The effects of low-intensity narrow-band blue-light treatment compared to bright white-light treatment in seasonal affective disorder.

BACKGROUND: Ever since a new photoreceptor was discovered with a highest sensitivity to 470-490 nm blue light, it has been speculated that blue light has some advantages in the treatment of Seasonal Affective Disorder (SAD) over more traditional treatments. In this study we compared the effects of exposure to narrow-band blue light (BLUE) to those of broad-wavelength white light (BLT) in the treatment of SAD. METHODS: In a 15-day design, 45 patients suffering from SAD completed 30-min sessions of light treatment on 5 consecutive days. 21 subjects received white-light treatment (BLT, broad-wavelength without UV, 10 000 lx, irradiance 31.7 W/m2), 24 subjects received narrow-band blue light (BLUE, 100 lx, irradiance 1.0 W/m2). All participants completed weekly questionnaires concerning mood and energy levels, and were also assessed by means of the SIGH-SAD, which is the primary outcome measure. RESULTS: On day 15, SIGH-SAD ratings were significantly lower than on day 1 (BLT 73.2%, effect size 3.37; BLUE 67%, effect size 2.63), which outcomes were not statistically significant different between both conditions. LIMITATIONS: Small sample size. CONCLUSIONS: Light treatment is an effective treatment for SAD. The use of narrow-band blue light is equally effective as a treatment using bright white-light.

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.

The effects of low-intensity narrow-band blue-light treatment compared to bright white-light treatment in sub-syndromal seasonal affective disorder.

BACKGROUND: The discovery of a novel photoreceptor in the retinal ganglion cells with a highest sensitivity of 470-490 nm blue light has led to research on the effects of short-wavelength light in humans. Several studies have explored the efficacy of monochromatic blue or blue-enriched light in the treatment of SAD. In this study, a comparison has been made between the effects of broad-wavelength light without ultraviolet (UV) wavelengths compared to narrow-band blue light in the treatment of sub-syndromal seasonal affective disorder (Sub-SAD). METHOD: In a 15-day design, 48 participants suffering from Sub-SAD completed 20-minute sessions of light treatment on five consecutive days. 22 participants were given bright white-light treatment (BLT, broad-wavelength light without UV 10 000 lux, irradiance 31.7 Watt/m(2)) and 26 participants received narrow-band blue light (BLUE, 100 lux, irradiance 1.0 Watt/m(2)). All participants completed daily and weekly questionnaires concerning mood, activation, sleep quality, sleepiness and energy. Also, mood and energy levels were assessed by means of the SIGH-SAD, the primary outcome measure. RESULTS: On day 15, SIGH-SAD ratings were significantly lower than on day 1 (BLT 54.8 %, effect size 1.7 and BLUE 50.7 %, effect size 1.9). No statistically significant differences were found on the main outcome measures. CONCLUSION: Light treatment is an effective treatment for Sub-SAD. The use of narrow-band blue-light treatment is equally effective as bright white-light treatment. TRIAL REGISTRATION: This study was registered in the Dutch Trial Register (Nederlands Trial Register TC = 4342 ) (20-12-2013).

A revision of existing Karolinska Sleepiness Scale responses to light: A melanopic perspective.

A new photometric measure of light intensity that takes into account the relatively large contribution of the ipRGCs to the non-image forming (NIF) system was recently proposed. We set out to revise publications reporting on alertness scores as measured by the Karolinska Sleepiness Scale (KSS) under different light conditions in order to assess the extendibility of the equivalent-melanopic function to NIF responses in humans. The KSS response (-Δ KSS) to the different light conditions used on previous studies, preferably including a comparison to a dim light condition, was assessed. Based on the light descriptions of the different studies, the equivalent melanopic lux (m-illuminance) was calculated. The -Δ KSS was plotted against photopic-illuminance and m-illuminance, and fitted to a sigmoidal function already shown to described KSS responses to different light intensities. The root mean-squared error and r(2) were used as criteria to explain the best-describing light unit measurement. Studies that compared only the influence of light under otherwise same conditions and in which participants were not totally sleep deprived were included. Our results show that the effects of light on KSS are better explained by a melanopic unit measurement than by photopic lux. The present analysis allowed for the construction of a melanopic alertness response curve. This curve needs to be validated with appropriate designs. Nonetheless, it may serve as starting point for the development of hypothesis of predictions on the relative changes in KSS under a given condition due to changes in light properties.

Dawn simulation light: a potential cardiac events protector.

OBJECTIVE/BACKGROUND: Major cardiovascular events frequently increase in the morning due to abrupt changes in the sympatho-vagal cardiac control during the transition from sleep to wakefulness. These neural changes are translated into stepwise increases in cardiac functions, resulting in a potential cardiovascular stress. Here, we explored whether light can "optimize" heart rate and its neural control, by actively promoting a less steep transition from sleep to wakefulness, thus minimizing morning cardiovascular vulnerability. METHODS: Seventeen healthy young men were awakened 2-hours before their habitual wake-time. In a counterbalanced within-subject design, we applied a control condition (darkness during sleep and dim light during wakefulness) or dawn-simulation-light (DSL) starting 30-minutes before and ending 30-minutes after scheduled wake-up time. RESULTS: Our data reveal a significantly gradient reduction in heart rate during the transition from sleep to wakefulness, when applying DSL as compared to a control condition. Likewise, cardiac sympatho-vagal control smoothly increased throughout the 30-min sleep episode preceding scheduled wake-up under DSL and remained stable for the first 30-min of wakefulness. Interestingly, these effects were mostly driven by changes in the parasympathetic cardiac control. CONCLUSIONS: Our data demonstrate for the first time that a non-invasive strategy, as light exposure surrounding the wake-up process, can significantly reduce the deleterious sleep-to-wake evoked cardiac modulation in healthy young men awakened under conditions of increased sleep pressure. A translational approach of this light exposure, which closely resembles natural lighting conditions in the morning, may therefore act as a potential protector for cardiac vulnerability in the critical morning hours.

Dawn simulation light impacts on different cognitive domains under sleep restriction.

Chronic sleep restriction (SR) has deleterious effects on cognitive performance that can be counteracted by light exposure. However, it is still unknown if naturalistic light settings (dawn simulating light) can enhance daytime cognitive performance in a sustainable matter. Seventeen participants were enrolled in a 24-h balanced cross-over study, subsequent to SR (6-h of sleep). Two different light settings were administered each morning: a) dawn simulating light (DsL; polychromatic light gradually increasing from 0 to 250 lx during 30 min before wake-up time, with light around 250 lx for 20 min after wake-up time) and b) control dim light (DL; <8 lx). Cognitive tests were performed every 2 h during scheduled wakefulness and questionnaires were completed hourly to assess subjective mood. The analyses yielded a main effect of "light condition" for the motor tracking task, sustained attention to response task and a working memory task (visual 1 and 3-back task), as well as for the Simple Reaction Time Task, such that participants showed better task performance throughout the day after morning DsL exposure compared to DL. Furthermore, low performers benefited more from the light effects compared to high performers. Conversely, no significant influences from the DsL were found for the Psychomotor Vigilance Task and a contrary effect was observed for the digit symbol substitution test. No light effects were observed for subjective perception of sleepiness, mental effort, concentration and motivation. Our data indicate that short exposure to artificial morning light may significantly enhance cognitive performance in a domain-specific manner under conditions of mild SR.

Effects of artificial dawn and morning blue light on daytime cognitive performance, well-being, cortisol and melatonin levels.

Light exposure elicits numerous effects on human physiology and behavior, such as better cognitive performance and mood. Here we investigated the role of morning light exposure as a countermeasure for impaired cognitive performance and mood under sleep restriction (SR). Seventeen participants took part of a 48h laboratory protocol, during which three different light settings (separated by 2 wks) were administered each morning after two 6-h sleep restriction nights: a blue monochromatic LED (light-emitting diode) light condition (BL; 100 lux at 470 nm for 20 min) starting 2 h after scheduled wake-up time, a dawn-simulating light (DsL) starting 30 min before and ending 20 min after scheduled wake-up time (polychromatic light gradually increasing from 0 to 250 lux), and a dim light (DL) condition for 2 h beginning upon scheduled wake time (<8 lux). Cognitive tasks were performed every 2 h during scheduled wakefulness, and questionnaires were administered hourly to assess subjective sleepiness, mood, and well-being. Salivary melatonin and cortisol were collected throughout scheduled wakefulness in regular intervals, and the effects on melatonin were measured after only one light pulse. Following the first SR, analysis of the time course of cognitive performance during scheduled wakefulness indicated a decrease following DL, whereas it remained stable following BL and significantly improved after DsL. Cognitive performance levels during the second day after SR were not significantly affected by the different light conditions. However, after both SR nights, mood and well-being were significantly enhanced after exposure to morning DsL compared with DL and BL. Melatonin onset occurred earlier after morning BL exposure, than after morning DsL and DL, whereas salivary cortisol levels were higher at wake-up time after DsL compared with BL and DL. Our data indicate that exposure to an artificial morning dawn simulation light improves subjective well-being, mood, and cognitive performance, as compared with DL and BL, with minimal impact on circadian phase. Thus, DsL may provide an effective strategy for enhancing cognitive performance, well-being, and mood under mild sleep restriction.

The melanopic sensitivity function accounts for melanopsin-driven responses in mice under diverse lighting conditions.

In addition to rods and cones, photoreception in mammals extends to a third retinal cell type expressing the photopigment melanopsin. The influences of this novel opsin are widespread, ranging from pupillary and circadian responses to brightness perception, yet established approaches to quantifying the biological effects of light do not adequately account for melanopsin sensitivity. We have recently proposed a novel metric, the melanopic sensitivity function (V(Z)λ), to address this deficiency. Here, we further validate this new measure with a variety of tests based on potential barriers to its applicability identified in the literature or relating to obvious practical benefits. Using electrophysiogical approaches and pupillometry, initially in rodless+coneless mice, our data demonstrate that under a very wide range of different conditions (including switching between stimuli with highly divergent spectral content) the V(Z)λ function provides an accurate prediction of the sensitivity of melanopsin-dependent responses. We further show that V(Z)λ provides the best available description of the spectral sensitivity of at least one aspect of the visual response in mice with functional rods and cones: tonic firing activity in the lateral geniculate nuclei. Together, these data establish V(Z)λ as an important new approach for light measurement with widespread practical utility.

The spectral composition of evening light and individual differences in the suppression of melatonin and delay of sleep in humans.

The effect of light on circadian rhythms and sleep is mediated by a multi-component photoreceptive system of rods, cones and melanopsin-expressing intrinsically photosensitive retinal ganglion cells. The intensity and spectral sensitivity characteristics of this system are to be fully determined. Whether the intensity and spectral composition of light exposure at home in the evening is such that it delays circadian rhythms and sleep also remains to be established. We monitored light exposure at home during 6-8wk and assessed light effects on sleep and circadian rhythms in the laboratory. Twenty-two women and men (23.1±4.7yr) participated in a six-way, cross-over design using polychromatic light conditions relevant to the light exposure at home, but with reduced, intermediate or enhanced efficacy with respect to the photopic and melanopsin systems. The evening rise of melatonin, sleepiness and EEG-assessed sleep onset varied significantly (P<0.01) across the light conditions, and these effects appeared to be largely mediated by the melanopsin, rather than the photopic system. Moreover, there were individual differences in the sensitivity to the disruptive effect of light on melatonin, which were robust against experimental manipulations (intra-class correlation=0.44). The data show that light at home in the evening affects circadian physiology and imply that the spectral composition of artificial light can be modified to minimize this disruptive effect on sleep and circadian rhythms. These findings have implications for our understanding of the contribution of artificial light exposure to sleep and circadian rhythm disorders such as delayed sleep phase disorder.

Femtosecond laser ablation elemental mass spectrometry.

Laser ablation mass spectrometry (LA-MS) has always been an interesting method for the elemental analysis of solid samples. Chemical analysis with a laser requires small amounts of material. Depending on the analytical detection system, subpicogram quantities may be sufficient. In addition, a focused laser beam permits the spatial characterization of heterogeneity in solid samples typically with micrometer resolution in terms of lateral and depth dimensions. With the advent of high-energy, ultra-short pulse lasers, new possibilities arise. The task of this review is to discuss the principle differences between the ablation process of short (>1 ps) and ultra-short (<1 ps) pulses. Based on the timescales and the energy balance of the process that underlies an ablation event, it will be shown that ultra-short pulses are less thermal and cause less collateral damages than longer pulses. The confinement of the pulse energy to the focal region guarantees a better spatial resolution in all dimensions and improves the analytical figures of merit (e.g., fractionation). Applications that demonstrate these features and that will be presented are in-depth profiling of multi-layer samples and the elemental analysis of biological materials.