Variation in photoperiod response corresponds to differences in circadian light sensitivity in northern and southern Nasonia vitripennis lines.

The circadian clock times physiological and behavioural processes and resets on a daily basis to synchronize with the environment. The involvement of the circadian clock in photoperiodic time measurement synchronising annual rhythms is still under debate and different models have been proposed explaining their integration. Insects overcome unfavourable conditions in diapause, a form of dormancy. A latitudinal cline in diapause induction in the parasitoid wasp Nasonia vitripennis as well as a difference in circadian light sensitivity between north and south provide us with additional evidence that the circadian system of Nasonia is involved in photoperiodic time measurement and that latitude-specific seasonality drives adaptive evolution in photoperiodism partly through adaptation responses in the circadian system. We tested diapause induction in a range of T-cycles and photoperiods and found diapause induction in short photoperiods in all T-cycles in the northern line but in the southern line, diapause only occurred in T-cycles close to 24 h. Due to a lower light sensitivity in the southern line, a wider distribution of phase angles of entrainment can be expected at a specific T-cycle duration, while the range of entrainment will decrease. Taking these oscillator properties into account, our data can be explained by an external coincidence model involving a single oscillator with a light-sensitive phase that drives annual timing of diapause in Nasonia vitripennis.

Railway Suicide in The Netherlands Lower Than Expected.

Background: Increasing rail transportation requires appropriate railway suicide preventive measures. Aims: The investigation of trends in railway suicide during 2008-2018, a period in which preventive measures were taken by Dutch railway infrastructure manager ProRail. Methods: Generalized linear regression models for railway suicide were developed for the period 1970-2007 with general suicide rate, railway traffic intensity, and a combination of these variables as regressors. Subsequently, the best-fitting model was used to investigate trends in railway suicide after 2007 by comparing in retrospect observed values with the expected outcomes of the regression model. Results: An adequate regression model for railway suicide was obtained using both general suicide rate and railway traffic intensity as regressors. Based on this model, while national suicide mortality and railway traffic increased, a distinct relative decline in railway suicides was found from 2012 onward. Conclusions: This decline of railway suicides in the Netherlands may indicate that preventive measures taken by ProRail were effective and prevented around 85 railway suicides annually, a reduction of 30%.

Lifespan is unaffected by size and direction of daily phase shifts in Nasonia, a hymenopteran insect with strong circadian light resetting.

Most organisms have an endogenous circadian clock with a period length of approximately 24 h that enables adaptation, synchronization and anticipation to environmental cycles. The circadian system (circa = about or around, diem = a day) may provide evolutionary benefits when entrained to the 24-h light-dark cycle. The more the internal circadian period (τ) deviates from the external light-dark cycle, the larger the daily phase shifts need to be to synchronize to the environment. In some species, large daily phase shifts reduce survival rate. Here we tested this 'resonance fitness hypothesis' on the diurnal wasp Nasonia vitripennis, which exhibits a large latitudinal cline in free-running period with longer circadian period lengths in the north than in the south. Longevity was measured in northern and southern wasps placed into light-dark cycles (T-cycles) with periods ranging from 20 h to 28 h. Further, locomotor activity was recorded to estimate range and phase angle of entrainment under these various T-cycles. A light pulse induced phase response curve (PRC) was measured in both lines to understand entrainment results. We expected a concave survival curve with highest longevity at T = τ and a reduction in longevity the further τ deviates from T (τ/T<>1). Our results do not support this resonance fitness hypothesis. We did not observe a reduction in longevity when τ deviates from T. Our results may be understood by the strong circadian light resetting mechanism (type 0 PRC) to single light pulses that we measured in Nasonia, resulting in: (1) the broad range of entrainment, (2) the wide natural variation in circadian free-running period, and (3) the lack of reduced survival when τ/T ratio's deviates from 1. Together this indicates that circadian adaption to latitude may lead to changes in circadian period and light response, without negative influences on survival.

Daytime melatonin and light independently affect human alertness and body temperature.

Light significantly improves alertness during the night (Cajochen, Sleep Med Rev, 11, 2007 and 453; Ruger et al., AJP Regul Integr Comp Physiol, 290, 2005 and R1413), but results are less conclusive at daytime (Lok et al., J Biol Rhythms, 33, 2018 and 589). Melatonin and core body temperature levels at those times of day may contribute to differences in alerting effects of light. In this experiment, the combined effect of daytime exogenous melatonin administration and light intensity on alertness, body temperature, and skin temperature was studied. The goal was to assess whether (a) alerting effects of light are melatonin dependent, (b) soporific effects of melatonin are mediated via the thermoregulatory system, and (c) light can improve alertness after melatonin-induced sleepiness during daytime. 10 subjects (5 females, 5 males) received melatonin (5 mg) in dim (10 lux) and, on a separate occasion, in bright polychromatic white light (2000 lux). In addition, they received placebo both under dim and bright light conditions. Subjects participated in all four conditions in a balanced order, yielding a balanced within-subject design, lasting from noon to 04:00 pm. Alertness and performance were assessed half hourly, while body temperature and skin temperature were measured continuously. Saliva samples to detect melatonin concentrations were collected half hourly. Melatonin administration increased melatonin concentrations in all subjects. Subjective sleepiness and distal skin temperature increased after melatonin ingestion. Bright light exposure after melatonin administration did not change subjective alertness scores, but body temperature and proximal skin temperature increased, while distal skin temperature decreased. Light exposure did not significantly affect these parameters in the placebo condition. These results indicate that (a) exogenous melatonin administration during daytime increases subjective sleepiness, confirming a role for melatonin in sleepiness regulation, (b) bright light exposure after melatonin ingestion significantly affected thermoregulatory parameters without altering subjective sleepiness, therefore temperature changes seem nonessential for melatonin-induced sleepiness, (c) subjective sleepiness was increased by melatonin ingestion, but bright light administration was not able to improve melatonin-induced sleepiness feelings nor performance. Other (physiological) factors may therefore contribute to differences in alerting effects of light during daytime and nighttime.

Light, Alertness, and Alerting Effects of White Light: A Literature Overview.

Light is known to elicit non-image-forming responses, such as effects on alertness. This has been reported especially during light exposure at night. Nighttime results might not be translatable to the day. This article aims to provide an overview of (1) neural mechanisms regulating alertness, (2) ways of measuring and quantifying alertness, and (3) the current literature specifically regarding effects of different intensities of white light on various measures and correlates of alertness during the daytime. In general, the present literature provides inconclusive results on alerting effects of the intensity of white light during daytime, particularly for objective measures and correlates of alertness. However, the various research paradigms employed in earlier studies differed substantially, and most studies tested only a limited set of lighting conditions. Therefore, the alerting potential of exposure to more intense white light should be investigated in a systematic, dose-dependent manner with multiple correlates of alertness and within one experimental paradigm over the course of day.

White Light During Daytime Does Not Improve Alertness in Well-rested Individuals.

Broad-spectrum light applied during the night has been shown to affect alertness in a dose-dependent manner. The goal of this experiment was to investigate whether a similar relationship could be established for light exposure during daytime. Fifty healthy participants were subjected to a paradigm (0730-1730 h) in which they were intermittently exposed to 1.5 h of dim light (<10 lux) and 1 h of experimental light (24-2000 lux). The same intensity of experimental light was used throughout the day, resulting in groups of 10 subjects per intensity. Alertness was assessed with subjective and multiple objective measures. A significant effect of time of day was found in all parameters of alertness ( p < 0.05). Significant dose-response relationships between light intensity and alertness during the day could be determined in a few of the parameters of alertness at some times of the day; however, none survived correction for multiple testing. We conclude that artificial light applied during daytime at intensities up to 2000 lux does not elicit significant improvements in alertness in non-sleep-deprived subjects.

Melanopsin- and L-cone-induced pupil constriction is inhibited by S- and M-cones in humans.

The human retina contains five photoreceptor types: rods; short (S)-, mid (M)-, and long (L)-wavelength-sensitive cones; and melanopsin-expressing ganglion cells. Recently, it has been shown that selective increments in M-cone activation are paradoxically perceived as brightness decrements, as opposed to L-cone increments. Here we show that similar effects are also observed in the pupillary light response, whereby M-cone or S-cone increments lead to pupil dilation whereas L-cone or melanopic illuminance increments resulted in pupil constriction. Additionally, intermittent photoreceptor activation increased pupil constriction over a 30-min interval. Modulation of L-cone or melanopic illuminance within the 0.25-4-Hz frequency range resulted in more sustained pupillary constriction than light of constant intensity. Opposite results were found for S-cone and M-cone modulations (2 Hz), mirroring the dichotomy observed in the transient responses. The transient and sustained pupillary light responses therefore suggest that S- and M-cones provide inhibitory input to the pupillary control system when selectively activated, whereas L-cones and melanopsin response fulfill an excitatory role. These findings provide insight into functional networks in the human retina and the effect of color-coding in nonvisual responses to light, and imply that nonvisual and visual brightness discrimination may share a common pathway that starts in the retina.

Linking Light Exposure and Subsequent Sleep: A Field Polysomnography Study in Humans.

Study objectives: To determine the effect of light exposure on subsequent sleep characteristics under ambulatory field conditions. Methods: Twenty healthy participants were fitted with ambulatory polysomnography (PSG) and wrist-actigraphs to assess light exposure, rest-activity, sleep quality, timing, and architecture. Laboratory salivary dim-light melatonin onset was analyzed to determine endogenous circadian phase. Results: Later circadian clock phase was associated with lower intensity (R2 = 0.34, χ2(1) = 7.19, p < .01), later light exposure (quadratic, controlling for daylength, R2 = 0.47, χ2(3) = 32.38, p < .0001), and to later sleep timing (R2 = 0.71, χ2(1) = 20.39, p < .0001). Those with later first exposure to more than 10 lux of light had more awakenings during subsequent sleep (controlled for daylength, R2 = 0.36, χ2(2) = 8.66, p < .05). Those with later light exposure subsequently had a shorter latency to first rapid eye movement (REM) sleep episode (R2 = 0.21, χ2(1) = 5.77, p < .05). Those with less light exposure subsequently had a higher percentage of REM sleep (R2 = 0.43, χ2(2) = 13.90, p < .001) in a clock phase modulated manner. Slow-wave sleep accumulation was observed to be larger after preceding exposure to high maximal intensity and early first light exposure (p < .05). Conclusions: The quality and architecture of sleep is associated with preceding light exposure. We propose that light exposure timing and intensity do not only modulate circadian-driven aspects of sleep but also homeostatic sleep pressure. These novel ambulatory PSG findings are the first to highlight the direct relationship between light and subsequent sleep, combining knowledge of homeostatic and circadian regulation of sleep by light. Upon confirmation by interventional studies, this hypothesis could change current understanding of sleep regulation and its relationship to prior light exposure. Clinical trial details: This study was not a clinical trial. The study was ethically approved and nationally registered (NL48468.042.14).

Plasticity in the Period of the Circadian Pacemaker Induced by Phase Dispersion of Its Constituent Cellular Clocks.

The mammalian circadian pacemaker is commonly thought to be a rigid oscillator that generates output under a variety of circumstances that differ only in phase, period, and/or amplitude. Yet the pacemaker is composed of many cells that each can respond to varying circumstances in different ways. Computer simulations demonstrate that networks of such pacemaker cells behave differently under a light-dark cycle compared with constant darkness. The differences demonstrate that the circadian pacemaker is plastic: The pacemaker shapes its properties in response to the circumstances. A consequence is that properties of a pacemaker under a light-dark cycle cannot be derived from studies of the same system in constant darkness. In this paper we show that the dispersion of phase in a network of coupled oscillators can influence ensemble period: For the considered type of coupling, it is demonstrated that the more synchronous the cells are, the longer is the ensemble period. This is consistent with various data sets obtained in mammals, and even with a data set from fruit flies, in which circadian variation in behavior is regulated in a distinctly differently way from that in mammals. We conclude that environmental circumstances such as photoperiod and exposure to light pulses in otherwise darkness modify the phase distribution of the network and, thereby, the period of the ensemble. Our study supports the view that such properties as circadian period are not solely determined by clock genes but are also determined by the genes that regulate the communication in cellular networks.

Daily Light Exposure Patterns Reveal Phase and Period of the Human Circadian Clock.

Light is the most potent time cue that synchronizes (entrains) the circadian pacemaker to the 24-h solar cycle. This entrainment process is an interplay between an individual's daily light perception and intrinsic pacemaker period under free-running conditions. Establishing individual estimates of circadian phase and period can be time-consuming. We show that circadian phase can be accurately predicted (SD = 1.1 h for dim light melatonin onset, DLMO) using 9 days of ambulatory light and activity data as an input to Kronauer's limit-cycle model for the human circadian system. This approach also yields an estimated circadian period of 24.2 h (SD = 0.2 h), with longer periods resulting in later DLMOs. A larger amount of daylight exposure resulted in an earlier DLMO. Individuals with a long circadian period also showed shorter intervals between DLMO and sleep timing. When a field-based estimation of tau can be validated under laboratory studies in a wide variety of individuals, the proposed methods may prove to be essential tools for individualized chronotherapy and light treatment for shift work and jetlag applications. These methods may improve our understanding of fundamental properties of human circadian rhythms under daily living conditions.

Climate change relaxes the time constraints for late-born offspring in a long-distance migrant.

Animals in seasonal environments need to fit their annual-cycle stages, such as moult and migration, in a tight schedule. Climate change affects the phenology of organisms and causes advancements in timing of these annual-cycle stages but not necessarily at the same rates. For migratory birds, this can lead to more severe or more relaxed time constraints in the time from fledging to migration, depending on the relative shifts of the different stages. We tested how a shift in hatch date, which has advanced due to climate change, impacts the organization of the birds' whole annual cycle. We experimentally advanced and delayed the hatch date of pied flycatcher chicks in the field and then measured the timing of their annual-cycle stages in a controlled laboratory environment. Hatch date affected the timing of moult and pre-migratory fattening, but not migration. Early-born birds hence had a longer time to fatten up than late-born ones; the latter reduced their interval between onset of fattening and migration to be able to migrate at the same time as the early-born birds. This difference in time constraints for early- and late-born individuals may explain why early-born offspring have a higher probability to recruit as a breeding bird. Climate change-associated advancements of avian egg-lay dates, which in turn advances hatch dates, can thus reduce the negative fitness consequences of reproducing late, thereby reducing the selection for early egg-laying migratory birds.

Short Blue Light Pulses (30 Min) in the Morning Support a Sleep-Advancing Protocol in a Home Setting.

Many people in our modern civilized society sleep later on free days compared to work days. This discrepancy in sleep timing will lead to so-called 'social jetlag' on work days with negative consequences for performance and health. Light therapy in the morning is often proposed as the most effective method to advance the circadian rhythm and sleep phase. However, most studies focus on direct effects on the circadian system and not on posttreatment effects on sleep phase and sleep integrity. In this placebo-controlled home study we investigated if blue light, rather than amber light therapy, can phase shift the sleep phase along with the circadian rhythm with preservation of sleep integrity and performance. We selected 42 participants who suffered from 'social jetlag' on workdays. Participants were randomly assigned to either high-intensity blue light exposure or amber light exposure (placebo) with similar photopic illuminance. The protocol consisted of 14 baseline days without sleep restrictions, 9 treatment days with either 30-min blue light pulses or 30-min amber light pulses in the morning along with a sleep advancing scheme and 7 posttreatment days without sleep restrictions. Melatonin samples were taken at days 1, 7, 14 (baseline), day 23 (effect treatment), and day 30 (posttreatment). Light exposure was recorded continuously. Sleep was monitored through actigraphy. Performance was measured with a reaction time task. As expected, the phase advance of the melatonin rhythm from day 14 to day 23 was significantly larger in the blue light exposure group, compared to the amber light group (84 min ± 51 (SD) and 48 min ± 47 (SD) respectively; t36 = 2.23, p < 0.05). Wake-up time during the posttreatment days was slightly earlier compared to baseline in the blue light group compared to slightly later in the amber light group (-21 min ± 33 (SD) and +12 min ± 33 (SD) respectively; F1,35 = 9.20, p < 0.01). The number of sleep bouts was significantly higher in the amber light group compared to the blue light group during sleep in the treatment period (F1,32 = 4.40, p < 0.05). Performance was significantly worse compared to baseline at all times during (F1,13 = 10.1, p < 0.01) and after amber light treatment (F1,13 = 17.1, p < 0.01), while only in the morning during posttreatment in the blue light condition (F1,10 = 9.8, p < 0.05). The data support the conclusion that blue light was able to compensate for the sleep integrity reduction and to a large extent for the performance decrement that was observed in the amber light condition, both probably as a consequence of the advancing sleep schedule. This study shows that blue light therapy in the morning, applied in a home setting, supports a sleep advancing protocol by phase advancing the circadian rhythm as well as sleep timing.

Phylogeny and oscillating expression of period and cryptochrome in short and long photoperiods suggest a conserved function in Nasonia vitripennis.

Photoperiodism, the ability to respond to seasonal varying day length with suitable life history changes, is a common trait in organisms that live in temperate regions. In most studied organisms, the circadian system appears to be the basis for photoperiodic time measurement. In insects this is still controversial: while some data indicate that the circadian system is causally involved in photoperiodism, others suggest that it may have a marginal or indirect role. Resonance experiments in the parasitic wasp Nasonia vitripennis have revealed a circadian component in photoperiodic time measurement compatible with a mechanism of internal coincidence where a two components oscillator system obtains information from dawn and dusk, respectively. The identity of this oscillator (or oscillators) is still unclear but possible candidates are the oscillating molecules of the auto-regulatory feedback loops in the heart of the circadian system. Here, we show for the first time the circadian oscillation of period and cryptochrome mRNAs in the heads of Nasonia females kept under short and long photoperiods. Period and cryptochrome mRNA levels display a synchronous oscillation in all conditions tested and persist, albeit with reduced amplitude, during the first day in constant light as well as constant darkness. More importantly, the signal for the period and cryptochrome oscillations is set by the light-on signal. These results, together with phylogenetic analyses, indicate that Nasonia's period and cryptochrome display characteristics of homologous genes in other hymenopteran species.

Effects of a chronic reduction of short-wavelength light input on melatonin and sleep patterns in humans: evidence for adaptation.

Light is an important environmental stimulus for the entrainment of the circadian clock and for increasing alertness. The intrinsically photosensitive ganglion cells in the retina play an important role in transferring this light information to the circadian system and they are elicited in particular by short-wavelength light. Exposure to short wavelengths is reduced, for instance, in elderly people due to yellowing of the ocular lenses. This reduction may be involved in the disrupted circadian rhythms observed in aged subjects. Here, we tested the effects of reduced blue light exposure in young healthy subjects (n = 15) by using soft orange contact lenses (SOCL). We showed (as expected) that a reduction in the melatonin suppressing effect of light is observed when subjects wear the SOCL. However, after chronic exposure to reduced (short wavelength) light for two consecutive weeks we observed an increase in sensitivity of the melatonin suppression response. The response normalized as if it took place under a polychromatic light pulse. No differences were found in the dim light melatonin onset or in the amplitude of the melatonin rhythms after chronic reduced blue light exposure. The effects on sleep parameters were limited. Our results demonstrate that the non-visual light system of healthy young subjects is capable of adapting to changes in the spectral composition of environmental light exposure. The present results emphasize the importance of considering not only the short-term effects of changes in environmental light characteristics.

The biological clock modulates the human cortisol response in a multiplicative fashion.

Human cortisol levels follow a clear circadian rhythm. We investigated the contribution of alternation of sleep and wakefulness and the circadian clock, using forced desynchrony. Cortisol levels were best described by a multiplication of a circadian and a wake-time component. The human cortisol response is modulated by circadian phase. Exposure to stress at an unnatural phase, as in shift work, is predicted to result in abnormal cortisol levels. Health of shift workers may therefore improve when stress is reduced at times when the clock produces high stress sensitivity.

Ambulatory estimation of human circadian phase using models of varying complexity based on non-invasive signal modalities.

In this work, we introduce a number of models for human circadian phase estimation in ambulatory conditions using various sensor modalities. Machine learning techniques have been applied to ambulatory recordings of wrist actigraphy, light exposure, electrocardiograms (ECG), and distal and proximal skin temperature to develop ARMAX models capturing the main signal dependencies on circadian phase and evaluating them versus melatonin onset times. The most accurate models extracted heart rate variability features from an ECG coupled with wrist activity information to produce phase estimations with prediction errors of ~30 minutes. Replacing the ECG features with skin temperature from the upper leg led to a slight degradation, while less accurate results, in the order of 1 hour, were obtained from wrist activity and light measurements. The trade-off between highest precision and least obtrusive configuration is discussed for applications to sleep and mood disorders caused by a misalignment of the internal phase with the external solar and social times.

Short-wavelength attenuated polychromatic white light during work at night: limited melatonin suppression without substantial decline of alertness.

Exposure to light at night increases alertness, but light at night (especially short-wavelength light) also disrupts nocturnal physiology. Such disruption is thought to underlie medical problems for which shiftworkers have increased risk. In 33 male subjects we investigated whether short-wavelength attenuated polychromatic white light (<530 nm filtered out) at night preserves dim light melatonin levels and whether it induces similar skin temperature, alertness, and performance levels as under full-spectrum light. All 33 subjects participated in random order during three nights (at least 1 wk apart) either under dim light (3 lux), short-wavelength attenuated polychromatic white light (193 lux), or full-spectrum light (256 lux). Hourly saliva samples for melatonin analysis were collected along with continuous measurements of skin temperature. Subjective sleepiness and activation were assessed via repeated questionnaires and performance was assessed by the accuracy and speed of an addition task. Our results show that short-wavelength attenuated polychromatic white light only marginally (6%) suppressed salivary melatonin. Average distal-to-proximal skin temperature gradient (DPG) and its pattern over time remained similar under short-wavelength attenuated polychromatic white light compared with dim light. Subjects performed equally well on an addition task under short-wavelength attenuated polychromatic white light compared with full-spectrum light. Although subjective ratings of activation were lower under short-wavelength attenuated polychromatic white light compared with full-spectrum light, subjective sleepiness was not increased. Short-wavelength attenuated polychromatic white light at night has some advantages over bright light. It hardly suppresses melatonin concentrations, whereas performance is similar to the bright light condition. Yet, alertness is slightly reduced as compared with bright light, and DPG shows similarity to the dim light condition, which is a physiological sign of reduced alertness. Short-wavelength attenuated polychromatic white light might therefore not be advisable in work settings that require high levels of alertness.

Human circadian phase estimation from signals collected in ambulatory conditions using an autoregressive model.

Phase estimation of the human circadian rhythm is a topic that has been explored using various modeling approaches. The current models range from physiological to mathematical, all attempting to estimate the circadian phase from different physiological or behavioral signals. Here, we have focused on estimation of the circadian phase from unobtrusively collected signals in ambulatory conditions using a statistically trained autoregressive moving average with exogenous inputs (ARMAX) model. Special attention has been given to the evaluation of heart rate interbeat intervals (RR intervals) as a potential circadian phase predictor. Prediction models were trained using all possible combinations of RR intervals, activity levels, and light exposures, each collected over a period of 24 hours. The signals were measured without any behavioral constraints, aside from the collection of saliva in the evening to determine melatonin concentration, which was measured in dim-light conditions. The model was trained and evaluated using 2 completely independent datasets, with 11 and 19 participants, respectively. The output was compared to the gold standard of circadian phase: dim-light melatonin onset (DLMO). The most accurate model that we found made use of RR intervals and light and was able to yield phase estimates with a prediction error of 2 ± 39 minutes (mean ± SD) from the DLMO reference value.