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.

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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 Ϯ 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. Neurology ® 2010;74:1732-1738 GLOSSARY AUC ϭ area under the curve; DLMO ϭ dim light melatonin onset; EOG ϭ electrooculogram; ESS ϭ Epworth Sleepiness Scale; HADS ϭ Hospital Anxiety and Depression Scale; MEQ ϭ Morningness Eveningness Questionnaire; NREM ϭ non-REM; PSQI ϭ Pittsburgh Sleep Quality Index; PTA ϭ posttraumatic amnesia; SE ϭ sleep efficiency; SOL ϭ sleep onset latency; SWS ϭ slow wave sleep; TBI ϭ traumatic brain injury; WASO ϭ wake after sleep onset.Sleep disturbances are common following traumatic brain injury (TBI), reported by 30%-75% of individuals and contributing to ongoing disability.

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.

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Although there is a circadian rhythm in blood melatonin concentrations in humans, the problems associated with frequent blood collection limit the use of this rhythm in the investigation of the circadian system and in the diagnosis and treatment of chronobiological disorders. Therefore, to establish a convenient, non-invasive technique for monitoring melatonin circadian rhythmicity, we compared the melatonin concentrations in blood samples collected from five subjects every 2-4 h over a 26 h period, with the melatonin concentrations in saliva samples and with the total amount of 6-hydroxymelatonin sulphate excreted in the urine during 2-h periods. There was significant correlation between serum and salivary melatonin concentrations (r = 0.81, P less than 0.001), and between serum melatonin concentrations and 6-hydroxymelatonin sulphate excretion rates (r = 0.72, P less than 0.001). The results demonstrate that both salivary melatonin concentrations and urinary 6-hydroxymelatonin sulphate excretion rates are reliable indices of serum melatonin concentrations. These measurements, in combination with frequent sample collection, provide two convenient, non-invasive techniques for monitoring melatonin circadian rhythmicity.

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.

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