to the growing body of evidence that sleep is involved in the physiologic processes underlying neural recovery. The association between anxiety and depression and the observed changes in sleep in TBI patients warrants further examination to determine whether a causative relationship exists.

Circadian Entrainment and Phase Shifting in Mammals with Melatonin

Circadian effects of exogenous melatonin, whereby daily administration induces entrainment or phase shifts, have been demonstrated in both nocturnal and diurnal mammals. In Long-Evans rats, as used in early studies, effects occur reliably when melatonin is administered late in the subjective day. A second period of sensitivity to melatonin, late in the subjective night, is evident in certain strains of mice and the diurnal Funambulus pennanti. This late night to early morning sensitive phase previously had been identified in human subjects. Different circadian responses to melatonin also may occur between rat strains. Circadian effects of melatonin in hamsters are diverse and vary with strain, developmental age, and method of administration. Characteristics of melatonin binding sites within the suprachiasmatic nuclei vary both between and within species, as do profiles of endogenous melatonin rhythms. These differences may explain the variations in circadian responses to melatonin.

Entrainment of Rat Circadian Rhythms by the Melatonin Agonist S-20098 Requires Intact Suprachiasmatic Nuclei But Not the Pineal

S-20098 is a potent nonindolic melatonin agonist that has been shown to entrain free-running circadian rhythms. The current experiments examined the role of the suprachiasmatic nuclei (SCN) and of the pineal gland in the entrainment of circadian rhythms by S-20098. First, daily injections of S-20098 (1 and 10 mg/kg s.c.) were administered to SCN-and sham-lesioned rats. At both dose levels, circadian effects were noted in all sham-lesioned animals. Locomotor activity and body temperature rhythms in 3 of 5 sham-lesioned rats were entrained by the daily injections. In SCN-lesioned rats, S-20098 had no synchronizing or entraining effects at either dose level. These results show that S-20098 exerts its entraining effects on circadian rhythms via the circadian pacemaker located in the SCN. Second, the effects of daily injections of S-20098 (10 mg/kg s.c.) were examined in pinealectomized, sham-pinealectomized, and intact rats. All rats receiving S-20098, irrespective of surgical treatment, showed circadian changes. Rhythms in 81% of these animals entrained to daily administration of the compound, indicating that entrainment induced by S-20098 does not depend on an intact pineal. When injected with 10 mg/kg S-20098, 69% of rats, irrespective of surgical treatment, showed long-term modifications of free-running period that still were evident several weeks after administration ceased. If confirmed, this finding may have therapeutic implications in humans regarding the optimal mode and administration of S-20098 in a clinical setting.

BLUE LIGHT Exposure Reduces Objective Measures of Sleepiness during Prolonged Nighttime Performance Testing

This study examined the effects of nocturnal exposure to dim, narrowband blue light (460 nm, ∼1 lux, 2 µW/cm2), compared to dim broad spectrum (white) ambient light (∼0.2 lux, 0.5 µW/cm2), on subjective and objective indices of sleepiness during prolonged nighttime performance testing. Participants were also exposed to a red light (640 nm, ∼1 lux, 0.7µW/cm2) placebo condition. Outcome measures were driving simulator and psychomotor vigilance task (PVT) performance, subjective sleepiness, salivary melatonin, and electroencephalographic (EEG) activity. The study had a repeated-measures design, with three counterbalanced light conditions and a four-week washout period between each condition. Participants (n = 8) maintained a regular sleep-wake schedule for 14 days prior to the ∼14 h laboratory study, which consisted of habituation to light conditions followed by neurobehavioral performance testing from 21:00 to 08:30 h under modified constant-routine conditions. A neurobehavioral test battery (2.5 h) was presented four times between 21:00 and 08:30 h, with a 30 min break between each. From 23:30 to 05:30 h, participants were exposed to blue or red light, or remained in ambient conditions. Compared to ambient light exposure, blue light exposure suppressed EEG slow wave delta (1.0–4.5 Hz) and theta (4.5–8 Hz) activity and reduced the incidence of slow eye movements. PVT reaction times were significantly faster in the blue light condition, but driving simulator measures, subjective sleepiness, and salivary melatonin levels were not significantly affected by blue light. Red light exposure, as compared to ambient light exposure, reduced the incidence of slow eye movements. The results demonstrate that low-intensity, blue light exposure can promote alertness, as measured by some of the objective indices used in this study, during prolonged nighttime performance testing. Low intensity, blue light exposure has the potential to be applied to situations where it is desirable to increase alertness but not practical or appropriate to use bright light, such as certain occupational settings.