maleficent
a potassium channel β-subunit couples mitochondrial electron transport to sleep
anissa kempf et al. 2019
http://dx.doi.org/10.1038/s41586-019-1034-5
oxidative stress leads to sleep. Oxidative stress is also believed to be a reason why we age and a cause of degenerative diseases.
The researchers say the discovery brings us closer to understanding the still-mysterious function of sleep and offers new hope for the treatment of sleep disorders. It may also explain why, as is suspected, chronic lack of sleep shortens life.
Professor Gero Miesenböck, Director of Oxford University's Centre for Neural Circuits and Behaviour, who led the Oxford team, said: 'It's no accident that oxygen tanks carry explosion hazard labels: uncontrolled combustion is dangerous. Animals, including humans, face a similar risk when they use the oxygen they breathe to convert food into energy: imperfectly contained combustion leads to "oxidative stress" in the cell. This is believed to be a cause of ageing and a culprit for the degenerative diseases that blight our later years. Our new research shows that oxidative stress also activates the neurons that control whether we go to sleep.'
The team studied the regulation of sleep in fruit flies -- the animal that also provided the first insight into the circadian clock nearly 50 years ago. Each fly has a special set of sleep-control neurons, brain cells that are also found in other animals and believed to exist in people. In previous research [Nature 2016; 536: 333-337], Professor Miesenböck's team discovered that these sleep-control neurons act like an on-off switch: if the neurons are electrically active, the fly is asleep; when they are silent, the fly is awake.
Dr Seoho Song, a former graduate student in the Miesenböck lab and one of the two lead authors of the study, said: 'We decided to look for the signals that switch the sleep-control neurons on. We knew from our earlier work that a main difference between sleep and waking is how much electrical current flows through two ion channels, called Shaker and Sandman. During sleep, most of the current goes through Shaker.'
Ion channels generate and control the electrical impulses through which brain cells communicate.
'This turned the big, intractable question "Why do we sleep?" into a concrete, solvable problem,' said Dr Song. 'What causes the electrical current to flow through Shaker?'
The team found the answer in a component of the Shaker channel itself.
Lead author and postdoctoral fellow in the Miesenböck group, Dr Anissa Kempf, explained: 'Suspended underneath the electrically conducting portion of Shaker is another part, like the gondola under a hot air balloon. A passenger in the gondola, the small molecule NADPH, flips back and forth between two chemical states -- this regulates the Shaker current. The state of NADPH, in turn, reflects the degree of oxidative stress the cell has experienced. Sleeplessness causes oxidative stress, and this drives the chemical conversion.'
In a striking demonstration of this mechanism, a flash of light that flipped the chemical state of NADPH put flies to sleep.
According to Professor Miesenböck, drugs that change the chemistry of Shaker-bound NADPH in the same way could be a powerful new type of sleeping pill.
'Sleep disturbances are very common,' he said, 'and sleeping pills are among the most commonly prescribed drugs. But existing medications carry risks of confusion, forgetfulness and addiction. Targeting the mechanism we have discovered could avoid some of these side effects.'
abstract The essential but enigmatic functions of sleep1,2 must be reflected in molecular changes sensed by the brain’s sleep-control systems. In the fruitfly Drosophila, about two dozen sleep-inducing neurons3 with projections to the dorsal fan-shaped body (dFB) adjust their electrical output to sleep need4, via the antagonistic regulation of two potassium conductances: the leak channel Sandman imposes silence during waking, whereas increased A-type currents through Shaker support tonic firing during sleep5. Here we show that oxidative byproducts of mitochondrial electron transport6,7 regulate the activity of dFB neurons through a nicotinamide adenine dinucleotide phosphate (NADPH) cofactor bound to the oxidoreductase domain8,9 of Shaker’s KVβ subunit, Hyperkinetic10,11. Sleep loss elevates mitochondrial reactive oxygen species in dFB neurons, which register this rise by converting Hyperkinetic to the NADP+-bound form. The oxidation of the cofactor slows the inactivation of the A-type current and boosts the frequency of action potentials, thereby promoting sleep. Energy metabolism, oxidative stress, and sleep—three processes implicated independently in lifespan, ageing, and degenerative disease6,12,13,14—are thus mechanistically connected. KVβ substrates8,15,16 or inhibitors that alter the ratio of bound NADPH to NADP+ (and hence the record of sleep debt or waking time) represent prototypes of potential sleep-regulatory drugs.
ultrastructural evidence for synaptic scaling across the wake/sleep cycle
luisa de vivo et al. 2018
http://dx.doi.org/10.1126/science.aah5982
a common neuroendocrine substrate for diverse general anesthetics and sleep
li-feng jiang-xie et al. 2019
http://dx.doi.org/10.1016/j.neuron.2019.03.033
several different general anesthesia drugs knock you out by hijacking the neural circuitry that makes you fall sleep.
The researchers traced this neural circuitry to a tiny cluster of cells at the base of the brain responsible for churning out hormones to regulate bodily functions, mood, and sleep. The finding is one of the first to suggest a role for hormones in maintaining the state of general anesthesia, and provides valuable insights for generating newer drugs that could put people to sleep with fewer side effects.
Ever since the first patient went under general anesthesia in 1846, scientists have been trying to figure out exactly how it works. The prevailing theory has been that many of these drugs tamp down the brain's normal activities, resulting in the inability to move or feel pain. Similar theories revolved around sleep, the sister state to general anesthesia. However, research over the last decade has shown that sleep is a more active process than previously recognized, with entire sets of neurons clocking in to work while you catch your Z's.
Fan Wang, Ph.D., a professor of neurobiology at the Duke University School of Medicine, and Li-Feng Jiang-Xie, a graduate student in her laboratory, wondered whether the predominant view of general anesthesia was also one-sided. "Perhaps rather than simply inhibiting neurons, anesthetics could also activate certain neurons in the brain," said Jiang-Xie.
To test their new theory, Jiang-Xie and Luping Yin, Ph.D., a postdoctoral fellow in the Wang lab, put mice under general anesthesia with several different but commonly used drugs. Then they used molecular markers to track down the neurons that were commonly activated by the anesthetics. They found a cluster of actively firing neurons buried in a tiny brain region called the supraoptic nucleus, which is known to have leggy projections that release large amounts of hormones like vasopressin directly into the bloodstream.
"Most of the anesthesia-activated cells were a kind of hybrid cell that connects the nervous system and the endocrine system," said Jiang-Xie. "That took us by surprise and led us into unexplored territory for understanding the neural pathways of general anesthesia."
Next, the researchers tapped a sophisticated technique developed in the Wang lab to turn on or off this specialized group of cells with chemicals or light. When they switched on the cells in mice, the animals stopped moving and fell into a deep slumber called slow wave sleep, typically associated with unconsciousness.
Then the research team killed off this group of cells. The mice continued to move around, unable to fall asleep.
Finally, the researchers performed similar experiments on mice under general anesthesia. They found that artificially pre-activating the neuroendocrine cells made the mice stay under general anesthesia for longer periods of time. Conversely, when they silenced these cells, the mice woke up from anesthesia more easily.
This study also revealed a previously unexpected role of the brain's hormone-secreting cells in promoting deep sleep.
"Many people, particularly those with Alzheimer's disease, have difficulty falling to sleep, yet current medications have troublesome side effects," said Yin. "If we can find ways to manipulate this neural circuitry, perhaps by targeting hormones or small peptides, then it could lead to the development of better sleeping pills."
abstract •General-anesthesia-activated neurons (AANs) are identified in hypothalamus
•AANs consist mainly of neuroendocrine cells in and near the supraoptic nucleus
•Activation of AANs promotes slow-wave sleep and extends general anesthesia
•Inhibition of AANs shortens general anesthesia and disrupts natural sleep
How general anesthesia (GA) induces loss of consciousness remains unclear, and whether diverse anesthetic drugs and sleep share a common neural pathway is unknown. Previous studies have revealed that many GA drugs inhibit neural activity through targeting GABA receptors. Here, using Fos staining, ex vivo brain slice recording, and in vivo multi-channel electrophysiology, we discovered a core ensemble of hypothalamic neurons in and near the supraoptic nucleus, consisting primarily of neuroendocrine cells, which are persistently and commonly activated by multiple classes of GA drugs. Remarkably, chemogenetic or brief optogenetic activations of these anesthesia-activated neurons (AANs) strongly promote slow-wave sleep and potentiates GA, whereas conditional ablation or inhibition of AANs led to diminished slow-wave oscillation, significant loss of sleep, and shortened durations of GA. These findings identify a common neural substrate underlying diverse GA drugs and natural sleep and reveal a crucial role of the neuroendocrine system in regulating global brain states.
discovery of key whole-brain transitions and dynamics during human wakefulness and non-rem sleep
a. b. a. stevner et al. 2019
http://dx.doi.org/10.1038/s41467-019-08934-3
0009 restless leg syndrome: does it start with a gut feeling?
daniel j blum et al. 2019
http://dx.doi.org/10.1093/sleep/zsz067.008
Small intestine bacterial overgrowth (SIBO) may be more prevalent among patients with restless legs syndrome (RLS), according to preliminary findings from a small, new study.
Results show that SIBO was found in all seven participants who have RLS. In contrast, the prevalence of SIBO in the general population is estimated to be no more than 15%.
"We've observed extremely high rates of small intestinal bacterial overgrowth in the RLS group," said lead author Daniel Jin Blum, Ph.D., D.B.S.M., an adjunct clinical instructor at Stanford Center for Sleep Sciences and Medicine in Redwood City, California. "Exploring the relationship between RLS and gut microbial health has the potential to open novel avenues for possible detection, prevention and treatment for RLS and other sleep disorders."
SIBO is a condition in which rare gut-residing bacteria are over-represented in the gut. RLS is a sensorimotor disorder characterized by a complaint of a strong, nearly irresistible urge to move the limbs that is often accompanied by other uncomfortable sensations. These symptoms begin or worsen during periods of rest or inactivity such as lying down or sitting, are partially or totally relieved by movement such as walking or stretching, and occur exclusively or predominantly in the evening or at night.
Low iron in the brain is a key risk factor for RLS. According to the authors, this brain iron deficiency may be secondary to dietary iron deficiency or, potentially, gut inflammation.
abstract Emerging research links gut microbial health with sleep. One common sleep disorder in which the microbiome may play a role is restless legs syndrome (RLS). While the pathogenesis of RLS is not fully understood, a relative state of brain iron deficiency has been described in patients with RLS and appears to induce changes in several pathways (adenosinergic, glutamatergic and dopaminergic) known to be involved in the disease. Insufficient iron may be secondary to dietary iron deficiency or, potentially, gut inflammation. We hypothesized that small intestinal bacterial overgrowth (SIBO), a condition associated with gut dysbiosis (i.e., normally rare gut-residing bacteria are over-represented in the gut), is associated with RLS and may moderate the observed inter-patient variability in serum iron availability.
Methods
Participants are being recruited at the Stanford Sleep Center for three groups: RLS and low peripheral iron stores (<50ng/mL and/or transferrin saturation <18%), RLS and normal peripheral iron stores, and insomnia (control). Participants complete questionnaires concerning sleep and SIBO symptoms and are sent home with a fecal collection kit (Fecal Swab Collection and Preservation System, Norgen Biotek) and a SIBO kit (SIBO Home Breath Test Kit, Quintron). Fecal samples are assayed by the University of Minnesota Genomics Center with microbial community profiling evaluated by 16S ribosomal RNA (16S rRNA) gene sequencing protocols. SIBO breath samples are evaluated by Aerodiagnostics for hydrogen and methane abnormalities.
Results
Seven participants diagnosed with RLS (3 men, 4 women) have thus far completed the protocol. All indicated poor sleep quality (PSQI ≥ 5) and moderate to severe symptoms of RLS (IRLS scores ranging from 13 to 34/40). SIBO was present in all 7 participants (100%) whereas general population rates are estimated to be 6-15%.
Conclusion
These preliminary data suggest that SIBO may be more prevalent among patients with RLS. Additional analyses will examine fecal microbial composition, subtypes of RLS iron deficiency, and comparisons with insomnia.
sleep architecture and the risk of incident dementia in the community
matthew pase et al. 2017
dx.doi.org/10.1212/WNL.0000000000004373
the effects of self-selected light-dark cycles and social constraints on human sleep and circadian timing: a modeling approach
anne c. skeldon, andrew j. k. phillips, derk-jan dijk 2017
dx.doi.org/10.1038/srep45158
alterations in glutamatergic signalling contribute to the decline of circadian photoentrainment in aged mice
s.m. biello et al. 2018
http://dx.doi.org/10.1016/j.neurobiolaging.2018.02.013
new learning while consolidating memory during sleep is actively blocked by a protein synthesis dependent process
roi levy, david levitan, abraham j susswein 2016
eLife.17769
implicit vocabulary learning during sleep is bound to slow-wave peaks
marc alain züst et al. 2019
http://dx.doi.org/10.1016/j.cub.2018.12.038
If re-play during sleep improves the storage of wake-learned information, then first-play -- i.e., the initial processing of new information -- should also be feasible during sleep, potentially carving out a memory trace that lasts into wakefulness. This was the research question of Katharina Henke, Marc Züst und Simon Ruch of the Institute of Psychology and of the Interfaculty Research Cooperation "Decoding Sleep" at the University of Bern, Switzerland. These investigators now showed for the first time that new foreign words and their translation words could be associated during a midday nap with associations stored into wakefulness. Following waking, participants could reactivate the sleep-formed associations to access word meanings when represented with the formerly sleep-played foreign words. The hippocampus, a brain structure essential for wake associative learning, also supported the retrieval of sleep-formed associations. The results of this experiment are published open access in the scientific journal Current Biology.
The brain cells' active states are central for sleep-learning
The research group of Katharina Henke examined whether a sleeping person is able to form new semantic associations between played foreign words and translation words during the brain cells' active states, the so-called "Up-states." When we reach deep sleep stages, our brain cells progressively coordinate their activity. During deep sleep, the brain cells are commonly active for a brief period of time before they jointly enter into a state of brief inactivity. The active state is called "Up-state" and the inactive state "Down-state." The two states alternate about every half-second.
Semantic associations between sleep-played words of an artificial language and their German translations words were only encoded and stored, if the second word of a pair was repeatedly (2, 3 or 4 times) played during an Up-state. E.g., when a sleeping person heard the word pairs "tofer = key" and "guga = elephant," then after waking they were able to categorize with a better-than-chance accuracy whether the sleep-played foreign words denominated something large ("Guga") or small ("Tofer"). "It was interesting that language areas of the brain and the hippocampus -- the brain's essential memory hub -- were activated during the wake retrieval of sleep-learned vocabulary because these brain structures normally mediate wake learning of new vocabulary," says Marc Züst, co-first-author of this paper. "These brain structures appear to mediate memory formation independently of the prevailing state of consciousness -- unconscious during deep sleep, conscious during wakefulness."
Memory formation does not require consciousness
Besides its practical relevance, this new evidence for sleep-learning challenges current theories of sleep and theories of memory. The notion of sleep as an encapsulated mental state, in which we are detached from the physical environment is no longer tenable. "We could disprove that sophisticated learning be impossible during deep sleep," says Simon Ruch, co-first-author. The current results underscore a new theoretical notion of the relationship between memory and consciousness that Katharina Henke published in 2010 (Nature Reviews Neuroscience). "In how far and with what consequences deep sleep can be utilized for the acquisition of new information will be a topic of research in upcoming years," says Katharina Henke.
•Humans can encode verbal associative information (word pairs) during slow-wave sleep
•Memory was best for pairs that were encoded in sync with ongoing slow-wave peaks
•Slow-wave sleep appears to entail windows of opportunity for synaptic potentiation
•The hippocampus mediated retrieval, suggesting episodic memory formation during sleep
Learning while asleep is a dream of mankind, but is often deemed impossible because sleep lacks the conscious awareness and neurochemical milieu thought to be necessary for learning. Current evidence for sleep learning in humans is inconclusive. To explore conditions under which verbal learning might occur, we hypothesized that peaks of slow waves would be conducive to verbal learning because the peaks define periods of neural excitability. While in slow-wave sleep during a nap, a series of word pairs comprising pseudowords, e.g., “tofer,” and actual German words, e.g., “Haus” (house), were played to young German-speaking women and men. When the presentation of the second word of a pair (e.g., “Haus” of “tofer-house”) coincided with an ongoing slow-wave peak, the chances increased that a new semantic association between the pair had been formed and retained. Sleep-formed associations translated into awake ones, where they guided forced choices on an implicit memory test. Reactivations of sleep-formed associations were mirrored by brain activation increases measured with fMRI in cortical language areas and the hippocampus, a brain structure critical for relational binding. We infer that implicit relational binding had occurred during peaks of slow oscillations, recruiting a hippocampal-neocortical network comparable to vocabulary learning in the waking state.
selective modulation of cortical state during spatial attention
t. a. engel, n. a. steinmetz, m. a. gieselmann, a. thiele, t. moore, k. boahen 2016
science.aag1420
animals harmed in this experiment
Attention changes local brain activity
There is a well-known correlation between arousal and neuronal activity in the brain. However, it is unclear how these general effects are reflected on a local scale. Engel et al. recorded from higher visual areas in behaving monkeys and discovered a new principle of cortical state fluctuations. A special type of electrodes revealed that the state changes affected neuronal excitability across all layers of the neocortex. When the animals attended to a stimulus, the vigorous spiking states became longer and the faint spiking states became shorter. These states correlated with fluctuations in the local field potential. A sophisticated computational model of the state changes fitted a two-state model of neuronal responsiveness.
Neocortical activity is permeated with endogenously generated fluctuations, but how these dynamics affect goal-directed behavior remains a mystery. We found that ensemble neural activity in primate visual cortex spontaneously fluctuated between phases of vigorous (On) and faint (Off) spiking synchronously across cortical layers. These On-Off dynamics, reflecting global changes in cortical state, were also modulated at a local scale during selective attention. Moreover, the momentary phase of local ensemble activity predicted behavioral performance. Our results show that cortical state is controlled locally within a cortical map according to cognitive demands and reveal the impact of these local changes in cortical state on goal-directed behavior.
memory refreshing in stage 2
memory consolidation is linked to spindle-mediated information processing during sleep
scott a. cairney et al. 2018
http://dx.doi.org/10.1016/j.cub.2018.01.087
(a proposal of) how memory replay in sleep boosts creative problem-solving
penelope lewis et al. 2018
http://dx.doi.org/10.1016/j.tics.2018.03.009
lack of sleep and adhd
eunetworkadultadhd.com/are-you-a-night-owl-about-adhd-and-late-sleep/
sensitivity of the circadian system to evening bright light in preschool-age children
lameese d. akacem et al. 2018
http://dx.doi.org/10.14814/phy2.13617
genome-wide analysis of insomnia disorder
murray b. stein et al. 2018
http://dx.doi.org/10.1038/s41380-018-0033-5
sleep duration, brain structure, and psychiatric and cognitive problems in children
wei cheng et al. 2020
http://dx.doi.org/10.1038/s41380-020-0663-2
depression, anxiety, impulsive behaviour and poor cognitive performance in the children were associated with shorter sleep duration. Moreover, the depressive problems were associated with short sleep duration one year later.
Lower brain volume of brain areas involved the orbitofrontal cortex, prefrontal and temporal cortex, precuneus, and supramarginal gyrus was found to be associated with the shorter sleep duration by using big data analysis approach.
Professor Jianfeng Feng, from the University of Warwick’s Department of Computer Science comments:
“The recommended amount of sleep for children 6 to 12 years of age is 9-12 hours. However, sleep disturbances are common among children and adolescents around the world due to the increasing demand on their time from school, increased screen time use, and sports and social activities.
A previous study showed that about 60% of adolescents in the United States receive less than eight hours of sleep on school nights.
“Our findings showed that the behaviour problems total score for children with less than 7 hours sleep was 53% higher on average and the cognitive total score was 7.8% lower on average than for children with 9-11 hours of sleep. It highlights the importance of enough sleep in both cognition and mental health in children.”
abstract Low sleep duration in adults is correlated with psychiatric and cognitive problems. We performed for the first time a large-scale analysis of sleep duration in children, and how this relates to psychiatric problems including depression, to cognition, and to brain structure. Structural MRI was analyzed in relation to sleep duration, and psychiatric and cognitive measures in 11,067 9–11-year-old children from the Adolescent Brain Cognitive Development (ABCD) Study, using a linear mixed model, mediation analysis, and structural equation methods in a longitudinal analysis. Dimensional psychopathology (including depression, anxiety, impulsive behavior) in the children was negatively correlated with sleep duration. Dimensional psychopathology in the parents was also correlated with short sleep duration in their children. The brain areas in which higher volume was correlated with longer sleep duration included the orbitofrontal cortex, prefrontal and temporal cortex, precuneus, and supramarginal gyrus. Longitudinal data analysis showed that the psychiatric problems, especially the depressive problems, were significantly associated with short sleep duration 1 year later. Further, mediation analysis showed that depressive problems significantly mediate the effect of these brain regions on sleep. Higher cognitive scores were associated with higher volume of the prefrontal cortex, temporal cortex, and medial orbitofrontal cortex. Public health implications are that psychopathology in the parents should be considered in relation to sleep problems in children. Moreover, we show that brain structure is associated with sleep problems in children, and that this is related to whether or not the child has depressive problems.
the effects of improving sleep on mental health (OASIS): a randomised controlled trial with mediation analysis
daniel freeman et al. 2017
dx.doi.org/10.1016/S2215-0366(17)30328-0
Sleep difficulties might be a contributory causal factor in the occurrence of mental health problems. If this is true, improving sleep should benefit psychological health. We aimed to determine whether treating insomnia leads to a reduction in paranoia and hallucinations.
paranoia as a deficit in non-social belief updating
erin j reed et al. 2020
dx.doi.org/10.7554/eLife.56345
“When our world changes unexpectedly, we want to blame that volatility on somebody, to make sense of it, and perhaps neutralize it,’’ said Yale’s Philip Corlett, associate professor of psychiatry and senior author of the study. “Historically in times of upheaval, such as the great fire of ancient Rome in 64 C.E. or the 9/11 terrorist attacks, paranoia and conspiratorial thinking increased.”
Paranoia is a key symptom of serious mental illness, marked by the belief that other people have malicious intentions. But it also manifests in varying degrees in the general population. For instance, one previous survey found that 20% of the population believed people were against them at some time during the past year; 8% believed that others were actively out to harm them.
The prevailing theory is that paranoia stems from an inability to accurately assess social threats. But Corlett and lead author Erin Reed of Yale hypothesized that paranoia is instead rooted in a more basic learning mechanism that is triggered by uncertainty, even in the absence of social threat.
“We think of the brain as a prediction machine; unexpected change, whether social or not, may constitute a type of threat — it limits the brain’s ability to make predictions,” Reed said. “Paranoia may be a response to uncertainty in general, and social interactions can be particularly complex and difficult to predict.”
In a series of experiments, they asked subjects with different degrees of paranoia to play a card game in which the best choices for success were changed secretly. People with little or no paranoia were slow to assume that the best choice had changed. However, those with paranoia expected even more volatility in the game. They changed their choices capriciously — even after a win. The researchers then increased the levels of uncertainty by changing the chances of winning halfway through the game without telling the participants. This sudden change made even the low-paranoia participants behave like those with paranoia, learning less from the consequences of their choices.
In a related experiment, Yale collaborators Jane Taylor and Stephanie Groman trained rats, a relatively asocial species, to complete a similar task where best choices of success changed. Rats who were administered methamphetamine — known to induce paranoia in humans — behaved just like paranoid humans. They, too, anticipated high volatility and relied more on their expectations than learning from the task.
Reed, Corlett and their team then used a mathematical model to compare choices made by rats and humans while performing these similar tasks. The results from the rats that received methamphetamine resembled those of humans with paranoia, researchers found.
“Our hope is that this work will facilitate a mechanistic explanation of paranoia, a first step in the development of new treatments that target those underlying mechanisms,” Corlett said.
“The benefit of seeing paranoia through a non-social lens is that we can study these mechanisms in simpler systems, without needing to recapitulate the richness of human social interaction,” Reed said.
abstract Paranoia is the belief that harm is intended by others. It may arise from selective pressures to infer and avoid social threats, particularly in ambiguous or changing circumstances. We propose that uncertainty may be sufficient to elicit learning differences in paranoid individuals, without social threat. We used reversal learning behavior and computational modeling to estimate belief updating across individuals with and without mental illness, online participants, and rats chronically exposed to methamphetamine, an elicitor of paranoia in humans. Paranoia is associated with a stronger prior on volatility, accompanied by elevated sensitivity to perceived changes in the task environment. Methamphetamine exposure in rats recapitulates this impaired uncertainty-driven belief updating and rigid anticipation of a volatile environment. Our work provides evidence of fundamental, domain-general learning differences in paranoid individuals. This paradigm enables further assessment of the interplay between uncertainty and belief-updating across individuals and species.
the mediating role of sleep in the fish consumption – cognitive functioning relationship: a cohort study
jianghong liu et al. 2017
http://dx.doi.org/10.1038/s41598-017-17520-w
the link between maternal sleep and permissive parenting during late adolescence
kelly m. tu et al. 2018
http://dx.doi.org/10.1111/jsr.12676
why we sleep
matthew walker 2017
sleep loss causes social withdrawal and loneliness
eti ben simon, matthew p. walker 2018
http://dx.doi.org/10.1038/s41467-018-05377-0
sleep and human aging
mander et al. 2017
dx.doi.org/10.1016/j.neuron.2017.02.004
sleep increases chromosome dynamics to enable reduction of accumulating dna damage in single neurons
d. zada et al. 2019
http://dx.doi.org/10.1038/s41467-019-08806-w
The role of sleep is to increase chromosome dynamics, and normalize the levels of DNA damage in each single neuron. Apparently, this DNA maintenance process is not efficient enough during the online wakefulness period and requires an offline sleep period with reduced input to the brain in order to occur. "It's like potholes in the road," says Prof. Lior Appelbaum, of Bar-Ilan University's Mina and Everard Goodman Faculty of Life Sciences and Gonda (Goldschmied) Multidisciplinary Brain Research Center, who led the study. "Roads accumulate wear and tear, especially during daytime rush hours, and it is most convenient and efficient to fix them at night, when there is light traffic."
Appelbaum calls the accumulation of DNA damage the "price of wakefulness." He and his doctoral student David Zada, first author of the study, as well as co-authors, Dr. Tali Lerer-Goldshtein, Dr. Irina Bronshtein, and Prof. Yuval Garini, hypothesized that sleep consolidates and synchronizes nuclear maintenance within individual neurons, and set out to confirm this theory.
Their discovery was achieved thanks to the characteristics of the zebrafish model. With their absolute transparency, and a brain very similar to humans, zebrafish are a perfect organism in which to study single cell within a live animal under physiological conditions. Using a high resolution microscope, the movement of DNA and nuclear proteins within the cell -- inside the fish -- can be observed while the fish are awake and asleep. The researchers were particularly surprised to find that chromosomes are more active at night, when the body rests, but this increased activity enables the efficiency of the repair to DNA damage.
The results establish chromosome dynamics as a potential marker for defining single sleeping cells and propose that the restorative function of sleep is nuclear maintenance. "We've found a causal link between sleep, chromosome dynamics, neuronal activity, and DNA damage and repair with direct physiological relevance to the entire organism," says Prof. Appelbaum. "Sleep gives an opportunity to reduce DNA damage accumulated in the brain during wakefulness."
"Despite the risk of reduced awareness to the environment, animals -- ranging from jellyfish to zebrafish to humans -- have to sleep to allow their neurons to perform efficient DNA maintenance, and this is possibly the reason why sleep has evolved and is so conserved in the animal kingdom," concludes Prof. Appelbaum
abstract Sleep is essential to all animals with a nervous system. Nevertheless, the core cellular function of sleep is unknown, and there is no conserved molecular marker to define sleep across phylogeny. Time-lapse imaging of chromosomal markers in single cells of live zebrafish revealed that sleep increases chromosome dynamics in individual neurons but not in two other cell types. Manipulation of sleep, chromosome dynamics, neuronal activity, and DNA double-strand breaks (DSBs) showed that chromosome dynamics are low and the number of DSBs accumulates during wakefulness. In turn, sleep increases chromosome dynamics, which are necessary to reduce the amount of DSBs. These results establish chromosome dynamics as a potential marker to define single sleeping cells, and propose that the restorative function of sleep is nuclear maintenance.
spike-based functional connectivity in cerebral cortex and hippocampus: loss of global connectivity is coupled to preservation of local connectivity during non-rem sleep
u. olcese et al. 2017
http://dx.doi.org/10.1523/jneurosci.4201-15.2016
old brains come uncoupled in sleep: slow wave-spindle synchrony, brain atrophy, and forgetting
randolph f. helfrich et al. 2017
http://dx.doi.org/10.1016/j.neuron.2017.11.020
•Precise coupling of NREM slow waves and spindles dictates memory consolidation
•Aging impairs slow wave-spindle coupling, leading to overnight forgetting
•Age-related atrophy in mPFC predicts the failure of such coupling and thus memory
The coupled interaction between slow-wave oscillations and sleep spindles during non-rapid-eye-movement (NREM) sleep has been proposed to support memory consolidation. However, little evidence in humans supports this theory. Moreover, whether such dynamic coupling is impaired as a consequence of brain aging in later life, contributing to cognitive and memory decline, is unknown. Combining electroencephalography (EEG), structural MRI, and sleep-dependent memory assessment, we addressed these questions in cognitively normal young and older adults. Directional cross-frequency coupling analyses demonstrated that the slow wave governs a precise temporal coordination of sleep spindles, the quality of which predicts overnight memory retention. Moreover, selective atrophy within the medial frontal cortex in older adults predicted a temporal dispersion of this slow wave-spindle coupling, impairing overnight memory consolidation and leading to forgetting. Prefrontal-dependent deficits in the spatiotemporal coordination of NREM sleep oscillations therefore represent one pathway explaining age-related memory decline
duration and timing of sleep are associated with repetitive negative thinking
jacob a. nota, meredith e. coles 2014
http://dx.doi.org/10.1007/s10608-014-9651-7
workplace incivility and employee sleep: the role of rumination and recovery experiences
caitlin a. demsky et al. 2018
http://dx.doi.org/10.1037/ocp0000116
sleepy anger: restricted sleep amplifies angry feelings
zlatan krizan, garrett hisler 2018
http://dx.doi.org/10.1037/xge0000522
dose-dependent associations between sleep duration and unsafe behaviors among us high school students
matthew d. weaver et al. 2018
http://dx.doi.org/10.1001/jamapediatrics.2018.2777
“We found the odds of unsafe behavior by high school students increased significantly with fewer hours of sleep,” said lead author Mathew Weaver, PhD, research fellow, Division of Sleep and Circadian Disorders, Brigham and Women’s Hospital. “Personal risk-taking behaviors are common precursors to accidents and suicides, which are the leading causes of death among teens and have important implications for the health and safety of high school students nationally.”
Compared to students who reported sleeping eight hours at night, high school students who slept less than six hours were twice as likely to self-report using alcohol, tobacco, marijuana or other drugs, and driving after drinking alcohol. They were also nearly twice as likely to report carrying a weapon or being in a fight. Researchers found the strongest associations were related to mood and self- harm. Those who slept less than six hours were more than three times as likely to consider or attempt suicide, and four times as likely to attempt suicide, resulting in treatment. Only 30 percent of the students in the study reported averaging more than eight hours of sleep on school nights.
The Youth Risk Behavior Surveys are administered biannually by the U.S. Centers for Disease Control and Prevention (CDC) at public and private schools across the country. Researchers used data from 67,615 high school students collected between 2007 and 2015. Personal safety risk-taking behaviors were examined individually and as composite categories. All analyses were weighted to account for the complex survey design and controlled for age, sex, race, and year of survey in mathematical models to test the association between sleep duration and each outcome of interest.
“Insufficient sleep in youth raises multiple public health concerns, including mental health, substance abuse, and motor vehicle crashes,” said senior author Elizabeth Klerman, MD, PhD, director of the Analytic Modeling Unit, Division of Sleep and Circadian Disorders, Brigham and Women’s Hospital. “More research is needed to determine the specific relationships between sleep and personal safety risk-taking behaviors. We should support efforts to promote healthy sleep habits and decrease barriers to sufficient sleep in this vulnerable population.”
abstract Youths in America are sleeping less than ever before. More than 70% of high school students average less than 8 hours of sleep,1 falling short of the 8 to 10 hours that adolescents need for optimal health.2 Insufficient sleep negatively affects learning and development and acutely alters judgment, particularly among youths.3 We estimated associations between sleep duration and personal safety risk-taking behaviors in US high school students.
effects of total sleep deprivation on procedural placekeeping: more than just lapses of attention
michelle e. stepan et al. 2019
http://dx.doi.org/10.1037/xge0000717
first to assess how sleep deprivation impacts placekeeping — or, the ability to complete a series of steps without losing one’s place, despite potential interruptions. This study builds on prior research from MSU’s sleep scientists to quantify the effect lack of sleep has on a person’s ability to follow a procedure and maintain attention.
“Our research showed that sleep deprivation doubles the odds of making placekeeping errors and triples the number of lapses in attention, which is startling,” Fenn said. “Sleep-deprived individuals need to exercise caution in absolutely everything that they do, and simply can’t trust that they won’t make costly errors. Oftentimes — like when behind the wheel of a car — these errors can have tragic consequences.”
By sharing their findings on the separate effects sleep deprivation has on cognitive function, Fenn — and co-authors Michelle Stepan, MSU doctoral candidate and Erik Altmann, professor of psychology — hope that people will acknowledge how significantly their abilities are hindered because of a lack of sleep.
“Our findings debunk a common theory that suggests that attention is the only cognitive function affected by sleep deprivation,” Stepan said. “Some sleep-deprived people might be able to hold it together under routine tasks, like a doctor taking a patient’s vitals. But our results suggest that completing an activity that requires following multiple steps, such as a doctor completing a medical procedure, is much riskier under conditions of sleep deprivation.”
The researchers recruited 138 people to participate in the overnight sleep assessment; 77 stayed awake all night and 61 went home to sleep. All participants took two separate cognitive tasks in the evening: one that measured reaction time to a stimulus; the other measured a participant’s ability to maintain their place in a series of steps without omitting or repeating a step — even after sporadic interruptions. The participants then repeated both tasks in the morning to see how sleep-deprivation affected their performance.
“After being interrupted there was a 15% error rate in the evening and we saw that the error rate spiked to about 30% for the sleep-deprived group the following morning,” Stepan said. “The rested participants’ morning scores were similar to the night before.
“There are some tasks people can do on auto-pilot that may not be affected by a lack of sleep,” Fenn said. “However, sleep deprivation causes widespread deficits across all facets of life.”
abstract Total sleep deprivation (TSD) impairs attention as well as higher-order cognitive processes. Because attention is a core component of many tasks, it may fully mediate the effect of sleep deprivation on higher-order processes. We examined this possibility using the Psychomotor Vigilance Task as a measure of attention and the UNRAVEL task as a measure of placekeeping, a higher-order process that involves memory operations and supports performance in a wide range of complex tasks. A large sample of participants (N = 138 contributing data) performed the Psychomotor Vigilance Task and UNRAVEL under rested or sleep-deprived conditions. TSD impaired placekeeping generally and memory maintenance processes specifically, above and beyond the effect of participants’ attentional state. The results suggest that TSD may impair a range of higher-order cognitive processes directly, not just fundamental processes such as attention, and that interventions that benefit attention may have limited scope.
measures of poor sleep quality are associated with higher energy intake and poor diet quality in a diverse sample of women from the go red for women strategically focused research network
faris m. zuraikat et al. 2020
http://dx.doi.org/10.1161/jaha.119.014587
Previous studies have shown that people who get less sleep are more likely to develop obesity, type 2 diabetes, and heart disease — and that the relationship may be partially explained by diet. But these studies were narrowly focused on specific foods or nutrients (such as fish, sweets, or saturated fat) or only measured sleep duration, not sleep quality.
The new study was designed to get a more comprehensive picture in women by examining associations between overall diet quality and multiple aspects of sleep quality.
“Women are particularly prone to sleep disturbances across the life span, because they often shoulder the responsibilities of caring for children and family and, later, because of menopausal hormones,” says Brooke Aggarwal, EdD, assistant professor of medical sciences at Columbia University Vagelos College of Physicians and Surgeons and senior author of the study.
The study of nearly 500 women was published online today in the Journal of the American Heart Association.
The researchers analyzed the sleep and eating habits of an ethnically diverse group of 495 women, ages 20 to 76. The study looked at sleep quality, the time it took to fall asleep, and insomnia. The women also reported on the types and amounts of foods they typically eat throughout the year, allowing researchers to measure their typical dietary patterns.
Similar to previous studies of sleep and diet, the study found that those with worse overall sleep quality consumed more of the added sugars associated with obesity and diabetes.
Women who took longer to fall asleep had higher caloric intake and ate more food by weight.
And women with more severe insomnia symptoms consumed more food by weight and fewer unsaturated fats than women with milder insomnia.
“Our interpretation is that women with poor-quality sleep could be overeating during subsequent meals and making more unhealthy food choices,” says Aggarwal.
The question remains: How might poor sleep contribute to poor eating?
“Poor sleep quality may lead to excessive food and calorie intake by stimulating hunger signals or suppressing signals of fullness,” says Faris Zuraikat, PhD, postdoctoral fellow at Columbia University Vagelos College of Physicians and Surgeons and lead author of the study. “Fullness is largely affected by the weight or volume of food consumed, and it could be that women with insomnia consume a greater amount of food in an effort to feel full.
“However, it’s also possible that poor diet has a negative impact on women’s sleep quality,” adds Zuraikat. “Eating more could also cause gastrointestinal discomfort, for instance, making it harder to fall asleep or remain asleep.”
“Given that poor diet and overeating may lead to obesity — a well-established risk factor for heart disease — future studies should test whether therapies that improve sleep quality can promote cardiometabolic health in women,” says Aggarwal.
abstract Poor sleep increases cardiovascular disease risk, and diet likely contributes to this relationship. However, there are limited epidemiological data on the relationship between measures of sleep quality and habitual dietary patterns. This study examined these associations in a diverse sample of women.
Methods and Results
Baseline data from 495 participants in the AHA Go Red for Women prospective cohort study (age: 20–76 years; 61% racial/ethnic minority) were examined. Sleep quality and sleep‐onset latency were measured using the Pittsburgh Sleep Quality Index (PSQI) and insomnia using the Insomnia Severity Index. The validated Block Brief Food Frequency Questionnaire was used to assess diet quantity and quality. Linear regression models adjusted for confounding variables tested relationships between sleep and diet variables. Results showed that higher PSQI scores, indicative of poorer sleep quality, were associated with lower unsaturated fat intake (β=−0.14, P<0.05) and higher food weight (β=14.9, P=0.02) and added sugars consumed (β=0.44, P=0.04). Women with sleep‐onset latency >60 minutes had higher intakes of food by weight (β=235.2, _P<_0.01) and energy (β=426, P<0.01), and lower intakes of whole grains (β=−0.37, P=0.01) than women with sleep‐onset latency ≤15 minutes. Greater insomnia severity was associated with higher food weight (β=9.4, P=0.02) and energy (β=17, P=0.01) consumed and lower total (β=−0.15, P=0.01) and unsaturated fat intakes (β=−0.11, P<0.01).
Conclusions
Poor sleep quality was associated with greater food intake and lower‐quality diet, which can increase cardiovascular disease risk. Future studies should test whether promoting sleep quality could augment efforts to improve cardiometabolic health in women.
the effects of bedtime writing on difficulty falling asleep: a polysomnographic study comparing to-do lists and completed activity lists
michael k. scullin et al. 2017
http://dx.doi.org/10.1037/xge0000374
peace of mind and anxiety in the waking state are related to the affective content of dreams
pilleriin sikka et al. 2018
http://dx.doi.org/10.1038/s41598-018-30721-1
lucid dreaming
https://aeon.co/ideas/the-lucid-dreaming-playbook-how-to-take-charge-of-your-dreams
reality testing and the mnemonic induction of lucid dreams: findings from the national australian lucid dream induction study
aspy, d. j. et al. 2017
https://www.researchgate.net/
effects of vitamin b6 (pyridoxine) and a b complex preparation on dreaming and sleep
denholm j. aspy et al. 2018
http://dx.doi.org/10.1177/0031512518770326
pre-sleep treatment with galantamine stimulates lucid dreaming: a double-blind, placebo-controlled, crossover study
stephen laberge et al. 2018
https://doi.org/10.1371/journal.pone.0201246
temperature
the effect of a cold environment on sleep and thermoregulation with insufficient bedding assuming an emergency evacuation
kazuyo tsuzuki et al. 2019
http://dx.doi.org/10.1016/j.enbuild.2019.109562
disasters, with more people being forced to live in shelters and temporary housing. The Japanese Cabinet Office has published guidelines for managing evacuation shelters with reference to efforts in the Sphere Project, but these guidelines provide no detailed instructions regarding power outages or necessary bedding and heating. Evacuation shelters are often large and have an uneven distribution of heat inside them. Power outages can also be expected, which can mean a lack of heating and a drop in temperature at the shelter. The Architecture and Building Environment Laboratory saw a need to study how people live and sleep at shelters and temporary housing, and to investigate the effect of power outages. The laboratory created a mock evacuation shelter in the school gymnasium, and compared the quality of sleep at this shelter with that of subjects’ own beds.
The results of the study indicate that emergency bedding did not provide sufficient thermal insulation, even when four of the emergency blankets were used from the stocked supply at the gymnasium. In terms of sleep quality, sleep efficiency decreased by 10% or more and fatigue increased compared to when subjects slept in their own beds. Details of this research has been published in the journal, Energy and Buidings on November 4th.
This study was performed in the gymnasium in winter, and it was found that the low temperature (5°C) inside the gymnasium adversely affected sleep, decreasing sleep efficiency by 10% when using basic emergency blankets that provide limited insulation. Further activities going forward include looking into providing down jackets to wear in addition to the emergency blankets, as well as other realistic ways to help regulate body temperature and improve sleep in order to prevent deterioration in people’s quality of sleep at low temperatures.
abstract •Sleep quality investigation in a gymnasium using a pair of mattresses or four disaster blankets
•"Blankets" and "Futon" provided insulation of 1.3clo and 3.1clo respectively
•Sleep efficiency indices decreased due to increased wakefulness during the night
•Skin temperature at foot decreased during sleep in "Blankets" at 5°C in the night
•Mean skin temperature decreased significantly in "Blankets" as compared to "Futon"
•Body heat storage had a good correlation with thermal sensation after waking up
•The insufficient insulation of bedding impaired sleep quality in the cold nights
The aim of this study is to investigate the effects of a cold environment on sleep, thermoregulatory responses, and subjective sensations during sleep in winter using disaster relief blankets (Blankets) and ordinary futons (Futon). The clo insulations of Blankets and Futon were 1.3 clo and 3.1clo respectively, measured using a thermal manikin in advance. The average air temperature in the gymnasium before going to bed was about 5.9°C, while at dawn it was about 3.6°C. The sleep efficiency index, which was measured by actigraphy, decreased significantly in the first night when using Blankets (85%) compared to Futon (94%). The average microclimate temperature between the human body and the bedding was 21.4°C for Blankets and 23.5°C for Futon. The mean skin temperature was significantly lower for sleeping times using Blankets (32°C) than when using Futon (32.8°C). However, no significant differences in rectal temperature and heart rate were found between the Blankets and Futon. After sleep, the participants felt significantly colder for whole body and upper body when using Blankets than Futon. Sleeping in a low temperature environment using insufficient bedding such as a disaster blanket significantly lowers the mean skin temperature by decreasing skin temperature at the distal end and back. Especially, regarding the first night of an emergency evacuation, it became clear that even in healthy young boys, sleep was disturbed in low temperature environments.
colour
a color vision circuit for non-image-forming vision in the primate retina
sara s. patterson et al. 2020
http://dx.doi.org/10.1016/j.cub.2020.01.040
identifies a cell in the retina, which plays an important role in signaling our brain centers that regulate circadian rhythms, boost alertness, help memory and cognitive function, and elevate mood.
These effects have been attributed to a pigment in the eye called melanopsin, which is sensitive to blue light, but researchers say cone photoreceptors are a thousand times more sensitive to light than melanopsin. The cone photoreceptor inputs to the circadian circuity respond to short wavelength blue light, but they also respond strongly to long wavelength oranges and yellows and contrasting light — the colors at sunrise and sunset. What makes good lighting, researchers discovered, is lighting capable of stimulating the cone photoreceptor inputs to specific neurons in the eye that regulate circadian rhythms.
Lead author Sara Patterson, a graduate student in neuroscience at the University of Washington School of Medicine, said how we set our internal clocks to the external light-dark cycle has been studied a lot. But how the changes in the color of light affect our brain has not.
“Color vision used for something other than color perception was the most exciting part for me,” she said.
In the study, Patterson and colleagues identified a cell known as an inhibitory interneuron or amacrine cell in the retina, which signals to photosensitive ganglion cells that affect our circadian brain centers. The researchers said these amacrine cells provide “the missing component of an evolutionary ancient color vision circuit capable of setting the circadian clock by encoding the spectral content of light.”
Patterson said so little is known about rare retinal circuitry that it was possible to find a new blue cone cell. She said there is a lot more to be discovered about how blue cone cells are projecting to other areas of the brain.
While sunrise lights, blue lights and seasonal affective disorder (SAD) lights have all tried to capture benefits of natural light, they haven’t been that effective because they are missing key science data, said corresponding author Jay Neitz, professor of ophthalmology at the UW School of Medicine, a scientist at the UW Medicine Eye Institute, and a well-known color vision researcher. He said the science behind SAD lights, for example, is to make lights hundreds of times brighter than normal lights to stimulate melanopsin.
“This research all started because of our interest in the health benefits of having natural light that occurs at the right time of day that helps regulate our circadian clock and our mood and alertness,” Neitz said.
The University of Washington has licensed technology based on this discovery to TUO, a lighting technology company that will be selling white LED lightbulbs that will incorporate undetectable sunrise and sunset wavelengths for commercial use.
abstract •3D reconstruction of the S-cone connectome revealed S-cone selective amacrine cells
•S-cone amacrine cells receive excitatory input from only S-cone ON bipolar cells
•S-cone amacrine cells make targeted inhibitory synapses onto ipRGCs
•Resulting short-wavelength sensitivity is distinct from that mediated by melanopsin
Melanopsin-expressing, intrinsically photosensitive retinal ganglion cells (ipRGCs) synchronize our biological clocks with the external light/dark cycle 1. In addition to photoentrainment, they mediate the effects of light experience as a central modulator of mood, learning, and health 2. This makes a complete account of the circuity responsible for ipRGCs’ light responses essential to understanding their diverse roles in our well-being. Considerable progress has been made in understanding ipRGCs’ melanopsin-mediated responses in rodents [3, 4, 5]. However, in primates, ipRGCs also have a rare blue-OFF response mediated by an unknown short-wavelength-sensitive (S)-cone circuit 6. Identifying this S-cone circuit is particularly important because ipRGCs mediate many of the wide-ranging effects of short-wavelength light on human biology. These effects are often attributed to melanopsin, but there is evidence for an S-cone contribution as well [7, 8]. Here, we tested the hypothesis that the S-OFF response is mediated by the S-ON pathway through inhibitory input from an undiscovered S-cone amacrine cell. Using serial electron microscopy in the macaque retina, we reconstructed the neurons and synapses of the S-cone connectome, revealing a novel inhibitory interneuron, an amacrine cell, receiving excitatory glutamatergic input exclusively from S-ON bipolar cells. This S-cone amacrine cell makes highly selective inhibitory synapses onto ipRGCs, resulting in a blue-OFF response. Identification of the S-cone amacrine cell provides the missing component of an evolutionarily ancient circuit using spectral information for non-image forming visual functions.
cyan
exploiting metamerism to regulate the impact of a visual display on alertness and melatonin suppression independent of visual appearance
annette allen et al. 2018
http://dx.doi.org/10.1093/sleep/zsy100
anxiety
overanxious and underslept
eti ben simon et al. 2019
http://dx.doi.org/10.1038/s41562-019-0754-8
identified a new function of deep sleep, one that decreases anxiety overnight by reorganizing connections in the brain," said study senior author Matthew Walker, a UC Berkeley professor of neuroscience and psychology. "Deep sleep seems to be a natural anxiolytic (anxiety inhibitor), so long as we get it each and every night."
The findings, published today, Nov. 4, in the journal Nature Human Behaviour, provide one of the strongest neural links between sleep and anxiety to date. They also point to sleep as a natural, non-pharmaceutical remedy for anxiety disorders, which have been diagnosed in some 40 million American adults and are rising among children and teens.
"Our study strongly suggests that insufficient sleep amplifies levels of anxiety and, conversely, that deep sleep helps reduce such stress," said study lead author Eti Ben Simon, a postdoctoral fellow in the Center for Human Sleep Science at UC Berkeley.
In a series of experiments using functional MRI and polysomnography, among other measures, Simon and fellow researchers scanned the brains of 18 young adults as they viewed emotionally stirring video clips after a full night of sleep, and again after a sleepless night. Anxiety levels were measured following each session via a questionnaire known as the state-trait anxiety inventory.
After a night of no sleep, brain scans showed a shutdown of the medial prefrontal cortex, which normally helps keep our anxiety in check, while the brain's deeper emotional centers were overactive.
"Without sleep, it's almost as if the brain is too heavy on the emotional accelerator pedal, without enough brake," Walker said.
After a full night of sleep, during which participants' brain waves were measured via electrodes placed on their heads, the results showed their anxiety levels declined significantly, especially for those who experienced more slow-wave NREM sleep.
"Deep sleep had restored the brain's prefrontal mechanism that regulates our emotions, lowering emotional and physiological reactivity and preventing the escalation of anxiety," Simon said.
Beyond gauging the sleep-anxiety connection in the 18 original study participants, the researchers replicated the results in a study of another 30 participants. Across all the participants, the results again showed that those who got more nighttime deep sleep experienced the lowest levels of anxiety the next day.
Moreover, in addition to the lab experiments, the researchers conducted an online study in which they tracked 280 people of all ages about how both their sleep and anxiety levels changed over four consecutive days.
The results showed that the amount and quality of sleep the participants got from one night to the next predicted how anxious they would feel the next day. Even subtle nightly changes in sleep affected their anxiety levels.
"People with anxiety disorders routinely report having disturbed sleep, but rarely is sleep improvement considered as a clinical recommendation for lowering anxiety," Simon said. "Our study not only establishes a causal connection between sleep and anxiety, but it identifies the kind of deep NREM sleep we need to calm the overanxious brain."
On a societal level, "the findings suggest that the decimation of sleep throughout most industrialized nations and the marked escalation in anxiety disorders in these same countries is perhaps not coincidental, but causally related," Walker said. "The best bridge between despair and hope is a good night of sleep."
abstract Are you feeling anxious? Did you sleep poorly last night? Sleep disruption is a recognized feature of all anxiety disorders. Here, we investigate the basic brain mechanisms underlying the anxiogenic impact of sleep loss. Additionally, we explore whether subtle, societally common reductions in sleep trigger elevated next-day anxiety. Finally, we examine what it is about sleep, physiologically, that provides such an overnight anxiety-reduction benefit. We demonstrate that the anxiogenic impact of sleep loss is linked to impaired medial prefrontal cortex activity and associated connectivity with extended limbic regions. In contrast, non-rapid eye movement (NREM) slow-wave oscillations offer an ameliorating, anxiolytic benefit on these brain networks following sleep. Of societal relevance, we establish that even modest night-to-night reductions in sleep across the population predict consequential day-to-day increases in anxiety. These findings help contribute to an emerging framework explaining the intimate link between sleep and anxiety and further highlight the prospect of non-rapid eye movement sleep as a therapeutic target for meaningfully reducing anxiety.
a hippocampal network for spatial coding during immobility and sleep
kenneth kay et al. 2018
http://dx.doi.org/10.1038/nature17144
“In consolidation, the hippocampal neural circuits send “sharp wave ripples” (SWRs) to regions of the neocortex. It really shouldn’t be a surprise that neuroscientists have found that an SWR duplicates the pattern of theta wave firing in the hippocampus. The surprise is that the pattern is compressed 10 times or more, from the second it took when it first occurred into milliseconds (Kay et al., 2016). The sharp wave ripple stimulates neural circuits in the much larger neocortex to take on the same pattern and theta wave firing rate that the place cell neural circuits did.”
alzheimers
the sleep-wake cycle regulates brain interstitial fluid tau in mice and csf tau in humans
holth jk et al. 2019
http://dx.doi.org/10.1126/science.aav2546
sleep deprivation increases levels of the key Alzheimer's protein tau. And, in follow-up studies in the mice, the research team has shown that sleeplessness accelerates the spread through the brain of toxic clumps of tau - a harbinger of brain damage and decisive step along the path to dementia.
These findings, published online Jan. 24 in the journal Science, indicate that lack of sleep alone helps drive the disease, and suggests that good sleep habits may help preserve brain health.
"The interesting thing about this study is that it suggests that real-life factors such as sleep might affect how fast the disease spreads through the brain," said senior author David Holtzman, MD, the Andrew B. and Gretchen P. Jones Professor and head of the Department of Neurology. "We've known that sleep problems and Alzheimer's are associated in part via a different Alzheimer's protein -- amyloid beta -- but this study shows that sleep disruption causes the damaging protein tau to increase rapidly and to spread over time."
Tau is normally found in the brain -- even in healthy people -- but under certain conditions it can clump together into tangles that injure nearby tissue and presage cognitive decline. Recent research at the School of Medicine has shown that tau is high in older people who sleep poorly. But it wasn't clear whether lack of sleep was directly forcing tau levels upward, or if the two were associated in some other way. To find out, Holtzman and colleagues including first authors Jerrah Holth, PhD, a staff scientist, and Sarah Fritschi, PhD, a former postdoctoral scholar in Holtzman's lab, measured tau levels in mice and people with normal and disrupted sleep.
Mice are nocturnal creatures. The researchers found that tau levels in the fluid surrounding brain cells were about twice as high at night, when the animals were more awake and active, than during the day, when the mice dozed more frequently. Disturbing the mice's rest during the day caused daytime tau levels to double.
Much the same effect was seen in people. Brendan Lucey, MD, an assistant professor of neurology, obtained cerebrospinal fluid -- which bathes the brain and spinal cord -- from eight people after a normal night of sleep and again after they were kept awake all night. A sleepless night caused tau levels to rise by about 50 percent, the researchers discovered.
Staying up all night makes people stressed and cranky and likely to sleep in the next chance they get. While it's hard to judge the moods of mice, they, too, rebounded from a sleepless day by sleeping more later. To rule out the possibility that stress or behavioral changes accounted for the changes in tau levels, Fritschi created genetically modified mice that could be kept awake for hours at a time by injecting them with a harmless compound. When the compound wears off, the mice return to their normal sleep-wake cycle -- without any signs of stress or apparent desire for extra sleep.
Using these mice, the researchers found that staying awake for prolonged periods causes tau levels to rise. Altogether, the findings suggest that tau is routinely released during waking hours by the normal business of thinking and doing, and then this release is decreased during sleep allowing tau to be cleared away. Sleep deprivation interrupts this cycle, allowing tau to build up and making it more likely that the protein will start accumulating into harmful tangles.
In people with Alzheimer's disease, tau tangles tend to emerge in parts of the brain important for memory -- the hippocampus and entorhinal cortex -- and then spread to other brain regions. As tau tangles mushroom and more areas become affected, people increasingly struggle to think clearly.
To study whether the spread of tau tangles is affected by sleep, the researchers seeded the hippocampi of mice with tiny clumps of tau and then kept the animals awake for long periods each day. A separate group of mice also was injected with tau tangles but was allowed to sleep whenever they liked. After four weeks, tau tangles had spread further in the sleep-deprived mice than their rested counterparts. Notably, the new tangles appeared in the same areas of the brain affected in people with Alzheimer's.
"Getting a good night's sleep is something we should all try to do," Holtzman said. "Our brains need time to recover from the stresses of the day. We don't know yet whether getting adequate sleep as people age will protect against Alzheimer's disease. But it can't hurt, and this and other data suggest that it may even help delay and slow down the disease process if it has begun."
The researchers also found that disrupted sleep increased release of synuclein protein, a hallmark of Parkinson's disease. People with Parkinson's -- like those with Alzheimer's -- often have sleep problems.
abstract The sleep-wake cycle regulates interstitial fluid (ISF) and cerebrospinal (CSF) levels of amyloid-β (Aβ) that accumulates in Alzheimer disease (AD). Furthermore, chronic sleep deprivation (SD) increases Aβ plaques. However, tau, not Aβ, accumulation appears to drive AD neurodegeneration. Here, we tested whether ISF/CSF tau and tau seeding/spreading was influenced by the sleep-wake cycle and SD. Mouse ISF tau was increased ~90% during normal wakefulness vs. sleep and ~100% during SD. Human CSF tau also increased over 50% during SD. In a tau seeding and spreading model, chronic SD increased tau pathology spreading. Chemogenetically-driven wakefulness in mice also significantly increased both ISF Aβ and tau. Thus, the sleep-wake cycle regulates ISF tau and sleep deprivation increases ISF and CSF tau as well as tau pathology spreading.
beyond the sleep-amyloid interactions in alzheimer’s disease pathogenesis
shen ning, mehdi jorfi et al. 2019
http://dx.doi.org/10.1152/jn.00118.2019
Alzheimer's research has largely focused on the presence of two proteins -- amyloid beta and tau -- in the brain. Amyloid beta is thought to be involved with learning and the ability of the brain to change and adapt, and tau helps regulate normal signaling between neuronal cells. People with Alzheimer's disease have been found to have both hallmarks: a buildup of amyloid beta and tau tangles in the brain.
Previous studies in healthy animals and humans have reported higher levels of amyloid beta after a single night of sleep deprivation. This is consistent with normal fluctuation patterns of the protein that occur before sleeping and upon waking. These findings suggest that sleep helps the body eliminate excess amyloid beta before too much accumulates in the brain. Research has also shown that disruption of slow-wave sleep -- a deep sleep phase -- causes amyloid beta levels to rise as much as 30 percent. "This evidence demonstrates the significance of sleep in clearing metabolic waste and sleep disruption as a significant mediator in the development of [Alzheimer's disease]," Shen Ning and Mehdi Jorfi, PhD, the authors of the article, wrote.
The presence of tau -- the protein that is found tangled in the brain of people with Alzheimer's disease -- in the fluid that surrounds the brain and spinal cord (cerebrospinal fluid) is a marker of injury to the nerve cells, the authors explained. Sleep deprivation for as little as one night has been found to increase tau levels by as much as 50 percent in cerebrospinal fluid.
The research suggests that increased production of amyloid beta and tau and reduced elimination of these proteins is the primary contributing factor to Alzheimer's disease. While quality sleep seems to be able to help the body clear excess proteins, "the question remains whether sleep disruption aggravates [Alzheimer's disease] symptoms and augments disease progression, or if sleep disruption actually initiates the cascade of [Alzheimer's disease] development," the researchers wrote.
Continuing study of the relationship between sleep and Alzheimer's disease "holds great promise in bridging the molecular and cellular biology of sleep in context of the development of [Alzheimer's disease]. It may even provide helpful therapeutic benefits in preventing not only [Alzheimer's disease], but also in improving diagnosis and treatments for psychiatric and metabolic diseases," the researchers wrote.
abstract Cognitive impairment in older adults is associated with sleep and circadian rhythm disturbances. Numerous studies have linked disrupted sleep and circadian rhythms with amyloid-β (A&β), a key pathological hallmark in Alzheimer's disease (AD). While previous evidence suggests that Aβ initiates AD pathogenesis, tau, another major hallmark of AD, seems to drive neurodegeneration. Recent studies imply that sleep-wake cycles affect brain tau more significantly than Aβ levels, leading to accelerated AD progression and cognitive decline. The study of sleep disturbances in AD is shedding light on our understanding of the mechanism underlying sleep disturbances in AD and dementia.
sleep as a potential biomarker of tau and β-amyloid burden in the human brain
joseph r. winer et al. 2019
http://dx.doi.org/10.1523/jneurosci.0503-19.2019
"Insufficient sleep across the lifespan is significantly predictive of your development of Alzheimer's disease pathology in the brain," said the study's senior author, Matthew Walker, a sleep researcher and professor of psychology. "Unfortunately, there is no decade of life that we were able to measure during which you can get away with less sleep. There is no Goldilocks decade during which you can say, 'This is when I get my chance to short sleep.'"
Walker and his colleagues, including graduate student and first author Joseph Winer, found that adults reporting a decline in sleep quality in their 40s and 50s had more beta-amyloid protein in their brains later in life, as measured by positron emission tomography, or PET. Those reporting a sleep decline in their 50s and 60s had more tau protein tangles. Both beta-amyloid and tau clusters are associated with a higher risk of developing dementia, though not everyone with protein tangles goes on to develop symptoms of dementia.
Based on the findings, the authors recommend that doctors ask older patients about changes in sleep patterns and intervene when necessary to improve sleep to help delay symptoms of dementia. This could include treatment for apnea, which leads to snoring and frequent halts in breathing that interrupt sleep, and cognitive behavioral therapy for insomnia (CBT-I), a highly effective way to develop healthy sleep habits. It may even include simple sleep counseling to convince patients to set aside time for a full eight hours of sleep and simple sleep hygiene tricks to accomplish that.
"The idea that there are distinct sleep windows across the lifespan is really exciting. It means that there might be high-opportunity periods when we could intervene with a treatment to improve people's sleep, such as using a cognitive behavioral therapy for insomnia," Winer said. "Beyond the scientific advance, our hope is that this study draws attention to the importance of getting more sleep and points us to the decades in life when intervention might be most effective."
The 95 subjects in the study were part of the Berkeley Aging Cohort Study (BACS), a group of healthy older adults -- some as old as 100 years of age -- who have had their brains scanned with PET, the only technique capable of detecting both beta-amyloid tangles and, very recently, tau tangles, in the brain.
Winer, Walker and their colleagues reported their results online last week in the Journal of Neuroscience.
Brain waves out of sync
The team also made a second discovery. They found that people with high levels of tau protein in the brain were more likely to lack the synchronized brain waves that are associated with a good night's sleep. The synchronization of slow brain waves throughout the cortex of the sleeping brain, in lockstep with bursts of fast brain waves called sleep spindles, takes place during deep or non-rapid eye movement (NREM) sleep. The team reported that the more tau protein older adults had, the less synchronized these brain waves were. This impaired electrical sleep signature may therefore act as a novel biomarker of tau protein in the human brain.
"There is something special about that synchrony," given the consequences of this tau protein disruption of sleep, Walker said. "We believe that the synchronization of these NREM brain waves provides a file-transfer mechanism that shifts memories from a short-term vulnerable reservoir to a more permanent long-term storage site within the brain, protecting those memories and making them safe. But when you lose that synchrony, that file-transfer mechanism becomes corrupt. Those memory packets don't get transferred, as well, so you wake up the next morning with forgetting rather than remembering."
Indeed, last year, Walker and his team demonstrated that synchronization of these brain oscillations helps consolidate memory, that is, hits the "save" button on new memories.
Several years ago, Walker and his colleagues initially showed that a dip in the amplitude of slow wave activity during deep NREM sleep was associated with higher amounts of beta-amyloid in the brain and memory impairment. Combined with these new findings, the results help identify possible biomarkers for later risk of dementia.
"It is increasingly clear that sleep disruption is an underappreciated factor contributing to Alzheimer's disease risk and the decline in memory associated with Alzheimer's," Walker said. "Certainly, there are other contributing factors: genetics, inflammation, blood pressure. All of these appear to increase your risk for Alzheimer's disease. But we are now starting to see a new player in this space, and that new player is called insufficient sleep."
The brain rhythms were recorded over a single eight-hour night in Walker's UC Berkeley sleep lab, during which most of the 31 subjects wore a cap studded with 19 electrodes that recorded a continual electroencephalogram (EEG). All had previously had brain scans to assess their burdens of tau and beta-amyloid that were done using a PET scanner at the Lawrence Berkeley National Laboratory and operated by study co-author William Jagust, professor of public health and a member of Berkeley's Helen Wills Neuroscience Institute.
Is sleep a biomarker for dementia?
Doctors have been searching for early markers of dementia for years, in hopes of intervening to stop the deterioration of the brain. Beta-amyloid and tau proteins are predictive markers, but only recently have they become detectable with expensive PET scans that are not widely accessible.
Yet, while both proteins escalate in the brain in old age and perhaps to a greater extent in those with dementia, it is still unknown why some people with large burdens of amyloid and tau do not develop symptoms of dementia.
"The leading hypothesis, the amyloid cascade hypothesis, is that amyloid is what happens first on the path to Alzheimer's disease. Then, in the presence of amyloid, tau begins to spread throughout the cortex, and if you have too much of that spread of tau, that can lead to impairment and dementia," Winer said.
Walker added that, "A lack of sleep across the lifespan may be one of the first fingers that flicks the domino cascade and contributes to the acceleration of amyloid and tau protein in the brain."
The hypothesis is supported, in part, by Jagust's PET studies, which have shown that higher levels of beta-amyloid and tau protein tangles in the brain are correlated with memory decline, tau more so than amyloid. Tau occurs naturally inside the brain's neurons, helping to stabilize their internal skeleton. With age, tau proteins seem to accumulate inside cells of the medial temporal lobe, including the hippocampus, the seat of short-term memory. Only later do they spread more widely throughout the cortex.
While Jagust has run PET scans on the brains of many healthy people, as well as those with dementia, many more subjects are needed to confirm the relationship between protein tangles and dementias like Alzheimer's disease. Because PET scanners are currently expensive and rare, and because they require injection of radioactive tracers, other biomarkers are needed, Walker said.
The new study suggests that sleep changes detectable in a simple overnight sleep study may be less intrusive biomarkers than a PET scan.
"As wearable technology improves, this need not be something you have to come to a sleep laboratory for," said Walker. "Our hope is that, in the future, a small head device could be worn by people at home and provide all the necessary sleep information we'd need to assess these Alzheimer's disease proteins. We may even be able to track the effectiveness of new drugs aimed at combating these brain proteins by assessing sleep."
"I think the message is very clear," Walker added. "If you are starting to struggle with sleep, then you should go and see your doctor and find ways, such as CBT-I, that can help you improve your sleep. The goal here is to decrease your chances of Alzheimer's disease."
abstract Recent proposals suggest that sleep may be a factor associated with accumulation of two core pathological features of Alzheimer's disease (AD): tau and β-amyloid (Aβ). Here we combined positron emission tomography measures of Aβ and tau, electroencephalogram sleep recordings, and retrospective sleep evaluations to investigate the potential utility of sleep measures in predicting in vivo AD pathology in male and female older adults. Regression analyses revealed that the severity of impaired slow oscillation-sleep spindle coupling predicted greater medial temporal lobe tau burden. Aβ burden was not associated with coupling impairment, but instead predicted the diminished amplitude of <1Hz slow-wave-activity—results that were statistically dissociable from each other. Additionally, comparisons of AD pathology and retrospective, self-reported changes in sleep duration demonstrated that changes in sleep across the lifespan can predict late-life Aβ and tau burden. Thus, quantitative and qualitative features of human sleep represent potential non-invasive, cost-effective and scalable biomarkers (current and future-forecasting) of AD pathology, and carry both therapeutic and public-health implications.
light pollution
daily blue-light exposure shortens lifespan and causes brain neurodegeneration in drosophila
trevor r. nash et al. 2019
http://dx.doi.org/10.1038/s41514-019-0038-6
examined how flies responded to daily 12-hour exposures to blue LED light -- similar to the prevalent blue wavelength in devices like phones and tablets -- and found that the light accelerated aging.
Flies subjected to daily cycles of 12 hours in light and 12 hours in darkness had shorter lives compared to flies kept in total darkness or those kept in light with the blue wavelengths filtered out. The flies exposed to blue light showed damage to their retinal cells and brain neurons and had impaired locomotion -- the flies' ability to climb the walls of their enclosures, a common behavior, was diminished.
Some of the flies in the experiment were mutants that do not develop eyes, and even those eyeless flies displayed brain damage and locomotion impairments, suggesting flies didn't have to see the light to be harmed by it.
"The fact that the light was accelerating aging in the flies was very surprising to us at first," said Giebultowicz, a professor of integrative biology. "We'd measured expression of some genes in old flies, and found that stress-response, protective genes were expressed if flies were kept in light. We hypothesized that light was regulating those genes. Then we started asking, what is it in the light that is harmful to them, and we looked at the spectrum of light. It was very clear cut that although light without blue slightly shortened their lifespan, just blue light alone shortened their lifespan very dramatically."
Natural light, Giebultowicz notes, is crucial for the body's circadian rhythm -- the 24-hour cycle of physiological processes such as brain wave activity, hormone production and cell regeneration that are important factors in feeding and sleeping patterns.
"But there is evidence suggesting that increased exposure to artificial light is a risk factor for sleep and circadian disorders," she said. "And with the prevalent use of LED lighting and device displays, humans are subjected to increasing amounts of light in the blue spectrum since commonly used LEDs emit a high fraction of blue light. But this technology, LED lighting, even in most developed countries, has not been used long enough to know its effects across the human lifespan."
Giebultowicz says that the flies, if given a choice, avoid blue light.
"We're going to test if the same signaling that causes them to escape blue light is involved in longevity," she said.
abstract Light is necessary for life, but prolonged exposure to artificial light is a matter of increasing health concern. Humans are exposed to increased amounts of light in the blue spectrum produced by light-emitting diodes (LEDs), which can interfere with normal sleep cycles. The LED technologies are relatively new; therefore, the long-term effects of exposure to blue light across the lifespan are not understood. We investigated the effects of light in the model organism, Drosophila melanogaster, and determined that flies maintained in daily cycles of 12-h blue LED and 12-h darkness had significantly reduced longevity compared with flies maintained in constant darkness or in white light with blue wavelengths blocked. Exposure of adult flies to 12 h of blue light per day accelerated aging phenotypes causing damage to retinal cells, brain neurodegeneration, and impaired locomotion. We report that brain damage and locomotor impairments do not depend on the degeneration in the retina, as these phenotypes were evident under blue light in flies with genetically ablated eyes. Blue light induces expression of stress-responsive genes in old flies but not in young, suggesting that cumulative light exposure acts as a stressor during aging. We also determined that several known blue-light-sensitive proteins are not acting in pathways mediating detrimental light effects. Our study reveals the unexpected effects of blue light on fly brain and establishes Drosophila as a model in which to investigate long-term effects of blue light at the cellular and organismal level.
regulation of lifespan by neural excitation and rest
joseph m. zullo et al. 2019
http://dx.doi.org/10.1038/s41586-019-1647-8
based on findings from human brains, mice and worms and suggests that excessive activity in the brain is linked to shorter life spans, while suppressing such overactivity extends life.
The findings offer the first evidence that the activity of the nervous system affects human longevity. Although previous studies had suggested that parts of the nervous system influence aging in animals, the role of neural activity in aging, especially in humans, remained murky.
"An intriguing aspect of our findings is that something as transient as the activity state of neural circuits could have such far-ranging consequences for physiology and life span," said study senior author Bruce Yankner, professor of genetics at HMS and co-director of the Paul F. Glenn Center for the Biology of Aging.
Neural excitation appears to act along a chain of molecular events famously known to influence longevity: the insulin and insulin-like growth factor (IGF) signaling pathway.
The key in this signaling cascade appears to be a protein called REST, previously shown by the Yankner Lab to protect aging brains from dementia and other stresses.
Neural activity refers to the constant flicker of electrical currents and transmissions in the brain. Excessive activity, or excitation, could manifest in numerous ways, from a muscle twitch to a change in mood or thought, the authors said.
It's not yet clear from the study whether or how a person's thoughts, personality or behavior affect their longevity.
"An exciting future area of research will be to determine how these findings relate to such higher-order human brain functions," said Yankner.
The study could inform the design of new therapies for conditions that involve neural overactivity, such as Alzheimer's disease and bipolar disorder, the researchers said.
The findings raise the possibility that certain medicines, such as drugs that target REST, or certain behaviors, such as meditation, could extend life span by modulating neural activity.
Human variation in neural activity might have both genetic and environmental causes, which would open future avenues for therapeutic intervention, Yankner said.
All roads lead to REST
Yankner and colleagues began their investigation by analyzing gene expression patterns -- the extent to which various genes are turned on and off -- in donated brain tissue from hundreds of people who died at ages ranging from 60 to over 100.
The information had been collected through three separate research studies of older adults. Those analyzed in the current study were cognitively intact, meaning they had no dementia.
Immediately, a striking difference appeared between the older and younger study participants, said Yankner: The longest-lived people -- those over 85 -- had lower expression of genes related to neural excitation than those who died between the ages of 60 and 80.
Next came the question that all scientists confront: correlation or causation? Was this disparity in neural excitation merely occurring alongside more important factors determining life span, or were excitation levels directly affecting longevity? If so, how?
The team conducted a barrage of experiments, including genetic, cell and molecular biology tests in the model organism Caenorhabditis elegans; analyses of genetically altered mice; and additional brain tissue analyses of people who lived for more than a century.
These experiments revealed that altering neural excitation does indeed affect life span -- and illuminated what might be happening on a molecular level.
All signs pointed to the protein REST.
REST, which is known to regulate genes, also suppresses neural excitation, the researchers found. Blocking REST or its equivalent in the animal models led to higher neural activity and earlier deaths, while boosting REST did the opposite. And human centenarians had significantly more REST in the nuclei of their brain cells than people who died in their 70s or 80s.
"It was extremely exciting to see how all these different lines of evidence converged," said study co-author Monica Colaiácovo, professor of genetics at HMS, whose lab collaborated on the C. elegans work.
The researchers found that from worms to mammals, REST suppresses the expression of genes that are centrally involved in neural excitation, such as ion channels, neurotransmitter receptors and structural components of synapses.
Lower excitation in turn activates a family of proteins known as forkhead transcription factors. These proteins have been shown to mediate a "longevity pathway" via insulin/IGF signaling in many animals. It's the same pathway that scientists believe can be activated by caloric restriction.
abstract The mechanisms that extend lifespan in humans are poorly understood. Here we show that extended longevity in humans is associated with a distinct transcriptome signature in the cerebral cortex that is characterized by downregulation of genes related to neural excitation and synaptic function. In Caenorhabditis elegans, neural excitation increases with age and inhibition of excitation globally, or in glutamatergic or cholinergic neurons, increases longevity. Furthermore, longevity is dynamically regulated by the excitatory–inhibitory balance of neural circuits. The transcription factor REST is upregulated in humans with extended longevity and represses excitation-related genes. Notably, REST-deficient mice exhibit increased cortical activity and neuronal excitability during ageing. Similarly, loss-of-function mutations in the C. elegans REST orthologue genes spr-3 and spr-4 elevate neural excitation and reduce the lifespan of long-lived daf-2 mutants. In wild-type worms, overexpression of spr-4 suppresses excitation and extends lifespan. REST, SPR-3, SPR-4 and reduced excitation activate the longevity-associated transcription factors FOXO1 and DAF-16 in mammals and worms, respectively. These findings reveal a conserved mechanism of ageing that is mediated by neural circuit activity and regulated by REST.
light pollution increases west nile virus competence of a ubiquitous passerine reservoir species
meredith e. kernbach et al. 2019
http://dx.doi.org/10.1098/rspb.2019.1051
infected house sparrows living in light polluted conditions remain infectious for two days longer than those who do not, enhancing their host competence, or propensity to generate infection in other hosts or vectors. In turn, mathematical models show this likely increases the potential for a WNV outbreak by about 41 percent.
"The findings may be the first indication that light pollution can affect the spread of zoonotic diseases," said lead author Meredith Kernbach, PhD student in the University of South Florida College of Public Health. "Many hosts and vectors use light cues to coordinate daily and seasonal rhythms, which is among the most reliable environmental cues, and disruption of these rhythms by light exposure at night could affect immune responses, generating the effects we see here."
Researchers studied 45 house sparrows, exposing half to artificial light at night. Following 7-25 days in captivity, the team exposed the birds to WNV and took blood samples 2, 4, 6, and 10 days post-exposure. Researchers found all birds were infected within 2-4 days, however after that, birds exposed to light at night maintained transmissible burdens of WNV.
Kernbach says they picked the little brown birds since they live in close proximity to humans in urban areas, play host to a number of parasites and diseases, and are frequent carriers of WNV. While birds exposed to light pollution remain infected for a longer period of time, this did not increase mortality rates.
These results follow a previous study led by the University of South Florida that found zebra finches that have the avian stress hormone corticosterone (CORT) are more susceptible to mosquito bites. Such stress is known to be caused by a number of factors such as road noise, pesticides and light pollution. Researchers suggest new lighting technologies be created that are detectable to humans, but not for wildlife.
abstract Among the many anthropogenic changes that impact humans and wildlife, one of the most pervasive but least understood is light pollution. Although detrimental physiological and behavioural effects resulting from exposure to light at night are widely appreciated, the impacts of light pollution on infectious disease risk have not been studied. Here, we demonstrate that artificial light at night (ALAN) extends the infectious-to-vector period of the house sparrow (Passer domesticus), an urban-dwelling avian reservoir host of West Nile virus (WNV). Sparrows exposed to ALAN maintained transmissible viral titres for 2 days longer than controls but did not experience greater WNV-induced mortality during this window. Transcriptionally, ALAN altered the expression of gene regulatory networks including key hubs (OASL, PLBD1 and TRAP1) and effector genes known to affect WNV dissemination (SOCS). Despite mounting anti-viral immune responses earlier, transcriptomic signatures indicated that ALAN-exposed individuals probably experienced pathogen-induced damage and immunopathology, potentially due to evasion of immune effectors. A simple mathematical modelling exercise indicated that ALAN-induced increases of host infectious-to-vector period could increase WNV outbreak potential by approximately 41%. ALAN probably affects other host and vector traits relevant to transmission, and additional research is needed to advise the management of zoonotic diseases in light-polluted areas.
outdoor artificial nighttime light and use of hypnotic medications in older adults: a population-based cohort study
jin-young min, kyoung-bok min 2018
http://dx.doi.org/10.5664/jcsm.7490
Results show that increasing nighttime levels of artificial, outdoor light exposure, stratified by quartile, were associated with an increased prevalence of hypnotic prescriptions and daily dose intake. Furthermore, older adults exposed to higher levels of artificial, outdoor light at night were more likely to use hypnotic drugs for longer periods or higher daily dosages.
"This study observed a significant association between the intensity of outdoor, artificial, nighttime lighting and the prevalence of insomnia as indicated by hypnotic agent prescriptions for older adults in South Korea," said Kyoung-bok Min, PhD, an associate professor in the Department of Occupational and Environmental Medicine at Seoul National University College of Medicine in South Korea. "Our results are supportive data that outdoor, artificial, nighttime light could be linked to sleep deprivation among those while inside the house."
The study results are published in the Nov. 15 issue of the Journal of Clinical Sleep Medicine.
According to the American Academy of Sleep Medicine, insomnia can involve struggling to fall asleep, having trouble maintaining sleep, or waking up too early. A variety of environmental factors, including excessive noise or light and extreme temperatures, will disrupt the sleep of most individuals.
The authors reported that the inappropriate or excessive use of artificial, outdoor light at night, referred to as "light pollution," has emerged as a novel environmental factor linked to human health. Research has shown that artificial nighttime lighting, whether indoor or outdoor, induces disruption of circadian rhythms, potentially leading to metabolic and chronic diseases, including cancer, diabetes, obesity and depression.
The study used data from the 2002-2013 National Health Insurance Service-National Sample Cohort (NHIS-NSC), a population-based cohort in South Korea. The final study sample, after excluding those with a diagnosed sleep disorder, comprised 52,027 adults who were 60 years of age or older. About 60 percent of participants were female.
Light exposure was based on satellite data provided by the National Centers for Environmental Information. The estimated light pollution level in each administrative district was matched with individuals' residential districts to determine an individual exposure level.
Usage data for two hypnotic drugs, zolpidem and triazolam, were extracted from health insurance records. About 22 percent of study participants had prescriptions for hypnotic drugs.
Min added that public health officials seem to be less concerned with light pollution than with other environmental pollutants. However, this study strengthens the potential link between light pollution and adverse health consequences.
"Given the recent scientific evidence including our results, bright outdoor lighting may be a novel risk factor for prescribing hypnotic drugs," Min said.
abstract
Study Objectives
Outdoor artificial nighttime light is increasingly recognized as a form of environmental pollution. Excessive nighttime light exposure, whether from indoor or outdoor sources, has been associated with a number of deleterious effects on human health. We performed a population-based cohort study in South Korea to assess the possible association between outdoor nocturnal lighting and insomnia in older adults, as measured by prescriptions for hypnotic drugs.
Methods
This study used data from the 2002–2013 National Health Insurance Service-National Sample Cohort (NHIS-NSC), and a total of 52,027 adults who were age 60 years or older were included in the study. Light data were based on satellite mapping of artificial light. The usage data of two hypnotic drugs, zolpidem (N05CF02) and triazolam (N05CD05), were extracted from the NHIS-NSC records.
Results
Of the 52,027 patients in this cohort, 11,738 (22%) had prescriptions for hypnotic drugs. Increasing outdoor artificial nighttime light exposure (stratified by quartile) was associated with an increased prevalence of hypnotic prescriptions and daily dose intake. Compared with individuals in the lowest quartile 1, the regression coefficients for prescription days and daily defined doses of all hypnotic drugs and certain hypotonic drugs were significantly higher among those living in areas with higher outdoor artificial nighttime light (quartiles 2 through 4).
Conclusions
Outdoor artificial nighttime light exposure was significantly associated with prescription of hypnotic drugs in older adults. These findings are consistent with the hypothesis that outdoor artificial nighttime light may cause sleep disturbances.
effects of evening exercise on sleep in healthy participants: a systematic review and meta-analysis
jan stutz et al. 2018
http://dx.doi.org/10.1007/s40279-018-1015-0
The scientists combed through the literature on the subject and analysed all 23 studies that met their quality requirements. They concluded that doing exercise in the four hours before going to bed does not have a negative effect on sleep. "If doing sport in the evening has any effect on sleep quality at all, it's rather a positive effect, albeit only a mild one," says Christina Spengler, head of the Exercise Physiology Lab at ETH Zurich.
By combining the data from the different studies, the researchers showed that in the night after study participants had done some sport in the evening, they spent 21.2 percent of their sleeping time in deep sleep. Following an evening without exercise, the average figure was 19.9 percent. While the difference is small, it is statistically significant. Deep sleep phases are especially important for physical recovery.
Intensive training late in the evening: an exception to the rule
Vigorous training within an hour before bedtime is an exception to the rule. According to this analysis, it is the only type of evening exercise that may have a negative effect on sleep. "However, this preliminary observation is based on just one study," Spengler says.
"As a rule of thumb, vigorous training is defined as training in which a person is unable to talk. Moderate training is physical activity of an intensity high enough that a person would no longer be able to sing, but they could speak," Spengler says. One example of vigorous training is the kind of high-intensity interval training that competitive athletes often perform. In many cases, though, a longer endurance run or a longer ride on a racing bike would fall into the moderate training category.
As the analysis showed, it took study participants who completed an intensive training session shortly before bedtime longer to fall asleep. The study also provided insight into why this is the case: the test subjects were not able to recover sufficiently in the hour before they went to bed. Their hearts were still beating more than 20 beats per minute faster than their resting heart rate.
Possible sleep problems are no excuse
According to the official recommendations of sport physicians, people should do at least 150 minutes of moderate exercise each week. Many may ask themselves: should I exercise in the evening if I didn't have time during the day, or will that have a negative effect on my sleep? "People can do exercise in the evening without hesitation. The data shows that moderate exercise in the evening is no problem at all," says Jan Stutz, a doctoral student in Spengler's research group and lead author of the analysis, which was published in the journal Sports Medicine. Moderate exercise did not cause sleep problems in any of the studies examined, not even when the training session ended just 30 minutes before bedtime. "However, vigorous training or competitions should be scheduled earlier in the day, if possible," Stutz says.
Stutz and Spengler point out that they examined average values over the course of their analysis, which made only general statements possible. "Not everyone reacts to exercise in the same way, and people should keep listening to their bodies. If they notice they are having problems falling asleep after doing sport, they should try to work out a little earlier," Stutz says.
"It is well known that doing exercise during the day improves sleep quality," Spengler says, adding: "Now we have shown that, at the very least, exercising in the evening doesn't have a negative effect."
abstract Current recommendations advise against exercising in the evening because of potential adverse effects on sleep.
Objectives
The aim of this systematic review was to investigate the extent to which evening exercise affects sleep and whether variables such as exercise intensity or duration modify the response.
Methods
A systematic search was performed in PubMed, Cochrane, EMBASE, PsycINFO, and CINAHL databases. Studies evaluating sleep after a single session of evening physical exercise compared to a no-exercise control in healthy adults were included. All analyses are based on random effect models.
Results
The search yielded 11,717 references, of which 23 were included. Compared to control, evening exercise significantly increased rapid eye movement latency (+ 7.7 min; p = 0.032) and slow-wave sleep (+ 1.3 percentage points [pp]; p = 0.041), while it decreased stage 1 sleep (− 0.9 pp; p = 0.001). Moderator analyses revealed that a higher temperature at bedtime was associated with lower sleep efficiency (SE) (b = − 11.6 pp; p = 0.020) and more wake after sleep onset (WASO; b = + 37.6 min; p = 0.0495). A higher level of physical stress (exercise intensity relative to baseline physical activity) was associated with lower SE (− 3.2 pp; p = 0.036) and more WASO (+ 21.9 min; p = 0.044). Compared to cycling, running was associated with less WASO (− 12.7 min; p = 0.037). All significant moderating effects disappeared after removal of one study.
Conclusion
Overall, the studies reviewed here do not support the hypothesis that evening exercise negatively affects sleep, in fact rather the opposite. However, sleep-onset latency, total sleep time, and SE might be impaired after vigorous exercise ending ≤ 1 h before bedtime.
better sleep enhances performance
the eight hour sleep challenge during final exams week
michael k. scullin et al. 2018
http://dx.doi.org/10.1177/0098628318816142
"Better sleep helped rather than harmed final exam performance, which is contrary to most college students' perceptions that they have to sacrifice either studying or sleeping. And you don't have to be an 'A' student or have detailed education on sleep for this to work," said Michael Scullin, Ph.D., director of Baylor's Sleep Neuroscience and Cognition Laboratory and assistant professor of psychology and neuroscience in Baylor's College of Arts & Sciences.
While students who successfully met the sleep challenge received extra points, the "mini-incentive" was not included in the analysis of how well they performed on the finals, stressed Elise King, assistant professor of interior design in Baylor's Robbins College of Health and Human Sciences.
"They didn't just perform well because they received extra points," she said. "Students know that sacrificing sleep to complete school work is not a healthy choice, but they assume they don't have a choice, often remarking that there aren't enough hours in the day for coursework, extracurriculars, jobs, etc. "
This removes that excuse."
Research participants included undergraduate interior design students and students in upper-level psychology and neuroscience classes. While the psychology classes emphasized education about sleep, the interior design students did not receive any formal training in sleep. Those who opted to take the challenge wore wristband sleep-monitoring devices for five days to ensure accurate study results.
"The students didn't need the extra credit to perform better, and they weren't really better students from the get-go," Scullin said. "If you statistically correct for whether a student was an A, B, C, or D student before their final exam, sleeping 8 hours was associated with a four-point grade boost -- even prior to applying extra credit."
The collaborative interior design study -- "The 8-Hour Challenge: Incentivizing Sleep During End-of-Term Assessments -- was published in the Journal of Interior Design. Scullin's study of psychology students -- "The 8-Hour Sleep Challenge During Final Exams Week" -- was published in Teaching of Psychology.
Poor sleep is common during finals as students cut back on sleep, deal with more stress, use more caffeine and are exposed to more bright light, all of which may disrupt sleep. Fewer than 10 percent of undergraduates maintain the recommended average of 8 hours a night or even the recommended minimum of 7 hours, previous research shows.
But with incentives, "we can potentially completely reverse the proportion of students meeting minimum sleep recommendations -- 7 hours a night -- from fewer than 15 percent up to 90 percent," Scullin said. "Half of students can even meet optimal sleep recommendations of 8 to 9 hours."
In the study of psychology students, 34 students in two undergraduate courses could earn extra credit if they averaged 8 hours of sleep during final exams week or at least improved upon their sleep from earlier in the semester.
The 24 who opted to take the challenge averaged 8.5 hours of sleep, with 17 meeting the goal. On the final exam, students who slept more than 8 hours nightly performed better than those who opted out or slept less than 7.9 hours. (The incentive was 8 points -- the equivalent of 1 percent of a student's overall class grade.)
"It's worth noting that one student who had a D-plus grade before the final but slept more than 8 hours a week during finals week, remarked that it was the 'first time my brain worked while taking an exam,'" Scullin said.
In the interior design study challenge, students earned credit (10 points on a 200-point project) if they averaged 8 or more hours a night but received no grade change if they averaged 7 to 7.9 hours a night.
Of the 27 students enrolled in the program, 22 attempted the challenge. Compared with a group of 22 students who did not try for the extra points, very few (9 percent) averaged 8 hours or even 7 hours (14 percent).
The 8 hour challenge increased the percentage of 8? and 7?hour sleepers to 59 percent and 86 percent respectively. Students who took part in the challenge slept an average of 98 minutes more per night compared to students who were not offered the incentive but were monitored.
"Critically, the additional sleep did not come at a cost to project performance," King said. "Students who showed more consistent sleep performed better than those who had less consistent sleep. And students who achieved the challenge performed as well or better than those who did not take the challenge."
In a study of sleep and creativity done in 2017, King and Scullin found that interior design students with highly variable sleep habits -- cycling between "all-nighters" and "catch-up" nights -- had decreased cognition in attention and creativity, especially with major projects. Design students customarily complete finals projects rather than final exams.
"Whether or not they 'pull an all-nighter,' when students cut their sleep, the effects are obvious," King said. "They have trouble paying attention during class, and they aren't as productive during studio time."
She noted that there is a cultural acceptability -- at least in design professions -- related to sleep deprivation, thanks in part to the notion of the "tortured artist" who finds inspiration in the wee hours.
"Some fields might find it unprofessional, but for many years, in design, sacrificing sleep was viewed as a rite of passage. That's something we're trying to change," King said. "Even during stressful deadline weeks, students can maintain healthy sleep habits."
"To be successful at the challenge, students need to manage their time better during the day. Getting more sleep at night then allows them to be more efficient the next day," Scullin said. "By training students in their first year of college, if not earlier, that they can sleep well during finals week without sacrificing performance, we may help to resolve the 'global sleep epidemic' that plagues students in America and abroad."
abstract Many students and educators know that sleep is important to learning, yet there exists a gap between their knowledge and behavior. For example, fewer than 10% of students sleep 8 hr before final exams. In the context of two undergraduate courses on sleep (N = 34), students could earn extra credit if they averaged ≥8.0 hr of sleep during final exams week. Sleep/wake patterns were monitored objectively using actigraphy. The 24 students who opted in to the challenge averaged 8.5 hr of sleep (n = 17 succeeded). Short sleep (≤6.9 hr) occurred on only 11% of nights, significantly less than early-semester baseline (51%) and comparison group (65%) data. On the final exam, students who slept ≥8.0 hr performed better than students who opted out or slept ≤7.9 hr, even after controlling for prefinal grades. The 8-hr sleep challenge provides proof of principle that many students can maintain optimal sleep while studying, without sacrificing test performance.
hyperoxia enhances slow-wave forebrain states in urethane-anesthetized and naturally sleeping rats
brandon e. hauer et al. 2018
http://dx.doi.org/10.1152/jn.00373.2018
"We found that when we administer oxygen, our subjects' brains switch out of active sleep, and remain in a deactivated, slow-wave state the entire time," explained Brandon Hauer, PhD student in the neuroscience graduate program administered by the cross-faculty Neuroscience and Mental Health Institute. "Interestingly, when we removed the oxygen, the brain started cycling back through active, or rapid-eye-movement, sleep again."
Deactivated or slow-wave sleep is the deepest stage of sleep, during which the brain oscillates at a very slow, once-per-second rhythm.
"This seems to be the stage where metabolites are cleared from the brain, muscles grow, and proteins reform," said Hauer, who conducted the research under the supervision of Professor Clay Dickson in the Department of Psychology. "Slow-wave sleep seems to be especially suited to recovery for both the brain and body." Slow-wave sleep also plays a role in memory consolidation.
The researchers also showed that when exposed to less than normal levels of oxygen, the brain remains in active, or rapid-eye-movement (REM) sleep. "Interestingly, we saw a rebound effect after the brain remained in REM sleep, in which the brain reverted to slow-wave sleep for a longer duration, as if it missed out on the slow-wave sleep during the activated stage," added Hauer.
The research highlights the potential for oxygen therapy for humans in a clinical setting.
"Oxygen therapy could be used to enhance slow-wave states during sleep to ensure that individuals who may have disrupted sleep are getting enough of the restorative, slow-wave sleep," said Dickson. "Of course, this has to be tested first before this could become a therapeutic reality."
abstract Oxygen (O2) is a crucial element for physiological functioning in mammals. In particular, brain function is critically dependent on a minimum amount of circulating blood levels of O2 and both immediate and lasting neural dysfunction can result following anoxic or hypoxic episodes. Although the effects of deficiencies in O2 levels on the brain have been reasonably well studied, less is known about the influence of elevated levels of O2 (hyperoxia) in inspired gas under atmospheric pressure. This is of importance due to its typical use in surgical anesthesia, in the treatment of stroke and traumatic brain injury, and even in its recreational or alternative therapeutic use. Using local field potential (EEG) recordings in spontaneously breathing urethane-anesthetized and naturally sleeping rats, we characterized the influence of different levels of O2 in inspired gases on brain states. While rats were under urethane anesthesia, administration of 100% O2 elicited a significant and reversible increase in time spent in the deactivated (i.e., slow-wave) state, with concomitant decreases in both heartbeat and respiration rates. Increasing the concentration of carbon dioxide (to 5%) in inspired gas produced the opposite result on EEG states, mainly a decrease in the time spent in the deactivated state. Consistent with this, decreasing concentrations of O2 (to 15%) in inspired gases decreased time spent in the deactivated state. Further confirmation of the hyperoxic effect was found in naturally sleeping animals where it similarly increased time spent in slow-wave (nonrapid eye movement) states. Thus alterations of O2 in inspired air appear to directly affect forebrain EEG states, which has implications for brain function, as well as for the regulation of brain states and levels of forebrain arousal during sleep in both normal and pathological conditions.
what does sleep hygiene have to offer children’s sleep problems?
wendy a hall, elizabeth nethery 2018
http://dx.doi.org/10.1016/j.prrv.2018.10.005
"Good sleep hygiene gives children the best chances of getting adequate, healthy sleep every day. And healthy sleep is critical in promoting children's growth and development," said Hall. "Research tells us that kids who don't get enough sleep on a consistent basis are more likely to have problems at school and develop more slowly than their peers who are getting enough sleep."
The American Academy of Sleep Medicine recommends the following amounts of sleep, based on age group:
4 to 12 months -- 12 to 16 hours
1 to 2 years -- 11 to 14 hours
3 to 5 years -- 10 to 13 hours
6 to 12 years -- 9 to 12 hours
13 to 18 years -- 8 to 10 hours
The UBC review aimed at systematically analyzing the evidence for sleep hygiene across different countries and cultures, and honed in on 44 studies from 16 countries. The focus was on four age groups in particular: infants and toddlers (four months to two years), preschoolers (three to five years), school-age children (six to 12 years) and adolescents (13 to 18 years). These studies involved close to 300,000 kids in North America, Europe and Asia.
"We found good-to-strong endorsement of certain sleep hygiene practices for younger kids and school-age kids: regular bedtimes, reading before bed, having a quiet bedroom, and self-soothing -- where you give them opportunities to go to sleep and go back to sleep on their own, if they wake up in the middle of the night," said Hall.
Even for older kids, keeping a regular bedtime was important. The review found papers that showed that adolescents whose parents set strict guidelines about their sleep slept better than kids whose parents didn't set any guidelines.
Hall and co-author Elizabeth Nethery, a nursing PhD student at UBC, also found extensive evidence for limiting technology use just before bedtime, or during the night when kids are supposed to be sleeping. Studies in Japan, New Zealand and the United States showed that the more exposure kids had to electronic media around bedtime, the less sleep they had.
"One big problem with school-age children is it can take them a long time to get to sleep, so avoiding activities like playing video games or watching exciting movies before bedtime was important," said Hall.
Many of the studies also highlighted the importance of routines in general. A study in New Zealand showed family dinner time was critical to helping adolescents sleep.
Information provided by Chinese studies and one Korean study linked school-age children's and adolescents' short sleep duration to long commute times between home and school and large amounts of evening homework. With more children coping with longer commutes and growing amounts of school work, Hall says this is an important area for future study in North America.
Surprisingly, there wasn't a lot of evidence linking caffeine use before bedtime to poor sleep; it appeared to be the total intake during the day that matters.
While Hall said more studies are needed to examine the effect of certain sleep hygiene factors on sleep quality, she would still strongly recommend that parents set bedtimes, even for older kids, and things like sitting down for a family dinner, establishing certain rituals like reading before bed, and limiting screen time as much as possible.
"Sleep education can form part of school programming," added Hall. "There was a project in a Montreal school where everyone was involved in designing and implementing a sleep intervention -- the principal, teachers, parents, kids, and even the Parent Advisory Council. The intervention was effective, because everyone was on board and involved from the outset."
abstract Sleep hygiene practices have been described extensively in the literature. There is considerably less clarity about relationships between particular elements of sleep hygiene and particular sleep outcomes, and which intervention approaches using sleep hygiene principles are effective. In this review, we describe themes extracted from a systematic review of the sleep hygiene literature. We systematically searched Psycinfo, CINAHL, Cochrane, Ovid Medline, Embase, and Web of Science Search Engines up to August, 2017. We included all studies that associated sleep hygiene (behaviors adjacent to bedtime and during the night) with sleep duration and/or sleep onset latency and/or night waking or that used sleep-hygiene based interventions to improve sleep duration and/or sleep onset latency and/or night waking (n=44). We organized our findings into themes by age group, sleep hygiene factors, and interventions. We provide evidence-based recommendations about areas of sleep hygiene that have significant empirical support and those that require urgent attention.
day-to-day variations in sleep quality affect standing balance in healthy adults
luis montesinos et al. 2018
http://dx.doi.org/10.1038/s41598-018-36053-4
The research shows that fragmented and disrupted sleep leads to acute balance deficit.
The study was conducted by the School of Engineering in collaboration with Warwick Medical School at the University of Warwick.
A sample of healthy adults underwent sleep and balance assessment over two consecutive days, in order to determine the links between day-to-day variations in sleep quality and balance.
State-of-the-art wearable sensors were used for in-home sleep monitoring and balance testing. These findings are relevant to pave the way to the design of fall prevention programs in populations and settings where normal sleep is frequently disrupted, such as older people and hospital wards.
Dr Leandro Pecchia, team leader of the research from the School of Engineering at the University of Warwick says:
"We all have direct experience of this. When we do not sleep well, we may feel a little dizzy and our capability to control our posture and balance is somehow diminished. When we are fit and in good health, our body is able to adapt and we develop a strategy to keep our balance, avoiding falls and incidents. This ability is reduced with ageing or when there are other concomitant conditions that may compromise our ability to adapt."
Prof Francesco Cappuccio, Head of the Sleep, Health & Society programme at the University of Warwick's medical school, explains:
"The results obtained in healthy normal volunteers are surprising, given the ability at younger ages to compensate for such acute and short-lived sleep disruptions. We would expect more dramatic effects when these experiments be replicated in older people, whose vulnerability to sleep disruption, postural hypotension and risk of falls is much greater."
Dr Lenadro Pecchia continues:
"These results could contribute to the understanding of in-hospital falls. Hospitalised older patients find themselves in a frail condition, sleeping in an unfamiliar environment, with unusual nocturnal light and noises from other patients and nurses, and perhaps being administered more than one drug. Waking-up to go to the toilet can be more challenging than we can imagine. Having a nurse for each bed is not practical in the modern NHS and not well accepted by many older people. We need to learn how to use available technology to detect early the changes in sleep so that we can design personalised interventions that may avoid falls in the next day. One of the problems in fall prevention is that we know a frail subject will fall, but it is very difficult to predict when. Our study is first step towards finding a solution."
abstract Acute sleep deprivation is known to affect human balance and posture control. However, the effects of variations in sleep quality and pattern over consecutive days have received less attention. This study investigated the associations between day-to-day variations in sleep quality and standing balance in healthy subjects. Twenty volunteers (12 females and 8 males; age: 28.8 ± 5.7 years, body mass index: 23.4 ± 3.4 kg/m2, resting heart rate: 63.1 ± 8.7 bpm) with no history of sleep disorders or balance impairments participated in the study. Sleep and balance were assessed over two consecutive days. Sleep quality variations were assessed using sleep diary, actigraphy and heart rate variability (HRV) measures. Sleep was monitored at home, using an unobtrusive wearable device. Balance was assessed in a gait lab using foot centre of pressure (COP) displacement during quiet standing. Subjects with a day-to-day deterioration in sleep quantity and quality (i.e., decreased duration and increased fragmentation, increased nocturnal activity and decreased HRV) exhibited significant changes in balance (i.e., larger COP area, amplitude and standard deviation). Conversely, subjects with no significant alterations in sleep quantity and quality showed no significant changes in COP displacements. These results confirmed our hypothesis that changes in sleep quality and pattern over consecutive days may affect balance.
snoring, apnea
the presence of snoring as well as its intensity is underreported by women
roi westreich et al. 2019
http://dx.doi.org/10.5664/jcsm.7678
Results show that objectively measured snoring was found in 88% of the women (591 of 675), but only 72% reported that they snore (496 of 675). In contrast, objective snoring (92.6%) and self-reported snoring (93.1%) were nearly identical in men. The study also found that women snored as loudly as men, with a mean maximal snoring intensity of 50 decibels among women and 51.7 decibels among men. About 49% of the women had severe or very severe snoring (329 of 675), but only 40% of the women rated their snoring at this level of severity (269 of 675).
"We found that although no difference in snoring intensity was found between genders, women tend to underreport the fact that they snore and to underestimate the loudness of their snoring," said Nimrod Maimon, MD, MHA, principal investigator and professor at the BGU Faculty of Health Sciences and the head of internal medicine (B Ward) at Soroka University Medical Center in Be'er Sheva, Israel. "Women reported snoring less often and described it as milder."
The study results are published in the March 15 issue of the Journal of Clinical Sleep Medicine.
Snoring is a respiratory sound generated in the upper airway during sleep. The intensity of snoring may vary and often will disturb the bed partner's sleep. Snoring is a common warning sign for obstructive sleep apnea, a chronic disease that involves the repeated collapse of the upper airway during sleep.
The study involved 1,913 patients who were referred to a sleep disorders center at a university hospital for a sleep evaluation. They had an average age of 49 years. Participants were given a questionnaire that asked them to rate the severity of their snoring. Objective snoring volume was quantified using a calibrated digital sound survey meter during a sleep study that lasted an entire night. Snoring intensity was classified as mild (40 -- 45 decibels), moderate (45 -- 55 decibels), severe (55 -- 60 decibels), or very severe (60 decibels or more).
According to the authors, there is a social stigma associated with snoring among women. Therefore, women may not reliably answer questions about snoring, which may contribute to the underdiagnosis of obstructive sleep apnea in women.
"The fact that women reported snoring less often and described it as milder may be one of the barriers preventing women from reaching sleep clinics for a sleep study," Maimon said.
Maimon added that health care providers who are screening women for suspected obstructive sleep apnea should consider other factors in addition to self-reported snoring. For example, women with sleep apnea may be more likely than men to report other symptoms such as daytime fatigue or tiredness.
abstract Study Objectives
Women are underrepresented and thus sleep conditions are underdiagnosed at sleep clinics that evaluate sleep-disordered breathing. The most common sign of obstructive sleep apnea (OSA) is snoring; therefore, it is one of the main red flags for suspected OSA. The aim of this study is to determine whether self-reported snoring and snoring intensity by women and men correlates with snoring volume measured objectively during sleep laboratory study.
Methods
Consecutive patients who were referred to a polysomnography (PSG) study in a university hospital over a 2-year period had their snoring volume quantified by means of a calibrated digital sound survey meter. Participants were given a questionnaire in which they were asked to rate the severity of their snoring. The correlation between objective snoring intensity as measured during PSG and the self-reported snoring intensity was evaluated.
Results
A total of 1,913 patients were enrolled in the study. A positive correlation was found between objectively measured snoring intensity and the intensity listed by each participant in the questionnaire. Measurement of the volume of snoring revealed that women snored as loudly as men; however, 28% of the females (189/675) considered themselves to be nonsnorers compared to only 6.9% of men (P < .05). Furthermore, 36.5% of women (69/189) who reported themselves as nonsnorers turned out to have severe or very severe snoring intensity, whereas, in contrast, only 11.7% of men (10/85) of men had this discrepancy. These findings are in concordance with the finding that fewer women quantified their snoring as very severe or severe (38.4%), significantly less than men of whom 61.5% reported their snoring to be severe or very severe.
Conclusions
In a population of individuals referred to a PSG study, although no difference in snoring intensity was found between sexes, women tend to underreport the fact that they snore and to underestimate the loudness of their snoring. Improved awareness of this discrepancy may increase women's access to sleep laboratories, and improve diagnostic rates of sleep apnea in females.
0291 sleep disordered breathing associated with epigenetic age acceleration: evidence from the multi-ethnic study of atherosclerosis
xiaoyu li et al. 2019
http://dx.doi.org/10.1093/sleep/zsz067.290
each standard deviation increase in the apnea-hypopnea index, a measure of sleep-disordered breathing severity, was associated with the equivalent of 215 days of biological age acceleration. Similarly, each standard deviation increase in the arousal index, a measure of sleep disruption, was associated with the equivalent of 321 days of age acceleration.
"People's biological age might not be the same as their chronological age," said lead author Xiaoyu Li, Sc.D., a postdoctoral research fellow in the Division of Sleep and Circadian Disorders in the Department of Medicine at Brigham and Women's Hospital and the Department of Social and Behavioral Sciences at the Harvard T.H. Chan School of Public Health in Boston, Massachusetts. "Individuals whose biological age is higher than their chronological age exhibit age acceleration or fast aging. In our study, we found that more severe sleep-disordered breathing is associated with epigenetic age acceleration. Our data provide biological evidence supporting adverse physiological and health effects of untreated sleep-disordered breathing."
Sleep-disordered breathing, such as obstructive sleep apnea, is characterized by abnormalities of respiration during sleep. Episodes often result in reductions in blood oxygen saturation and are usually terminated by brief arousals from sleep. Nearly 30 million adults in the U.S. have obstructive sleep apnea. Common warning signs include snoring and excessive daytime sleepiness.
According to the authors, epigenetic age acceleration is a DNA methylation-based marker of fast biological aging, and it is associated with modifiable lifestyle factors. Although sleep-disordered breathing is associated with multiple age-related health disorders, its relationship with epigenetic aging has not been well studied.
The study involved 622 adults with a mean age of 69 years; 53.2% were women. Participants were measured for blood DNA methylation, and their sleep was evaluated at home by polysomnography. Age acceleration measures were calculated as residuals from the regression of each epigenetic age on chronological age. The association of each sleep-disordered breathing trait with age acceleration was estimated using linear regression, controlling for socio-demographics, health behaviors, body mass index, and study site.
Another surprising finding was that the associations were stronger in women than in men, suggesting that women may be particularly vulnerable to the adverse effects of sleep-disordered breathing.
"While women are often considered to be at lower risk for health outcomes related to sleep-disordered breathing, our findings suggest increased biological susceptibility," said Li.
The authors suggested that future work should study whether treatment reduces epigenetic age acceleration among people who have sleep-disordered breathing.
"Since sleep-disordered breathing is not only common and treatable, but often undiagnosed and under-treated, our data highlight the potential for sleep-disordered breathing treatment to improve age-related chronic conditions and longevity," said Li. "Because epigenetic changes are reversible, epigenetic age estimators may be useful for identifying and validating anti-aging interventions."
abstract Identifying contributors to accelerated aging may elucidate risks and mechanisms for age-related diseases and mortality. A DNA methylation (DNAm)-based marker of fast biological aging, epigenetic age acceleration, is associated with modifiable lifestyle factors. Sleep disordered breathing (SDB) is a common disorder that results in oxidative stress and inflammation and is associated with multiple age-related health disorders; however, SBD has not been well studied with respect to epigenetic aging. We examined the association of SDB traits with epigenetic age acceleration, and whether the association differed by sex.
Methods
A diverse sample (N = 622) had blood DNA methylation measured and underwent Type 2 in-home polysomnography, which assessed apnea-hypopnea index (AHI), percentage of sleep time that oxygen saturation is lower than 90% (Per90), and arousal index. Using DNA methylation, two validated epigenetic age measures were computed: DNAm PhenoAge and DNAm age. Age acceleration measures were calculated as residuals from the regression of each epigenetic age on chronological age. The association of each SDB trait with age acceleration was estimated using linear regression, controlling for socio-demographics, health behaviors, BMI, and study site.
Results
Participants were 53.2% female with a mean age of 68.7 (SD: 9.2) years. AHI was associated with greater DNAm PhenoAge acceleration (β = 0.03; 95% CI [0.00, 0.06]), equivalent to 215 days of DNAm PhenoAge acceleration for 1-SD increase in AHI. Arousal index was associated with greater DNAm age acceleration (β = 0.04; 95% CI [0.01, 0.07]), equivalent to 321 days of DNAm age acceleration for 1-SD increase in arousal index. Both associations were stronger in women compared to men. There was no evidence that Per90 was associated with epigenetic age acceleration or exhibited sex differences.
Conclusion
Increasing SDB severity and sleep disruption was associated with epigenetic age acceleration, independent of measured confounders. These associations were stronger in women than in men, suggesting that women may be particularly vulnerable to the adverse effects of SDB. Future work should study whether treatment reduces epigenetic age acceleration among those individuals with SBD.
prospective study of chronotype and incident depression among middle- and older-aged women in the nurses’ health study ii
céline vetter et al. 2018
http://dx.doi.org/10.1016/j.jpsychires.2018.05.022
staying awake: the surprisingly effective way to treat depression
linda geddes 2018
https://mosaicscience.com/story/staying-awake-surprisingly-effective-way-treat-depression
bereavement, self-reported sleep disturbances and inflammation
diana a. chirinos et al. 2018
http://dx.doi.org/10.1097/PSY.0000000000000645
alarm tones, music and their elements: analysis of reported waking sounds to counteract sleep inertia
stuart j. mcfarlane et al. 2020
http://dx.doi.org/10.1371/journal.pone.0215788
melodic alarms could improve alertness levels, with harsh alarm tones linked to increased levels of morning grogginess.
The surprising finding, published in PLoS One, could have important implications for anyone who needs to perform at their peak soon after waking, such as shift workers and emergency first responders.
Lead author, RMIT doctoral researcher Stuart McFarlane, said morning grogginess — or sleep inertia — was a serious problem in our 24-hour world.
“If you don’t wake properly, your work performance can be degraded for periods up to four hours, and that has been linked to major accidents,” McFarlane said.
“You would assume that a startling ‘beep beep beep’ alarm would improve alertness, but our data revealed that melodic alarms may be the key element. This was unexpected.
abstract Sleep inertia is a potentially dangerous reduction in human alertness and occurs 0–4 hours after waking. The type of sound people set as their alarm for waking has been shown to reduce the effects of sleep inertia, however, the elemental musical factors that underpin these waking sounds and their relationships remain unclear. The goal of this research is to understand how a particular sound or music chosen to assist waking may counteract sleep inertia, and more specifically, what elements of these sounds may contribute to its reduction. Through an anonymous, self-report online questionnaire, fifty participants (N = 50) reported attributes of their preferred waking sound, their feeling towards the waking sound, and perceived sleep inertia after waking. This data enabled the analysis and comparison between these responses to identify statistically significant relationships. Our results did not return any significant association between sleep inertia and the reported waking sound type, nor the subject’s feeling towards their sound. However, the analysis did reveal that a sound which is ranked as melodic by participants shows a significant relationship to reports of reductions in perceived sleep inertia, and in contrast, sound rated as neutral (neither unmelodic nor melodic) returns a significant relationship to the reports of increases in perceived sleep inertia. Additionally, our secondary analysis revealed that a sound rated as melodic is considered to be more rhythmic than a melodically neutral interpretation. Together these findings raise questions regarding the impact melody and rhythm may hold with respect to sleep inertia intensity. Considering that the implementation of auditory assisted awakening is a common occurrence, the musical elements of a chosen waking sound may be an area to further interrogate with respect to counteracting sleep inertia.
how to sleep the art, biology and culture of unconsciousness
matthew fuller 2018toreadnext
the magic of sleep thinking how to solve problems, reduce stress, and increase creativity while you sleep
eric maisel 2018 to read next
the secret world of sleep: the surprising science of the mind at rest
penelope lewis 2013
snooze: the lost art of sleep
michael mcgirr 2017
sleep: the myth of 8 hours, the power of naps... and the new plan to recharge your body and mind
nick littlehales 2016
the circadian code
satchin panda 2018
sustained melanopsin photoresponse is supported by specific roles of β-arrestin 1 and 2 in deactivation and regeneration of photopigment
ludovic s. mure et al. 2018
http://dx.doi.org/10.1016/j.celrep.2018.11.008
“We are continuously exposed to artificial light, whether from screen time, spending the day indoors or staying awake late at night,” says Salk Professor Satchin Panda, senior author of the study. “This lifestyle causes disruptions to our circadian rhythms and has deleterious consequences on health.”
The backs of our eyes contain a sensory membrane called the retina, whose innermost layer contains a tiny subpopulation of light-sensitive cells that operate like pixels in a digital camera. When these cells are exposed to ongoing light, a protein called melanopsin continually regenerates within them, signaling levels of ambient light directly to the brain to regulate consciousness, sleep and alertness. Melanopsin plays a pivotal role in synchronizing our internal clock after 10 minutes of illumination and, under bright light, suppresses the hormone melatonin, responsible for regulating sleep.
“Compared to other light-sensing cells in the eye, melanopsin cells respond as long as the light lasts, or even a few seconds longer,” says Ludovic Mure, staff scientist and first author of the paper. “That’s critical, because our circadian clocks are designed to respond only to prolonged illumination.”
In the new work, the Salk researchers used molecular tools to turn on production of melanopsin in retinal cells in mice. They discovered that some of these cells have the ability to sustain light responses when exposed to repeated long pulses of light, while others become desensitized.
Conventional wisdom has held that proteins called arrestins, which stop the activity of certain receptors, should halt cells’ photosensitive response within seconds of lights coming on. The researchers were surprised to find that arrestins are in fact necessary for melanopsin to continue responding to prolonged illumination.
In mice lacking either version of the arrestin protein (beta arrestin 1 and beta arrestin 2), the melanopsin-producing retinal cells failed to sustain their sensitivity to light under prolonged illumination. The reason, it turns out, is that arrestin helps melanopsin regenerate in the retinal cells.
“Our study suggests the two arrestins accomplish regeneration of melanopsin in a peculiar way,” Panda says. “One arrestin does its conventional job of arresting the response, and the other helps the melanopsin protein reload its retinal light-sensing co-factor. When these two steps are done in quick succession, the cell appears to respond continuously to light.”
By better understanding the interactions of melanopsin in the body and how the eyes react to light, Panda hopes to find new targets to counter skewed circadian rhythms due to, for example, artificial illumination. Previously, Panda’s research team discovered that chemicals called opsinamides could block melanopsin’s activity in mice without affecting their vision, offering a potential therapeutic avenue to address hypersensitivity to light experienced by migraine sufferers. Next, the researchers aim to find ways to influence melanopsin to reset the internal clocks and help with insomnia
abstract
•Phosphorylation of melanopsin upon activation primes binding to β-arrestin 1 and 2
•Each β-arrestin regulates different aspects of melanopsin photoresponses
•β-Arrestin 2 mediates signal termination, and β-arrestin 1 mediates melanopsin recycling
•Both β-arrestins are necessary to sustain melanopsin continuous response
Melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs) are indispensable for non-image-forming visual responses that sustain under prolonged illumination. For sustained signaling of ipRGCs, the melanopsin photopigment must continuously regenerate. The underlying mechanism is unknown. We discovered that a cluster of Ser/Thr sites within the C-terminal region of mammalian melanopsin is phosphorylated after a light pulse. This forms a binding site for β-arrestin 1 (βARR1) and β-arrestin 2. β-arrestin 2 primarily regulates the deactivation of melanopsin; accordingly, _βαrr2_−/− mice exhibit prolonged ipRGC responses after cessation of a light pulse. β-arrestin 1 primes melanopsin for regeneration. Therefore, _βαrr1_−/− ipRGCs become desensitized after repeated or prolonged photostimulation. The lack of either β-arrestin attenuates ipRGC response under prolonged illumination, suggesting that β-arrestin 2-mediated deactivation and β-arrestin 1-dependent regeneration of melanopsin function in sequence. In conclusion, we discovered a molecular mechanism by which β-arrestins regulate different aspects of melanopsin photoresponses and allow ipRGC-sustained responses under prolonged illumination.
nodding off: the science of sleep from cradle to grave
alice gregory 2018
lucid dreaming: a beginner’s guide to becoming conscious in your dreams
charlie morley 2015
the nocturnal brain: nightmares, neuroscience, and the secret world of sleep
guy leschziner 2019
let’s talk about sleep: a guide to understanding and improving your slumber
daniel a. barone 2018
once upon a dream
maleficent/sleeping beauty
Link: soundcloud.com/makiaea/once-upon-a-dream-sleeping-beauty-cover-makiaea-vocal-solo
i know you
i danced with you
once upon a dream
i know you
the gleam in your eyes
is so familiar a gleam
i know its true
visions are seldom
all they seem
but if i know you
i know what you’ll do
you’ll love me at once
the way you did once
upon a dream
sneezing
irritant expulsion, rehydration of airways
shortage of oxygen
overheating leads to nightmares
avoid overheating e.g. by not eating close to time for sleep, keeping blankets to suitable minimum
eat last heavy meal of day at least four hours before bedtime to minimise sleep disturbance
dynamic rem sleep modulation by ambient temperature and the critical role of the melanin-concentrating hormone system
noëmie komagata et al. 2019
http://dx.doi.org/10.1016/j.cub.2019.05.009
Every night while sleeping, we cycle between two very different states of sleep. Upon falling asleep, we enter non-rapid eye movement (non-REM) sleep where our breathing is slow and regular and movement of our limbs or eyes are minimal. Approximately 90 minutes later, how-ever, we enter rapid eye movement (REM) sleep. This is a paradoxical state where our breathing becomes fast and irregular, our limbs twitch, and our eyes move rapidly. In REM sleep, our brain is highly active, but we also become paralyzed and we lose the ability to thermoregulate or maintain our constant body temperature. "This loss of thermoregulation in REM sleep is one of the most peculiar aspects of sleep, particularly since we have finely-tuned mechanisms that control our body temperature while awake or in non-REM sleep," says Markus Schmidt of the Department for BioMedical Research (DBMR) of the University of Bern, and the Department of Neurology, Inselspital, Bern University Hospital. On the one hand, the findings confirm a hypothesis proposed earlier by Schmidt, senior author of the study, and on the other hand represent a breakthrough for sleep medicine. The paper was published in Current Biology and highlighted by the editors with a comment.
A control mechanism saving energy
The need to maintain a constant body temperature is our most expensive biological function. Panting, piloerection, sweating, or shivering are all energy consuming body reactions. In his hypothesis, Markus Schmidt suggested that REM sleep is a behavioral strategy that shifts energy resources away from costly thermoregulatory defense toward, instead, the brain to enhance many brain functions. According to this energy allocation hypothesis of sleep, mammals have evolved mechanisms to increase REM sleep when the need for defending our body temperature is minimized or, rather, to sacrifice REM sleep when we are cold. "My hypothesis predicts that we should have neural mechanisms to dynamically modulate REM sleep expression as a function of our room temperature," says Schmidt. Neuroscientists at the DBMR at the University of Bern and the Department of Neurology at Inselspital, Bern University Hospital, now confirmed his hypothesis and found neurons in the hypothalamus that specifically increase REM sleep when the room temperature is "just right."
REM sleep promoting neurons
The researchers discovered that a small population of neurons within the hypothalamus, called melanin-concentrating hormone (MCH) neurons, play a critical role in how we modulate REM sleep expression as a function of ambient (or room) temperature. The researchers showed that mice will dynamically increase REM sleep when the room temperature is warmed to the high end of their comfort zone, similar to what has been shown for human sleep. However, genetically engineered mice lacking the receptor for MCH are no longer able to increase REM sleep during warming, as if they are blind to the warming temperature. The authors used optogenetics technics to specifically turn on or off MCH neurons using a laser light time locked to the temperature warming periods. Their work confirms the necessity of the MCH system to increase REM sleep when the need for body temperature control is minimized.
Breakthrough for sleep medicine
This is the first time that an area of the brain has been found to control REM sleep as a function of room temperature. "Our discovery of these neurons has major implications for the control of REM sleep," says Schmidt. "It shows that the amount and timing of REM sleep are finely tuned with our immediate environment when we do not need to thermoregulate. It also con-firms how dream sleep and the loss of thermoregulation are tightly integrated."
REM sleep is known to play an important role in many brain functions such as memory consolidation. REM sleep comprises approximately one quarter of our total sleep time. "These new data suggest that the function of REM sleep is to activate important brain functions specifically at times when we do not need to expend energy on thermoregulation, thus optimizing use of energy resources," says Schmidt.
•Wild-type mice dynamically increase REM sleep with ambient temperature (T a) warming
•Optogenetic MCH activation overdrives REM sleep expression during T a warming
•Optogenetic MCH silencing or lack of MCH receptor blocks T a modulation of REM sleep
•The MCH system plays a critical role in modulating REM sleep as a function of T a
Ambient temperature (T a) warming toward the high end of the thermoneutral zone (TNZ) preferentially increases rapid eye movement (REM) sleep over non-REM (NREM) sleep across species. The control and function of this temperature-induced REM sleep expression have remained unknown. Melanin-concentrating hormone (MCH) neurons play an important role in REM sleep control. We hypothesize that the MCH system may modulate REM sleep as a function of T a. Here, we show that wild-type (WT) mice dynamically increased REM sleep durations specifically during warm T a pulsing within the TNZ, compared to both the TNZ cool and baseline constant T a conditions, without significantly affecting either wake or NREM sleep durations. However, genetically engineered MCH receptor-1 knockout (MCHR1-KO) mice showed no significant changes in REM sleep as a function of T a, even with increased sleep pressure following a 4-h sleep deprivation. Using MCH-cre mice transduced with channelrhodopsin, we then optogenetically activated MCH neurons time locked with T a warming, showing an increase in REM sleep expression beyond what T a warming in yellow fluorescent protein (YFP) control mice achieved. Finally, in mice transduced with archaerhodopsin-T, semi-chronic optogenetic MCH neuronal silencing during T a warming completely blocked the increase in REM sleep seen in YFP controls. These data demonstrate a previously unknown role for the MCH system in the dynamic output expression of REM sleep during T a manipulation. These findings are consistent with the energy allocation hypothesis of sleep function, suggesting that endotherms have evolved neural circuits to opportunistically express REM sleep when the need for thermoregulatory defense is minimized.
sleep cycles
exhaustion as a preventative measure by the brain
yoga
relaxation