How sleep aids recovery from infection, may protect brain from Alzheimer's disease

Dimitrov et al. show how a good night's sleep accelerates recovering from an infection. Glue like proteins (integrins) used by immune system T cells to attach to virus particles and mark them for destruction are produced at greater levels during sleep. In the awake state, signaling molecules like adrenaline are produced at greater levels and inhibit integrin production, reducing the ability of T cells to attach to invading microbes. Here is their technical abstract:

Efficient T cell responses require the firm adhesion of T cells to their targets, e.g., virus-infected cells, which depends on T cell receptor (TCR)–mediated activation of β2-integrins. Gαs-coupled receptor agonists are known to have immunosuppressive effects, but their impact on TCR-mediated integrin activation is unknown. Using multimers of peptide major histocompatibility complex molecules (pMHC) and of ICAM-1—the ligand of β2-integrins—we show that the Gαs-coupled receptor agonists isoproterenol, epinephrine, norepinephrine, prostaglandin (PG) E2, PGD2, and adenosine strongly inhibit integrin activation on human CMV- and EBV-specific CD8+ T cells in a dose-dependent manner. In contrast, sleep, a natural condition of low levels of Gαs-coupled receptor agonists, up-regulates integrin activation compared with nocturnal wakefulness, a mechanism possibly underlying some of the immune-supportive effects of sleep. The findings are also relevant for several pathologies associated with increased levels of Gαs-coupled receptor agonists (e.g., tumor growth, malaria, hypoxia, stress, and sleep disturbances).

Also, Holth et al. show that sleep appears to have a direct protective effect on a key protein that drives AD pathology. They provide direct evidence that disrupting sleep, or stimulating excitatory neurons in brain nuclei that control wakefulness and arousal, promotes the release and spread of damaging tau aggregates across the brains of mice, and that sleep deprivation leads to increased extracellular Aβ and tau in people.

The sleep-wake cycle regulates interstitial fluid (ISF) and cerebrospinal fluid (CSF) levels of β-amyloid (Aβ) that accumulates in Alzheimer’s disease (AD). Furthermore, chronic sleep deprivation (SD) increases Aβ plaques. However, tau, not Aβ, accumulation appears to drive AD neurodegeneration. We tested whether ISF/CSF tau and tau seeding and spreading were influenced by the sleep-wake cycle and SD. Mouse ISF tau was increased ~90% during normal wakefulness versus sleep and ~100% during SD. Human CSF tau also increased more than 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 SD increases ISF and CSF tau as well as tau pathology spreading.

The Neuroscience of ‘Rock-a-Bye Baby’

I've always wondered why I sleep like a baby when on a boat being slowly rocked by waves, so was intrigued by Friedman's recent piece pointing to work by Perrault et al. showing that a slow rocking motion not only improves sleep but also can help people consolidate memories overnight. This is because continuous rocking stimulation strengthens deep sleep via the neural entrainment of intrinsic sleep oscillations. The Perrault et al. summary:

Highlights

•Rocking boosts deep sleep, sleep maintenance, and memory in healthy sleepers

•Fast spindles increase during rocking and synchronize with the slow oscillation up-state

• Rocking-induced overnight memory improvement relates to increased sigma activity

• Continuous rocking stimulation actively entrains intrinsic sleep oscillations

Summary

Sensory processing continues during sleep and can influence brain oscillations. We previously showed that a gentle rocking stimulation (0.25 Hz), during an afternoon nap, facilitates wake-sleep transition and boosts endogenous brain oscillations (i.e., EEG spindles and slow oscillations [SOs]). Here, we tested the hypothesis that the rhythmic rocking stimulation synchronizes sleep oscillations, a neurophysiological mechanism referred to as “neural entrainment.” We analyzed EEG brain responses related to the stimulation recorded from 18 participants while they had a full night of sleep on a rocking bed. Moreover, because sleep oscillations are considered of critical relevance for memory processes, we also investigated whether rocking influences overnight declarative memory consolidation. We first show that, compared to a stationary night, continuous rocking shortened the latency to non-REM (NREM) sleep and strengthened sleep maintenance, as indexed by increased NREM stage 3 (N3) duration and fewer arousals. These beneficial effects were paralleled by an increase in SOs and in slow and fast spindles during N3, without affecting the physiological SO-spindle phase coupling. We then confirm that, during the rocking night, overnight memory consolidation was enhanced and also correlated with the increase in fast spindles, whose co-occurrence with the SO up-state is considered to foster cortical synaptic plasticity. Finally, supporting the hypothesis that a rhythmic stimulation entrains sleep oscillations, we report a temporal clustering of spindles and SOs relative to the rocking cycle. Altogether, these findings demonstrate that a continuous rocking stimulation strengthens deep sleep via the neural entrainment of intrinsic sleep oscillations.

Sleeping in standby mode

In the editor's choice section of the current Science Magazine, Claudia Pama points to work by Legendre et al. showing that sleepers process surrounding events sufficiently to know when it might be a good idea to rapidly wake up. Here is the article abstract:

Sleep is a vital need, forcing us to spend a large portion of our life unable to interact with the external world. Current models interpret such extreme vulnerability as the price to pay for optimal learning. Sleep would limit external interferences on memory consolidation and allow neural systems to reset through synaptic downscaling. Yet, the sleeping brain continues generating neural responses to external events, revealing the preservation of cognitive processes ranging from the recognition of familiar stimuli to the formation of new memory representations. Why would sleepers continue processing external events and yet remain unresponsive? Here we hypothesized that sleepers enter a ‘standby mode’ in which they continue tracking relevant signals, finely balancing the need to stay inward for memory consolidation with the ability to rapidly awake when necessary. Using electroencephalography to reconstruct competing streams in a multitalker environment, we demonstrate that the sleeping brain amplifies meaningful speech compared to irrelevant signals. However, the amplification of relevant stimuli was transient and vanished during deep sleep. The effect of sleep depth could be traced back to specific oscillations, with K-complexes promoting relevant information in light sleep, whereas slow waves actively suppress relevant signals in deep sleep. Thus, the selection of relevant stimuli continues to operate during sleep but is strongly modulated by specific brain rhythms.

REM sleep in naps and memory consolidation in typical and Down syndrome children.

From Spano et al.:

Sleep is recognized as a physiological state associated with learning, with studies showing that knowledge acquisition improves with naps. Little work has examined sleep-dependent learning in people with developmental disorders, for whom sleep quality is often impaired. We examined the effect of natural, in-home naps on word learning in typical young children and children with Down syndrome (DS). Despite similar immediate memory retention, naps benefitted memory performance in typical children but hindered performance in children with DS, who retained less when tested after a nap, but were more accurate after a wake interval. These effects of napping persisted 24 h later in both groups, even after an intervening overnight period of sleep. During naps in typical children, memory retention for object-label associations correlated positively with percent of time in rapid eye movement (REM) sleep. However, in children with DS, a population with reduced REM, learning was impaired, but only after the nap. This finding shows that a nap can increase memory loss in a subpopulation, highlighting that naps are not universally beneficial. Further, in healthy preschooler’s naps, processes in REM sleep may benefit learning.

Too much or too little sleep correlates with cognitive deficits.

Wild et al. collected sleep and cognitive performance data from ~10,000 people to find that less than 7 or more than 8 hours of sleep a night diminishes high-level cognitive functioning.

Most people will at some point experience not getting enough sleep over a period of days, weeks, or months. However, the effects of this kind of everyday sleep restriction on high-level cognitive abilities—such as the ability to store and recall information in memory, solve problems, and communicate—remain poorly understood. In a global sample of over 10000 people, we demonstrated that cognitive performance, measured using a set of 12 well-established tests, is impaired in people who reported typically sleeping less, or more, than 7–8 hours per night—which was roughly half the sample. Crucially, performance was not impaired evenly across all cognitive domains. Typical sleep duration had no bearing on short-term memory performance, unlike reasoning and verbal skills, which were impaired by too little, or too much, sleep. In terms of overall cognition, a self-reported typical sleep duration of 4 hours per night was equivalent to aging 8 years. Also, sleeping more than usual the night before testing (closer to the optimal amount) was associated with better performance, suggesting that a single night’s sleep can benefit cognition. The relationship between sleep and cognition was invariant with respect to age, suggesting that the optimal amount of sleep is similar for all adult age groups, and that sleep-related impairments in cognition affect all ages equally. These findings have significant real-world implications, because many people, including those in positions of responsibility, operate on very little sleep and may suffer from impaired reasoning, problem-solving, and communications skills on a daily basis.

Old brains come uncoupled in sleep.

From Helfrich et al.:

Highlights

•Precise coupling of NREM (Non-rapid-eye-movement) slow waves and spindles dictates memory consolidation 

•Aging impairs slow wave-spindle coupling, leading to overnight forgetting 

•Age-related atrophy in mPFC (medial prefrontal cortex) predicts the failure of such coupling and thus memory

Summary

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.

The purpose of sleep? To forget.

In two recent Science papers de Vivo et al. and Diering et al. probe the nightlife of the synapses that control the signalling between cells in our brain. They find substantial alterations in the structure and molecular machinery of synapses during sleep, providing strong evidence for synaptic downscaling during sleep and upscaling during wake, as well as clues to the molecular mechanisms. The idea is that our brain synapses grow during the day, and our brain circuits get more noisy. During sleep our brains pare back the connections to enhance the signal to noise ratio, as we forget some of the things learned during the day. Here is a summary graphic taken from the review by Acsády and Harris:

Most effective learning?... sleep between two practice sessions

From Mazza et al.:

Both repeated practice and sleep improve long-term retention of information. The assumed common mechanism underlying these effects is memory reactivation, either on-line and effortful or off-line and effortless. In the study reported here, we investigated whether sleep-dependent memory consolidation could help to save practice time during relearning. During two sessions occurring 12 hr apart, 40 participants practiced foreign vocabulary until they reached a perfect level of performance. Half of them learned in the morning and relearned in the evening of a single day. The other half learned in the evening of one day, slept, and then relearned in the morning of the next day. Their retention was assessed 1 week later and 6 months later. We found that interleaving sleep between learning sessions not only reduced the amount of practice needed by half but also ensured much better long-term retention. Sleeping after learning is definitely a good strategy, but sleeping between two learning sessions is a better strategy.

Dreams and revelations.

I want to pass on a few clips from an engaging essay by Patrick McNamara, and suggest you read the entire piece. He begins by noting religious movements that trace their origins to dreams of their founders, and then notes:

 ...most people from across most cultures and all of history have treated dreams as direct evidence of a spirit realm. And that raises an obvious question: what is it about dreams that make them such potent vehicles for the supernatural? 

We know that rapid eye movement sleep (REM), when eyes move rapidly back and forth under closed eyelids, is the phase when we have the most vivid dreams. REM is associated with heightened levels of the neurotransmitters dopamine (associated with reward and movement) and acetylcholine (associated with memory), as well as a surge of activity in the limbic system, the amygdala, and the ventromedial prefrontal cortex, all areas of the brain that handle emotion. Conversely, there is lowered activity in the dorsolateral prefrontal cortex, the area of the brain that handles personal insight, rationality and judgement; likewise, the neurochemicals noradrenaline and serotonin, involved in vigilance and self-control, are regulated down. The very low levels of serotonin allow steady release of the excitatory transmitter glutamate, which overstimulates the brain activity thought to underlie the cognitive and perceptual effects of hallucinogens. In other words, in REM sleep, our emotional centres are overstimulated while our reflective rational centres are impeded or narrowly refocused on issues of emotional significance. We are left free to ponder the endless meanings of the emotions and interactions that we experience but we do so with wildly fluctuating levels of reflective insight.

It only makes sense that these REM-related brain changes are also associated with schizophrenia and the high of hallucinogenic drugs such as LSD. REM, schizophrenia and hallucinogens are all associated with the neurologic conditions that produce altered states of consciousness. The neurochemistry of dreams produces an emotionally intense state of mind in the absence of an ability to critically reflect on the images produced by that state. When the hallucinatory REM dream or an acid trip ends, individuals can then reflect on and attempt to interpret the intense experiences they’ve just undergone…The greater the interpretive difficulty, the more significance we impute to the experience – up to a point. That might explain why schizophrenics with positive hallucinations – including visual hallucinations, hearing voices, and delusions – report such high levels of religiosity, attempting to interpret their aberrant experiences through religious symbols, language and tropes.

Where does all this leave us today? On one hand, the link between REM dreams and spiritual experience disturbs some religious people because they fear it suggests that religion is nothing but delusional dreaming and hallucinations. On the other hand, the connection upsets some die-hard atheists, who dislike the idea that spirituality is rooted in our biology – that it is functional and adaptive, and central to who we are. 

What we do with the demonstration that spirituality is rooted in REM sleep and dreams is a personal – perhaps spiritual – choice. But science and society itself would benefit from taking the connection seriously. If our dreams generate spiritual ideas, they might also contribute to a generation of religious-based terrorism and fanaticism. After all, REM sleep has been studied as a model for psychosis. The same chemical brew that produces the dream state can, if tweaked, produce obsessional psychoses and related neuropsychiatric symptoms. Religious fanaticism has a kind of obsessional and paranoid feel to it that links it with REM intrusion into waking life and the subsequent delusional states that follow. The future neuroscience of the spiritual, rooted in the study of dreams, could help us to confront some of our era’s greatest challenges.

Alerting or Somnogenic light - pick your color

Bourgin and Hubbard summarize work by Pilorz et al.

Light exerts profound effects on our physiology and behaviour, setting our biological clocks to the correct time and regulating when we are asleep and we are awake. The photoreceptors mediating these responses include the rods and cones involved in vision, as well as a subset of photosensitive retinal ganglion cells (pRGCs) expressing the blue light-sensitive photopigment melanopsin. Previous studies have shown that mice lacking melanopsin show impaired sleep in response to light. However, other studies have shown that light increases glucocorticoid release—a response typically associated with stress. To address these contradictory findings, we studied the responses of mice to light of different colours. We found that blue light was aversive, delaying sleep onset and increasing glucocorticoid levels. By contrast, green light led to rapid sleep onset. These different behavioural effects appear to be driven by different neural pathways. Surprisingly, both responses were impaired in mice lacking melanopsin. These data show that light can promote either sleep or arousal. Moreover, they provide the first evidence that melanopsin directly mediates the effects of light on glucocorticoids. This work shows the extent to which light affects our physiology and has important implications for the design and use of artificial light sources.

Sleep deprivation, brain structure, and learning

Saletin et al. find that individual differences in the anatomy of the human hippocampus explain many of the differences in learning impairment after sleep loss. These structural differences also predict the subsequent EEG slow-wave activity during recovery sleep and the restoration of learning after sleep.

Significance statement

Sleep deprivation does not impact all people equally. Some individuals show cognitive resilience to the effects of sleep loss, whereas others express striking vulnerability, the reasons for which remain largely unknown. Here, we demonstrate that structural features of the human brain, specifically those within the hippocampus, accurately predict which individuals are susceptible (or conversely, resilient) to memory impairments caused by sleep deprivation. Moreover, this same structural feature determines the success of memory restoration following subsequent recovery sleep. Therefore, structural properties of the human brain represent a novel biomarker predicting individual vulnerability to (and recovery from) the effects of sleep loss, one with occupational relevance in professions where insufficient sleep is pervasive yet memory function is paramount.

Abstract

Sleep deprivation impairs the formation of new memories. However, marked interindividual variability exists in the degree to which sleep loss compromises learning, the mechanistic reasons for which are unclear. Furthermore, which physiological sleep processes restore learning ability following sleep deprivation are similarly unknown. Here, we demonstrate that the structural morphology of human hippocampal subfields represents one factor determining vulnerability (and conversely, resilience) to the impact of sleep deprivation on memory formation. Moreover, this same measure of brain morphology was further associated with the quality of nonrapid eye movement slow wave oscillations during recovery sleep, and by way of such activity, determined the success of memory restoration. Such findings provide a novel human biomarker of cognitive susceptibility to, and recovery from, sleep deprivation. Moreover, this metric may be of special predictive utility for professions in which memory function is paramount yet insufficient sleep is pervasive (e.g., aviation, military, and medicine).

For further reading on insomnia, this article notes several other studies, one noting several right brain regions of lowered connectivity in people with primary insomnia.

How much sleep do we really need?

A study by Yetish et al. casts fascinating light on the widespread idea that a large fraction of us in modern industrial societies are sleep-deprived, going to bed later than is "natural" and sleeping less than our bodies need. They monitored the sleep patterns of three hunter-gatherer cultures in Bolivia, Tanzania, and South Africa. Here is their summary:

Highlights

•Preindustrial societies in Tanzania, Namibia, and Bolivia show similar sleep parameters
•They do not sleep more than “modern” humans, with average durations of 5.7–7.1 hr
•They go to sleep several hours after sunset and typically awaken before sunrise
•Temperature appears to be a major regulator of human sleep duration and timing

Summary 

How did humans sleep before the modern era? Because the tools to measure sleep under natural conditions were developed long after the invention of the electric devices suspected of delaying and reducing sleep, we investigated sleep in three preindustrial societies. We find that all three show similar sleep organization, suggesting that they express core human sleep patterns, most likely characteristic of pre-modern era Homo sapiens. Sleep periods, the times from onset to offset, averaged 6.9–8.5 hr, with sleep durations of 5.7–7.1 hr, amounts near the low end of those industrial societies. There was a difference of nearly 1 hr between summer and winter sleep. Daily variation in sleep duration was strongly linked to time of onset, rather than offset. None of these groups began sleep near sunset, onset occurring, on average, 3.3 hr after sunset. Awakening was usually before sunrise. The sleep period consistently occurred during the nighttime period of falling environmental temperature, was not interrupted by extended periods of waking, and terminated, with vasoconstriction, near the nadir of daily ambient temperature. The daily cycle of temperature change, largely eliminated from modern sleep environments, may be a potent natural regulator of sleep. Light exposure was maximal in the morning and greatly decreased at noon, indicating that all three groups seek shade at midday and that light activation of the suprachiasmatic nucleus is maximal in the morning. Napping occurred on fewer than 7% of days in winter and fewer than 22% of days in summer. Mimicking aspects of the natural environment might be effective in treating certain modern sleep disorders.

Watching sleep deprivation cause a decline in prefrontal control of emotion.

From Simon et al.:

Sleep deprivation has been shown recently to alter emotional processing possibly associated with reduced frontal regulation. Such impairments can ultimately fail adaptive attempts to regulate emotional processing (also known as cognitive control of emotion), although this hypothesis has not been examined directly. Therefore, we explored the influence of sleep deprivation on the human brain using two different cognitive–emotional tasks, recorded using fMRI and EEG. Both tasks involved irrelevant emotional and neutral distractors presented during a competing cognitive challenge, thus creating a continuous demand for regulating emotional processing. Results reveal that, although participants showed enhanced limbic and electrophysiological reactions to emotional distractors regardless of their sleep state, they were specifically unable to ignore neutral distracting information after sleep deprivation. As a consequence, sleep deprivation resulted in similar processing of neutral and negative distractors, thus disabling accurate emotional discrimination. As expected, these findings were further associated with a decrease in prefrontal connectivity patterns in both EEG and fMRI signals, reflecting a profound decline in cognitive control of emotion. Notably, such a decline was associated with lower REM sleep amounts, supporting a role for REM sleep in overnight emotional processing. Altogether, our findings suggest that losing sleep alters emotional reactivity by lowering the threshold for emotional activation, leading to a maladaptive loss of emotional neutrality.

Consolidating motor skills in our sleep.

It is well known that sleep, in ourselves and in other animals, helps in consolidating learned motor tasks. (When I am learning difficult passage in a new piano piece I’m preparing for performance, during initial stages of waking I observe my mind playing through the notes.) Ramanathan et al. examine the neurophysiological basis for this by recording from single motor cells in the rat brain to examine the replay of synchronous neural activity during sleep that mediates large-scale neural plasticity and stabilizes kinematics during early motor learning:

Sleep has been shown to help in consolidating learned motor tasks. In other words, sleep can induce “offline” gains in a new motor skill even in the absence of further training. However, how sleep induces this change has not been clearly identified. One hypothesis is that consolidation of memories during sleep occurs by “reactivation” of neurons engaged during learning. In this study, we tested this hypothesis by recording populations of neurons in the motor cortex of rats while they learned a new motor skill and during sleep both before and after the training session. We found that subsets of task-relevant neurons formed highly synchronized ensembles during learning. Interestingly, these same neural ensembles were reactivated during subsequent sleep blocks, and the degree of reactivation was correlated with several metrics of motor memory consolidation. Specifically, after sleep, the speed at which animals performed the task while maintaining accuracy was increased, and the activity of the neuronal assembles were more tightly bound to motor action. Further analyses showed that reactivation events occurred episodically and in conjunction with spindle-oscillations—common bursts of brain activity seen during sleep. This observation is consistent with previous findings in humans that spindle-oscillations correlate with consolidation of learned tasks. Our study thus provides insight into the neuronal network mechanism supporting consolidation of motor memory during sleep and may lead to novel interventions that can enhance skill learning in both healthy and injured nervous systems.

More bad things about sleep debt.

This post is to point to two recent articles on pathologies induced by sleep debt. He et al. show that sleep restriction impairs blood-brain barrier function:

The blood–brain barrier (BBB) is a large regulatory and exchange interface between the brain and peripheral circulation. We propose that changes of the BBB contribute to many pathophysiological processes in the brain of subjects with chronic sleep restriction (CSR). To achieve CSR that mimics a common pattern of human sleep loss, we quantified a new procedure of sleep disruption in mice by a week of consecutive sleep recording. We then tested the hypothesis that CSR compromises microvascular function. CSR not only diminished endothelial and inducible nitric oxide synthase, endothelin1, and glucose transporter expression in cerebral microvessels of the BBB, but it also decreased 2-deoxy-glucose uptake by the brain. The expression of several tight junction proteins also was decreased, whereas the level of cyclooxygenase-2 increased. This coincided with an increase of paracellular permeability of the BBB to the small tracers sodium fluorescein and biotin. CSR for 6 d was sufficient to impair BBB structure and function, although the increase of paracellular permeability returned to baseline after 24 h of recovery sleep. This merits attention not only in neuroscience research but also in public health policy and clinical practice.

And, Weljie et al. find cross-species molecular markers of sleep debt:

Reduced sleep duration is a hallmark of modern-day society and is increasingly associated with medical conditions, such as diabetes, obesity, metabolic syndrome, and cardiovascular disease. Here we present data from a rat model and human clinical study of chronic sleep restriction, both revealing that two metabolites in blood, oxalic acid and diacylglycerol 36:3, are quantitatively depleted under sleep-restricted conditions and restored after recovery sleep. Our findings also reveal a significant overall shift in lipid metabolism, with higher levels of phospholipids in both species and evidence of a systemic oxidative environment. This work provides a potential link between the known pathologies of reduced sleep duration and metabolic dysfunction.

Unlearning social biases during sleep

Feld and Born note that tenacious implicit prejudices of race or gender drive discrimination seen in the rise of nationalistic groups, excessive police violence against minority group members, persisting unequal pay for women, and sexual harassment all across the developed world. They point to work by Hu et al. that shows how such unwanted attitudes may be persistently changed by a social counterbias training when the fresh memories of this training are systematically reactivated during sleep after training. Here is part of their summary:

Sleep, and specifically deep or slow-wave sleep [non–rapid eye movement (REM) sleep], benefits memory formation by reactivating neuronal traces that were formed during the preceding period of wakefulness. This reactivation of specific memories leads to their strengthening and transformation. Such reactivation can be experimentally induced during slow-wave sleep by presenting cues that were present during the prior period of memory acquisition. Initial studies showed that an odor present during learning of object locations enhances these memories when the participant is reexposed to the odor during slow-wave sleep after learning. These findings have been confirmed in numerous studies investigating different memory systems and also when auditory instead of olfactory cues are used. This basic research has firmly established the possibility of influencing sleep to enhance specific newly learned memories by targeted memory reactivation.

The findings by Hu et al. now suggest that this method can also be used to influence implicit attitudes that are known to typically manifest themselves early during childhood and remain very stable into adulthood. Before a 90-min nap, participants underwent training aimed at countering typical implicit gender and racial biases by learning to associate genders and races with opposing attributes; that is, to associate female faces with science-related words and black faces with “good” words. Critically, presentation of the to-be-learned counterassociations was combined with a sound, which served as a cue to promote the reactivation of the newly learned associations during a subsequent nap while the participant was deep in slow-wave sleep. Only when this sound was re-presented during slow-wave sleep did the posttraining reduction in implicit social bias survive and was even evident 1 week later. These findings are all the more convincing as the authors conducted the reactivation step during a 90-min daytime nap. During normal sleep at night, the effects are expected to be even stronger, owing to the generally deeper and longer periods of slow-wave sleep and REM sleep. Additionally, the accompanying neuroendocrine milieu makes nocturnal sleep even more efficient for memory reinforcement.

Previous studies have shown that such targeted reactivation of memory during sleep can effectively extinguish unwanted behavior such as experimentally induced fear in humans. The present study is the first to demonstrate that this method can be used to break long-lived, highly pervasive response habits deeply rooted in memory and thereby influence behavior at an entirely unconscious level.

A caution:

However, Aldous Huxley's description of a dystopian “brave new world” where young children are conditioned to certain values during sleep reminds us that this research also needs to be guided by ethical considerations. Sleep is a state in which the individual is without willful consciousness and therefore vulnerable to suggestion. Beyond that, Hu et al.'s findings highlight the breadth of possible applications to permanently modify any unwanted behavior by targeted memory reactivation during sleep.

Sleep stabilizes, but does not enhance, motor performance training.

From Nettersheim et al., a result challenging the prominent model that sleep enhances the performance of a newly learned skill (which is my experience in learning difficulat new piano passages):

Sleep supports the consolidation of motor sequence memories, yet it remains unclear whether sleep stabilizes or actually enhances motor sequence performance. Here we assessed the time course of motor memory consolidation in humans, taking early boosts in performance into account and varying the time between training and sleep. Two groups of subjects, each participating in a short wake condition and a longer sleep condition, were trained on the sequential finger-tapping task in the evening and were tested (1) after wake intervals of either 30 min or 4 h and (2) after a night of sleep that ensued either 30 min or 4 h after training. The results show an early boost in performance 30 min after training and a subsequent decay across the 4 h wake interval. When sleep followed 30 min after training, post-sleep performance was stabilized at the early boost level. Sleep at 4 h after training restored performance to the early boost level, such that, 12 h after training, performance was comparable regardless of whether sleep occurred 30 min or 4 h after training. These findings indicate that sleep does not enhance but rather stabilizes motor sequence performance without producing additional gains.

Metacognitive mechanisms underlying lucid dreaming.

Metacognition is the ability to observe, reflect on, and report one's own mental states during wakefulness. Dreaming is not typically accessible to this kind of monitoring, except in people who are lucid dreamers, aware that they are dreaming while in the sleep state (I can do this). Filevich et al. have looked for relationships between the neural correlates of lucid dreaming and thought monitoring:

Lucid dreaming is a state of awareness that one is dreaming, without leaving the sleep state. Dream reports show that self-reflection and volitional control are more pronounced in lucid compared with nonlucid dreams. Mostly on these grounds, lucid dreaming has been associated with metacognition. However, the link to lucid dreaming at the neural level has not yet been explored. We sought for relationships between the neural correlates of lucid dreaming and thought monitoring.

Human participants completed a questionnaire assessing lucid dreaming ability, and underwent structural and functional MRI. We split participants based on their reported dream lucidity. Participants in the high-lucidity group showed greater gray matter volume in the frontopolar cortex (BA9/10) compared with those in the low-lucidity group. Further, differences in brain structure were mirrored by differences in brain function. The BA9/10 regions identified through structural analyses showed increases in blood oxygen level-dependent signal during thought monitoring in both groups, and more strongly in the high-lucidity group.

Our results reveal shared neural systems between lucid dreaming and metacognitive function, in particular in the domain of thought monitoring. This finding contributes to our understanding of the mechanisms enabling higher-order consciousness in dreams.

Memory reactivation during rest supports upcoming learning of related content.

I have found that a brief period of rest, around 20 minutes or so, after I have worked on learning the notes and fingering of a new piano piece, has a huge effect on the ease of my subsequent learning and consolidation of the difficult passage when I return to practice. Now Schlicting and Preston have looked at the neural basis of this enhancement of subsequent learning of related material. I pass on both their statement of significance and their abstract:

Significance

How our brains capture and store new information is heavily influenced by what we already know. While prior work demonstrates that existing memories are spontaneously reactivated and strengthened in the brain during passive rest periods, the prospective benefits of spontaneous offline reactivation for future learning remain unknown. Here, we use functional MRI to interrogate how reactivation and interregional coupling support the ability to learn related content in later situations. We find that offline processing of prior memories is associated with better subsequent learning. Our results provide a mechanistic account of the circumstances under which prior knowledge can come to facilitate—as opposed to interfere with—new learning, serving as a strong foundation upon which new content is encoded.

Abstract

Although a number of studies have highlighted the importance of offline processes for memory, how these mechanisms influence future learning remains unknown. Participants with established memories for a set of initial face–object associations were scanned during passive rest and during encoding of new related and unrelated pairs of objects. Spontaneous reactivation of established memories and enhanced hippocampal–neocortical functional connectivity during rest was related to better subsequent learning, specifically of related content. Moreover, the degree of functional coupling during rest was predictive of neural engagement during the new learning experience itself. These results suggest that through rest-phase reactivation and hippocampal–neocortical interactions, existing memories may come to facilitate encoding during subsequent related episodes.

Our sleep cycle started 700 million years ago in a worm?

Zimmer points to a nice piece of work by Tosches et al. suggesting that the melatonin rhythm that regulates our sleep may have arisen ~700 million years ago in a marine worm larvae - to regulate swarming up to the surface of the sea at twilight to feed and then sink back to lower depths during light to avoid sunlight and predation. A clip from the Zimmer review:

The new study offers an intriguing idea for how our vertebrate ancestors adapted the melatonin genes as they evolved a complex brain.

Originally, the day-night cycle was run by all-purpose cells that could catch light and make melatonin. But then the work was spread among specialized cells. The eyes now took care of capturing light, for example, while the pineal gland made melatonin.

The new study may also help explain how sleep cuts us off from the world. When we’re awake, signals from our eyes and other senses pass through the thalamus, a gateway in the brain. Melatonin shuts the thalamus down by causing its neurons to produce a regular rhythm of bursts. “They’re busy doing their own thing, so they can’t relay information to the rest of the brain,” Dr. Tosches said.

It may be no coincidence that in worms, melatonin also produces electrical rhythms that jam the normal signals of the day. We may sink into sleep the way our ancestors sank into the depths of the ocean.