Category: articles

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.

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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

Abstract

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.

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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

Abstract:

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.

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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.

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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.
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