Ziad Boulos

Light Treatment for Sleep Disorders: Consensus Report VI. Shift Work

The unhealthy symptoms and many deleterious consequences of shift work can be explained by a mismatch between the work-sleep schedule and the internal circadian rhythms. This mismatch occurs because the 24-h zeitgebers, such as the natural light-dark cycle, keep the circadian rhythms from phase shifting to align with the night-work, day-sleep schedule. This is a review of studies in which the sleep schedule is shifted several hours, as in shift work, and bright light is used to try to phase shift circadian rhythms. Phase shifts can be produced in laboratory studies, when subjects are kept indoors, and faster phase shifting occurs with appropriately timed bright light than with ordinary indoor (dim) light. Bright light field studies, in which subjects live at home, show that the use of artificial nocturnal bright light combined with enforced daytime dark (sleep) periods can phase shift circadian rhythms despite exposure to the conflicting 24-h zeitgebers. So far, the only studies on the use of bright light for real shift workers have been conducted at National Aeronautics and Space Administration (NASA). In general, the bright light studies support the idea that the control of light and dark can be used to overcome many of the problems of shift work. However, despite ongoing practical applications (such as at NASA), much basic research is still needed.

Light Treatment for Sleep Disorders: Consensus Report III. Alerting and Activating Effects

In addition to the well-established phase-shifting properties of timed exposure to bright light, some investigators have reported an acute alerting, or activating, effect of bright light exposure. To the extent that bright light interventions for sleep disturbance may cause subjective and/or central nervous system activation, such a property may adversely affect the efficacy of treatment. Data obtained from patient samples and from healthy subjects generally support the notion that exposure to bright light may be associated with enhanced subjective alertness, and there is limited evidence of objective changes (EEG, skin conductance levels) that are consistent with true physiological arousal. Such activation appears to be quite transient, and there is little evidence to suggest that bright light-induced activation interferes with subsequent sleep onset. Some depressed patients, however, have experienced insomnia and hypomanic activation following bright-light exposure.

Light Treatment for Sleep Disorders: Consensus Report V. Age-Related Disturbances

Sleep maintenance insomnia is a major complaint among the elderly. As a result, an inordinate proportion of sleeping pill prescriptions go to individuals over 65 y of age. Because of the substantial problems associated with use of hypnotics in older populations, efforts have been made to develop nondrug treatments for age-related sleep disturbance, including timed exposure to bright light. Such bright light treatments are based on the assumption that age-related sleep disturbance is the consequence of alterations in the usual temporal relationship between body temperature and sleep. Although studies are limited, results strongly suggest that evening bright light exposure is beneficial in alleviating sleep maintenance insomnia in healthy elderly subjects. Less consistent, but generally positive, findings have been reported with regard to bright light treatment of sleep and behavioral disturbance in demented patients. For both groups, it is likely that homeostatic factors also contribute to sleep disturbance, and these may be less influenced by bright light interventions.

Light Treatment for Sleep Disorders: Consensus Report VII. Jet Lag

Sleep disturbances are an all-too-familiar symptom of jet lag and a prime source of complaints for transmeridian travelers and flight crews alike. They are the result of a temporary loss of synchrony between an abruptly shifted sleep period, timed in accordance with the new local day-night cycle, and a gradually reentraining circadian system. Scheduled exposure to bright light can, in principle, alleviate the symptoms of jet lag by accelerating circadian reentrainment to new time zones. Laboratory simulations, in which sleep time is advanced by 6 to 8 h and the subjects exposed to bright light for 3 to 4 h during late subjective night on 2 to 4 successive days, have not all been successful. The few field studies conducted to date have had encouraging results, but their applicability to the population at large remains uncertain due to very limited sample sizes. Unresolved issues include optimal times for light exposure on the first as well as on subsequent treatment days, whether a given, fixed, light exposure time is likely to benefit a majority of travelers or whether light treatment should be scheduled instead according to some individual circadian phase marker, and if so, can such a phase marker be found that is both practical and reliable.

Light treatment for sleep disorders: consensus report. IV. Sleep phase and duration disturbances.

Advanced and delayed sleep phase disorders, and the hypersomnia that can accompany winter depression, have been treated successfully by appropriately timed artificial bright light exposure. Under entrainment to the 24-h day-night cycle, the sleep-wake pattern may assume various phase relationships to the circadian pacemaker, as indexed, for example, by abnormally long or short intervals between the onset of melatonin production or the core body temperature minimum and wake-up time. Advanced and delayed sleep phase syndromes and non-24-h sleep-wake syndrome have been variously ascribed to abnormal intrinsic circadian periodicity, deficiency of the entrainment mechanism, or—most simply—patterns of daily light exposure insufficient for adequate phase resetting. The timing of sleep is influenced by underlying circadian phase, but psychosocial constraints also play a major role. Exposure to light early or late in the subjective night has been used therapeutically to produce corrective phase delays or advances, respectively, in both the sleep pattern and circadian rhythms. Supplemental light exposure in fall and winter can reduce the hypersomnia of winter depression, although the therapeutic effect may be less dependent on timing.

Effects of an afternoon nap on nighttime alertness and performance in long-haul drivers

The effects of an afternoon nap on alertness and psychomotor performance were assessed during a simulated night shift. After a night of partial sleep restriction, eight professional long-haul drivers either slept (nap condition) or engaged in sedentary activities (no-nap condition) from 14:00 to 17:00 h. Alertness and performance testing sessions were conducted at 12:00 (pre-nap baseline), 24:00, 02:30, 05:00 and 07:30 h, and followed 2-h runs in a driving simulator. In the nap condition, the subjects showed lower subjective sleepiness and fatigue, as measured by visual analog scales, and faster reaction times and less variability on psychomotor performance tasks. Electrophysiological indices of arousal during the driving runs also reflected the beneficial effects of the afternoon nap, with lower spectral activity in the theta (4-7.75 Hz), alpha (8-11.75 Hz) and fast theta-slow alpha (6-9.75 Hz) frequency bands of the electroencephalogram, indicating higher arousal levels. Thus, a 3-h napping opportunity ending at 17:00 h improved significantly several indices of alertness and performance measured 7-14 h later.

Twilights widen the range of photic entrainment in hamsters.

The range of entrainment of the circadian rhythm of locomotor activity was compared in four groups of Syrian hamsters (eight animals per group) initially exposed to daily light-dark (LD) cycles with either abrupt transitions between light and darkness (LD-rectangular) or simulated twilights (LD- twilight). Lighting was provided by arrays of white light-emitting diodes; daytime illuminance (10 lux) and the total amount of light emitted per day were the same in the two conditions. The period (T) of the LD cycles was then gradually increased to 26.5 h or gradually decreased to 21.5 h, at the rate of 5 min/day. Under LD-rectangular, the upper and lower limits of entrainment were 25.0 to 25.5 h and 22.0 to 22.5 h, respectively, whereas under LD-twilight, 50% of the animals exposed to the lengthening cycles were still entrained at T = 26.5 h and 50% of those exposed to the shortening cycles were still entrained at T = 21.5 h. In a second experiment, two groups of hamsters were exposed to fixedT=25hLD- rectangular (n = 15) or LD-twilight cycles (n = 7). Only 33% of the animals entrained in LD-rectangular, whereas 86% of the animals entrained in LD- twilight. Free-running periods in constant darkness were longer following successful entrainment toT=25hbutdidnotdiffer between the animals that entrained to LD-rectangular and those that entrained to LD-twilight. The widening of the range of entrainment observed in LD-twilight indicates that twilight transitions increase the strength of the LD zeitgeber. In LD-twilight, successful entrainment to T = 26.5 h was accompanied by an expansion of activity time to 16.52 ± 1.22 h, with activity onsets preceding mid-dusk by 12.56 ± 2.15 h. Together with earlier data showing similar phase response curves for hour-long dawn, dusk, and rectangular light pulses, these results suggest that the effect of twilights on the range of entrainment may involve parametric rather than nonpara- metric mechanisms.

Photic Entrainment in Hamsters: Effects of Simulated Twilights and Nest Box Availability

Entrainment of wheel-running activity rhythms was compared in hamsters exposed to daily light-dark (LD) cycles with abrupt transitions between 0 and 10 lux or with artificial twilights simulating summer solstice conditions at 41°N latitude but truncated at 10 lux. The photoperiod in LD-rectangular was set at 16.24 h, equating the total light (in lux • min) emitted under the two schedules. The LD cycles were maintained for 35 days and were followed by 14 days of constant darkness (DD). Half the animals in each condition had access to a dark nest box connected to the outer compartment by a tunnel, the remaining animals being confined to a single compartment. Body temperature and locomotor activity inside the nest boxes were recorded by telemetry. Movements between the nest box and the outer compartment were monitored and the data were used to calculate light exposure at different times of the day. In all groups, the phase angle difference between wheel-running onset and dusk was more positive than that between activity offset and dawn. Hamsters with access to nest boxes, however, had later onsets, earlier offsets, and shorter activity durations (αs) than those without. These effects could be accounted for by the difference in light exposure between the nest and no-nest animals, particularly light exposure in the morning. The inclusion of twilights also resulted in later onsets and shorter αs, but the differences were relatively small and were only observed in the nest animals. The day-to-day variability in activity onset was negatively correlated with onset time and was smaller in the twilight/nest animals than in the other three groups. Most animals showed an expansion of α during the first few days of DD, resulting from a rapid advance of activity onsets relative to offsets. The period of the rhythms, determined from the first five activity onsets in DD, was negatively correlated with the balance of evening and morning light exposure. These results are discussed in the context of nonparametric entrainment of compound pacemakers.

Season- and latitude-dependent effects of simulated twilights on circadian entrainment

Groups of Syrian hamsters were exposed to LD cycles with twilight transitions and photoperiods simulating natural lighting conditions at the summer solstice (SS), equinox, and winter solstice (WS) at 41°N and at the winter solstice at the Arctic Circle (WS 66°N) but with daytime illuminance truncatedat10 lux (LD-twilight). Separate groups were kept under matching rectangular cycles (LD-rectangular). The inclusion of twilights affected several circadian parameters in a season-and latitude-dependent manner. The most striking difference was in the timing of activity onsets, which followed dusk in the presence of twilights but were more closely related to dawn (lights-on) in their absence. Activity offsets and midpoints were also earlier in LD-twilight than in LD-rectangular, with the differences being most pronounced under WS 66°N. In LD-twilight, longer nights resulted in earlier offsets and midpoints, but in LD-rectangular, midpoints were later under long than under short nights while offsets did not vary significantly. In LD-twilight, activity duration (alpha) increased monotonically with increasing nighttime duration, but in LD-rectangular, alpha was shorter under WS 66°N than under WS conditions. These effects of season and latitude observed in LD-twilight were similar to those reported in animals exposed to natural illumination, while those observed in LD-rectangular differed in several respects. The presence of twilights also resulted in lower day-to-day variability in activity onset times (greater precision), supporting the earlier conclusion that twilights increase the strength of the LD zeitgeber. Free-running periods in constant darkness (DD) were shorter in LD-twilight than in LD-rectangular, especially under WS 66°N, raising the possibility that the effects of twilights on the timing of the entrained activity rhythm reflect their effects on the period of that rhythm. Increasing daytime illuminance to 100 lux (WS conditions only) resulted in earlier activity offsets and midpoints and a shorter alpha but had no effect on activity onsets or on subsequent period in DD. These results indicate that exposure to low twilight illuminances alone can account for several of the documented differences between the effects of natural and rectangular light cycles on circadian entrainment.

Light Treatment for Sleep Disorders: Consensus Report I. Chronology of Seminal Studies in Humans

Examination of the influence of the light-dark cycle on circadian rhythmicity has been a fundamental aspect of chronobiology since its inception as a scientific discipline. Beginning with Bünnings hypothetical phase response curve in 1936, the impact of timed light exposure on circadian rhythms of literally hundreds of species has been described. The view that the light-dark cycle was an important zeitgeber for the human circadian system, as well, seemed to be supported by early studies of blind and sighted subjects. Yet, by the early 1970s, based primarily on a series of studies conducted at Erling-Andechs, Germany, the notion became widely accepted that the light-dark cycle had only a weak influence on the human circadian system and that social cues played a more important role in entrainment. In 1980, investigators at the National Institute of Mental Health reported that bright light could suppress melatonin production in humans, thereby demonstrating unequivocally the powerful effects of light on the human central nervous system. This finding led directly to the use of timed bright light exposure as a tool for the study and treatment of human circadian rhythms disorders.