Living in Biological Darkness: Objective Sleepiness and the Pupillary Light Responses Are Affected by Different Metameric Lighting Conditions during Daytime.

Nighttime melatonin suppression is the most commonly used method to indirectly quantify acute nonvisual light effects. Since light is the principal zeitgeber in humans, there is a need to assess its strength during daytime as well. This is especially important since humans evolved under natural daylight but now often spend their time indoors under artificial light, resulting in a different quality and quantity of light. We tested whether the pupillary light response (PLR) could be used as a marker for nonvisual light effects during daytime. We also recorded the wake electroencephalogram to objectively determine changes in daytime sleepiness between different illuminance levels and/or spectral compositions of light. In total, 72 participants visited the laboratory 4 times for 3-h light exposures. All participants underwent a dim-light condition and either 3 metameric daytime light exposures with different spectral compositions of polychromatic white light (100 photopic lux, peak wavelengths at 435 nm or 480 nm, enriched with longer wavelengths of light) or 3 different illuminances (200, 600, and 1200 photopic lux) with 1 metameric lighting condition (peak wavelength at 435 nm or 480 nm; 24 participants each). The results show that the PLR was sensitive to both spectral differences between metameric lighting conditions and different illuminances in a dose-responsive manner, depending on melanopic irradiance. Objective sleepiness was significantly reduced, depending on melanopic irradiance, at low illuminance (100 lux) and showed fewer differences at higher illuminance. Since many people are exposed to such low illuminance for most of their day-living in biological darkness-our results imply that optimizing the light spectrum could be important to improve daytime alertness. Our results suggest the PLR as a noninvasive physiological marker for ambient light exposure effects during daytime. These findings may be applied to assess light-dependent zeitgeber strength and evaluate lighting improvements at workplaces, schools, hospitals, and homes.

Applying Melanopic Lux to Measure Biological Light Effects on Melatonin Suppression and Subjective Sleepiness.

OBJECTIVE: At the beginning of this century, a novel photopigment, melanopsin, was discovered in a sub-class of retinal ganglion cells and its action spectrum was described. Shortly after, it became evident that melanopsin is a major contributor to non-visual eye-mediated effects of light on e.g. the circadian, neuroendocrine and neurobehavioral systems. First applied studies pointed out that these non-visual effects of light are relevant for wellbeing, performance and general health. A standardized measurement metric for these nonvisual effects does not exist, but would ease application. Such a metric termed as 'melanopic lux' has been recently introduced and was shown to be superior to describe non-visual effects in animal studies compared to standard metrics. METHODS: We aimed at showing some validity of melanopic lux in humans using a seminaturalistic setting. Therefore, we analyzed the impact of different lighting conditions on melatonin suppression and subjective sleepiness by calculating effective illuminance based on single photopigment sensitivities. We retrospectively analyzed data from our laboratory, where young participants were exposed to a total of 19 different polychromatic lighting conditions, for 30 minutes in the evening, one hour prior to habitual bedtime. Saliva samples for melatonin concentration measures and subjective sleepiness were regularly assessed. The photopic illuminance of all lighting conditions ranged from 3 to 604 lx. Stepwise for- and backward regression analyses showed that melanopic lux was the best predictor for changes in melatonin concentrations (but not subjective sleepiness); R²=0.16 (p<0.05). In addition, we found a significant dose-response relationship between melanopic lux and changes in melatonin concentrations for 18 different lighting conditions (adjusted R²=0.52; p=0.004), similarly to what was previously reported for photopic lux. RESULTS: Our results indicate some new relevance for the application of melanopic lux as an additional metric to predict non-visual light effects of electrical light sources for nursing homes, work places, and homes.

Blue-Enriched Morning Light as a Countermeasure to Light at the Wrong Time: Effects on Cognition, Sleepiness, Sleep, and Circadian Phase.

Light during the day and darkness at night are crucial factors for proper entrainment of the human circadian system to the solar 24-h day. However, modern life and work styles have led to much more time spent indoors, often with lower daytime and higher evening/nighttime light intensity from electrical lighting than outdoors. Whether this has long-term consequences for human health is being currently investigated. We tested if bright blue-enriched morning light over several days could counteract the detrimental effects of inadequate daytime and evening lighting. In a seminaturalistic, within-between subject study design, 18 young participants were exposed to different lighting conditions on 3 evenings (blue-enriched, bright orange, or dim light), after exposure to 2 lighting conditions (mixed blue-enriched light and control light, for 3 days each) in the mornings. Subjective sleepiness, reaction times, salivary melatonin concentrations, and nighttime sleep were assessed. Exposure to the blue-enriched morning lighting showed acute wake-promoting effects and faster reaction times than with control lighting. Some of these effects persisted until the evening, and performance improved over several days. The magnitude of circadian phase shifts induced by combinations of 3 different evening and 2 morning lighting conditions were significantly smaller with the blue-enriched morning light. During the night, participants had longer total sleep times after orange light exposure than after blue light exposure in the evening. Our results indicate that bright blue-enriched morning light stabilizes circadian phase, and it could be an effective counterstrategy for poor lighting during the day and also light exposure at the wrong time, such as in the late evening.

Effects of age and sex on the concentrations of glutamate and glutamine in the human brain.

PURPOSE: To determine the effects of age and sex on cerebral glutamate and glutamine concentrations in a large sample of healthy humans using a dedicated measuring and evaluation procedure. Exploratory examinations of other brain metabolites were also conducted. MATERIALS AND METHODS: In 118 healthy subjects aged 19 to 55 years (59 female) absolute concentrations of glutamate, glutamine, N-acetylaspartate (NAA), total creatine, and total choline (tCho) in voxels comprising the left hippocampus (HC) and the anterior cingulate cortex (ACC) were investigated using point-resolved spectroscopy with an echo time of 80 ms at 3 Tesla in combination with a reliable quantification procedure. Special care was taken to correct for multiple comparisons. RESULTS: An age-related decline of the concentrations of glutamate in both regions studied was observed whereas glutamine levels in ACC increased with age. Statistically significant sex-related differences were detected for glutamate in the HC and for tCho in the ACC. NAA decreased with age in both regions, the significance not surviving Bonferroni correction. CONCLUSION: The results demonstrate effects of age and gender on glutamate, glutamine, choline containing compounds, and NAA in healthy human brain. They add to the growing evidence for gender-specific differences in cerebral neurotransmission, metabolism, and structure across the lifespan.

Degree of pineal calcification (DOC) is associated with polysomnographic sleep measures in primary insomnia patients.

OBJECTIVE: Melatonin plays a key role in the proper functioning of the circadian timing system (CTS), and exogenous melatonin has been shown to be beneficial in cases of CTS and sleep disturbances. Nevertheless, the concept of "melatonin deficit" has yet to be defined. The aim of our study was, therefore, to determine the relationship between the degree of pineal calcification (DOC) and a range of sleep parameters measured objectively using polysomnography (PSG). METHODS: A total of 31 outpatients (17 women, 14 men, mean age 45.9 years; SD 14.4) with primary insomnia were included in our study. Following an adaptation night, a PSG recording night was performed in the sleep laboratory. Urine samples were collected at predefined intervals over a 32-h period that included both PSG nights. The measurement of 6-sulphatoxymelatonin (aMT6s) levels was determined using ELISA. DOC and volume of calcified pineal tissue (CPT) and uncalcified pineal tissue (UPT) were estimated by means of cranial computed tomography. RESULTS: UPT was positively associated with 24-h aMT6s excretion (r=0.569; P=0.002), but CPT was not. After controlling for age, aMT6s parameters, CPT, and UPT did not correlate with any of the PSG parameters evaluated. In contrast, DOC was negatively associated with REM sleep percentage (r=-0.567, P=0.001), total sleep time (r=-0.463, P=0.010), and sleep efficiency (r=-0.422, P=0.020). CONCLUSION: DOC appears to be a superior indicator of melatonin deficit compared to the absolute amount of melatonin in the circulation. High DOC values indicate changes predominantly in the PSG parameters governed by the circadian timing system. DOC may thus serve as a marker of CTS instability.