Category: Studies

Non-visual effects of light on melatonin, alertness and cognitive performance: can blue-enriched light keep us alert?

2011 study

Chellappa SL  Centre for Chronobiology, Psychiatric Hospital of the University of Basel, Basel, Switzerland
Steiner R, Blattner P, Oelhafen P, Götz T, Cajochen C,


Light exposure can cascade numerous effects on the human circadian process via the non-imaging forming system, whose spectral relevance is highest in the short-wavelength range. Here we investigated if commercially available compact fluorescent lamps with different colour temperatures can impact on alertness and cognitive performance.


Sixteen healthy young men were studied in a balanced cross-over design with light exposure of 3 different light settings (compact fluorescent lamps with light of 40 lux at 6500K and at 2500K and incandescent lamps of 40 lux at 3000K) during 2 h in the evening.


Exposure to light at 6500K induced greater melatonin suppression, together with enhanced subjective alertness, well-being and visual comfort. With respect to cognitive performance, light at 6500K led to significantly faster reaction times in tasks associated with sustained attention (Psychomotor Vigilance and GO/NOGO Task), but not in tasks associated with executive function (Paced Visual Serial Addition Task). This cognitive improvement was strongly related with attenuated salivary melatonin levels, particularly for the light condition at 6500K.


Our findings suggest that the sensitivity of the human alerting and cognitive response to polychromatic light at levels as low as 40 lux, is blue-shifted relative to the three-cone visual photopic system. Thus, the selection of commercially available compact fluorescent lights with different colour temperatures significantly impacts on circadian physiology and cognitive performance at home and in the workplace.

The study can be found at this link

Blue-enriched white light in the workplace improves self-reported alertness, performance and sleep quality.

2088 study

Viola AU, Surrey Sleep Research Centre, Clinical Research Centre, Egerton Road, Guildford, United Kingdom
James LM, Schlangen LJ, Dijk DJ


Specifications and standards for lighting installations in occupational settings are based on the spectral sensitivity of the classical visual system and do not take into account the recently discovered melanopsin-based, blue-light-sensitive photoreceptive system. The authors investigated the effects of exposure to blue-enriched white light during daytime workhours in an office setting.


The experiment was conducted on 104 white-collar workers on two office floors. After baseline assessments under existing lighting conditions, every participant was exposed to two new lighting conditions, each lasting 4 weeks. One consisted of blue-enriched white light (17 000 K) and the other of white light (4000 K). The order was balanced between the floors. Questionnaire and rating scales were used to assess alertness, mood, sleep quality, performance, mental effort, headache and eye strain, and mood throughout the 8-week intervention.


Altogether 94 participants [mean age 36.4 (SD 10.2) years] were included in the analysis. Compared with white light (4000 K), blue-enriched white light (17 000 K) improved the subjective measures of alertness (P<0.0001), positive mood (P=0.0001), performance (P<0.0001), evening fatigue (P=0.0001), irritability (P=0.004), concentration (P<0.0001), and eye discomfort (P=0.002). Daytime sleepiness was reduced (P=0.0001), and the quality of subjective nocturnal sleep (P=0.016) was improved under blue-enriched white light. When the participants‘ expectation about the effect of the light treatments was entered into the analysis as a covariate, significant effects persisted for performance, alertness, evening fatigue, irritability, difficulty focusing, concentrating, and blurred vision.


Exposure to blue-enriched white light during daytime workhours improves subjective alertness, performance, and evening fatigue.

The study can be found at this link.

Opponent melanopsin and S-cone signals in the human pupillary light response

2014 study

Manuel Spitschan, Sandeep Jain, David H. Brainard, and Geoffrey K. Aguirre. Departments of Psychology and Neurology, University of Pennsylvania, Philadelphia, PA 19104

In the human, cone photoreceptors (L, M, and S) and the melanopsincontaining, intrinsically photosensitive retinal ganglion cells (ipRGCs) are active at daytime light intensities. Signals from cones are combined both additively and in opposition to create the perception of overall light and color. Similar mechanisms seem to be at work in the control of the pupil’s response to light. Uncharacterized however, is the relative contribution of melanopsin and S cones, with their overlapping, short-wavelength spectral sensitivities. We measured the response of the human pupil to the separate stimulation of the cones and melanopsin at a range of temporal frequencies under photopic conditions. The S-cone and melanopsin photoreceptor channels were found to be low-pass, in contrast to a band-pass response of the pupil to L- and M-cone signals. An examination of the phase relationships of the evoked responses revealed that melanopsin signals add with signals from L and M cones but are opposed by signals from S cones in control of the pupil. The opposition of the S cones is revealed in a seemingly paradoxical dilation of the pupil to greater S-cone photon capture. This surprising result is explained by the neurophysiological properties of ipRGCs found in animal studies.

Results Using an infrared camera, we measured the consensual PLR of human participants while they observed sinusoidal modulations in the spectrum of a light (Fig. 1B). The stimulus modulations were designed to target specific photoreceptors. The cones and melanopsin have different but overlapping spectral sensitivities. Despite the overlap, it is possible to create sets of light spectra such that the absorption of photons is constant for all of the photoreceptor classes except one (14–16) (Fig. 1C). Modulation between a pair of these “silent substitution” spectra increases and decreases the response of (for example) melanopsin-containing ipRGCs while maintaining nominally constant stimulation of the cones. Separate modulations were designed for melanopsin, S cones, and L+M cones together (a modulation that varied luminance as well as chromaticity). An isochromatic modulation (melanopsin+S+M+L) was also used. All modulations were designed to produce 50% contrast on their targeted photoreceptor(s). Rods were silenced by modulating the spectra about a photopic background (∼800 cd/m2 ). The stimulus was wide-field (27.5°), spatially uniform, and had the central 5° obscured to avoid variation in photoreceptor spectral sensitivity across the visual field caused by the presence of the foveal macular pigment (17). Simulations and control experiments support the specificity of the photoreceptor isolation (Figs. S1–S5 and Table S1). We measured pupil responses from 16 subjects while they observed the different photoreceptor-directed modulations at two for each combination of photoreceptor target and modulation frequency. The two-filter model fits the average amplitude and phase data (Fig. 5A) with parameters similar to those found for subject 01 (Table S2). When expressed as a polar plot (Fig. 5B), the agreement between the group data and model fits is apparent. Interestingly, there is systematic “rotation” of the phase of both the pupil brightness and S-cone responses at the lower temporal frequency that is not captured by the model. This may result from individual differences in the phase of S-cone responses at low temporal frequencies, as is seen between subject 01 and subject 02 (Fig. 4), because the average data do not fully constrain the model and the fits shown are based on parameters obtained for subject 01.

Whole study on this link

A neural mechanism for exacerbation of headache by light

2010 study

Rodrigo Noseda,1 Vanessa Kainz,1 Moshe Jakubowski,1Joshua J. Gooley,2 Clifford B. Saper,2,3Kathleen Digre,4 and Rami Burstein1,3

1Department of Anesthesia, Harvard Medical School, Boston, Massachusetts, USA
2Department of Neurology, Harvard Medical School, Boston, Massachusetts, USA
3Beth Israel Deaconess Medical Center and Program in Neuroscience, Harvard Medical School, Boston, Massachusetts, USA
4Department of Neurology and Ophthalmology, Moran Eye Center, University of Utah, Salt Lake City, Utah

The perception of migraine headache, which is mediated by nociceptive signals transmitted from the cranial dura mater to the brain, is uniquely exacerbated by exposure to light. Here we show that exacerbation of migraine headache by light is prevalent among blind persons who maintain non-image-forming photoregulation in the face of massive rod/cone degeneration. Using single-unit recording and neural tract-tracing in the rat, we identified dura-sensitive neurons in the posterior thalamus, whose activity was distinctly modulated by light, and whose axons projected extensively across layers I through V of somatosensory, visual and associative cortices. The cell bodies and dendrites of such dura/light-sensitive neurons were apposed by axons originating from retinal ganglion cells, predominantly from intrinsically-photosensitive retinal ganglion cells – the principle conduit of non-image-forming photoregulation. We propose that photoregulation of migraine headache is exerted by a non-image-forming retinal pathway that modulates the activity of dura-sensitive thalamocortical neurons.

Whole study on this link.

Human pineal physiology and functional significance of melatonin

2004 study

M. Mila Macchia, Jeffrey N. Bruceb

a New York State Psychiatric Institute, College of Physicians and Surgeons, Columbia University, 1051 Riverside Drive, Unit 50, New York, NY 10032, United States
b Bartoli Brain Tumor Research Laboratory, Neurological Institute, Columbia Presbyterian Medical Center New York, NY, United States


Descriptions of the pineal gland date back to antiquity, but its functions in humans are still poorly understood. In both diurnal and nocturnal vertebrates, its main product, the hormone melatonin, is synthesized and released in rhythmic fashion, during the dark portion of the day–night cycle. Melatonin production is controlled by an endogenous circadian timing system and is also suppressed by light. In lower vertebrates, the pineal gland is photosensitive, and is the site of a self-sustaining circadian clock. In mammals, including humans, the gland has lost direct photosensitivity, but responds to light via a multisynaptic pathway that includes a subset of retinal ganglion cells containing the newly discovered photopigment, melanopsin. The mammalian pineal also shows circadian oscillations, but these damp out within a few days in the absence of input from the primary circadian pacemaker in the suprachiasmatic nuclei (SCN). The duration of the nocturnal melatonin secretory episode increases with nighttime duration, thereby providing an internal calendar that regulates seasonal cycles in reproduction and other functions in photoperiodic species. Although humans are not considered photoperiodic, the occurrence of seasonal affective disorder (SAD) and its successful treatment with light suggest that they have retained some photoperiodic responsiveness. In humans, exogenous melatonin has a soporific effect, but only when administered during the day or early evening, when endogenous levels are low. Some types of primary insomnia have been attributed to diminished melatonin production, particularly in the elderly, but evidence of a causal link is still inconclusive. Melatonin administration also has mild hypothermic and hypotensive effects. A role for the pineal in human reproduction was initially hypothesized on the basis of clinical observations on the effects of pineal tumors on sexual development. More recent data showing an association between endogenous melatonin levels and the onset of puberty, as well as observations of elevated melatonin levels in both men and women with hypogonadism and/or infertility are consistent with such a hypothesis, but a regulatory role of melatonin has yet to be established conclusively. A rapidly expanding literature attests to the involvement of melatonin in immune function, with high levels promoting and low levels suppressing a number of immune system parameters. The detection of melatonin receptors in various lymphoid organs and in lymphocytes suggests multiple mechanisms of action. Melatonin has been shown to be a powerful antioxidant, and has oncostatic properties as well, both direct and indirect, the latter mediated by its effects on reproductive hormones. Finally, there are reports of abnormal daily melatonin profiles in a number of psychiatric and neurological disorders, but the significance of such abnormalities is far from clear.

Whole study here

Sleep in the Critically ill Patient

2006 study

Gerald L. Weinhouse, MD1 ; Richard J. Schwab, MD2

1 The Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Boston, MA;

2 the Division of Pulmonary, Critical Care, and Sleep Medicine, University of Pennsylvania Medical Center, Philadelphia, PA


Critically ill patients are known to suffer from severely fragmented sleep with a predominance of stage I sleep and a paucity of slow wave and REM sleep. The causes of this sleep disruption include the intensive care unit (ICU) environment, medical illness, psychological stress, and many of the medications and other treatments used to help those who are critically ill. The clinical importance of this type of sleep disruption in critically ill patients, however, is not known. This article reviews the literature on sleep disruption in the ICU, the effects of sepsis on sleep, the effects of commonly used ICU medications on sleep, the relationship between sleep and sedation, and the literature on the biological and psychological consequences of sleep deprivation specifically as it relates to the critically ill. Finally, an integrative approach to improving sleep in the ICU is described.

Whole study here

Opponent melanopsin and S-cone signals in the human pupillary light response

2014 study

Manuel Spitschana , Sandeep Jainb , David H. Brainarda,1, and Geoffrey K. Aguirreb,1

Departments of a Psychology and b Neurology, University of Pennsylvania, Philadelphia, PA 19104

Edited by Dennis M. Dacey, The University of Washington, Seattle, WA, and accepted by the Editorial Board September 12, 2014 (received for review January 17, 2014)

In the human, cone photoreceptors (L, M, and S) and the melanopsincontaining, intrinsically photosensitive retinal ganglion cells (ipRGCs) are active at daytime light intensities. Signals from cones are combined both additively and in opposition to create the perception of overall light and color. Similar mechanisms seem to be at work in the control of the pupil’s response to light. Uncharacterized however, is the relative contribution of melanopsin and S cones, with their overlapping, short-wavelength spectral sensitivities. We measured the response of the human pupil to the separate stimulation of the cones and melanopsin at a range of temporal frequencies under photopic conditions. The S-cone and melanopsin photoreceptor channels were found to be low-pass, in contrast to a band-pass response of the pupil to L- and M-cone signals. An examination of the phase relationships of the evoked responses revealed that melanopsin signals add with signals from L and M cones but are opposed by signals from S cones in control of the pupil. The opposition of the S cones is revealed in a seemingly paradoxical dilation of the pupil to greater S-cone photon capture. This surprising result is explained by the neurophysiological properties of ipRGCs found in animal studies.

Whole study on this link

Melanopsin and Rod–Cone Photoreceptors Play Different Roles in Mediating Pupillary Light Responses during Exposure to Continuous Light in Humans

2012 study

Joshua J. Gooley,1,2,3 Ivan Ho Mien,4 Melissa A. St. Hilaire,2,3 Sing-Chen Yeo,5 Eric Chern-Pin Chua,1 Eliza van Reen,2,3 Catherine J. Hanley,2 Joseph T. Hull,2,3 Charles A. Czeisler,2,3 and Steven W. Lockley2,3

1 Program in Neuroscience and Behavioral Disorders, Duke–National University of Singapore Graduate Medical School Singapore, Singapore 169857,
2 Division of Sleep Medicine, Department of Medicine, Brigham and Women’s Hospital, and 3 Division of Sleep Medicine, Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, 4 Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore 117456, and 5 National Neuroscience Institute, Singapore 308433

In mammals, the pupillary light reflex is mediated by intrinsically photosensitive melanopsin-containing retinal ganglion cells that also
receive input from rod– cone photoreceptors. To assess the relative contribution of melanopsin and rod– cone photoreceptors to the
pupillary light reflex in humans, we compared pupillary light responses in normally sighted individuals (n  24) with a blind individual
lacking rod– cone function. Here, we show that visual photoreceptors are required for normal pupillary responses to continuous light
exposure at low irradiance levels, and for sustained pupillary constriction during exposure to light in the long-wavelength portion of the
visual spectrum. Inthe absence of rod– conefunction, pupillomotor responses are slow and sustained, and cannottrackintermittent light
stimuli, suggesting that rods/cones are required for encoding fast modulations in light intensity. In sighted individuals, pupillary
constriction decreased monotonically for at least 30 min during exposureto continuous low-irradiance light, indicatingthat steady-state
pupillary responses are an order of magnitude slower than previously reported. Exposure to low-irradiance intermittent green light (543
nm; 0.1– 4 Hz)for 30 min, which was givento activate cone photoreceptors repeatedly, elicited sustained pupillary constriction responses
that were more than twice as great compared with exposure to continuous green light. Our findings demonstrate nonredundant roles for
rod– cone photoreceptors and melanopsin in mediating pupillary responses to continuous light. Moreover, our results suggest that it
might be possible to enhance nonvisual light responses to low-irradiance exposures by using intermittent light to activate cone photoreceptors
repeatedly in humans.

Whole study here


2011 study

National Center On Sleep Disorders Research

Sleep and circadian disturbances and disorders affect millions of Americans across all demographic groups. An estimated 25-30% of the general adult population, and a comparable percentage of children and adolescents, is affected by decrements in sleep health that are proven contributors to disability, morbidity, and mortality. As a result, sleep and circadian disturbances and disorders have been recognized by Congress and the Department of Health and Human Services1,2 as high priority targets for basic and clinical scientific investigation. Three general categories of sleep and circadian disorders and disturbances have been described: 1) disorders of sleep and circadian rhythms; 2) sleep deficiency; and 3) environmental disruption of circadian functions. In addition to clinical sleep and circadian disorders, sleep deficiency and circadian disruption resulting from lifestyle factors are increasingly common societal problems that increase disease risk through complex pathways. Advances sweeping across the spectrum of biomedical inquiry have transformed the sleep and circadian research landscape since the first NIH Sleep Disorders Research Plan was developed in 1996. The scientific domain is well-poised today to contribute knowledge advances and emerging technologies to the goals of understanding mechanisms of disease risk, accelerating translation from bench to bedside to community, and developing the evidence based evaluation of intervention effectiveness. Opportunities for research training exist in all areas of sleep and circadian biology and at multiple levels of the educational ladder. Scientific cross-fertilization and the development of an interdisciplinary workforce would stimulate the application of sleep and circadian scientific advances in cross-cutting domains.
Whole study here

MMWR – Morbidity and Mortality Weekly Report

March 4, 2011 article

Centers for Diseases Control and Prevention

National Sleep Awareness Week

March 7–13, 2011 March 7–13, 2011, is National Sleep Awareness Week. Sleep impairment is linked as a contributing factor to motor vehicle crashes, industrial disasters, and medical and other occupational errors (1). Persons experiencing sleep insufficiency are more likely to have chronic diseases such as cardiovascular disease, diabetes, depression, or obesity (2,3). In 2008, approximately 28% of surveyed adults in the United States reported frequent insufficient sleep (≥14 days in the past 30 days) (4), which has been associated with fair/poor general health, frequent mental and physical distress, depressive symptoms, anxiety, and pain (3). Sleep insufficiency and poor sleep quality also can result from sleep disorders such as chronic insomnia, restless legs syndrome, sleep apnea, or narcolepsy (1). The National Sleep Foundation suggests that healthy adults need 7–9 hours of sleep per day, and school-age children might require 10–11 hours of sleep (5). Additional information regarding the public health importance of sleep is available at Information regarding sleep health and safety is available from the National Sleep Foundation at


Unhealthy Sleep-Related Behaviors

12 States, 2009 An estimated 50–70 million adults in the United States have chronic sleep and wakefulness disorders (1). Sleep difficulties, some of which are preventable, are associated with chronic diseases, mental disorders, health-risk behaviors, limitations of daily functioning, injury, and mortality (1,2). The National Sleep Foundation suggests that most adults need 7–9 hours of sleep per night, although individual variations exist. To assess the prevalence and distribution of selected sleep difficulties and behaviors, CDC analyzed data from a new sleep module added to the Behavioral Risk Factor Surveillance System (BRFSS) in 2009. This report summarizes the results of that analysis, which determined that, among 74,571 adult respondents in 12 states, 35.3% reported having <7 hours of sleep on average during a 24-hour period, 48.0% reported snoring, 37.9% reported unintentionally falling asleep during the day at least 1 day in the preceding 30 days, and 4.7% reported nodding off or falling asleep while driving in the preceding 30 days. Continued public health surveillance of sleep quality, duration, behaviors, and disorders is needed to understand and address sleep difficulties and their impact on health. As a first step, a multifaceted approach that includes increased public awareness and education and training in sleep medicine for appropriate health-care professionals is needed; however, broad societal factors, including technology use and work policies, also must be considered.

Whole paper here