Why We Sleep? A manifesto in defence of sleep

Why We Sleep? A manifesto in defence of sleep In the Western world of the 21st Century, we face a culture of increasing demand and distraction, where we are constantly expected to be connected, with the result that time allocated to sleep is increasingly truncated and neglected. This is the point made by Professor Matthew Walker in the first paragraph of his bestselling book ‘Why We Sleep’, stating that two-thirds of adults in all developed nations fail to obtain the recommended 8 h of sleep advocated by the WHO and the National Sleep Foundation in the USA. Matthew Walker is Professor of Neuroscience and Psychology at the University of California, Berkeley, and founder and Director of the Centre for Human Sleep Science, and more interestingly a self-appointed sleep diplomat. Western society’s attitude to sleep was blithely encapsulated in a comment made by a lawyer to her therapist in a popular current TV series. In expressing how time-pressured she was, she asked whether the intervention being discussed could be employed during sleep as ‘this was 4 hours in her day that she didn’t need’. Indeed, as Professor Walker states, much of Western society’s apathy towards sleep can be accounted for by science’s failure to explain the evolutionary purpose of sleep or why we need it. This in turn has led to a scenario in which neglecting sleep has become the norm, to the point that the WHO has declared that there is a sleep deficiency epidemic in industrialized countries. If sleep is unnecessary, he argues, why is some form of sleep ubiquitous across all species studied, but also why are humans the only species that regularly (and routinely) chooses to deprive itself of adequate sleep time? (Fig. 1). Figure 1 View largeDownload slide Sleep-time and well-being. Reduced average sleeping time and ill-health. Figure 1 View largeDownload slide Sleep-time and well-being. Reduced average sleeping time and ill-health. View largeDownload slide WHY WE SLEEP: THE NEW SCIENCE OF SLEEP AND DREAMS By Matthew Walker, 2018 Penguin, London ISBN-13: 978-0141983769 Price: £9.99 View largeDownload slide WHY WE SLEEP: THE NEW SCIENCE OF SLEEP AND DREAMS By Matthew Walker, 2018 Penguin, London ISBN-13: 978-0141983769 Price: £9.99 Nevertheless no one is advocating that people can do without sleep completely. It has been shown experimentally in rats that total sleep deprivation is rapidly fatal in a comparable time frame to total food deprivation, on average 15 days. Absence of rapid eye movement (REM) sleep was similarly fatal in about 15 days whilst selective suppression of non-REM sleep was also fatal but in a longer time frame (around 45 days) (Rechtschaffen et al., 1983). The fact that complete sleep deprivation is similarly fatal is illustrated by the rare prion disorder ‘fatal familial insomnia’ and the tragic case of Michael Corke, who contracted the disease at the age of 40, dying 2 years later bedbound and aphasic in a state comparable to end-stage dementia. Our understanding of sleep physiology and the role of the different sleep stages has increased significantly since the seminal work of Eugene Aserinsky and Nathaniel Kleitman in 1952 when they recognized that sleep could be subdivided into different stages based on their defining ocular features (Aserinsky and Kleitman, 2003). The oscillation between non-REM sleep, which can be further subdivided into light (stages 1 and 2) and deep non-REM (stages 3 and 4), and REM sleep, constitutes the sleep cycle. REM sleep, which predominates in the later stages of the sleep cycle, also predominates in early life, both in the foetus and early childhood, progressively decreasing thereafter. Non-REM, especially deep non-REM, appears to be instrumental in brain maturation and seems to be particularly important in teenagers for the healthy transition into adulthood. Indeed, suppression of deep non-REM sleep in juvenile rats prevented maturational refinement of brain connectivity (Frank et al., 2001). Moreover, caffeine has been shown to disrupt deep non-REM sleep in juvenile rats, delaying several measures of brain maturation as well as the development of appropriate social activity (Olini et al., 2013). Could increasing use of caffeine potentially have similar consequences in teenagers? The importance of recognizing the differences in the circadian rhythm between people of different ages is a major point in Walker’s book, with the author strongly advocating later school starts (for example 10 am) in line with teenagers’ natural circadian rhythm (late to bed, late to rise). Potential benefits might include improved academic performance and a reduction in behavioural issues. Whilst the title of the book asks why we sleep, the book is mainly focused on the deleterious effects of a lack of sleep, in particular a predisposition to ill health. Indeed, chronic sleep deprivation appears to be associated with myriad poor health outcomes including poorer cognitive function, impaired immunological responses (and reduced efficacy of vaccines) and an increased risk of diabetes and obesity, to name but a few. Epidemiological data from the USA, for example, demonstrate an inverse relationship between the average number of hours slept (9 h in the 1940s to under 7 h in the 2000s) and the prevalence of obesity in the population (12.5% in the 1940s to 35% in the 2000s) (Fig. 2). Figure 2 View largeDownload slide Sleep loss and obesity. The inverse relationship between decreasing levels of sleep and increasing obesity levels (US National Demographic Data). Figure 2 View largeDownload slide Sleep loss and obesity. The inverse relationship between decreasing levels of sleep and increasing obesity levels (US National Demographic Data). In addition to the increased risk of comorbidities with chronic sleep deprivation, sleep deprivation also increases the risk of occupational injury and in particular road traffic accidents. Walker describes a study using a driving stimulator, in which the number of off-road deviations was compared in participants who had been divided into four groups with different experimental conditions: (i) 8 h of sleep; (ii) 4 h of sleep; (iv) 8 h of sleep plus alcohol to the point of being legally drunk; and (iv) 4 h of sleep plus alcohol to the point of being legally drunk. Those who had slept 8 h made few if any off-road errors. The subjects who had slept 4 h and those who were legally drunk had a comparable level of errors, making six times more off-road errors than the first group. In contrast, those in the fourth group, who had had only 4 h of sleep and were also legally drunk made almost 30 times more off-road deviations compared to the sober well-rested group, indicating a multiplicative effect of sleep deprivation and alcohol (Horne et al., 2003). This effect seems to be exacerbated in the presence of a pre-existing (untreated) sleep condition. In addition to the negative effects of sleep deprivation, Walker also discusses the benefits and restorative effects of sleep on memory and learning consolidation. In a study examining the effects of a daytime nap on learning and memory, healthy volunteers were divided into nap and no-nap groups. Both underwent a rigorous session of learning involving 100 face-name pairs at 12 pm, with the two groups obtaining comparable results. Thereafter one group was allowed to sleep for 90 min (with EEG recording to monitor the depth of sleep) whilst the no-nap group stayed awake and continued performing mental activities throughout the day. At 6 pm the two groups underwent a further session of intensive learning. Those who had stayed awake (no-nap group) demonstrated a progressive deterioration in learning ability despite a stable level of concentration. In contrast, those in the nap group demonstrated improved memory capacity, with a not insignificant learning advantage of 20% in the 6 pm test (Mander et al., 2011). Further analysis of why sleep was beneficial to memory suggested that the benefits may be related to the amount of lighter stage 2 non-REM sleep obtained, and in particular the number of sleep spindles. This was predictive of the change in learning from before relative to after sleep, i.e. the more sleep spindles an individual generated, the greater the restorative effect of sleep on learning ability. In a further study participants learned a list of facts before going to bed, being allowed a full 8 h of sleep (with EEG recording). Participants were tested the following morning for memory retention, and the quality of their sleep was analysed. The amount of deep non-REM sleep (and sleep spindles) correlated with the number of facts retained. This is of interest as the amount and quality of deep non-REM sleep deteriorates with age. Individuals aged 60–80 years generate 40% fewer sleep spindles compared to healthy young adults (Mander et al., 2014). Moreover, Walker and colleagues showed that the fewer sleep spindles an elderly individual produced in a particular night, the poorer their learning ability and retention of material presented to them the night before. Those who routinely sleep less than 6 h a night seem to be at particular risk of depriving themselves of deep non-REM, which typically occurs later in the sleep cycle. The association between sleep disruption and the risk of Alzheimer’s disease is an area of significant public health importance. Sleep disorders such as insomnia are relatively common in people with dementia, and the association between the two appears to be more than casual. In Alzheimer’s disease, the accumulation of amyloid-β starts early (and later becomes most severe) in the medial prefrontal cortex (mPFC), which also appears crucial for the generation of deep non-REM sleep in healthy individuals (Mander et al., 2013). Walker and colleagues have subsequently shown in studies using PET scans, that the greater the amount of amyloid-β deposited in the mPFC, the lower the quality of deep non-REM sleep in an individual (Mander et al., 2015). In another study, they presented elderly individuals showing varying degrees of amyloid deposition with a list of new facts and tested their memory retention the following morning. Those with severe amyloid deposits in the frontal lobes had the most severe loss of deep non-REM sleep and in addition performed the worst in the memory test (Mander et al., 2015). This led Walker to make the prediction that chronic sleep deprivation throughout adult life significantly increases the risk of Alzheimer’s disease in later life, a link that has been shown in several epidemiological studies of people with chronic insomnia and sleep-disrupting conditions (Lim et al., 2013). Two conclusions can be drawn from such studies: (i) diagnosing and treating disorders that result in chronic sleep deprivation such as obstructive sleep apnoea is of paramount importance as a public health initiative to reduce the overall burden of dementia; and (ii) it raises the intriguing possibility that finding a means of restoring the quality and amount of deep non-REM sleep in elderly individuals and people with dementia, as Walker and others are trying to do, may be protective against Alzheimer’s disease or slow progression in individuals already affected (Mander et al., 2016). In summary, Walker does a commendable job in bridging the gap between cutting edge sleep research and popular science. In so doing, he performs an important public service in highlighting the importance (and benefits) of a good night’s sleep in our society where such a goal is increasingly marginalized. On an individual level, I doubt if anyone who reads this book will ever feel comfortable getting only 5–6 h of sleep per night or indeed with the normalized state of sleep deprivation that increasingly exists and indeed is lauded, in Western societies. Perhaps that, in writing this book, will be Walker’s greatest achievement. References Aserinsky E , Kleitman N . Regularly occurring periods of eye motility, and concomitant phenomena, during sleep. 1953. Comment in Fiftieth anniversary of the discovery of rapid eye movement (REM) sleep . J Neuropsychiatry Clin Neurosci 2003 ; 15 : 454 – 5 . Google Scholar CrossRef Search ADS PubMed Frank MG , Issa NP , Stryker MP . Sleep enhances plasticity in the developing visual cortex . Neuron 2001 ; 30 : 275 – 87 . Google Scholar CrossRef Search ADS PubMed Horne JA , Reyner LA , Barrett PR . Driving impairment due to sleepiness is exacerbated by low alcohol intake . Occup Environ Med 2003 ; 60 : 689 – 92 . Google Scholar CrossRef Search ADS PubMed Lim AS , Kowgier M , Yu L , Buchman AS , Bennett DA . Sleep fragmentation and the risk of incident Alzheimer's disease and cognitive decline in older persons . Sleep 2013 ; 36 : 1027 – 32 . Google Scholar CrossRef Search ADS PubMed Mander BA , Marks SM , Vogel JW , Rao V , Lu B , Saletin JM , et al. β-amyloid disrupts human NREM slow waves and related hippocampus-dependent memory consolidation . Nat Neurosci 2015 ; 18 : 1051 – 7 . Google Scholar CrossRef Search ADS PubMed Mander BA , Rao V , Lu B , Saletin JM , Ancoli-Israel S , Jagust WJ , et al. Impaired prefrontal sleep spindle regulation of hippocampal-dependent learning in older adults . Cereb Cortex 2014 ; 24 : 3301 – 9 . Google Scholar CrossRef Search ADS PubMed Mander BA , Rao V , Lu B , Saletin JM , Lindquist JR , Ancoli-Israel S , et al. Prefrontal atrophy, disrupted NREM slow waves and impaired hippocampal-dependent memory in aging . Nat Neurosci 2013 ; 16 : 357 – 64 . Google Scholar CrossRef Search ADS PubMed Mander BA , Santhanam S , Saletin JM , Walker MP . Wake deterioration and sleep restoration of human learning . Curr Biol 2011 ; 21 : R183 – 4 . Google Scholar CrossRef Search ADS PubMed Mander BA , Winer JR , Jagust WJ , Walker MP . Sleep: a novel mechanistic pathway, biomarker, and treatment target in the pathology of Alzheimer's disease? Trends Neurosci 2016 ; 39 : 552 – 66 . Google Scholar CrossRef Search ADS PubMed Olini N , Kurth S , Huber R . The effects of caffeine on sleep and maturational markers in the rat . PLoS One 2013 ; 8 : e72539 . Google Scholar CrossRef Search ADS PubMed Rechtschaffen A , Gilliland MA , Bergmann BM , Winter JB . Physiological correlates of prolonged sleep deprivation in rats . Science 1983 ; 221 : 182 – 4 . Google Scholar CrossRef Search ADS PubMed © The Author(s) (2018). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email: journals.permissions@oup.com This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Brain Oxford University Press

Why We Sleep? A manifesto in defence of sleep

Brain , Volume Advance Article (6) – Apr 27, 2018

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Abstract

In the Western world of the 21st Century, we face a culture of increasing demand and distraction, where we are constantly expected to be connected, with the result that time allocated to sleep is increasingly truncated and neglected. This is the point made by Professor Matthew Walker in the first paragraph of his bestselling book ‘Why We Sleep’, stating that two-thirds of adults in all developed nations fail to obtain the recommended 8 h of sleep advocated by the WHO and the National Sleep Foundation in the USA. Matthew Walker is Professor of Neuroscience and Psychology at the University of California, Berkeley, and founder and Director of the Centre for Human Sleep Science, and more interestingly a self-appointed sleep diplomat. Western society’s attitude to sleep was blithely encapsulated in a comment made by a lawyer to her therapist in a popular current TV series. In expressing how time-pressured she was, she asked whether the intervention being discussed could be employed during sleep as ‘this was 4 hours in her day that she didn’t need’. Indeed, as Professor Walker states, much of Western society’s apathy towards sleep can be accounted for by science’s failure to explain the evolutionary purpose of sleep or why we need it. This in turn has led to a scenario in which neglecting sleep has become the norm, to the point that the WHO has declared that there is a sleep deficiency epidemic in industrialized countries. If sleep is unnecessary, he argues, why is some form of sleep ubiquitous across all species studied, but also why are humans the only species that regularly (and routinely) chooses to deprive itself of adequate sleep time? (Fig. 1). Figure 1 View largeDownload slide Sleep-time and well-being. Reduced average sleeping time and ill-health. Figure 1 View largeDownload slide Sleep-time and well-being. Reduced average sleeping time and ill-health. View largeDownload slide WHY WE SLEEP: THE NEW SCIENCE OF SLEEP AND DREAMS By Matthew Walker, 2018 Penguin, London ISBN-13: 978-0141983769 Price: £9.99 View largeDownload slide WHY WE SLEEP: THE NEW SCIENCE OF SLEEP AND DREAMS By Matthew Walker, 2018 Penguin, London ISBN-13: 978-0141983769 Price: £9.99 Nevertheless no one is advocating that people can do without sleep completely. It has been shown experimentally in rats that total sleep deprivation is rapidly fatal in a comparable time frame to total food deprivation, on average 15 days. Absence of rapid eye movement (REM) sleep was similarly fatal in about 15 days whilst selective suppression of non-REM sleep was also fatal but in a longer time frame (around 45 days) (Rechtschaffen et al., 1983). The fact that complete sleep deprivation is similarly fatal is illustrated by the rare prion disorder ‘fatal familial insomnia’ and the tragic case of Michael Corke, who contracted the disease at the age of 40, dying 2 years later bedbound and aphasic in a state comparable to end-stage dementia. Our understanding of sleep physiology and the role of the different sleep stages has increased significantly since the seminal work of Eugene Aserinsky and Nathaniel Kleitman in 1952 when they recognized that sleep could be subdivided into different stages based on their defining ocular features (Aserinsky and Kleitman, 2003). The oscillation between non-REM sleep, which can be further subdivided into light (stages 1 and 2) and deep non-REM (stages 3 and 4), and REM sleep, constitutes the sleep cycle. REM sleep, which predominates in the later stages of the sleep cycle, also predominates in early life, both in the foetus and early childhood, progressively decreasing thereafter. Non-REM, especially deep non-REM, appears to be instrumental in brain maturation and seems to be particularly important in teenagers for the healthy transition into adulthood. Indeed, suppression of deep non-REM sleep in juvenile rats prevented maturational refinement of brain connectivity (Frank et al., 2001). Moreover, caffeine has been shown to disrupt deep non-REM sleep in juvenile rats, delaying several measures of brain maturation as well as the development of appropriate social activity (Olini et al., 2013). Could increasing use of caffeine potentially have similar consequences in teenagers? The importance of recognizing the differences in the circadian rhythm between people of different ages is a major point in Walker’s book, with the author strongly advocating later school starts (for example 10 am) in line with teenagers’ natural circadian rhythm (late to bed, late to rise). Potential benefits might include improved academic performance and a reduction in behavioural issues. Whilst the title of the book asks why we sleep, the book is mainly focused on the deleterious effects of a lack of sleep, in particular a predisposition to ill health. Indeed, chronic sleep deprivation appears to be associated with myriad poor health outcomes including poorer cognitive function, impaired immunological responses (and reduced efficacy of vaccines) and an increased risk of diabetes and obesity, to name but a few. Epidemiological data from the USA, for example, demonstrate an inverse relationship between the average number of hours slept (9 h in the 1940s to under 7 h in the 2000s) and the prevalence of obesity in the population (12.5% in the 1940s to 35% in the 2000s) (Fig. 2). Figure 2 View largeDownload slide Sleep loss and obesity. The inverse relationship between decreasing levels of sleep and increasing obesity levels (US National Demographic Data). Figure 2 View largeDownload slide Sleep loss and obesity. The inverse relationship between decreasing levels of sleep and increasing obesity levels (US National Demographic Data). In addition to the increased risk of comorbidities with chronic sleep deprivation, sleep deprivation also increases the risk of occupational injury and in particular road traffic accidents. Walker describes a study using a driving stimulator, in which the number of off-road deviations was compared in participants who had been divided into four groups with different experimental conditions: (i) 8 h of sleep; (ii) 4 h of sleep; (iv) 8 h of sleep plus alcohol to the point of being legally drunk; and (iv) 4 h of sleep plus alcohol to the point of being legally drunk. Those who had slept 8 h made few if any off-road errors. The subjects who had slept 4 h and those who were legally drunk had a comparable level of errors, making six times more off-road errors than the first group. In contrast, those in the fourth group, who had had only 4 h of sleep and were also legally drunk made almost 30 times more off-road deviations compared to the sober well-rested group, indicating a multiplicative effect of sleep deprivation and alcohol (Horne et al., 2003). This effect seems to be exacerbated in the presence of a pre-existing (untreated) sleep condition. In addition to the negative effects of sleep deprivation, Walker also discusses the benefits and restorative effects of sleep on memory and learning consolidation. In a study examining the effects of a daytime nap on learning and memory, healthy volunteers were divided into nap and no-nap groups. Both underwent a rigorous session of learning involving 100 face-name pairs at 12 pm, with the two groups obtaining comparable results. Thereafter one group was allowed to sleep for 90 min (with EEG recording to monitor the depth of sleep) whilst the no-nap group stayed awake and continued performing mental activities throughout the day. At 6 pm the two groups underwent a further session of intensive learning. Those who had stayed awake (no-nap group) demonstrated a progressive deterioration in learning ability despite a stable level of concentration. In contrast, those in the nap group demonstrated improved memory capacity, with a not insignificant learning advantage of 20% in the 6 pm test (Mander et al., 2011). Further analysis of why sleep was beneficial to memory suggested that the benefits may be related to the amount of lighter stage 2 non-REM sleep obtained, and in particular the number of sleep spindles. This was predictive of the change in learning from before relative to after sleep, i.e. the more sleep spindles an individual generated, the greater the restorative effect of sleep on learning ability. In a further study participants learned a list of facts before going to bed, being allowed a full 8 h of sleep (with EEG recording). Participants were tested the following morning for memory retention, and the quality of their sleep was analysed. The amount of deep non-REM sleep (and sleep spindles) correlated with the number of facts retained. This is of interest as the amount and quality of deep non-REM sleep deteriorates with age. Individuals aged 60–80 years generate 40% fewer sleep spindles compared to healthy young adults (Mander et al., 2014). Moreover, Walker and colleagues showed that the fewer sleep spindles an elderly individual produced in a particular night, the poorer their learning ability and retention of material presented to them the night before. Those who routinely sleep less than 6 h a night seem to be at particular risk of depriving themselves of deep non-REM, which typically occurs later in the sleep cycle. The association between sleep disruption and the risk of Alzheimer’s disease is an area of significant public health importance. Sleep disorders such as insomnia are relatively common in people with dementia, and the association between the two appears to be more than casual. In Alzheimer’s disease, the accumulation of amyloid-β starts early (and later becomes most severe) in the medial prefrontal cortex (mPFC), which also appears crucial for the generation of deep non-REM sleep in healthy individuals (Mander et al., 2013). Walker and colleagues have subsequently shown in studies using PET scans, that the greater the amount of amyloid-β deposited in the mPFC, the lower the quality of deep non-REM sleep in an individual (Mander et al., 2015). In another study, they presented elderly individuals showing varying degrees of amyloid deposition with a list of new facts and tested their memory retention the following morning. Those with severe amyloid deposits in the frontal lobes had the most severe loss of deep non-REM sleep and in addition performed the worst in the memory test (Mander et al., 2015). This led Walker to make the prediction that chronic sleep deprivation throughout adult life significantly increases the risk of Alzheimer’s disease in later life, a link that has been shown in several epidemiological studies of people with chronic insomnia and sleep-disrupting conditions (Lim et al., 2013). Two conclusions can be drawn from such studies: (i) diagnosing and treating disorders that result in chronic sleep deprivation such as obstructive sleep apnoea is of paramount importance as a public health initiative to reduce the overall burden of dementia; and (ii) it raises the intriguing possibility that finding a means of restoring the quality and amount of deep non-REM sleep in elderly individuals and people with dementia, as Walker and others are trying to do, may be protective against Alzheimer’s disease or slow progression in individuals already affected (Mander et al., 2016). In summary, Walker does a commendable job in bridging the gap between cutting edge sleep research and popular science. In so doing, he performs an important public service in highlighting the importance (and benefits) of a good night’s sleep in our society where such a goal is increasingly marginalized. On an individual level, I doubt if anyone who reads this book will ever feel comfortable getting only 5–6 h of sleep per night or indeed with the normalized state of sleep deprivation that increasingly exists and indeed is lauded, in Western societies. Perhaps that, in writing this book, will be Walker’s greatest achievement. References Aserinsky E , Kleitman N . Regularly occurring periods of eye motility, and concomitant phenomena, during sleep. 1953. Comment in Fiftieth anniversary of the discovery of rapid eye movement (REM) sleep . J Neuropsychiatry Clin Neurosci 2003 ; 15 : 454 – 5 . Google Scholar CrossRef Search ADS PubMed Frank MG , Issa NP , Stryker MP . Sleep enhances plasticity in the developing visual cortex . Neuron 2001 ; 30 : 275 – 87 . Google Scholar CrossRef Search ADS PubMed Horne JA , Reyner LA , Barrett PR . Driving impairment due to sleepiness is exacerbated by low alcohol intake . Occup Environ Med 2003 ; 60 : 689 – 92 . Google Scholar CrossRef Search ADS PubMed Lim AS , Kowgier M , Yu L , Buchman AS , Bennett DA . Sleep fragmentation and the risk of incident Alzheimer's disease and cognitive decline in older persons . Sleep 2013 ; 36 : 1027 – 32 . Google Scholar CrossRef Search ADS PubMed Mander BA , Marks SM , Vogel JW , Rao V , Lu B , Saletin JM , et al. β-amyloid disrupts human NREM slow waves and related hippocampus-dependent memory consolidation . Nat Neurosci 2015 ; 18 : 1051 – 7 . Google Scholar CrossRef Search ADS PubMed Mander BA , Rao V , Lu B , Saletin JM , Ancoli-Israel S , Jagust WJ , et al. Impaired prefrontal sleep spindle regulation of hippocampal-dependent learning in older adults . Cereb Cortex 2014 ; 24 : 3301 – 9 . Google Scholar CrossRef Search ADS PubMed Mander BA , Rao V , Lu B , Saletin JM , Lindquist JR , Ancoli-Israel S , et al. Prefrontal atrophy, disrupted NREM slow waves and impaired hippocampal-dependent memory in aging . Nat Neurosci 2013 ; 16 : 357 – 64 . Google Scholar CrossRef Search ADS PubMed Mander BA , Santhanam S , Saletin JM , Walker MP . Wake deterioration and sleep restoration of human learning . Curr Biol 2011 ; 21 : R183 – 4 . Google Scholar CrossRef Search ADS PubMed Mander BA , Winer JR , Jagust WJ , Walker MP . Sleep: a novel mechanistic pathway, biomarker, and treatment target in the pathology of Alzheimer's disease? Trends Neurosci 2016 ; 39 : 552 – 66 . Google Scholar CrossRef Search ADS PubMed Olini N , Kurth S , Huber R . The effects of caffeine on sleep and maturational markers in the rat . PLoS One 2013 ; 8 : e72539 . Google Scholar CrossRef Search ADS PubMed Rechtschaffen A , Gilliland MA , Bergmann BM , Winter JB . Physiological correlates of prolonged sleep deprivation in rats . Science 1983 ; 221 : 182 – 4 . Google Scholar CrossRef Search ADS PubMed © The Author(s) (2018). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email: journals.permissions@oup.com This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices)

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BrainOxford University Press

Published: Apr 27, 2018

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