Sleep deprivation triggers a set of bidirectional changes in brain activity and connectivity, depending on the specific cognitive or affective behaviours engaged.
Changes in brain activity are observed when averaged across a session of task performance and during on-task performance, wherein marked brain network instability seems to be a neural hallmark of sleep deprivation.
Not all changes in brain function that are associated with sleep loss are maladaptive and thus represent deficiencies, as some predict resilience in behavioural ability and are therefore compensatory.
These basic scientific findings offer causal mechanistic insights into select neurological and psychiatric disorders in which abnormalities in sleep and cognition or emotion are highly comorbid, indicating that sleep intervention is an underappreciated and novel target for disease treatment and/or prevention.
The robust neural and behavioural phenotypes characterized by this Review can inform debates regarding sleep recommendations for both public and professional health policies, especially in light of the escalating sleep-loss epidemic prevalent throughout industrialized nations.
How does a lack of sleep affect our brains? In contrast to the benefits of sleep, frameworks exploring the impact of sleep loss are relatively lacking. Importantly, the effects of sleep deprivation (SD) do not simply reflect the absence of sleep and the benefits attributed to it; rather, they reflect the consequences of several additional factors, including extended wakefulness. With a focus on neuroimaging studies, we review the consequences of SD on attention and working memory, positive and negative emotion, and hippocampal learning. We explore how this evidence informs our mechanistic understanding of the known changes in cognition and emotion associated with SD, and the insights it provides regarding clinical conditions associated with sleep disruption.
This is a preview of subscription content, access via your institution
Open Access articles citing this article.
Sleep fragmentation affects glymphatic system through the different expression of AQP4 in wild type and 5xFAD mouse models
Acta Neuropathologica Communications Open Access 18 January 2023
Nature Communications Open Access 13 December 2022
Communications Biology Open Access 28 November 2022
Subscribe to Nature+
Get immediate online access to Nature and 55 other Nature journal
Subscribe to Journal
Get full journal access for 1 year
only $6.58 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Tax calculation will be finalised during checkout.
Get time limited or full article access on ReadCube.
All prices are NET prices.
Benca, R. M. Sleep in psychiatric disorders. Neurol. Clin. 14, 739–764 (1996).
Wulff, K., Gatti, S., Wettstein, J. G. & Foster, R. G. Sleep and circadian rhythm disruption in psychiatric and neurodegenerative disease. Nat. Rev. Neurosci. 11, 589–599 (2010).
Centers for Disease Control and Prevention. Insufficient sleep is a public health problem. CDC https://www.cdc.gov/features/dssleep (2015).
Durmer, J. S. & Dinges, D. F. Neurocognitive consequences of sleep deprivation. Semin. Neurol. 25, 117–129 (2005).
Van Dongen, H. P., Maislin, G., Mullington, J. M. & Dinges, D. F. The cumulative cost of additional wakefulness: dose-response effects on neurobehavioral functions and sleep physiology from chronic sleep restriction and total sleep deprivation. Sleep 26, 117–126 (2003). This article provides a comparison of the cumulative, dose-dependent deficits in sustained attention resulting from chronic sleep restriction of varied amount, relative to total SD.
Belenky, G. et al. Patterns of performance degradation and restoration during sleep restriction and subsequent recovery: a sleep dose-response study. J. Sleep Res. 12, 1–12 (2003).
Borbély, A. A. A two process model of sleep regulation. Hum. Neurobiol. 1, 195–204 (1982).
Goel, N., Basner, M., Rao, H. & Dinges, D. F. Circadian rhythms, sleep deprivation, and human performance. Prog. Mol. Biol. Transl Sci. 119, 155 (2013).
Chee, M. W. et al. Effects of sleep deprivation on cortical activation during directed attention in the absence and presence of visual stimuli. Neuroimage 58, 595–604 (2011).
Chee, M. W. & Tan, J. C. Lapsing when sleep deprived: neural activation characteristics of resistant and vulnerable individuals. Neuroimage 51, 835–843 (2010). This paper describes the differences in fMRI signal in frontoparietal attention networks, thalamus and extrastriate cortex that differentiate individuals who are vulnerable (or, conversely, resilient) to impairments in attention following acute SD.
Chee, M. W., Tan, J. C., Parimal, S. & Zagorodnov, V. Sleep deprivation and its effects on object-selective attention. Neuroimage 49, 1903–1910 (2010).
Chee, M. W. et al. Lapsing during sleep deprivation is associated with distributed changes in brain activation. J. Neurosci. 28, 5519–5528 (2008).
Czisch, M. et al. On the need of objective vigilance monitoring: effects of sleep loss on target detection and task-negative activity using combined EEG/fMRI. Front. Neurol. 3, 67 (2012).
Drummond, S. P. et al. Sleep deprivation-induced reduction in cortical functional response to serial subtraction. Neuroreport 10, 3745–3748 (1999).
Thomas, M. et al. Neural basis of alertness and cognitive performance impairments during sleepiness. I. Effects of 24 h of sleep deprivation on waking human regional brain activity. J. Sleep Res. 9, 335–352 (2000).
Tomasi, D. et al. Impairment of attentional networks after 1 night of sleep deprivation. Cereb. Cortex 19, 233–240 (2009).
Kong, D., Soon, C. S. & Chee, M. W. Functional imaging correlates of impaired distractor suppression following sleep deprivation. Neuroimage 61, 50–55 (2012).
Mander, B. A. et al. Sleep deprivation alters functioning within the neural network underlying the covert orienting of attention. Brain Res. 1217, 148–156 (2008).
Muto, V. et al. Local modulation of human brain responses by circadian rhythmicity and sleep debt. Science 353, 687–690 (2016).
Chee, M. W. & Choo, W. C. Functional imaging of working memory after 24 hr of total sleep deprivation. J. Neurosci. 24, 4560–4567 (2004). This article provides a characterization of the changes in fMRI signal activity associated with working-memory impairments following acute SD, and how these patterns change as a function of task complexity.
Choo, W. C., Lee, W. W., Venkatraman, V., Sheu, F. S. & Chee, M. W. Dissociation of cortical regions modulated by both working memory load and sleep deprivation and by sleep deprivation alone. Neuroimage 25, 579–587 (2005).
Habeck, C. et al. An event-related fMRI study of the neurobehavioral impact of sleep deprivation on performance of a delayed-match-to-sample task. Brain Res. Cogn. Brain Res. 18, 306–321 (2004).
Portas, C. M. et al. A specific role for the thalamus in mediating the interaction of attention and arousal in humans. J. Neurosci. 18, 8979–8989 (1998).
Doran, S. M., Van Dongen, H. P. & Dinges, D. F. Sustained attention performance during sleep deprivation: evidence of state instability. Arch. Ital. Biol. 139, 253–267 (2001).
Drummond, S. P. et al. The neural basis of the psychomotor vigilance task. Sleep 28, 1059–1068 (2005).
Sridharan, D., Levitin, D. J. & Menon, V. A critical role for the right fronto-insular cortex in switching between central-executive and default-mode networks. Proc. Natl Acad. Sci. USA 105, 12569–12574 (2008).
Ma, N., Dinges, D. F., Basner, M. & Rao, H. How acute total sleep loss affects the attending brain: a meta-analysis of neuroimaging studies. Sleep 38, 233–240 (2015).
Gumenyuk, V. et al. Habitual short sleep impacts frontal switch mechanism in attention to novelty. Sleep 34, 1659–1670 (2011).
Gazes, Y. et al. Dual-tasking alleviated sleep deprivation disruption in visuomotor tracking: an fMRI study. Brain Cogn. 78, 248–256 (2012).
Drummond, S. P., Anderson, D. E., Straus, L. D., Vogel, E. K. & Perez, V. B. The effects of two types of sleep deprivation on visual working memory capacity and filtering efficiency. PLoS ONE 7, e35653 (2012).
Turner, T. H., Drummond, S. P., Salamat, J. S. & Brown, G. G. Effects of 42 hr of total sleep deprivation on component processes of verbal working memory. Neuropsychology 21, 787–795 (2007).
Chee, M. W. & Chuah, Y. M. Functional neuroimaging and behavioral correlates of capacity decline in visual short-term memory after sleep deprivation. Proc. Natl Acad. Sci. USA 104, 9487–9492 (2007).
Lythe, K. E., Williams, S. C., Anderson, C., Libri, V. & Mehta, M. A. Frontal and parietal activity after sleep deprivation is dependent on task difficulty and can be predicted by the fMRI response after normal sleep. Behav. Brain Res. 233, 62–70 (2012).
Chengyang, L. et al. Short-term memory deficits correlate with hippocampal-thalamic functional connectivity alterations following acute sleep restriction. Brain Imaging Behav. http://dx.doi.org/10.1007/s11682-016-9570-1 (2016).
Lei, Y. et al. Large-scale brain network coupling predicts total sleep deprivation effects on cognitive capacity. PLoS ONE 10, e0133959 (2015).
Yoo, S., Hu, P., Gujar, N., Jolesz, F. & Walker, M. A deficit in the ability to form new human memories without sleep. Nat. Neurosci. 10, 385–392 (2007). This paper characterizes the effects of acute SD on fMRI hippocampal encoding activity and function connectivity during fact-based learning.
Luber, B. et al. Remediation of sleep-deprivation-induced working memory impairment with fMRI-guided transcranial magnetic stimulation. Cereb. Cortex 18, 2077–2085 (2008). This report demonstrates that repetitive TMS applied to visual occipital cortex can partially rescue performance impairments in a visual working-memory task following acute SD.
Luber, B. et al. Extended remediation of sleep deprived-induced working memory deficits using fMRI-guided transcranial magnetic stimulation. Sleep 36, 857–871 (2013).
Luber, B. et al. Facilitation of performance in a working memory task with rTMS stimulation of the precuneus: frequency-and time-dependent effects. Brain Res. 1128, 120–129 (2007).
Volkow, N. D. et al. Evidence that sleep deprivation downregulates dopamine D2R in ventral striatum in the human brain. J. Neurosci. 32, 6711–6717 (2012). This PET ligand-binding study in humans provides evidence of dopamine D2/3R downregulation in the striatum following acute SD.
Tufik, S. Changes of response to dopaminergic drugs in rats submitted to REM-sleep deprivation. Psychopharmacology 72, 257–260 (1981).
Mullin, B. C. et al. Sleep deprivation amplifies striatal activation to monetary reward. Psychol. Med. 43, 2215–2225 (2013).
Venkatraman, V., Chuah, Y. M., Huettel, S. A. & Chee, M. W. Sleep deprivation elevates expectation of gains and attenuates response to losses following risky decisions. Sleep 30, 603–609 (2007).
Libedinsky, C. et al. Sleep deprivation alters valuation signals in the ventromedial prefrontal cortex. Front. Behav. Neurosci. 5, 70 (2011).
Olson, E. A., Weber, M., Rauch, S. L. & Killgore, W. D. Daytime sleepiness is associated with reduced integration of temporally distant outcomes on the Iowa Gambling Task. Behav. Sleep Med. 14, 200–211 (2016).
Killgore, W. D., Balkin, T. J. & Wesensten, N. J. Impaired decision making following 49 h of sleep deprivation. J. Sleep Res. 15, 7–13 (2006).
Gujar, N., Yoo, S. S., Hu, P. & Walker, M. P. Sleep deprivation amplifies reactivity of brain reward networks, biasing the appraisal of positive emotional experiences. J. Neurosci. 31, 4466–4474 (2011).
Greer, S. M., Goldstein, A. N. & Walker, M. P. The impact of sleep deprivation on food desire in the human brain. Nat. Commun. 4, 2259 (2013). This paper reports decreased fMRI signal in insular and frontal cortex, and increased amygdala activity, in response to desirable, high-calorie food item choices following acute SD.
Menz, M. M., Buchel, C. & Peters, J. Sleep deprivation is associated with attenuated parametric valuation and control signals in the midbrain during value-based decision making. J. Neurosci. 32, 6937–6946 (2012).
Franken, I. H., van Strien, J. W., Nijs, I. & Muris, P. Impulsivity is associated with behavioral decision-making deficits. Psychiatry Res. 158, 155–163 (2008).
Bechara, A., Tranel, D. & Damasio, H. Characterization of the decision-making deficit of patients with ventromedial prefrontal cortex lesions. Brain 123, 2189–2202 (2000).
Cedernaes, J. et al. Increased impulsivity in response to food cues after sleep loss in healthy young men. Obesity 22, 1786–1791 (2014).
Demos, K. et al. Partial sleep deprivation impacts impulsive action but not impulsive decision-making. Physiol. Behav. 164, 214–219 (2016).
Acheson, A., Richards, J. B. & de Wit, H. Effects of sleep deprivation on impulsive behaviors in men and women. Physiol. Behav. 91, 579–587 (2007).
Ayalon, L., Ancoli-Israel, S. & Drummond, S. Altered brain activation during response inhibition in obstructive sleep apnea. J. Sleep Res. 18, 204–208 (2009).
Anderson, C. & Platten, C. R. Sleep deprivation lowers inhibition and enhances impulsivity to negative stimuli. Behav. Brain Res. 217, 463–466 (2011).
Libedinsky, C. et al. Sleep deprivation alters effort discounting but not delay discounting of monetary rewards. Sleep 36, 899–904 (2013).
Rossa, K. R., Smith, S. S., Allan, A. C. & Sullivan, K. A. The effects of sleep restriction on executive inhibitory control and affect in young adults. J. Adolesc. Health 55, 287–292 (2014).
Womack, S. D., Hook, J. N., Reyna, S. H. & Ramos, M. Sleep loss and risk-taking behavior: a review of the literature. Behav. Sleep Med. 11, 343–359 (2013).
Greer, S. M., Goldstein, A. N., Knutson, B. & Walker, M. P. A genetic polymorphism of the human dopamine transporter determines the impact of sleep deprivation on brain responses to rewards and punishments. J. Cogn. Neurosci. 28, 803–810 (2016).
Perogamvros, L. & Schwartz, S. The roles of the reward system in sleep and dreaming. Neurosci. Biobehav. Rev. 36, 1934–1951 (2012).
McCann, U. D. et al. Effects of catecholamine depletion on alertness and mood in rested and sleep deprived normal volunteers. Neuropsychopharmacology 8, 345–356 (1993).
Curb, J. D., Schneider, K., Taylor, J. O., Maxwell, M. & Shulman, N. Antihypertensive drug side effects in the Hypertension Detection and Follow-up Program. Hypertension 11, II51–II55 (1988).
Hershey, T. & Chad, J. Effect of sleep deprivation on brain metabolism of depressed patients. Am. J. Psychiatry 1, 539 (1992).
Tomasi, D., Wang, G.-J. & Volkow, N. Involvement of striatal dopamine D2/D3 receptors in the modulation of visual attention during rested wakefulness and sleep deprivation. Neuropsychopharmacology 40, S247–S248 (2015).
Wu, J. C. et al. Frontal lobe metabolic decreases with sleep deprivation not totally reversed by recovery sleep. Neuropsychopharmacology 31, 2783–2792 (2006).
Elmenhorst, D. et al. Sleep deprivation increases A1 adenosine receptor binding in the human brain: a positron emission tomography study. J. Neurosci. 27, 2410–2415 (2007). This human PET ligand-binding study demonstrates adenosine A 1 receptor upregulation in numerous cortical regions (maximal in OFC) and subcortical striatum following acute SD.
Bonaventura, J. et al. Allosteric interactions between agonists and antagonists within the adenosine A2A receptor–dopamine D2 receptor heterotetramer. Proc. Natl Acad. Sci. USA 112, E3609–E3618 (2015).
Richard, J. M. & Berridge, K. C. Nucleus accumbens dopamine/glutamate interaction switches modes to generate desire versus dread: D1 alone for appetitive eating but D1 and D2 together for fear. J. Neurosci. 31, 12866–12879 (2011).
Park, K., Volkow, N. D., Pan, Y. & Du, C. Chronic cocaine dampens dopamine signaling during cocaine intoxication and unbalances D1 over D2 receptor signaling. J. Neurosci. 33, 15827–15836 (2013).
Berro, L. et al. Sleep deprivation impairs the extinction of cocaine-induced environmental conditioning in mice. Pharmacol. Biochem. Behav. 124, 13–18 (2014).
Brondel, L., Romer, M. A., Nougues, P. M., Touyarou, P. & Davenne, D. Acute partial sleep deprivation increases food intake in healthy men. Am. J. Clin. Nutr. 91, 1550–1559 (2010).
Knutson, B. & Gibbs, S. E. Linking nucleus accumbens dopamine and blood oxygenation. Psychopharmacology 191, 813–822 (2007).
Horne, J. A. Sleep function, with particular reference to sleep deprivation. Ann. Clin. Res. 17, 199–208 (1985).
Dinges, D. F. et al. Cumulative sleepiness, mood disturbance, and psychomotor vigilance performance decrements during a week of sleep restricted to 4–5 hours per night. Sleep 20, 267–277 (1997). This article provides a detailed behavioural characterization of the cognition and affective impact of cumulative, extended sleep restriction using subjective and objective measures.
Zohar, D., Tzischinsky, O., Epstein, R. & Lavie, P. The effects of sleep loss on medical residents' emotional reactions to work events: a cognitive-energy model. Sleep 28, 47–54 (2005).
Minkel, J. D. et al. Sleep deprivation and stressors: evidence for elevated negative affect in response to mild stressors when sleep deprived. Emotion 12, 1015–1020 (2012).
Bernert, R. A. & Joiner, T. E. Sleep disturbances and suicide risk: a review of the literature. Neuropsychiatr. Dis. Treat. 3, 735–743 (2007).
Kamphuis, J., Meerlo, P., Koolhaas, J. M. & Lancel, M. Poor sleep as a potential causal factor in aggression and violence. Sleep Med. 13, 327–334 (2012).
Stubbs, B., Wu, Y.-T., Prina, A. M., Leng, Y. & Cosco, T. D. A population study of the association between sleep disturbance and suicidal behaviour in people with mental illness. J. Psychiatr. Res. 82, 149–154 (2016).
Yoo, S. S., Gujar, N., Hu, P., Jolesz, F. A. & Walker, M. P. The human emotional brain without sleep — a prefrontal amygdala disconnect. Curr. Biol. 17, R877–R878 (2007). This paper describes amplified amygdala fMRI activity in response to negative experiences following acute SD, further associated with a loss of top-down connectivity with the mPFC.
Motomura, Y. et al. Sleep debt elicits negative emotional reaction through diminished amygdala–anterior cingulate functional connectivity. PLoS ONE 8, e56578 (2013).
Prather, A. A., Bogdan, R. & Hariri, A. R. Impact of sleep quality on amygdala reactivity, negative affect, and perceived stress. Psychosom. Med. 75, 350–358 (2013).
Goldstein, A. N. & Walker, M. P. The role of sleep in emotional brain function. Annu. Rev. Clin. Psychol. 10, 679 (2014).
Chuah, L. Y. et al. Sleep deprivation and interference by emotional distracters. Sleep 33, 1305–1313 (2010).
Killgore, W. D. Self-reported sleep correlates with prefrontal-amygdala functional connectivity and emotional functioning. Sleep 36, 1597–1608 (2013).
Goldstein, A. N. et al. Tired and apprehensive: anxiety amplifies the impact of sleep loss on aversive brain anticipation. J. Neurosci. 33, 10607–10615 (2013).
Franzen, P. L., Buysse, D. J., Dahl, R. E., Thompson, W. & Siegle, G. J. Sleep deprivation alters pupillary reactivity to emotional stimuli in healthy young adults. Biol. Psychol. 80, 300–305 (2009).
Etkin, A. & Wager, T. D. Functional neuroimaging of anxiety: a meta-analysis of emotional processing in PTSD, social anxiety disorder, and specific phobia. Am. J. Psychiatry 164, 1476–1488 (2007).
Simmons, A., Strigo, I., Matthews, S. C., Paulus, M. P. & Stein, M. B. Anticipation of aversive visual stimuli is associated with increased insula activation in anxiety-prone subjects. Biol. Psychiatry 60, 402–409 (2006).
Simmons, A. N. et al. Anxiety positive subjects show altered processing in the anterior insula during anticipation of negative stimuli. Hum. Brain Mapp. 32, 1836–1846 (2011).
Harvey, A. G., Murray, G., Chandler, R. A. & Soehner, A. Sleep disturbance as transdiagnostic: consideration of neurobiological mechanisms. Clin. Psychol. Rev. 31, 225–235 (2011).
Van Der Helm, E., Gujar, N. & Walker, M. P. Sleep deprivation impairs the accurate recognition of human emotions. Sleep 33, 335–342 (2010).
Daniela, T. et al. Lack of sleep affects the evaluation of emotional stimuli. Brain Res. Bull. 82, 104–108 (2010).
Goldstein-Piekarski, A. N., Greer, S. M., Saletin, J. M. & Walker, M. P. Sleep deprivation impairs the human central and peripheral nervous system discrimination of social threat. J. Neurosci. 35, 10135–10145 (2015). This study characterizes a failure in the accurate discrimination of anti-social versus pro-social facial signals at the behaviourally, brain (salience-detection network) and peripheral autonomic nervous system levels following acute SD.
Simon, E. B. et al. Losing neutrality: the neural basis of impaired emotional control without sleep. J. Neurosci. 35, 13194–13205 (2015).
Alfarra, R., Fins, A. I., Chayo, I. & Tartar, J. L. Changes in attention to an emotional task after sleep deprivation: neurophysiological and behavioral findings. Biol. Psychol. 104, 1–7 (2015).
Guadagni, V., Burles, F., Ferrara, M. & Iaria, G. The effects of sleep deprivation on emotional empathy. J. Sleep Res. 23, 657–663 (2014).
Guadagni, V. et al. The relationship between quality of sleep and emotional empathy. J. Psychophysiol. http://dx.doi.org/10.1027/0269-8803/a000177 (2016).
Craig, A. D. How do you feel? Interoception: the sense of the physiological condition of the body. Nat. Rev. Neurosci. 3, 655–666 (2002).
Minkel, J., Htaik, O., Banks, S. & Dinges, D. Emotional expressiveness in sleep-deprived healthy adults. Behav. Sleep Med. 9, 5–14 (2011).
Berger, R. H., Miller, A. L., Seifer, R., Cares, S. R. & LeBourgeois, M. K. Acute sleep restriction effects on emotion responses in 30- to 36-month-old children. J. Sleep Res. 21, 235–246 (2012).
Schwarz, J. F. et al. Shortened night sleep impairs facial responsiveness to emotional stimuli. Biol. Psychol. 93, 41–44 (2013).
McGlinchey, E. L. et al. The effect of sleep deprivation on vocal expression of emotion in adolescents and adults. Sleep 34, 1233 (2011).
Porges, S. W. The polyvagal theory: phylogenetic substrates of a social nervous system. Int. J. Psychophysiol. 42, 123–146 (2001).
Hoedlmoser, K., Kloesch, G., Wiater, A. & Schabus, M. Self-reported sleep patterns, sleep problems, and behavioral problems among school children aged 8–11 years. Somnologie (Berl.) 14, 23–31 (2010).
Baum, K. T. et al. Sleep restriction worsens mood and emotion regulation in adolescents. J. Child Psychol. Psychiatry 55, 180–190 (2014).
Killgore, W. D. et al. Sleep deprivation reduces perceived emotional intelligence and constructive thinking skills. Sleep Med. 9, 517–526 (2008).
Sadeh, A. et al. Sleep and psychological characteristics of children on a psychiatric inpatient unit. J. Am. Acad. Child Adolesc. Psychiatry 34, 813–819 (1995).
Gordon, A. M. & Chen, S. The role of sleep in interpersonal conflict: do sleepless nights mean worse fights? Soc. Psychol. Personal. Sci. 5, 168–175 (2014).
Mallick, B. N. & Singh, A. REM sleep loss increases brain excitability: role of noradrenaline and its mechanism of action. Sleep Med. Rev. 15, 165–178 (2011).
Siegel, J. M. & Rogawski, M. A. A function for REM sleep: regulation of noradrenergic receptor sensitivity. Brain Res. 472, 213–233 (1988).
Kametani, H. & Kawamura, H. Alterations in acetylcholine release in the rat hippocampus during sleep-wakefulness detected by intracerebral dialysis. Life Sci. 47, 421–426 (1990).
Marrosu, F. et al. Microdialysis measurement of cortical and hippocampal acetylcholine release during sleep-wake cycle in freely moving cats. Brain Res. 671, 329–332 (1995).
Abel, T., Havekes, R., Saletin, J. M. & Walker, M. P. Sleep, plasticity and memory from molecules to whole-brain networks. Curr. Biol. 23, R774–R788 (2013).
McDermott, C. M. et al. Sleep deprivation causes behavioral, synaptic, and membrane excitability alterations in hippocampal neurons. J. Neurosci. 23, 9687–9695 (2003).
Fernandes, C. et al. Detrimental role of prolonged sleep deprivation on adult neurogenesis. Front. Cell. Neurosci. 9, 140 (2015).
Drummond, S. P. et al. Altered brain response to verbal learning following sleep deprivation. Nature 403, 655–657 (2000). This article provides evidence that bidirectional changes in fMRI cortical and subcortical activity predict performance impairments and performance compensation during verbal learning following acute SD.
Van Der Werf, Y. D. et al. Sleep benefits subsequent hippocampal functioning. Nat. Neurosci. 12, 122–123 (2009).
Antonenko, D., Diekelmann, S., Olsen, C., Born, J. & Molle, M. Napping to renew learning capacity: enhanced encoding after stimulation of sleep slow oscillations. Eur. J. Neurosci. 37, 1142–1151 (2013).
Saletin, J. M. et al. Human hippocampal structure: a novel biomarker predicting mnemonic vulnerability to, and recovery from, sleep deprivation. J. Neurosci. 36, 2355–2363 (2016).
Chuah, L. Y. et al. Donepezil improves episodic memory in young individuals vulnerable to the effects of sleep deprivation. Sleep 32, 999–1010 (2009).
Poh, J.-H. & Chee, M. W. Degradation of cortical representations during encoding following sleep deprivation. Neuroimage 153, 131–138 (2017).
Gujar, N., Yoo, S.-S., Hu, P. & Walker, M. P. The unrested resting brain: sleep deprivation alters activity within the default-mode network. J. Cogn. Neurosci. 22, 1637–1648 (2010).
Pepeu, G., Giovannini, M. G. & Bracco, L. Effect of cholinesterase inhibitors on attention. Chem. Biol. Interact. 203, 361–364 (2013).
Sato, H., Hata, Y., Masui, H. & Tsumoto, T. A functional role of cholinergic innervation to neurons in the cat visual cortex. J. Neurophysiol. 58, 765–780 (1987).
Chuah, L. Y. & Chee, M. W. Cholinergic augmentation modulates visual task performance in sleep-deprived young adults. J. Neurosci. 28, 11369–11377 (2008).
Mander, B. A., Winer, J. R., Jagust, W. J. & Walker, M. P. Sleep: a novel mechanistic pathway, biomarker, and treatment target in the pathology of Alzheimer's disease? Trends Neurosci. 39, 552–566 (2016).
Mander, B. et al. Age-related impairments of memory and fast sleep spindles are mediated by deterioration of cortico-thalamic white matter pathways [abstract]. Sleep 35, A23 (2012).
Frey, D. J., Badia, P. & Wright, K. P. Inter- and intra-individual variability in performance near the circadian nadir during sleep deprivation. J. Sleep Res. 13, 305–315 (2004). This study characterizes the variability in behavioural performance across several task domains in response to SD, both within and between individuals.
Porkka-Heiskanen, T. et al. Adenosine: a mediator of the sleep-inducing effects of prolonged wakefulness. Science 276, 1265–1268 (1997).
Van Dongen, H. P., Belenky, G. & Krueger, J. M. A local, bottom-up perspective on sleep deprivation and neurobehavioral performance. Curr. Top. Med. Chem. 11, 2414–2422 (2011).
Saper, C. B., Fuller, P. M., Pedersen, N. P., Lu, J. & Scammell, T. E. Sleep state switching. Neuron 68, 1023–1042 (2010).
Van Dongen, H., Baynard, M. D., Maislin, G. & Dinges, D. F. Systematic interindividual differences in neurobehavioral impairment from sleep loss: evidence of trait-like differential vulnerability. Sleep 27, 423–433 (2004). This behavioural study describes inter-individual differences in behavioural task impairments following SD and how these relate to prior sleep history of those individuals.
Mollicone, D. J., Van Dongen, H., Rogers, N. L., Banks, S. & Dinges, D. F. Time of day effects on neurobehavioral performance during chronic sleep restriction. Aviat. Space Environ. Med. 81, 735–744 (2010).
Rupp, T. L., Wesensten, N. J. & Balkin, T. J. Trait-like vulnerability to total and partial sleep loss. Sleep 35, 1163–1172 (2012).
Kuna, S. T. et al. Heritability of performance deficit accumulation during acute sleep deprivation in twins. Sleep 35, 1223–1233 (2012).
Basner, M., Rao, H., Goel, N. & Dinges, D. F. Sleep deprivation and neurobehavioral dynamics. Curr. Opin. Neurobiol. 23, 854–863 (2013).
Cui, J. et al. Microstructure of frontoparietal connections predicts individual resistance to sleep deprivation. Neuroimage 106, 123–133 (2015).
Vandewalle, G. et al. Functional magnetic resonance imaging-assessed brain responses during an executive task depend on interaction of sleep homeostasis, circadian phase, and PER3 genotype. J. Neurosci. 29, 7948–7956 (2009).
Marcus, E. R. Two views of brain function. Trends Cogn. Sci. 14, 180–190 (2010).
Fox, M. D. & Raichle, M. E. Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging. Nat. Rev. Neurosci. 8, 700–711 (2007).
Yeo, B. T., Tandi, J. & Chee, M. W. Functional connectivity during rested wakefulness predicts vulnerability to sleep deprivation. Neuroimage 111, 147–158 (2015).
Kaufmann, T. et al. The brain functional connectome is robustly altered by lack of sleep. Neuroimage 127, 324–332 (2016).
Gao, L. et al. Frequency-dependent changes of local resting oscillations in sleep-deprived brain. PLoS ONE 10, e0120323 (2015).
Wang, Y., Liu, H., Hitchman, G. & Lei, X. Module number of default mode network: inter-subject variability and effects of sleep deprivation. Brain Res. 1596, 69–78 (2015).
Fox, M. D. et al. The human brain is intrinsically organized into dynamic, anticorrelated functional networks. Proc. Natl Acad. Sci. USA 102, 9673–9678 (2005).
De Havas, J. A., Parimal, S., Soon, C. S. & Chee, M. W. Sleep deprivation reduces default mode network connectivity and anti-correlation during rest and task performance. Neuroimage 59, 1745–1751 (2012).
Bosch, O. G. et al. Sleep deprivation increases dorsal nexus connectivity to the dorsolateral prefrontal cortex in humans. Proc. Natl Acad. Sci. USA 110, 19597–19602 (2013).
Sämann, P. G. et al. Increased sleep pressure reduces resting state functional connectivity. MAGMA 23, 375–389 (2010).
Shao, Y. et al. Decreased thalamocortical functional connectivity after 36 hours of total sleep deprivation: evidence from resting state fMRI. PLoS ONE 8, e78830 (2013).
Shao, Y. et al. Altered resting-state amygdala functional connectivity after 36 hours of total sleep deprivation. PLoS ONE 9, e112222 (2014).
Leech, R. & Sharp, D. J. The role of the posterior cingulate cortex in cognition and disease. Brain 137, 12–32 (2014).
Tagliazucchi, E. et al. Large-scale brain functional modularity is reflected in slow electroencephalographic rhythms across the human non-rapid eye movement sleep cycle. Neuroimage 70, 327–339 (2013).
Vyazovskiy, V. V. et al. Local sleep in awake rats. Nature 472, 443–447 (2011).
Horovitz, S. G. et al. Decoupling of the brain's default mode network during deep sleep. Proc. Natl Acad. Sci. USA 106, 11376–11381 (2009).
Brower, K. J., Aldrich, M. S., Robinson, E. A., Zucker, R. A. & Greden, J. F. Insomnia, self-medication, and relapse to alcoholism. Am. J. Psychiatry 158, 399–404 (2001).
Thomas, R. J., Rosen, B. R., Stern, C. E., Weiss, J. W. & Kwong, K. K. Functional imaging of working memory in obstructive sleep-disordered breathing. J. Appl. Physiol. (1985) 98, 2226–2234 (2005).
Wong, M. M., Brower, K. J., Fitzgerald, H. E. & Zucker, R. A. Sleep problems in early childhood and early onset of alcohol and other drug use in adolescence. Alcohol. Clin. Exp. Res. 28, 578–587 (2004).
Van Cauter, E. et al. Impact of sleep and sleep loss on neuroendocrine and metabolic function. Horm. Res. 67 (Suppl. 1), 2–9 (2007).
Markwald, R. R. et al. Impact of insufficient sleep on total daily energy expenditure, food intake, and weight gain. Proc. Natl Acad. Sci. USA 110, 5695–5700 (2013).
Michaelides, M. et al. PET imaging predicts future body weight and cocaine preference. Neuroimage 59, 1508–1513 (2012).
Germain, A. Sleep disturbances as the hallmark of PTSD: where are we now? Am. J. Psychiatry 170, 372–382 (2013).
Mellman, T. A., Nolan, B., Hebding, J., Kulick-Bell, R. & Dominguez, R. A polysomnographic comparison of veterans with combat-related PTSD, depressed men, and non-ill controls. Sleep 20, 46–51 (1997).
Lavie, P., Hefez, A., Halperin, G. & Enoch, D. Long-term effects of traumatic war-related events on sleep. Am. J. Psychiatry 136, 175–178 (1979).
Breslau, N. et al. Sleep in lifetime posttraumatic stress disorder: a community-based polysomnographic study. Arch. Gen. Psychiatry 61, 508–516 (2004).
Habukawa, M., Uchimura, N., Maeda, M., Kotorii, N. & Maeda, H. Sleep findings in young adult patients with posttraumatic stress disorder. Biol. Psychiatry 62, 1179–1182 (2007).
Mellman, T. A., Bustamante, V., Fins, A. I., Pigeon, W. R. & Nolan, B. REM sleep and the early development of posttraumatic stress disorder. Am. J. Psychiatry 159, 1696–1701 (2002).
Mellman, T. A., Kumar, A., Kulick-Bell, R., Kumar, M. & Nolan, B. Nocturnal/daytime urine noradrenergic measures and sleep in combat-related PTSD. Biol. Psychiatry 38, 174–179 (1995).
Calohan, J., Peterson, K., Peskind, E. R. & Raskind, M. A. Prazosin treatment of trauma nightmares and sleep disturbance in soldiers deployed in Iraq. J. Trauma. Stress 23, 645–648 (2010).
Raskind, M. A. et al. Reduction of nightmares and other PTSD symptoms in combat veterans by prazosin: a placebo-controlled study. Am. J. Psychiatry 160, 371–373 (2003).
Raskind, M. A. et al. A parallel group placebo controlled study of prazosin for trauma nightmares and sleep disturbance in combat veterans with post-traumatic stress disorder. Biol. Psychiatry 61, 928–934 (2007).
Taylor, F. B. et al. Prazosin effects on objective sleep measures and clinical symptoms in civilian trauma posttraumatic stress disorder: a placebo-controlled study. Biol. Psychiatry 63, 629–632 (2008).
Jovanovic, T. et al. Posttraumatic stress disorder may be associated with impaired fear inhibition: relation to symptom severity. Psychiatry Res. 167, 151–160 (2009).
Jovanovic, T., Kazama, A., Bachevalier, J. & Davis, M. Impaired safety signal learning may be a biomarker of PTSD. Neuropharmacology 62, 695–704 (2012).
Grillon, C. & Morgan, C. A. III. Fear-potentiated startle conditioning to explicit and contextual cues in Gulf War veterans with posttraumatic stress disorder. J. Abnorm. Psychol. 108, 134–142 (1999).
Menz, M. M. et al. The role of sleep and sleep deprivation in consolidating fear memories. Neuroimage 75, 87–96 (2013).
Spoormaker, V. I. et al. Effects of rapid eye movement sleep deprivation on fear extinction recall and prediction error signaling. Hum. Brain Mapp. 33, 2362–2376 (2012).
Straus, L. D., Acheson, D. T., Risbrough, V. B. & Drummond, S. P. Sleep deprivation disrupts recall of conditioned fear extinction. Biol. Psychiatry Cogn. Neurosci. Neuroimaging 2, 123–129 (2017).
Marshall, A. J., Acheson, D. T., Risbrough, V. B., Straus, L. D. & Drummond, S. P. Fear conditioning, safety learning, and sleep in humans. J. Neurosci. 34, 11754–11760 (2014).
Greicius, M. D., Krasnow, B., Reiss, A. L. & Menon, V. Functional connectivity in the resting brain: a network analysis of the default mode hypothesis. Proc. Natl Acad. Sci. USA 100, 253–258 (2003).
Spreng, R. N. & Grady, C. L. Patterns of brain activity supporting autobiographical memory, prospection, and theory of mind, and their relationship to the default mode network. J. Cogn. Neurosci. 22, 1112–1123 (2010).
Spreng, R. N., Stevens, W. D., Chamberlain, J. P., Gilmore, A. W. & Schacter, D. L. Default network activity, coupled with the frontoparietal control network, supports goal-directed cognition. Neuroimage 53, 303–317 (2010).
This work was supported by awards R01-AG031164, R01-AG054019, RF1-AG054019 and R01-MH093537 to M.P.W. from the US National Institutes of Health.
The authors declare no competing financial interests.
- Sleep disruption
Abnormal sleep that can be described in measures of deficient sleep quantity, structure (reflected by, for example, sleep cycle architecture) and/or sleep quality (assessed using, for example, spectral electroencephalogram power).
- Functional connectivity
In functional MRI, the statistical association between time series of blood-oxygen-level-dependent signal in two or more anatomically distinct brain regions.
The ability to selectively maintain focus on behaviourally relevant stimuli, while disregarding irrelevant stimuli.
- Working memory
The ability to maintain, manipulate and integrate mental representations of relevant information even when it is no longer present in the environment.
- Sleep pressure
Also called 'homeostatic sleep drive' or 'Process S'. A set of homeostatic neurobiological processes that increase the likelihood of sleep, or 'sleep propensity'.
- Partial sleep restriction
The state associated with a reduction (but not total absence) of sleep in the prior night or nights, usually ranging from 1–6 hours of sleep reduction. Sleep restriction is chronic if it persists for more than 24 hours.
- Default mode network
(DMN). Collection of brain areas, including midline frontoparietal regions, that usually disengage during externally driven, goal-directed task performance and re-engage upon task termination.
- Frontoparietal attention network
A bilateral brain network with core regions in the frontal and parietal lobes that exerts top-down control of sensory cortex to bias stimulus processing.
Acting without deliberation, or choosing short-term gains over long-term gains.
Relating to corporeal information propagated by the spinal cord to brain regions involved in the sensation and coordination of bodily functions and associated behaviours.
- Iowa Gambling Task
A test of reward processing that challenges the participant to maximize their earnings by forgoing short-term gains in return for eventual long-term gains.
- Total sleep deprivation
The state associated with a complete absence of sleep in the prior night or nights.
- Balloon Analogue Risk Task
(BART). A computerized measure of risk-taking behaviour. Participants are rewarded for inflating a 'balloon' but lose their reward if they overinflate and 'burst' the balloon.
- Wake propensity
The likelihood of an organism maintaining the state of sustained wakefulness.
An endogenous compound involved in biochemical and neuromodulatory processes, including metabolism and sleep–wake regulation. It accumulates extracellularly with time spent awake and dissipates during slow-wave sleep.
- Sleep quality
Measured subjectively, by means of self-reported perception of prior sleep, and objectively, using sleep-stage or quantitative electroencephalography sleep measures.
- Rapid eye movement
(REM). Also known as paradoxical sleep. Sleep characterized by high-frequency, low-amplitude desynchronized electroencephalogram (particularly in the theta band), rapid eye movements, muscle paralysis and dreaming.
- Non-rapid eye movement
(NREM). A type of sleep that consists of sleep stages 1–4 and that occurs towards the beginning of a sleep episode, and reflects homeostatic sleep processes.
- Slow-wave sleep
Stage 3 and stage 4 of non-rapid eye movement sleep that is characterized by low-frequency (∼0.8–4 Hz), high-amplitude synchronized electroencephalogram (called delta waves).
- Sleep spindles
Synchronized phasic bursts of electrical activity often measured in the cortex or scalp surface electroencephalogram lasting several seconds in the 11–15 Hz frequency range.
About this article
Cite this article
Krause, A., Simon, E., Mander, B. et al. The sleep-deprived human brain. Nat Rev Neurosci 18, 404–418 (2017). https://doi.org/10.1038/nrn.2017.55
This article is cited by
Sleep fragmentation affects glymphatic system through the different expression of AQP4 in wild type and 5xFAD mouse models
Acta Neuropathologica Communications (2023)
U-shaped association between sleep duration and subjective cognitive complaints in Chinese elderly: a cross-sectional study
BMC Psychiatry (2022)
Communications Biology (2022)
Nature Reviews Psychology (2022)