Pietro Badia

Bright Light Effects on Body-Temperature, Alertness, EEG and Behavior

The immediate psychophysiological and behavioral effects of photic stimulation on humans [bright light (BL) of 5K lux or dim light (DL) of 50 lux] were assessed in male subjects (N = 43) under four different conditions. For one condition the same subjects (N = 16) received alternating 90-min blocks of BL and DL during the nighttime h (2300-0800 h) under sustained wakefulness conditions. A second condition was similar to the first except that subjects (N = 8) received photic stimulation during the daytime hours. For the third and fourth conditions different subjects received either continuous BL (N = 10) or continuous DL (N = 9) during the nighttime hours. For the nighttime alternating condition body temperature decreased under DL but either increased or maintained under BL. For the continuous light condition, body temperature dropped sharply across the night under DL but dropped only slightly under BL. Sleepiness was considerably greater under DL than under BL, and the difference became larger as the night progressed. Similarly, alertness, measured by EEG beta activity, was greater under BL, and nighttime performance on behavioral tasks was also generally better. There were no differential effects between BL and DL on any measure during the daytime. These data indicate that light exerts a powerful, immediate effect on physiology and behavior in addition to its powerful influence on circadian organization.

Changes in circadian rhythms and sleep quality with aging : mechanisms and interventions

Literature is reviewed indicating that aging is characterized by changes in circadian rhythms and sleep quality. The most marked change is an attenuation of amplitude. An advance of phase, a shortening of period, and a desynchronization of rhythms are also evident. The mechanisms underlying these changes are unknown. However, age-related changes in the retina, suprachiasmatic nucleus, and pineal gland seem relevant along with behavioral changes such as a reduction in physical activity and exposure to photic stimulation. Changes in circadian rhythms are frequently associated with a reduction in nighttime sleep quality, a decrease in daytime alertness, and an attenuation in cognitive performance; reversing such changes could enhance the quality of life for a large and rapidly increasing percentage of the population. Reversal appears possible by increasing melatonin levels with either appropriately timed exposure to photic stimulation and/or appropriately timed administration of exogenous melatonin. These interventions may increase aspects of genetic expression that have changed with aging. A hypothesis concerning the potential benefits of enhanced circadian amplitude is also offered.

Combination of bright light and caffeine as a countermeasure for impaired alertness and performance during extended sleep deprivation

Effects of four conditions (Dim Light‐Placebo, Dim Light‐Caffeine, Bright Light‐Placebo and Bright Light‐Caffeine) on alertness, and performance were studied during the night‐time hours across 45.5 h of sleep deprivation. Caffeine (200 mg) was administered at 20.00 and 02.00 hours and bright‐light exposure (>2000 lux) was from 20.00 to 08.00 hours each night. The three treatment conditions, compared to the Dim Light‐Placebo condition, enhanced night‐time performance. Further, the combined treatment of caffeine and all‐night bright light (Bright Light‐Caffeine) enhanced performance to a larger degree than either the Dim Light‐Caffeine or the Bright Light‐Placebo condition. Beneficial effects of the treatments on performance were largest during the early morning hours (e.g. after 02.00 hours) when performance in the Dim Light‐Placebo group was at its worst. Notably, the Bright Light‐Caffeine condition was able to overcome the circadian drop in performance for most tasks measured. Both caffeine conditions improved objective alertness on the Maintenance of Wakefulness Test. Taken together, the above results suggest that the combined treatment of bright light and caffeine provides an effective intervention for enhancing alertness and performance during sleep loss.

Inter- and intra-individual variability in performance near the circadian nadir during sleep deprivation

The study purpose was to assess inter‐ and intra‐individual variability in neurobehavioral function near the circadian nadir during sleep deprivation and conduct exploratory factor analyses to assess relationships among alertness and performance measures during sleep deprivation. Twenty‐five healthy individuals (16 females) aged 18–25 years participated. Participants were sleep deprived for two nights under controlled laboratory conditions using a modified constant routine procedure. A comprehensive battery of neurobehavioral performance tests, subjective sleepiness (SSS), and objective alertness (MWT) were assessed. Seventeen of the 22 neurobehavioral measures were impaired by sleep deprivation (all P < 0.01). The use of multiple neurobehavioral performance measures revealed impairments for all individuals during sleep deprivation. However, sleep deprivation effects were task dependent within and between individuals. Gender contributed minimally to inter‐individual variability in performance. Exploratory factor analysis reduced the 22 measures to seven independent factors. Our findings indicate that no individual was especially vulnerable or resistant to the performance impairing effects of sleep deprivation. Instead, inter‐ and intra‐individual variability in performance during sleep deprivation was task dependent. The finding that subjective sleepiness and objective alertness were not related to any performance measure during sleep deprivation suggests that these measures may assess independent brain functions.

Nonsteroidal anti-inflammatory drugs alter body temperature and suppress melatonin in humans.

Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit prostaglandin synthesis in humans. Prostaglandins are involved in thermoregulation, melatonin synthesis, and sleep. To determine effects of NSAIDs on body temperature (BT) and melatonin synthesis (MT) in humans, and to elucidate mechanisms by which NSAIDs may alter sleep patterns, a series of experiments using the NSAIDs aspirin and ibuprofen was conducted. Seventy-five subjects were tested under several experimental protocols. BT after NSAID or placebo was assessed in both between- and within-subjects designs at night and during the day. MT levels were assessed after NSAID or placebo at night in a within-subjects design. The normal nocturnal BT decrease was attenuated and MT was suppressed after NSAID relative to after placebo administration. Lower MT levels were associated with a relative flattening of BT. Daytime BT was not affected by NSAIDs. These results are compatible with the hypothesis that some of the behavioral changes associated with NSAIDs, including changes in sleep, are due to changes in BT and MT. We speculate that NSAID effects on sleep and BT are related to prostaglandin synthesis inhibition and/or suppression of MT.

Effects of menstrual cycle phase and oral contraceptives on alertness, cognitive performance, and circadian rhythms during sleep deprivation

The influence of menstrual cycle phase and oral contraceptive use on neurobehavioral function and circadian rhythms were studied in healthy young women (n = 25) using a modified constant routine procedure during 24 h of sleep deprivation. Alertness and performance worsened across sleep deprivation and also varied with circadian phase. Entrained circadian rhythms of melatonin and body temperature were evident in women regardless of menstrual phase or oral contraceptive use. No significant difference in melatonin levels, duration, or phase was observed between women in the luteal and follicular phases, whereas oral contraceptives appeared to increase melatonin levels. Temperature levels were higher in the luteal phase and in oral contraceptive users compared to women in the follicular phase. Alertness on the maintenance of wakefulness test and some tests of cognitive performance were poorest for women in the follicular phase especially near the circadian trough of body temperature. These observations suggest that hormonal changes associated with the menstrual cycle and the use of oral contraceptives contribute to changes in nighttime waking neurobehavioral function and temperature level whereas these factors do not appear to affect circadian phase.

Caffeine and light effects on nighttime melatonin and temperature levels in sleep-deprived humans

The effects of caffeine ingestion and exposure to bright light, both separately and in combination, on salivary melatonin and tympanic temperature were assessed in humans. Four treatments during a 45.5 h sleep deprivation period were compared: Dim Light-Placebo, Dim Light-Caffeine, Bright Light-Placebo and Bright-Light Caffeine. The Dim Light-Caffeine condition (200 mg twice each night) relative to the Dim Light-Placebo condition suppressed nighttime melatonin levels and attenuated the normal decrease in temperature. Combining caffeine ingestion with bright light exposure (> or = 2000 lux) suppressed melatonin and attenuated the normal nighttime drop in temperature to a larger degree than either condition alone; i.e. effects were additive. Circadian effects were also observed in that the amplitude and phase of the temperature rhythm were altered during treatment. These findings establish that the human melatonin system is responsive to caffeine. Other evidence suggests that caffeine may influence melatonin and temperature levels through antagonism of the neuromodulator adenosine.

Nonsteroidal anti-inflammatory drugs affect normal sleep patterns in humans

Previous studies have demonstrated that some nonsteroidal anti-inflammatory drugs (NSAIDs), specifically aspirin and indomethacin, have acute negative effects on sleep in humans and animals. Whether this finding can be replicated and extended to other NSAIDs, particularly the widely used over-the-counter drugs ibuprofen and acetaminophen, was the focus of the present investigation. Thirty-seven male and female subjects slept in the sleep laboratory on 2 consecutive nights; sleep was polygraphically recorded on the second night. Three doses of a prostaglandin-inhibiting drug (i.e., aspirin, acetaminophen, or ibuprofen) or placebo were administered, one each at 2300 h on the day prior to sleep recording, and at 0815 h and 2300 h on the day sleep was recorded. Subjects slept from 2400-0800 h both nights. Aspirin and ibuprofen disrupted sleep in comparison to placebo by increasing the number of awakenings and percentage of time spent in stage wake, and by decreasing sleep efficiency. Ibuprofen also delayed the onset of the deeper stages of sleep. Acetaminophen did not differ significantly from placebo on any measure of polygraphically recorded sleep. However, every index of objective sleep reflected slight, albeit nonsignificant, sleep disruption for each drug group relative to placebo. The mechanisms of sleep disruption after NSAID administration may relate to direct and indirect consequences of inhibiting prostaglandin synthesis, including decreases in prostaglandin D2, suppression of nighttime melatonin levels, and changes in body temperature.

Responsiveness to olfactory stimuli presented in sleep.

Whether humans react to olfactory stimuli presented in sleep was assessed. Responses of ten participants (mean age = 22.8 years) were recorded to repeated three-minute periods of either air alone or to a peppermint odor (0.26 mg/liter) during stage 2 sleep. These responses included behavioral (awakening, microswitch closure), autonomic (heart rate, EMG, respiration), and central (EEG) components. An odor delivery system is described comprised of an aquarium pump, Teflon and TYGON tubing, oxygen mask, filtering, and air flow valves. The data indicate that humans react behaviorally, autonomically and centrally to olfactory stimuli presented while sleeping. Although the percentage of overall responsivity to olfactory stimuli was low, significant differences (ANOVA) in responsivity to odor periods vs. nonodor periods were found for microswitch closures, EEG, EMG, and heart rate. For these measures eight or more of the ten participants showed this pattern of differential responsivity during odor and nonodor periods (Sign test = p less than 0.05). A time-of-night effect was also observed in that responsivity tended to be greatest early in the night. The effect on responsivity of other durations, concentrations, and odors requires additional research.

Immediate effects of different light intensities on body temperature and alertness

The effects of different light intensities on temperature and alertness were investigated. It was hypothesized that temperature and alertness would be affected by certain light intensities but only during the melatonin release period (after 2100 h). Fifteen subjects were tested under three levels of light known to suppress melatonin (500, 1000, and 5000 lx) and a level known not to affect melatonin (50 lx). Subjects were tested on four occasions from 1700 until 2300 h. Tympanic temperature and measures of alertness (EEG power and frequency and self-reports) were obtained before and after melatonin onset. There were no differences in any measure prior to the melatonin onset, increases in temperature and alertness occurred only after melatonin onset. Temperatures and self-reported alertness scores obtained under light intensities of 500, 1000, and 5000 lx were elevated relative to those obtained under 50 lx but were not significantly different from each other. The results suggest that melatonin may be involved in mediating the effects of light on temperature and alertness and that 500 lx may be near the threshold for significant melatonin suppression, temperature enhancement, and increases in alertness.