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.

Temporal profile of prolonged, night-time driving performance: breaks from driving temporarily reduce time-on-task fatigue but not sleepiness.

Breaks are often used by drivers to counteract sleepiness and time-on-task fatigue during prolonged driving. We examined the temporal profile of changes in driving performance, electroencephalogram (EEG) activity and subjective measures of sleepiness and fatigue during prolonged nocturnal driving in a car simulator. In addition, the study examined the impact of regular breaks from driving on performance, sleepiness and fatigue. Healthy volunteers (n=12, 23-45 years) maintained a regular sleep-wake pattern for 14 days and were then in a laboratory from 21:00 to 08:30 hours. The driving simulator scene was designed to simulate monotonous night-time rural driving. Participants drove 4 × 2-h test sessions, with a break from driving of 1 h between each session. During the break participants performed tests assessing sleepiness and fatigue, and psychomotor performance (~30 mins), and then were permitted to sit quietly. They were monitored for wakefulness, and not permitted to nap or ingest caffeine. EEG was recorded during the driving task, and subjective assessments of sleepiness and fatigue were obtained at the start and completion of each session. We found that driving performance deteriorated (2.5-fold), EEG delta, theta and alpha activity increased, and subjective sleepiness and fatigue ratings increased across the testing period. Driving performance and fatigue ratings improved following the scheduled breaks from driving, while the breaks did not affect EEG activity and subjective sleepiness. Time-on-task effects increased through the testing period, indicating that these effects are exacerbated by increasing sleepiness. Breaks from driving without sleep temporarily ameliorate time-on-task fatigue, but provide little benefit to the sleepy driver.

Ecstasy use and self-reported disturbances in sleep.

OBJECTIVE: Ecstasy users report a number of complaints after its use including disturbed sleep. However, little is known regarding which attributes of ecstasy use are associated with sleep disturbances, which domains of sleep are affected or which factors may predict those ecstasy users likely to have poor sleep quality and/or excessive daytime sleepiness. METHODS: This study examined questionnaire responses of social drug users (n = 395) to the Pittsburgh Sleep Quality Index and the Epworth Sleepiness Scale. RESULTS: A significant proportion of ecstasy users (69.5%) had Pittsburgh Sleep Quality Index scores above the threshold used to identify sleep disturbance. Although frequency of ecstasy use did not affect the degree of reported sleep disturbance, participants who used larger amounts of ecstasy had poorer sleep. In addition, participants who perceived harmful consequences arising from their ecstasy use or had experienced remorse following ecstasy use had poorer sleep. Clinically relevant levels of sleep disturbance were still evident after controlling for polydrug use. Risk factors for poor sleep quality were younger age, injury post-ecstasy use and having been told to cut down on ecstasy use. CONCLUSIONS: Many ecstasy users report poor sleep quality, which likely contributes to the negative effects reported following ecstasy use.

Effects of modafinil on simulator driving and self-assessment of driving following sleep deprivation.

OBJECTIVES: While it has been suggested that the novel wake promoting drug modafinil may have some utility with respect to drowsy driving in healthy adults, this has not been investigated until now. The present study was designed to assess the effects of modafinil on objective and self-assessed driving simulator performance during an overnight period of sleep loss. METHODS: Sixteen healthy participants (eight males and eight females) remained awake overnight on two separate occasions during which they ingested either a single 300 mg dose of modafinil or a placebo capsule at either 0230 or 0330 h. Two hours post-treatment, participants were evaluated using measures of driving simulator performance, self-assessed driving performance and subjective alertness. RESULTS: Modafinil treatment reduced lane deviation but had less effect on speed deviation, off-road incidents and reaction time to a concurrent task. Modafinil also improved subjective appraisals of driving performance, although its use may have resulted in overconfidence in driving ability during short trips. CONCLUSIONS: Modafinil offers some benefits with respect to objective driving performance under conditions of sleep loss. However it may induce overconfidence, suggesting that its use as a countermeasure to drowsiness when driving requires further examination.

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.

Effect of opioid substitution therapy on alcohol metabolism.

Forty opioid substitution patients (methadone, n = 14; LAAM, n = 14; and buprenorphine, n = 12) who were participating in a study on the impact of opiate substitution treatment on driving ability and 22 non-opiate-using control subjects were administered 14.7 g/70 kg of alcohol in two separate sessions, one 2-3 hours before opioid pharmacotherapy dosing and the other 1-2 hours after dosing. The mean blood alcohol concentration (BAC) in the post-opioid dose session was significantly lower than that in the pre-opioid dose session (p < .05). There was a significant effect of experimental group (LAAM, methadone, buprenorphine, or control) on BAC in sessions conducted 1-2 hours after the opioid substitution dose (p < .01). There was a trend for a reduced effect of experimental group on BAC in the pre-opioid substitution dose session (p = .06). The BAC of non-opioid substitution control subjects was significantly higher than that of the LAAM (before and after LAAM dosing) and methadone (after methadone dosing; p < .05) patients. These findings provide evidence for the first time of an interaction between opiates and alcohol in humans that is strongest at the time of peak opiate plasma levels in the hours after opioid dosing.

Daytime exposure to bright light, as compared to dim light, decreases sleepiness and improves psychomotor vigilance performance.

STUDY OBJECTIVES: This study examined the effects of bright light exposure, as compared to dim light, on daytime subjective sleepiness, incidences of slow eye movements (SEMs), and psychomotor vigilance task (PVT) performance following 2 nights of sleep restriction. DESIGN: The study had a mixed factorial design with 2 independent variables: light condition (bright light, 1,000 lux; dim light, < 5 lux) and time of day. The dependent variables were subjective sleepiness, PVT performance, incidences of SEMs, and salivary melatonin levels. SETTING: Sleep research laboratory at Monash University. PARTICIPANTS: Sixteen healthy adults (10 women and 6 men) aged 18 to 35 years (mean age 25 years, 3 months). INTERVENTIONS: Following 2 nights of sleep restriction (5 hours each night), participants were exposed to modified constant routine conditions. Eight participants were exposed to bright light from noon until 5:00 pm. Outside the bright light exposure period (9:00 am to noon, 5:00 pm to 9:00 pm) light levels were maintained at less than 5 lux. A second group of 8 participants served as controls for the bright light exposure and were exposed to dim light throughout the entire protocol. MEASUREMENTS AND RESULTS: Bright light exposure reduced subjective sleepiness, decreased SEMs, and improved PVT performance compared to dim light. Bright lights had no effect on salivary melatonin. A significant positive correlation between PVT reaction times and subjective sleepiness was observed for both groups. Changes in SEMs did not correlate significantly with either subjective sleepiness or PVT performance. CONCLUSIONS: Daytime bright light exposure can reduce the impact of sleep loss on sleepiness levels and performance, as compared to dim light. These effects appear to be mediated by mechanisms that are separate from melatonin suppression. The results may assist in the development of treatments for daytime sleepiness.

The effects of the opioid pharmacotherapies methadone, LAAM and buprenorphine, alone and in combination with alcohol, on simulated driving.

While methadone is currently the primary pharmacotherapy used in the treatment of heroin dependence in Australia, levo-alpha-acetyl-methodol (LAAM) and buprenorphine are new pharmacotherapies that are being examined as alternatives to methadone maintenance treatment. The aim of this research is to consider the effects of the methadone, buprenorphine and LAAM, as used in maintenance pharmacotherapy for heroin dependence, upon simulated driving. Clients stabilised in methadone, LAAM and buprenorphine treatment programs for 3 months, and a control group of non-drug-using participants, took part in this study which involved operating a driving simulator over a 75 min period. All participants attended one session without alcohol and one session with alcohol at around the 0.05% blood alcohol level. Simulated driving skill was measured through standard deviations of lateral position, speed and steering wheel angle, and reaction time to a subsidiary task was also measured. While alcohol impaired all measures of driving performance, there were no differences in driving skills across the four participant groups. These findings suggest that typical community standards around driving safety should be applied to clients stabilised in methadone, LAAM and buprenorphine treatment. The findings are important in terms of the widespread implementation of these treatment options in Victoria given that a large proportion of pharmacotherapy clients drive.

The effects of a nap opportunity in quiet and noisy environments on driving performance.

While napping has previously been shown to alleviate the effects of sleep loss, before advocating the use of naps in transport accident campaigns it is necessary to consider whether a nap opportunity in a noisy uncomfortable environment can produce the same benefits as a nap opportunity in conditions that are conducive to sleep. To examine this, eight participants drove a driving simulator for 50 min at 11:00h on three different test days. The simulator used has previously been found to be sensitive to the effects of sleep loss, alcohol consumption, and time of day. All three sessions were conducted after one night of sleep loss. Prior to driving during each session the participants either had a 60 min nap opportunity in a quiet or noisy environment, or no nap opportunity. Driving performance and reaction time while driving were measured, as were subjective sleepiness and ratings of sleep quality. No significant benefits of nap opportunities on driving performance were found. Levels of subjective sleepiness were not affected by the nap opportunity condition; however, sleep was rated as more refreshing and restful after a nap in a quiet environment compared to noisy environment. The measures of effect size reported suggest further research is required to unequivocally test the effects of nap opportunities on driving ability.

Acute MDMA administration alters the distribution and circadian rhythm of wheel running activity in the rat.

Ecstasy users report a number of adverse events following use including disturbed sleep. Previous research has suggested that MDMA affects the circadian system, however, the acute effects following a single, moderate dose have not been well characterised. The current study investigated how MDMA affected the circadian system, as measured by the amount and temporal distribution of wheel-running activity in male rats (n=90), housed individually under a 12-12 h light-dark (LD) cycle prior to treatment. MDMA (5 or 10 mg/kg) or saline was administered in a single i.p. injection during the light phase of the LD cycle and post-treatment activity was monitored during subsequent LD cycles (Experiment 1), or under constant darkness (Experiment 2). MDMA treatment disrupted wheel running activity in both experimental paradigms. In Experiment 1, 10 mg/kg MDMA significantly increased the amount of activity during the rest phase on the day of treatment and 1-day post treatment. This was accompanied by a change in the distribution of activity across the LD cycle during the first 24 h period after treatment, without a change in the overall daily activity level. Experiment 2 found that MDMA affected the circadian system as reflected by changes in the duration of the active phase, tau and activity offset. As a single dose of MDMA was able to disrupt the circadian rhythmicity of locomotor activity, this finding has implications for other behaviours that are under circadian control including the sleep/wake cycle.

Timing of sleep and its relationship with the endogenous melatonin rhythm.

While much research has investigated the effects of exogenous melatonin on sleep, less is known about the relationship between the timing of the endogenous melatonin rhythm and the sleep-wake cycle. Significant inter-individual variability in the phase relationship between sleep and melatonin rhythms has been reported although the extent to which the variability reflects intrinsic and/or environmental differences is unknown. We examined the effects of different sleeping schedules on the time of dim light melatonin onset (DLMO) in 28 young, healthy adults. Participants chose to maintain either an early (22:30-06:30 h) or a late (00:30-08:30 h) sleep schedule for at least 3 weeks prior to an overnight laboratory visit. Saliva samples were collected under dim light (<2 lux) and controlled posture conditions to determine salivary DLMO. The 2-h difference between groups in the enforced sleep-wake schedule was associated with a concomitant 1.75-h delay in DLMO. The mean phase relationship between sleep onset and DLMO remained constant (~2 h). The variance in DLMO time, however, was greater in the late group (range 4.5 h) compared to the early group (range 2.4 h) perhaps due to greater effect of environmental influences in delayed sleep types or greater intrinsic instability in their circadian system. The findings contribute to our understanding of individual differences in the human circadian clock and have important implications for the diagnosis and treatment of circadian rhythm sleep disorders, in particular if a greater normative range for phase angle of entrainment occurs in individuals with later sleep-wake schedules.

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.

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, approximately 1 lux, 2 microW/cm2), compared to dim broad spectrum (white) ambient light ( approximately 0.2 lux, 0.5 microW/cm2), on subjective and objective indices of sleepiness during prolonged nighttime performance testing. Participants were also exposed to a red light (640 nm, approximately 1 lux, 0.7 microW/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 approximately 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.

Self-reported changes to nighttime sleep after traumatic brain injury.

OBJECTIVES: To explore subjective sleep reports from people in the chronic stages of traumatic brain injury (TBI) and to examine the extent and nature of sleep complaints in this population. DESIGN: Survey. SETTING: All participants were community based at the time of data collection. PARTICIPANTS: Sixty-three subjects with TBI consecutively recruited after discharge from rehabilitation and 63 age- and sex-matched controls from the general community. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: A 7-day self-reported sleep-wake diary assessing sleep and wake times, sleep onset latency, frequency, and duration of nocturnal awakenings and daytime naps; a general sleep questionnaire used to evaluate sleep changes and quality; and the Epworth Sleepiness Scale to measure daytime sleepiness. RESULTS: Group-wise comparisons showed a significantly higher frequency of reported sleep changes after TBI (80%) relative to the control group (23%), supporting previous findings. The TBI group reported more nighttime awakenings and longer sleep onset latency; these changes were more frequently reported by participants with TBI with milder injuries. Increased levels of anxiety and depression were associated with increased reporting of sleep changes. CONCLUSIONS: These findings confirm the experience of changes to sleep after TBI and may at least in part account for the reported increased daytime sleepiness in this population. Sleep disturbance should be addressed during rehabilitation. Treatments need to focus on correcting the underlying cause of the sleep problem and to address patients' subjective experiences of their sleep, possibly through education and mood stabilization.

Chronic partial sleep loss increases the facilitatory role of a masked prime in a word recognition task.

Neurobehavioural performance deficits associated with sleep loss have been extensively studied, in particular, the effects on psychomotor performance. However, there is no consensus as to which, if any, cognitive functions are impaired by sleep loss. To examine how sleep loss might affect cognition, the automatic processes supporting word recognition were examined using the masked priming paradigm in participants who had been exposed to two consecutive days of sleep restriction. Twelve healthy volunteers (mean age 24.5 years) were recruited. Nocturnal sleep duration was restricted to 60% of each participant's habitual sleep duration for two consecutive nights by delaying scheduled time of sleep onset and advancing time of awakening. In controlled laboratory conditions, participants completed the Psychomotor Vigilance Task and Karolinska Sleepiness Scale and a masked priming word recognition task. As expected, significant increases in subjective sleepiness and impaired psychomotor performance were observed after sleep loss. In contrast, response times and error rate on the masked priming task were not significantly affected. However, the magnitude of the masked priming effect, which can be taken as an index of automaticity of lexical processing, increased following sleep loss. These findings suggest that while no evidence of impairment to lexical access was observed after sleep loss, an increase in automatic processing may occur as a consequence of compensatory mechanisms.

Language use of older Italian-background persons with dementia in mainstream and ethno-specific residential care.

BACKGROUND: Australia has a growing aging migrant population and rates of dementia in residential care are high. The communication of persons with dementia and limited English language proficiency in residential care is an area that has received little attention in the research literature. METHOD: Thirty-nine Italian-background older persons with severe dementia residing in either mainstream (n = 20) or Italian-specific (n = 19) aged care facilities were observed and language use was recorded. Medication regime and language proficiency information was obtained. RESULTS: Participants in mainstream facilities engaged in less communication with co-residents and were prescribed daytime benzodiazepines at a higher rate than those in Italian-specific facilities. CONCLUSIONS: Older persons in mainstream facilities with dementia and lower levels of English proficiency may benefit from additional language-relevant resources. The finding of higher prescription rate of daytime benzodiazepines requires further investigation.

Opioid dependence and driving ability: a review in the context of proposed legislative change in Victoria.

There is debate in Victoria, Australia concerning the effects of various drugs, including opioids, on driving skills and accident rates, and the development of appropriate legislative responses. There are legislative difficulties around drugs and driving because of the lack of adequate epidemiological and performance-based studies. In relation to opioids, although there are studies that have shown the prevalence of opioids in both non-fatal and fatal crashes, these studies do not demonstrate that the use of opioids is associated with any elevated crash risk and they fail to take into account issues regarding tolerance. A review of the performance studies, including only a small number of driving studies, suggests that opioids, and in particular methadone, have limited effects on driving skills. None the less, recommendations have been made in other countries, such as Germany, that place driving restrictions upon methadone clients. This paper reviews the available evidence concerning the effects of opioids on driving skills and accident risk, with reference to the proposed changes to legislation in the area of drugs and driving in Victoria.