The transition from sleep to wakefulness entails a temporary period of reduced alertness and impaired performance known as sleep inertia. The extent to which its severity varies with task and cognitive processes remains unclear. We examined sleep inertia in alertness, attention, working memory and cognitive throughput with the Karolinska Sleepiness Scale (KSS), the Psychomotor Vigilance Task (PVT), n-back and add tasks, respectively. The tasks were administered 2 hours before bedtime and at regular intervals for four hours, starting immediately after awakening in the morning, in eleven participants, in a four-way cross-over laboratory design. We also investigated whether exposure to Blue-Enhanced or Bright Blue-Enhanced white light would reduce sleep inertia. Alertness and all cognitive processes were impaired immediately upon awakening (p
Robertson MD, Russell-Jones D, Umpleby AM, Dijk DJ (2012) Effects of three weeks of mild sleep restriction implemented in the home environment on multiple metabolic and endocrine markers in healthy young men., Metabolism
OBJECTIVES: Evidence for a causal relationship between sleep-loss and metabolism is derived primarily from short-term sleep deprivation studies in the laboratory. The objective of this study was to investigate whether small changes in sleep duration over a three week period while participants are living in their normal environment lead to changes in insulin sensitivity and other metabolic parameters. METHODS: Nineteen healthy, young, normal-weight men were randomised to either sleep restriction (habitual bedtime minus 1.5h) or a control condition (habitual bedtime) for three weeks. Weekly assessments of insulin sensitivity by hyperinsulinaemic-euglycaemic clamp, anthropometry, vascular function, leptin and adiponectin were made. Sleep was assessed continuously using actigraphy and diaries. RESULTS: Assessment of sleep by actigraphy confirmed that the intervention reduced daily sleep duration by 01:19 ± 00:15 (SE; p
Rajaratnam SM, Dijk DJ, Middleton B, Stone BM, Arendt J (2003) Melatonin phase-shifts human circadian rhythms with no evidence of changes in the duration of endogenous melatonin secretion or the 24-hour production of reproductive hormones., J Clin Endocrinol Metab 88 (9) pp. 4303-4309
The pineal hormone melatonin is a popular treatment for sleep and circadian rhythm disruption. Melatonin administered at optimal times of the day for treatment often results in a prolonged melatonin profile. In photoperiodic (day length-dependent) species, changes in melatonin profile duration influence the timing of seasonal rhythms. We investigated the effects of an artificially prolonged melatonin profile on endogenous melatonin and cortisol rhythms, wrist actigraphy, and reproductive hormones in humans. Eight healthy men took part in this double-blind, crossover study. Surge/sustained release melatonin (1.5 mg) or placebo was administered for 8 d at the beginning of a 16-h sleep opportunity (1600 h to 0800 h) in dim light. Compared with placebo, melatonin administration advanced the timing of endogenous melatonin and cortisol rhythms. Activity was reduced in the first half and increased in the second half of the sleep opportunity with melatonin; however, total activity during the sleep opportunities and wake episodes was not affected. Melatonin treatment did not affect the endogenous melatonin profile duration, pituitary/gonadal hormone levels (24-h), or sleepiness and mood levels on the subsequent day. In the short term, suitably timed sustained-release melatonin phase-shifts circadian rhythms and redistributes activity during a 16-h sleep opportunity, with no evidence of changes in the duration of endogenous melatonin secretion or pituitary/gonadal hormones.
Dijk DJ, Larkin W (2004) Fatigue and performance models: General background and commentary on the circadian alertness simulator for fatigue risk assessment in transportation, Aviation Space and Environmental Medicine 75 (SUPPL.1)
Mathematical models of fatigue and performance are potentially powerful tools to predict the effects of duty-rest schedules in many situations. Most current models, including the Circadian Alertness Simulator (CAS), derive from the two-process theory of sleep regulation. In these models, performance and fatigue are determined by a homeostatic process that depends solely on sleep/wake history, and a circadian process, driven by the biological clock. These models assume: 1) performance capability recovers in an exponential manner during sleep; 2) the homeostatic and circadian processes are additive. Current evidence suggests that both assumptions require modification. An attractive feature of the CAS is that it computes alertness curves for individuals, based on individual sleep/wake histories and other data. However, statistical evaluation is usually based on group data, with few performance metrics. As in other models, there is no substantive theory to connect the alertness computation with specific cognitive or psychomotor functions. © by Aerospace Medical Association, Alexandria, VA.
Dijk DJ (2014) Sleep and metabolism: you sleep what you eat?, J Sleep Res 23 (1) pp. 1-2
Lo JC, Groeger JA, Cheng GH, Dijk D-J, Chee MWL (2016) Self-reported sleep duration and cognitive performance in older adults: a systematic review and meta-analysis, SLEEP MEDICINE 17 pp. 87-98 ELSEVIER SCIENCE BV
Dijk D (2008) Role of clock genes in sleep homeostasis in humans, JOURNAL OF SLEEP RESEARCH 17 pp. 30-30 WILEY-BLACKWELL PUBLISHING, INC
Archer SN, Laing EE, Moller-Levet CS, van der Veen DR, Bucca G, Lazar AS, Lo JCY, Santhi N, Slak A, Kabiljo R, von Schantz M, Smith CP, Dijk DJ (2014) Mistimed sleep disrupts the circadian regulation of the human transcriptome, JOURNAL OF SLEEP RESEARCH 23 pp. 15-15 WILEY-BLACKWELL
Landolt HP, Dijk DJ, Gaus SE, Borbély AA (1995) Caffeine reduces low-frequency delta activity in the human sleep EEG., Neuropsychopharmacology 12 (3) pp. 229-238
In view of the hypothesis that adenosine is involved in sleep regulation, the effects of the adenosine antagonist caffeine on sleep and sleep EEG were investigated in eight young males. Compared to the placebo condition, caffeine (100 mg) administered at bedtime prolonged sleep latency and reduced sleep efficiency and stage 4 of non-rapid eye movement sleep (NREMS). Electroencephalographic slow-wave activity (SWA, spectral power density in the 1.75-4.5-Hz band) was reduced, whereas power density in the spindle frequency range was slightly enhanced. The suppression of SWA was limited to the first NREMS episode. Caffeine reduced the power density mainly in the lowest delta band, in contrast to the changes during physiological sleep that encompass both the delta and theta bands. Caffeine levels in saliva, assessed in a separate experiment, decreased from 7.5 mumol/l in the first hour of sleep to 3.5 mumol/l in the seventh hour. In the night following caffeine administration, stage 4 sleep had reverted to the baseline level, but sleep latency was still increased, and stage 2 sleep, as well as SWA in the first NREMS episode, were reduced. The data show that even a low dose of caffeine affects the sleep EEG. However, the effects of caffeine did not completely mimic the spectral changes observed during physiological sleep.
Dijk D (2008) Reduction in sleep propensity with ageing, JOURNAL OF SLEEP RESEARCH 17 pp. 63-63 WILEY-BLACKWELL PUBLISHING, INC
Archer SN, Kitamura S, Santhi N, Dijk D-J (2014) Effects of circadian typology and partial and total sleep deprivation on the human transcriptome, JOURNAL OF SLEEP RESEARCH 23 pp. 55-55 WILEY-BLACKWELL
Brunner DP, Dijk DJ, Münch M, Borbély AA (1991) Effect of zolpidem on sleep and sleep EEG spectra in healthy young men., Psychopharmacology (Berl) 104 (1) pp. 1-5
A single 10 mg dose of zolpidem, an imidazopyridine hypnotic, was administered to young, healthy male volunteers prior to bedtime. The drug reduced REM sleep but did not significantly affect other sleep stages and subjective sleep parameters. All-night spectral analysis of the EEG revealed that power density in nonREM sleep was reduced in the low-frequency range (1.25-2.5 Hz; 5.25-10.0 Hz) and increased in the spindle frequency range (12.25-13.0 Hz). Significant changes in the EEG spectrum were present in the first 4 h of sleep. The pattern of the spectral changes was similar to those induced by other hypnotics that bind to the GABAA/benzodiazepine receptor complex. There were no residual effects of zolpidem on psychomotor performance in the morning, on the self-rated state in the morning and at noon, and on sleep and EEG parameters in the subsequent drug-free night.
Increasing sleep pressure is associated with highly predictable changes in the dynamics of the sleep electroencephalogram (EEG). To investigate whether the effects of reduced sleep pressure also can be accounted for by homeostatic mechanisms, nighttime sleep following an evening nap was recorded in healthy young men. In comparison with the baseline night, sleep latency in the postnap night was prolonged, rapid eye movement sleep (REMS) latency was reduced, and EEG power density in non-REMS was decreased in the delta and theta band. The buildup of both EEG slow-wave activity (SWA; power density in the 0.75-to 4.5-Hz range) and spindle frequency activity (SFA; power density in the 12.25-to 15.0-Hz range) in non-REMS episodes was diminished (SWA: episodes 1-3; SFA: episode 1). The typical declining trend of SWA over consecutive non-REM sleep episodes was attenuated. The time course of SWA could be closely simulated with a homeostatic model of sleep regulation, although some discrepancies in level and buildup of SWA were apparent. We conclude that homeostatic mechanisms can largely account for the dynamics of the sleep EEG under conditions of reduced sleep pressure.
Dijk DJ, Neri DF, Wyatt JK, Ronda JM, Riel E, Ritz-De Cecco A, Hughes RJ, Elliott AR, Prisk GK, West JB, Czeisler CA (2001) Sleep, performance, circadian rhythms, and light-dark cycles during two space shuttle flights., Am J Physiol Regul Integr Comp Physiol 281 (5) pp. R1647-R1664
Sleep, circadian rhythm, and neurobehavioral performance measures were obtained in five astronauts before, during, and after 16-day or 10-day space missions. In space, scheduled rest-activity cycles were 20-35 min shorter than 24 h. Light-dark cycles were highly variable on the flight deck, and daytime illuminances in other compartments of the spacecraft were very low (5.0-79.4 lx). In space, the amplitude of the body temperature rhythm was reduced and the circadian rhythm of urinary cortisol appeared misaligned relative to the imposed non-24-h sleep-wake schedule. Neurobehavioral performance decrements were observed. Sleep duration, assessed by questionnaires and actigraphy, was only approximately 6.5 h/day. Subjective sleep quality diminished. Polysomnography revealed more wakefulness and less slow-wave sleep during the final third of sleep episodes. Administration of melatonin (0.3 mg) on alternate nights did not improve sleep. After return to earth, rapid eye movement (REM) sleep was markedly increased. Crewmembers on these flights experienced circadian rhythm disturbances, sleep loss, decrements in neurobehavioral performance, and postflight changes in REM sleep.
Lazar AS, Lazar ZI, Dijk D-J (2014) Circadian regulation of EEG slow waves and phase coherence in human sleep, JOURNAL OF SLEEP RESEARCH 23 pp. 9-9 WILEY-BLACKWELL
Van Oortmerssen GA, Dijk DJ, Schuurman T (1987) Studies in wild house mice. II. Testosterone and aggression., Horm Behav 21 (2) pp. 139-152
The relationship between testosterone level and attack latency was studied in genetically different wild house mice by means of castration and subsequent testosterone therapy. This was done to provide adequate physiological knowledge for further research on the genetic basis of individual differences in these mice. The findings show that individual variation in attack latency is related not only to variation in baseline plasma testosterone level (via a dose-response relation), but also to variation in responsiveness to testosterone that is induced before puberty. In addition it is shown that in fast-attacking mice the maintenance of the attack latency level reached by maturation is independent of testosterone, whereas this is not the case in mice that are reluctant to attack.
Lo JC, Dijk D, Groeger JA (2008) Napping and paired associate declarative memory: effects of semantic relatedness and level of learning, JOURNAL OF SLEEP RESEARCH 17 pp. 11-11 WILEY-BLACKWELL PUBLISHING, INC
Arbon EL, Knurowska M, Dijk DJ (2015) Randomized clinical trial of the effects of prolonged-release melatonin, temazepam and zolpidem on slow-wave activity during sleep in healthy people, Journal of Psychopharmacology Sage Journals
Archer S, Viola A, Von Schantz M, Dijk D (2007) Endogenous circadian rhythm of PER3 RNA in human leucocytes: Association with sleep timing, melatonin rhythm, and PER3 genotype, SLEEP 30 pp. A54-A55 AMER ACADEMY SLEEP MEDICINE
Dijk DJ (2015) Sleep loss: effects on brain and body in the very young and very old., Journal of sleep research 24 (6) pp. 591-592
Rajaratnam SMW, Dijk DJ, Middleton B, Stone BM, Arendt J (2004) Erratum: Melatonin phase-shifts human Circadian rhythms with no evidence of changes in the duration of endogenous melatonin secretion or the 24-hour production of reproductive hormones (The Journal of Clinical Endocrinology and Metabolism (2003) 88 (4303-4309)), Journal of Clinical Endocrinology and Metabolism 89 (6)
Dijk DJ, Beersma DG, Daan S, Bloem GM, Van den Hoofdakker RH (1987) Quantitative analysis of the effects of slow wave sleep deprivation during the first 3 h of sleep on subsequent EEG power density., Eur Arch Psychiatry Neurol Sci 236 (6) pp. 323-328
The relation between EEG power density during slow wave sleep (SWS) deprivation and power density during subsequent sleep was investigated. Nine young male adults slept in the laboratory for 3 consecutive nights. Spectral analysis of the EEG on the 2nd (baseline) night revealed an exponential decline in mean EEG power density (0.25-15.0 Hz) over successive nonrapid eye movement--rapid eye movement sleep cycles. During the first 3 h of the 3rd night the subjects were deprived of SWS by means of acoustic stimuli, which did not induce wakefulness. During SWS deprivation an attenuation of EEG power densities was observed in the delta frequencies, as well as in the theta band. In the hours of sleep following SWS deprivation both the power densities in the frequency range from 1 to 7 Hz and the amount of SWS were enhanced, relative to the same period of the baseline night. Both the amount of EEG energy accumulating subsequent to SWS deprivation and its time course could be predicted accurately from the EEG energy deficit caused by SWS deprivation. The data show that the level of integral EEG power density during a certain period after sleep onset depends on the amount of EEG energy accumulated during the preceding sleep rather than on the time elapsed since sleep onset. In terms of the two-process model of sleep regulation (Borbély 1982; Daan et al. 1984) this finding indicates that EEG power density reflects the rate of decay of the regulating variable, S, rather than S itself, as was originally postulated.
Dijk DJ (2010) A sleep-centric view, Journal of Sleep Research 19 (4) pp. 505-507
Klerman EB, Rimmer DW, Dijk DJ, Kronauer RE, Rizzo JF, Czeisler CA (1998) Nonphotic entrainment of the human circadian pacemaker (vol 43, pg R991, 1998), AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY 275 (6) AMER PHYSIOLOGICAL SOC
Hasan S, Winsky-Sommerer R, Dijk D-J, Archer SN (2012) Sleep in transgenic mouse models for a polymorphism in the human PER3 gene, JOURNAL OF SLEEP RESEARCH 21 pp. 79-79 WILEY-BLACKWELL
DIJK DJ, BEERSMA DGM, BLOEM GM, DAAN S, VANDENHOOFDAKKER RH (1985) THE TIME COURSE OF EEG POWER-DENSITY DURING NIGHT AND DAY SLEEP IN RELATION TO THE 2 PROCESS MODEL OF SLEEP REGULATION, JOURNAL OF INTERDISCIPLINARY CYCLE RESEARCH 16 (4) pp. 248-249 SWETS ZEITLINGER PUBLISHERS
Dijk DJ, Franken P (2005) Interaction of Sleep Homeostasis and Circadian Rhythmicity: Dependent or Independent Systems?, pp. 418-434
Aeschbach D, Dijk DJ, Borbély AA (1997) Dynamics of EEG spindle frequency activity during extended sleep in humans: relationship to slow-wave activity and time of day., Brain Res 748 (1-2) pp. 131-136
The dynamics of EEG spindle frequency activity (SFA; spectral power density in the 12.25-15.0 Hz range) and its relationship to slow-wave activity (SWA; 0.75-4.5 Hz) were investigated in long sleep episodes (> 12 h). Young healthy men went to bed at either 19:00 h (early sleep; prior waking 36 h, n = 9) or 24:00 h (late sleep; prior waking 17 h, n = 8). In both nights, SWA in non-rapid-eye-movement sleep (NREMS) decreased over the first three to four 1.5-h intervals and remained at a low level in the subsequent five to six 1.5-h intervals. In contrast, the changes of SFA were more variable and differed between the lower (12.25-13.0 Hz), middle (13.25-14.0 Hz) and higher frequency bin (14.25-15.0 Hz). A pronounced influence of time of day was present in the lower and higher SFA bin, when the dynamics were analyzed with respect to clock time. In both the early and late sleep condition, power density in the lower bin was highest between 2:00 and 5:00 h in the morning and decreased thereafter. In the higher bin, power density was low in the early morning hours and increased as sleep was extended into the daytime hours. The results provide further evidence for a frequency-specific circadian modulation of SFA which becomes more evident at a time when SWA is low.
Dijk DJ, Roth C, Landolt HP, Werth E, Aeppli M, Achermann P, Borbély AA (1995) Melatonin effect on daytime sleep in men: suppression of EEG low frequency activity and enhancement of spindle frequency activity., Neurosci Lett 201 (1) pp. 13-16
The effect of melatonin (5 mg, p.o.) on electroencephalographic (EEG) activity during sleep was investigated in eight men in a placebo-controlled cross-over design. Melatonin was administered immediately prior to a 4-h daytime sleep episode (13-17 h) after a partial sleep deprivation. The non-REM sleep stages and REM sleep duration were not significantly affected. Melatonin enhanced EEG power density in non-REM sleep in the 13.75-14.0 Hz bin (i.e., within the frequency range of sleep spindles), and reduced activity in the 15.25-16.5 Hz band. In the first 2 h spectral values within the 2.25-5.0 Hz range were reduced. These changes in the EEG are to some extent similar to those induced by benzodiazepine hypnotics and to the contribution of the endogenous circadian pacemaker to the spectral composition of the sleep EEG when sleep occurs at night.
Aeschbach D, Lockyer BJ, Dijk D, Lockley SW, Nuwayser ES, Nichols LD, Czeisler CA (2006) Approaching an endogenous melatonin secretion profile to improve daytime sleep by dermal melatonin delivery, SLEEP 29 pp. A41-A42 AMER ACADEMY SLEEP MEDICINE
Achermann P, Werth E, Dijk DJ, Borbely AA (1995) Time course of sleep inertia after nighttime and daytime sleep episodes., Arch Ital Biol 134 (1) pp. 109-119
Sleep inertia refers to the period of reduced vigilance following upon awakening from sleep. To investigate the time course of sleep inertia, self-ratings of alertness and reaction time in a memory task were repeatedly assessed after nighttime and daytime sleep episodes in healthy young men. Alertness gradually increased and reaction time gradually decreased within the first hour after awakening. Their time course could be described by exponential functions with time constants of 0.45 h and 0.3 h, respectively. The data demonstrate that sleep inertia is a robust, quantifiable process that can be incorporated in models of sleep and vigilance.
Jaspar M, Meyer C, Muto V, Shaffii-Le Bourdiec A, Kusse C, Vandewalle G, Collette F, Archer S, Dijk D-J, Maquet P (2012) Influence of sleep homeostasis and circadian rhythm on executive discriminative ability during a constant routine, JOURNAL OF SLEEP RESEARCH 21 pp. 328-328 WILEY-BLACKWELL
Johnson MP, Duffy JF, Dijk DJ, Ronda JM, Dyal CM, Czeisler CA (1992) Short-term memory, alertness and performance: a reappraisal of their relationship to body temperature., J Sleep Res 1 (1) pp. 24-29
Previous studies have led to the beliefs: (1) that short-term memory is best during the night when the body temperature is at its nadir, and (2) that the circadian rhythms of short-term memory and subjective alertness are driven by oscillators independent from each other and from the body temperature cycle. Unfortunately, these conclusions, which would have major implications for understanding the organization of the human circadian timing system, are largely based on field and laboratory studies, which in many cases sampled data infrequently and/or limited data collection to normal waking hours. In order to investigate these points further, we have monitored behavioural variables in two different protocols under controlled laboratory conditions: (1) during a period of 36-60 h of sustained wakefulness; and (2) during forced desynchrony between the body temperature and sleep/wake cycles, allowing testing of non-sleep-deprived subjects at all circadian phases. Contrary to earlier findings, we report here that the circadian rhythm of short-term memory varies in parallel with the circadian rhythms of subjective alertness, calculation performance, and core body temperature under both these experimental conditions. These results challenge the notion that short-term memory is inversely linked to the body temperature cycle and suggest that the human circadian pacemaker, which drives the body temperature cycle, is the primary determinant of endogenous circadian variations in subjective alertness and calculation performance as well as in the immediate recall of meaningful material.
Dijk DJ, Groeger J, Deacon S, Stanley N (2006) Association between individual differences in slow wave sleep, slow wave activity and sleep continuity in young, middle-aged and older men and women, EUROPEAN NEUROPSYCHOPHARMACOLOGY 16 pp. S538-S538 ELSEVIER SCIENCE BV
Campbell S, Czeisler CA, Dijk DJ, Kronauer RE, Brown EN, Duffy JF, Allan JS, Shanahan TL, Rimmer DW, Ronda JM, Mitchell JF, Silva EJ, Emens JS (2000) Is there an intrinsic period of the circadian clock?  (multiple letters), Science 288 (5469) pp. 1174-1175
Wyatt JK, Dijk DJ, Czeisler CA (2002) Negative effects of wake duration, circadian phase, and caffeine administration on self-assessment, SLEEP 25 pp. A425-A426 AMER ACAD SLEEP MEDICINE
Boyle J, Dijk D-J (2012) Pharmacology of sleep- and wake-promoting compounds in humans: novel trials, JOURNAL OF SLEEP RESEARCH 21 pp. 47-48 WILEY-BLACKWELL
Shaffii-Le Bourdiec A, Muto V, Jaspar M, Kusse C, Foret A, Archer SN, Le Bourdiec F, Vandewalle G, Collette F, Dijk DJ, Maquet P (2012) Difference in neural correlates of discrimination during sleep deprivation in PER3 homozygous, JOURNAL OF SLEEP RESEARCH 21 pp. 82-82 WILEY-BLACKWELL
James LM, Viola AU, Archer SN, Dijk D (2008) Topography of the effects of a PER3 polymorphism on alpha activity in REM sleep under baseline and recovery conditions, JOURNAL OF SLEEP RESEARCH 17 pp. 1-1 WILEY-BLACKWELL PUBLISHING, INC
Dijk DJ (2012) Imaging and monitoring sleep and its disorders: local sleep, circadian rhythms and variability., J Sleep Res 21 (5) pp. 485-486
Zeitzer JM, Duffy JF, Klerman EB, Shanahan TL, Dijk DJ, Czeisler CA (2000) Plasma melatonin concentrations decline with age? Reply, AMERICAN JOURNAL OF MEDICINE 109 (4) pp. 345-345 EXCERPTA MEDICA INC
Dijk DJ, Brunner DP, Borbély AA (1991) EEG power density during recovery sleep in the morning., Electroencephalogr Clin Neurophysiol 78 (3) pp. 203-214
Sleep was recorded under baseline conditions (waking prior to sleep 16 h; lights off 23.00 h) and during recovery sleep in the morning (waking prior to sleep 24 h; lights off 07.00 h). Slow-wave activity (SWA; EEG power density in the range of 0.75-4.5 Hz) declined progressively over consecutive nonREM-REM cycles in both conditions despite the different circadian phase at which sleep occurred. SWA in nonREM sleep in the first 5 h of sleep was significantly higher in recovery than in baseline. Also SWA within the first 20 min of nonREM-episodes 2 and 3 was significantly higher in recovery sleep, and a tendency in the same direction was seen for nonREM-episode 1. These data show that homeostatic processes are expressed in the EEG also when sleep is initiated at a circadian phase where REM sleep propensity is high. However, comparison of the power spectrum in the first cycle of day-time recovery sleep with published data on recovery sleep at various circadian phases suggests that circadian factors influence the EEG spectra.
Cohen DA, Wang W, Wyatt JK, Kronauer RE, Dijk D-J, Czeisler CA, Klerman EB (2010) Uncovering Residual Effects of Chronic Sleep Loss on Human Performance, SCIENCE TRANSLATIONAL MEDICINE 2 (14) ARTN 14ra3 AMER ASSOC ADVANCEMENT SCIENCE
KLEIN T, MARTENS H, DIJK DJ, KRONAUER RE, SEELY EW, CZEISLER CA (1993) CHRONIC NON-24-HOUR CIRCADIAN-RHYTHM SLEEP DISORDER IN A BLIND MAN WITH A REGULAR 24-HOUR SLEEP-WAKE SCHEDULE (VOL 16, PG 333, 1993), SLEEP 16 (5) pp. 510-510 AMER SLEEP DISORDERS ASSOC
Cajochen C, Jewett ME, Dijk DJ (2003) Human circadian melatonin rhythm phase delay during a fixed sleep-wake schedule interspersed with nights of sleep deprivation., J Pineal Res 35 (3) pp. 149-157
The human circadian pacemaker, with an intrinsic period between 23.9 and 24.5 hr, can be reset by low levels of light. Biomathematical models of the human clock predict that light-dark cycles consisting of only approximately 3.5 lux during 16 hr of wakefulness and 0 lux during 8 hr of sleep should entrain approximately 45% of the population. However, under real-life conditions, sleep-wake schedules and the associated light-dark exposures are often irregular. It remains unclear whether the phase of the pacemaker would remain stable under such conditions. We investigated the stability of the circadian phase in dim light by assessing the plasma melatonin rhythm during nine consecutive circadian cycles. Ten subjects were scheduled to sleep for 8 hr (0.03 lux) and to be awake for 16 hr (5-13 lux) during all days except on days 4 and 8, during which the subjects were sleep deprived for 40 hr (5-13 lux), either in a sitting/standing or supine body posture. In all subjects, the phase of the melatonin rhythm occurred at a later clock time on day 9 than on day 2 (average delay: 1.4 hr). Largest delays in the melatonin onset were observed in subjects with low amplitude melatonin rhythms. The area under the curve during active melatonin secretion was significantly reduced when subjects were sleep deprived in the 40-hr supine body posture condition compared with either the 40-hr sitting/standing sleep deprivation (SD) or the ambulatory condition under non-SD conditions. Posture differences did not significantly affect the relative phase position of the melatonin profiles. The data indicate that under conditions of reduced zeitgeber strength, the phase of the human circadian pacemaker, using plasma melatonin as a marker, can be phase delayed by one night of SD and the associated dim light exposure.
Lo JC, Groeger JA, Santhi N, Arbon EL, Lazar AS, Hasan S, von Schantz M, Archer SN, Dijk DJ (2012) Effects of partial and acute total sleep deprivation on performance across cognitive domains, individuals and circadian phase., PLoS One 7 (9)
Cognitive performance deteriorates during extended wakefulness and circadian phase misalignment, and some individuals are more affected than others. Whether performance is affected similarly across cognitive domains, or whether cognitive processes involving Executive Functions are more sensitive to sleep and circadian misalignment than Alertness and Sustained Attention, is a matter of debate.
Czeisler CA, Dijk DJ (1995) Use of bright light to treat maladaptation to night shift work and circadian rhythm sleep disorders., J Sleep Res 4 (S2) pp. 70-73
Night work is associated with increased sleepiness and disturbed sleep. Maladaptation of the circadian system, which is phase-adjusted to day time work and thus promotes sleepiness during its nadir at night and wakefulness (or disturbed sleep) during the day, contributes substantially to this problem. A major cause of suboptimal circadian phase adjustment among night workers is the exposure to morning light, which prevents the delay needed for optimal adjustment to night work. Several laboratory studies indicate that careful application of bright light may cause the circadian system to shift to any desired phase. Furthermore, studies of simulated night work demonstrate that night exposure to bright light can virtually eliminate circadian maladjustment among night workers. While the results are promising, there is still, however, an urgent need for longitudinal studies of bright light application in real-life settings.
Dijk DJ, Beersma DG, van den Hoofdakker RH (1989) All night spectral analysis of EEG sleep in young adult and middle-aged male subjects., Neurobiol Aging 10 (6) pp. 677-682
The sleep EEGs of 9 young adult males (age 20-28 years) and 8 middle-aged males (42-56 years) were analyzed by visual scoring and spectral analysis. In the middle-aged subjects power density in the delta, theta and sigma frequencies were attenuated as compared to the young subjects. In both age groups power density in the delta and theta frequencies declined from NREM period 1 to 3. In the sigma frequencies, however, no systematic changes in power density were observed over the sleep episode. In both age groups the decay of EEG power (0.75-7.0 Hz) over successive NREM-REM cycles and the time course of EEG power during NREM sleep was analyzed. The decay rate of both EEG power density over successive NREM-REM cycles and EEG power density during NREM sleep was smaller in the middle-aged subjects than in the young subjects. It is concluded that the age-related differences in human sleep EEG power spectra are not identical to the changes in EEG power spectra observed in the course of the sleep episode. Therefore age-related differences in EEG power spectra cannot be completely explained by assuming a reduced need for sleep in older subjects. The smaller decay rate of EEG power during NREM sleep in the middle-aged subjects is interpreted as a reduced sleep efficiency. The results are discussed in the frame work of the two-process model of sleep regulation.
Eriksson M, Kerr D, Mills SL, Coppini DV, Dijk D, Boyle J (2009) Objective Evidence of Poor Sleep and Daytime Consequences in Diabetic Patients with Painful Diabetic Peripheral Neuropathy When Compared with Healthy Controls: A Polysomnography Study, DIABETES 58 pp. A224-A224 AMER DIABETES ASSOC
Dijk D-J, Groeger JA, Stanley N, Deacon S (2010) Age-related Reduction in Daytime Sleep Propensity and Nocturnal Slow Wave Sleep, SLEEP 33 (2) pp. 211-223 AMER ACAD SLEEP MEDICINE
DAAN S, BEERSMA DGM, DIJK DJ (1986) SLEEP CYCLE OR REM-SLEEP GENERATOR, BEHAVIORAL AND BRAIN SCIENCES 9 (3) pp. 402-403 CAMBRIDGE UNIV PRESS
Dijk D-J (2013) Sleep fragmentation, metabolism, and sleepiness, Journal of Sleep Research 22 (1) pp. 1-2
Dijk DJ, Duffy JF, Czeisler CA (2001) Age-related increase in awakenings: impaired consolidation of nonREM sleep at all circadian phases., Sleep 24 (5) pp. 565-577
STUDY OBJECTIVES: (1) To assess the circadian and sleep-dependent regulation of the frequency and duration of awakenings in young and older people; (2) to determine whether age-related deterioration of sleep consolidation is related to an increase in the frequency or duration of awakenings; (3) to determine whether pre-awakening sleep structure is preferentially enriched by REM sleep or nonREM sleep and (4) to determine whether sleep structure prior to awakenings is affected by age. DESIGN: Between age-group comparison of sleep consolidation and sleep structure preceding awakenings. SETTING: Environmental Scheduling Facility, General Clinical Research Center. PARTICIPANTS: Eleven healthy young men (21-30 years) and 13 older healthy men (n=9) and women (n=4) (64-74 years). INTERVENTIONS: Forced desynchrony between the sleep-wake cycle and circadian rhythms by scheduling of the rest-activity cycle to 28-h for 21-25 cycles. MEASUREMENTS AND RESULTS: Circadian and sleep-dependent regulation of the frequency and duration of awakenings and of sleep structure preceding awakenings were assessed in 482 sleep episodes (9h 20 min each). The circadian modulation of wakefulness within sleep episodes was primarily related to a variation in the duration of awakenings. In contrast, the age-related reduction of sleep consolidation was primarily related to an increase in the frequency of awakenings. Whereas in both young and older subjects pre-awakening sleep contained more REM sleep than overall sleep, this enrichment of REM sleep (i.e., the gating of wakefulness by REM sleep) was diminished in older people. In older people, preawakening sleep contained more nonREM sleep and stage two sleep in particular, than in young people. CONCLUSIONS: At all circadian phases, the age-related reduction of sleep consolidation is primarily related to a reduction in the consolidation of nonREM sleep.
Archer SN, Dijk DJ (2006) Delayed sleep phase disorder, circadian genes, sleep homeostasis and light sensitivity, pp. 327-334
© Cambridge University Press 2013.In humans, the sleep?wake cycle is determined by the interaction of the endogenous circadian clock and sleep homeostat, and exogenous factors such as the light/dark cycle, which is important for circadian entrainment, and social influences such as work and recreation (Figure 31.1). These factors interact and it is often difficult to determine the causes and nature of altered sleep?wake timing. Abnormal sleep?wake timing may be a simple consequence of an abnormal phase relationship of the circadian clock and environmental time. This may be caused by aberrant light exposure patterns or extreme intrinsic periods of the circadian clock. The timing of the sleep?wake cycle relative to the circadian sleep propensity rhythm may be altered because of fast or slow build-up of homeostatic sleep pressure. Recent mathematical models of the sleep?wake cycle have indeed demonstrated that one particular phenotype may be related to parameters of very different processes . Here, we focus on some of the genetic factors that are associated with abnormally delayed sleep timing, and explore to what extent the effects of these factors can be attributed to physiological processes such as light sensitivity, sleep homeostasis or circadian period. Circadian rhythm sleep disorders (CRSDs) refer to sleep disturbances that are primarily due to alterations of the circadian time-keeping system or are related to a misalignment of endogenous circadian rhythms and the required sleep?wake time (see ). The latter distinction is important because social factors may necessitate a non-desirable sleep?wake schedule, as occurs in shift work, for example. Shift work disorder and jet lag disorder are CRSDs that are caused by exogenous factors, whereas dysfunction of the endogenous circadian clock is thought to be the primary cause of delayed sleep phase disorder (DSPD). A better understanding of what causes CRSDs and inter-individual vulnerability differences is important because of the large proportion of the population who regularly undertake shift work, the epidemiological evidence linking insufficient sleep with negative health outcomes , and known associations between extreme evening preference and health problems such as mood disorders, metabolic disorders, and cardiovascular risk (see ).
Viola AU, James LM, Schlangen LJM, Dijk D-J (2008) Blue-enriched white light in the workplace improves self-reported alertness, performance and sleep quality, SCANDINAVIAN JOURNAL OF WORK ENVIRONMENT & HEALTH 34 (4) pp. 297-306 SCAND J WORK ENV HEALTH
Nesbitt AD, Dijk DJ (2014) Out of synch with society: An update on delayed sleep phase disorder, Current Opinion in Pulmonary Medicine 20 (6) pp. 581-587
© 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins.Purpose of review: Delayed sleep phase disorder is the most common of the circadian rhythm sleep disorders. Its treatment involves exploiting the intrinsic biological properties of the circadian pacemaker to advance biological rhythms, most notably the sleep-wake cycle, to a time which affords the individual an appropriate sleep opportunity compatible with normal societal functioning. This review highlights several new studies published in the last 18 months concerning sleep and circadian physiology relevant to the disorder and its management. Recent findings: In addition to new information regarding the epidemiology and associations of the disorder, the pathophysiological importance of light exposure across the entire day, with special relevance to the phasedelaying effects of artificial evening light, is being unravelled. Furthermore, disorder-specific differences in period length and sleep homeostasis are being considered as pathophysiological contributors to delayed sleep phase disorder. The molecular effects of chronic sleep deprivation and circadian misalignment are currently being explored as potential mechanistic markers of the deleterious health consequences associated with these states. Summary: Advances in our understanding of the dynamics of circadian physiology, sleep-wake regulation and the deleterious effects of misalignment and sleep deprivation, are spurring on efforts to find optimal treatment paradigms for patients presenting to sleep clinics with delayed sleep phase disorder.
Dijk DJ, Archer SN (2009) Circadian and Homeostatic Regulation of Human Sleep and Cognitive Performance and Its Modulation by PERIOD3, Sleep Medicine Clinics 4 (2) pp. 111-125
Sleep physiology and waking performance are regulated through the interaction of an endogenous circadian process and a sleep-wake-dependent homeostatic process. The two processes are not independent: the observed circadian amplitude of waking performance depends on homeostatic sleep pressure, so that the negative effects of sleep loss are most pronounced in the early morning if homeostatic sleep pressure is high. These findings underscore the close interrelations between sleep, circadian rhythmicity, and waking performance and suggest that some circadian phenotypes are related to changes in sleep-regulatory processes. Understanding the effects of these alterations in clock genes, such as PER3, at the cellular and biochemical level may provide insights into the nature of the sleep homeostat and its interaction with circadian rhythmicity in the regulation of waking performance. © 2009 Elsevier Inc. All rights reserved.
Dijk DJ, Duffy JF, Czeisler CA (1992) Circadian and sleep/wake dependent aspects of subjective alertness and cognitive performance., J Sleep Res 1 (2) pp. 112-117
Circadian and sleep/wake dependent processes underlying variations in subjective alertness and cognitive performance were assessed in a constant routine protocol and in a protocol in which the sleep/wake cycle was uncoupled from the output of the endogenous circadian pacemaker. In the latter protocol, the contribution of a sleep/wake dependent process and a circadian process to alertness and performance were separated by folding the data at either the period of the sleep/wake cycle or at the period of the endogenous circadian body temperature rhythm. This analysis revealed that prior wakefulness within a range of 0-18 h significantly reduced alertness and performance and that the circadian rhythm of core body temperature paralleled the circadian rhythm of alertness and performance. During the first 16 h of the constant routine protocol, which coincided with the subjects' habitual period of wakefulness, alertness and performance remained at a stable level. The latter finding was explained by assuming that during our usual waking day the circadian system counteracts the detrimental effects of increasing duration of prior wakefulness.
Lazar A, Santhi N, Lo J, Slak A, Hasan S, Von Schantz M, Archer S, Dijk D-J (2012) The circadian and homeostatic regulation of sleep spindle activity: effect of the PER3 VNTR polymorphism, JOURNAL OF SLEEP RESEARCH 21 pp. 82-82 WILEY-BLACKWELL
Dijk DJ, Duffy JF, Czeisler CA (2000) Contribution of circadian physiology and sleep homeostasis to age-related changes in human sleep., Chronobiol Int 17 (3) pp. 285-311
The circadian pacemaker and sleep homeostasis play pivotal roles in vigilance state control. It has been hypothesized that age-related changes in the human circadian pacemaker, as well as sleep homeostatic mechanisms, contribute to the hallmarks of age-related changes in sleep, that is, earlier wake time and reduced sleep consolidation. Assessments of circadian parameters in healthy young (approximately 20-30 years old) and older people (approximately 65-75 years old)--in the absence of the confounding effects of sleep, changes in posture, and light exposure--have demonstrated that an earlier wake time in older people is accompanied by about a 1 h advance of the rhythms of core body temperature and melatonin. In addition, older people wake up at an earlier circadian phase of the body temperature and plasma melatonin rhythm. The amplitude of the endogenous circadian component of the core body temperature rhythm assessed during constant routine and forced desynchrony protocols is reduced by 20-30% in older people. Recent assessments of the intrinsic period of the human circadian pacemaker in the absence of the confounding effects of light revealed no age-related reduction of this parameter in both sighted and blind individuals. Wake maintenance and sleep initiation are not markedly affected by age except that sleep latencies are longer in older people when sleep initiation is attempted in the early morning. In contrast, major age-related reductions in the consolidation and duration of sleep occur at all circadian phases. Sleep of older people is particularly disrupted when scheduled on the rising limb of the temperature rhythm, indicating that the sleep of older people is more susceptible to arousal signals generated by the circadian pacemaker. Sleep-homeostatic mechanisms, as assayed by the sleep-deprivation-induced increase of EEG slow-wave activity (SWA), are operative in older people, although during both baseline sleep and recovery sleep SWA in older people remains at lower levels. The internal circadian phase advance of awakening, as well as the age-related reduction in sleep consolidation, appears related to an age-related reduction in the promotion of sleep by the circadian pacemaker during the biological night in combination with a reduced homeostatic pressure for sleep. Early morning light exposure associated with this advance of awakening in older people could reinforce the advanced circadian phase. Quantification of the interaction between sleep
Dijk D-J (2010) Sleep variety: physiology, psychology and epidemiology, JOURNAL OF SLEEP RESEARCH 19 (3) pp. 381-383 WILEY-BLACKWELL
Dijk DJ (2011) Sleep for all ages: at home or in the laboratory?, J Sleep Res 20 (1 Pt 1) pp. 1-2
Dijk DJ (2012) Sleep and health: beyond sleep duration and sleepiness?, J Sleep Res 21 (4) pp. 355-356
Klerman EB, Dijk D (2004) Sleep during a bedrest extension protocol in older and younger individuals, SLEEP 27 pp. 129-130 AMER ACADEMY SLEEP MEDICINE
Rajaratnam SMW, Dijk DJ, Middleton B, Stone BM, Arendt J (2004) Melatonin phase-shifts human circadian rhythms with no evidence of changes in the duration of endogenous melatonin secretion or the 24-hour production of reproductive hormones (vol 88, pg 4303, 2003), JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM 89 (6) pp. 2997-2997 ENDOCRINE SOC
Dijk DJ (2015) Napping: when sleep is bad for you?, Journal of sleep research 24 (5)
Terman M, Lewy AJ, Dijk DJ, Boulos Z, Eastman CI, Campbell SS (1995) Light treatment for sleep disorders: consensus report. IV. Sleep phase and duration disturbances., J Biol Rhythms 10 (2) pp. 135-147
Advanced and delayed sleep phase disorders, and the hypersomnia that can accompany winter depression, have been treated successfully by appropriately timed artificial bright light exposure. Under entrainment to the 24-h day-night cycle, the sleep-wake pattern may assume various phase relationships to the circadian pacemaker, as indexed, for example, by abnormally long or short intervals between the onset of melatonin production or the core body temperature minimum and wake-up time. Advanced and delayed sleep phase syndromes and non-24-h sleep-wake syndrome have been variously ascribed to abnormal intrinsic circadian periodicity, deficiency of the entrainment mechanism, or--most simply--patterns of daily light exposure insufficient for adequate phase resetting. The timing of sleep is influenced by underlying circadian phase, but psychosocial constraints also play a major role. Exposure to light early or late in the subjective night has been used therapeutically to produce corrective phase delays or advances, respectively, in both the sleep pattern and circadian rhythms. Supplemental light exposure in fall and winter can reduce the hypersomnia of winter depression, although the therapeutic effect may be less dependent on timing.
Viola AU, Chellappa SL, Archer SN, Pugin F, Götz T, Dijk DJ, Cajochen C (2012) Interindividual differences in circadian rhythmicity and sleep homeostasis in older people: effect of a PER3 polymorphism., Neurobiology of aging 33 (5)
Aging is associated with marked changes in the timing, consolidation and structure of sleep. Older people wake up frequently, get up earlier and have less slow wave sleep than young people, although the extent of these age-related changes differs considerably between individuals. Interindividual differences in homeostatic sleep regulation in young volunteers are associated with the variable-number, tandem-repeat (VNTR) polymorphism (rs57875989) in the coding region of the circadian clock gene PERIOD3 (PER3). However, predictors of these interindividual differences have yet to be identified in older people. Sleep electroencephalographic (EEG) characteristics and circadian rhythms were assessed in 26 healthy older volunteers (55-75 years) selected on the basis of homozygosity for either the long or short allele of the PER3 polymorphism. Homozygosity for the longer allele (PER3(5/5)) associated with a phase-advance in the circadian melatonin profile and an earlier occurrence of the melatonin peak within the sleep episode. Furthermore, older PER3(5/5) participants accumulated more nocturnal wakefulness, had increased EEG frontal delta activity (0.75-1.50 Hz), and decreased EEG frontal sigma activity (11-13 Hz) during non-rapid eye movement (REM) sleep compared with PER3(4/4) participants. Our results indicate that the polymorphism in the clock gene PER3 may contribute to interindividual differences in sleep and circadian physiology in older people. Copyright Â© 2012 Elsevier Inc. All rights reserved.
Dijk DJ, Daan S (1989) Sleep EEG spectral analysis in a diurnal rodent: Eutamias sibiricus., J Comp Physiol A 165 (2) pp. 205-215
1. Sleep was studied in the diurnal rodent Eutamias sibiricus, chronically implanted with EEG and EMG electrodes. Analysis of the distribution of wakefulness, nonrapid eye movement (NREM) sleep, and rapid eye movement (REM) sleep over the 24 h period (LD 12:12) showed that total sleep time was 27.5% of recording time during the 12 h light period and 74.4% during the 12 h dark period. Spectral analysis of the sleep EEG revealed a progressive decay in delta power density in NREM sleep during darkness. Power density of the higher frequencies increased at the end of darkness. Power density of the higher frequencies decreased and that of the lower frequencies increased during light. 2. Analysis of the distribution of vigilance states under three different photoperiods (LD 18:6; 12:12; 6:18) revealed that changes in daylength mainly resulted in a redistribution of sleep and wakefulness over light and darkness. Under long days the percentage of sleep during light was enhanced. The time course of delta power density in NREM sleep was characterized by a long rising part and a short falling part under long days, while a reversed picture emerged under short days. As a consequence, the power density during days. As a consequence, the power density during light was relatively high under long days. 3. After 24 h sleep deprivation by forced activity, no significant changes in the percentages of wakefulness and NREM were observed, whereas REM sleep was slightly enhanced. EEG power density, however, was significantly increased by ca. 50% in the 1.25-10.0 Hz range in the first 3 h of recovery sleep. This increase gradually decayed over the recovery night. 4. The same 24 h sleep deprivation technique led to a ca. 25% increase in oxygen consumption during recovery nights. While the results of the EEG spectral analysis are compatible with the hypothesis that delta power density reflects the 'intensity' of NREM sleep as enhanced by prior wakefulness and reduced by prior sleep, such enhanced sleep depth after sleep deprivation is not associated with reduced energy expenditure as might be anticipated by some energy conservation hypotheses on sleep function.
Czeisler CA, Duffy JF, Shanahan TL, Brown EN, Mitchell JF, Rimmer DW, Ronda JM, Silva EJ, Allan JS, Emens JS, Dijk DJ, Kronauer RE (1999) Stability, precision, and near-24-hour period of the human circadian pacemaker., Science 284 (5423) pp. 2177-2181
Regulation of circadian period in humans was thought to differ from that of other species, with the period of the activity rhythm reported to range from 13 to 65 hours (median 25.2 hours) and the period of the body temperature rhythm reported to average 25 hours in adulthood, and to shorten with age. However, those observations were based on studies of humans exposed to light levels sufficient to confound circadian period estimation. Precise estimation of the periods of the endogenous circadian rhythms of melatonin, core body temperature, and cortisol in healthy young and older individuals living in carefully controlled lighting conditions has now revealed that the intrinsic period of the human circadian pacemaker averages 24.18 hours in both age groups, with a tight distribution consistent with other species. These findings have important implications for understanding the pathophysiology of disrupted sleep in older people.
Herron K, Dijk D, Ellis J, Sanders J, Sterr AM (2008) Sleep correlates of motor recovery in chronic stroke: a pilot study using sleep diaries and actigraphy., Journal of Sleep Research 17 pp. 103-103
Dijk DJ (2014) Not so fast: sleep and media use., J Sleep Res 23 (4)
Van der Veen DR, Dijk D-J, Archer SN (2012) A role for PERIOD3 in sleep/wake rhythms: photic responses in humanised knock-in mice and gene expression correlates of PER3 expression, JOURNAL OF SLEEP RESEARCH 21 pp. 333-333 WILEY-BLACKWELL
Dijk DJ, Jewett ME, Czeisler CA, Kronauer RE (1999) Reply to technical note: nonlinear interactions between circadian and homeostatic processes: models or metrics?, J Biol Rhythms 14 (6) pp. 604-605
Landolt HP, Roth C, Dijk DJ, Borbély AA (1996) Late-afternoon ethanol intake affects nocturnal sleep and the sleep EEG in middle-aged men., J Clin Psychopharmacol 16 (6) pp. 428-436
The effect of a moderate dose of ethanol (0.55 g/kg of body weight), administered 6 hours before scheduled bedtime, on performance, nocturnal sleep, and the sleep electroencephalogram (EEG) was investigated in 10 healthy, middle-aged men (mean age: 61.6 +/- 0.9 years). By the beginning of the sleep episode, breath-ethanol concentrations had declined to zero in all subjects. Compared with the control condition (mineral water), sleep was perceived as more superficial. Sleep efficiency, total sleep time, stage 1, and rapid eye movement (REM) sleep were reduced. In the second half of the sleep episode, wakefulness exhibited a twofold increase. EEG power density in low delta frequencies was enhanced in non-REM sleep (1.25-2.5 Hz) and REM sleep (1.25-1.5 Hz). In slow wave sleep (i.e., stages 3 + 4), power density was increased not only in the low-frequency range (1.25-1.5, 2.25-4.0, 4.75-5.0 Hz) but also within the alpha (8.25-9.0 Hz) and sigma (12.25-13.0 Hz) band. The data demonstrate that late-afternoon ethanol intake in middle-aged men disrupts sleep consolidation, affects the sleep stage distribution, and alters the sleep EEG.
Groeger JA, Stanley N, Deacon S, Dijk DJ (2014) Dissociating effects of global SWS disruption and healthy aging on waking performance and daytime sleepiness., Sleep 37 (6) pp. 1127-1142
STUDY OBJECTIVE: To contrast the effects of slow wave sleep (SWS) disruption and age on daytime functioning. DESIGN: Daytime functioning was contrasted in three age cohorts, across two parallel 4-night randomized groups (baseline, two nights of SWS disruption or control, recovery sleep). SETTING: Sleep research laboratory. PARTICIPANTS: 44 healthy young (20-30 y), 35 middle-aged (40-55 y), and 31 older (66-83 y) men and women. INTERVENTIONS: Acoustic stimulation contingent on appearance of slow waves. MEASUREMENTS AND RESULTS: Cognitive performance was assessed before sleep latency tests at five daily time-points. SWS disruption resulted in less positive affect, slower or impaired information processing and sustained attention, less precise motor control, and erroneous implementation, rather than inhibition, of well-practiced actions. These performance impairments had far smaller effect sizes than the increase in daytime sleepiness and differed from baseline to the same extent for each age group. At baseline, younger participants performed better than older participants across many cognitive domains, with largest effects on executive function, response time, sustained attention, and motor control. At baseline, the young were sleepier than other age groups. CONCLUSIONS: SWS has been considered a potential mediator of age-related decline in performance, although the effects of SWS disruption on daytime functioning have not been quantified across different cognitive domains nor directly compared to age-related changes in performance. The data imply that two nights of SWS disruption primarily leads to an increase in sleepiness with minor effects on other aspects of daytime functioning, which are different from the substantial effects of age.
Viola AU, James LM, Schlangen LJ, Dijk D (2008) Blue-enriched light improves self-reported alertness and performance in the workplace, JOURNAL OF SLEEP RESEARCH 17 pp. 117-117 WILEY-BLACKWELL PUBLISHING, INC
Dijk DJ, Archer SN (2010) PERIOD3, circadian phenotypes, and sleep homeostasis, SLEEP MED REV 14 (3) pp. 151-160 W B SAUNDERS CO LTD
Circadian rhythmicity and sleep homeostasis contribute to sleep phenotypes and sleep-wake disorders, some of the genetic determinants of which are emerging. Approximately 10% of the population are homozygous for the 5-repeat allele (PER3(5/5)) of a variable number tandem repeat polymorphism in the clock gene PERIOD3 (PER3). We review recent data on the effects of this polymorphism on sleep-wake regulation. PER3(5/5) are more likely to show morning preference, whereas homozygosity for the four-repeat allele (PER3(4/4)) associates with evening preferences. The association between sleep timing and the circadian rhythms of melatonin and PER3 RNA in leukocytes is stronger in PER3(5/5) than in PER3(4/4). EEG alpha activity in REM sleep, theta/alpha activity during wakefulness and slow wave activity in NREM sleep are elevated in PER3(5/5). PER3(5/5) show a greater cognitive decline, and a greater reduction in fMRI-assessed brain responses to an executive task, in response to total sleep deprivation. These effects are most pronounced during the late circadian night/early morning hours, i.e., approximately 0-4 h after the crest of the melatonin rhythm. We interpret the effects of the PER3 polymorphism within the context of a conceptual model in which higher homeostatic sleep pressure in PER3(5/5) through feedback onto the circadian pacemaker modulates the amplitude of diurnal variation in performance. These findings highlight the interrelatedness of circadian rhythmicity and sleep homeostasis. (C) 2009 Elsevier Ltd. All rights reserved.
Bliwise DL, Dijk DJ, Juul KV (2015) Nocturia is associated with loss of deep sleep independently from sleep apnea, Neurourology and Urodynamics 34 (4)
In humans, a primate-specific variable-number tandem-repeat (VNTR) polymorphism (4 or 5 repeats 54 nt in length) in the circadian gene PER3 is associated with differences in sleep timing and homeostatic responses to sleep loss. We investigated the effects of this polymorphism on circadian rhythmicity and sleep homeostasis by introducing the polymorphism into mice and assessing circadian and sleep parameters at baseline and during and after 12 h of sleep deprivation (SD). Microarray analysis was used to measure hypothalamic and cortical gene expression. Circadian behavior and sleep were normal at baseline. The response to SD of 2 electrophysiological markers of sleep homeostasis, electroencephalography (EEG) ¸ power during wakefulness and ´ power during sleep, were greater in the Per3(5/5) mice. During recovery, the Per3(5/5) mice fully compensated for the SD-induced deficit in ´ power, but the Per3(4/4) and wild-type mice did not. Sleep homeostasis-related transcripts (e.g., Homer1, Ptgs2, and Kcna2) were differentially expressed between the humanized mice, but circadian clock genes were not. These data are in accordance with the hypothesis derived from human data that the PER3 VNTR polymorphism modifies the sleep homeostatic response without significantly influencing circadian parameters.
Wulff K, Joyce EM, Middleton B, Foster RG, Dijk DJ (2007) Sleep and circadian activity/rest disturbances in schizophrenia patients in comparison to unemployed healthy controls, EUROPEAN NEUROPSYCHOPHARMACOLOGY 17 pp. S415-S416 ELSEVIER SCIENCE BV
Dijk DJ, Visscher CA, Bloem GM, Beersma DG, Daan S (1987) Reduction of human sleep duration after bright light exposure in the morning., Neurosci Lett 73 (2) pp. 181-186
In 8 subjects the spontaneous termination of sleep was determined after repetitive exposure to either bright or dim light, between 6.00 and 9.00 h, on 3 days preceding sleep assessment. Sleep duration was significantly shorter following bright light than following dim light. During sleep the time course of EEG energy was not affected by the light treatment. Analysis of the time course of body temperature during sleep indicated an earlier rise of body temperature following the bright light treatment. In terms of the two-process model of sleep regulation this can be interpreted as a direct effect of light on the circadian phase of the wake up threshold.
DIJK DJ (1995) CIRCADIAN REGULATION OF SLEEP PROPENSITY, SLEEP STRUCTURE AND ALERTNESS - A SYMPHONY OF PARADOXES, ACTA NEUROPSYCHIATRICA 7 (2) pp. 24-26 REED HEALTHCARE COMMUNICATIONS
Klerman E, Dijk D (2006) Changes in mood and performance during sleep extension in younger and older people, SLEEP 29 pp. A374-A374 AMER ACADEMY SLEEP MEDICINE
Khalsa SB, Conroy DA, Duffy JF, Czeisler CA, Dijk DJ (2002) Sleep- and circadian-dependent modulation of REM density., J Sleep Res 11 (1) pp. 53-59
Rapid eye movement (REM) density, a measure of the frequency of rapid eye movements during REM sleep, is known to increase over the course of the sleep episode. However, the circadian modulation of REM density has not been thoroughly evaluated. Data from a forced desynchrony protocol, in which 20 consecutive sleep opportunities were systematically scheduled over the entire circadian cycle, were analysed. The REM density was evaluated from polysomnographically recorded REM sleep episodes, and analyzed as a function of time in the sleep opportunity and as a function of phase in the circadian cycle. The REM density showed a robust increase over the course of the sleep episode. This sleep-dependent increase was observed regardless of circadian phase, because data analyzed from different thirds of the circadian cycle exhibited a similar pattern. The REM density did not show a significant circadian-dependent modulation for data from the entire sleep opportunity. However, analysis of circadian modulation from separate thirds of the sleep opportunity revealed a significant circadian modulation in the last third of the sleep episode. Maximum REM densities were observed when the last third of the sleep episode coincided with the wake-maintenance zone, i.e.;8-10 h before the crest of the circadian rhythm of REM sleep propensity. These results confirm the dominant sleep-dependent modulation of REM density, and indicate that the density of REMs is greatest when sleep pressure is low, such as in the latter part of the sleep episode, at which time the circadian modulation of REM density is also appreciable.
Dean DA, Wyatt JK, Dijk D, Czeisler CA, Klerman EB (2008) Quantifying practice effects within groups and individuals: Examples from a month long forced desynchrony protocol, SLEEP 31 pp. A54-A54 AMER ACAD SLEEP MEDICINE
Zeitzer JM, Dijk DJ, Kronauer R, Brown E, Czeisler C (2000) Sensitivity of the human circadian pacemaker to nocturnal light: melatonin phase resetting and suppression., J Physiol 526 Pt 3 pp. 695-702
Ocular exposure to early morning room light can significantly advance the timing of the human circadian pacemaker. The resetting response to such light has a non-linear relationship to illuminance. The dose-response relationship of the human circadian pacemaker to late evening light of dim to moderate intensity has not been well established. Twenty-three healthy young male and female volunteers took part in a 9 day protocol in which a single experimental light exposure6.5 h in duration was given in the early biological night. The effects of the light exposure on the endogenous circadian phase of the melatonin rhythm and the acute effects of the light exposure on plasma melatonin concentration were calculated. We demonstrate that humans are highly responsive to the phase-delaying effects of light during the early biological night and that both the phase resetting response to light and the acute suppressive effects of light on plasma melatonin follow a logistic dose-response curve, as do many circadian responses to light in mammals. Contrary to expectations, we found that half of the maximal phase-delaying response achieved in response to a single episode of evening bright light ( approximately 9000 lux (lx)) can be obtained with just over 1 % of this light (dim room light of approximately 100 lx). The same held true for the acute suppressive effects of light on plasma melatonin concentrations. This indicates that even small changes in ordinary light exposure during the late evening hours can significantly affect both plasma melatonin concentrations and the entrained phase of the human circadian pacemaker.
Archer SN, Laing EE, Moeller-Levet CS, van der Veen DR, Bucca G, Lazar AS, Santhi N, Slak A, Kabiljo R, von Schantz M, Smith CP, Dijk D-J (2014) Mistimed sleep disrupts circadian regulation of the human transcriptome, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 111 (6) pp. E682-E691
Meyer C, Jaspar M, Muto V, Kusse C, Chellappa SL, Degueldre C, Balteau E, Luxen A, Collette F, Middleton B, Phillips C, Archer SN, Dijk D-J, Vandewalle G, Maquet P (2014) Seasonal variation in human executive brain responses, JOURNAL OF SLEEP RESEARCH 23 pp. 171-171 WILEY-BLACKWELL
Dijk D-J, Winsky-Sommerer R (2012) Sleep: The way we snooze now, New Scientist 213 (2850) pp. vi-vii
Dijk DJ (2012) Sleep spindles, mobile phones, lucid dreaming and sleep in Parkinson's disease and autism spectrum disorders., J Sleep Res 21 (6) pp. 601-602
Arbon EL, Lazar AS, Lo JC, Slak A, Mccabe PJ, Boyle J, Archer SN, Dijk D-J (2012) Individual differences in sleep revisited: stability across sleep restriction, extension and total sleep loss, JOURNAL OF SLEEP RESEARCH 21 pp. 207-208 WILEY-BLACKWELL
BEERSMA D, DIJK DJ (1993) SELECTIVE SWS SUPPRESSION DOES NOT AFFECT THE TIME-COURSE OF CORE BODY-TEMPERATURE IN MEN (VOL 1, PG 201, 1992), JOURNAL OF SLEEP RESEARCH 2 (3) pp. 186-186 BLACKWELL SCIENCE LTD
Dijk D (2008) Neural mechanisms of sleep and wakefulness: implications for insomnia treatment, EUROPEAN NEUROPSYCHOPHARMACOLOGY 18 pp. S603-S603 ELSEVIER SCIENCE BV
Dijk DJ (2014) Daily variations in sleep: associated genes and effects on affect., J Sleep Res 23 (6) pp. 607-608
Dijk DJ (2010) Journal of Sleep Research: present and future, J SLEEP RES 19 (2) pp. 259-259 WILEY-BLACKWELL PUBLISHING, INC
Wilson SJ, Nutt DJ, Alford C, Argyropoulos SV, Baldwin DS, Bateson A, Britton T, Crowe C, Dijk DJ, Espie C, Gringras P, Hajak G, Idzikowski C, Krystal A, Nash JR, Selsick H, Sharpley AL, Wade AG (2010) British Association for Psychopharmacology consensus statement on evidence-based treatment of insomnia, parasomnias and circadian rhythm disorders., J Psychopharmacol
Sleep disorders are common in the general population and even more so in clinical practice, yet are relatively poorly understood by doctors and other health care practitioners. These British Association for Psychopharmacology guidelines are designed to address this problem by providing an accessible up-to-date and evidence-based outline of the major issues, especially those relating to reliable diagnosis and appropriate treatment. A consensus meeting was held in London in May 2009. Those invited to attend included BAP members, representative clinicians with a strong interest in sleep disorders and recognized experts and advocates in the field, including a representative from mainland Europe and the USA. Presenters were asked to provide a review of the literature and identification of the standard of evidence in their area, with an emphasis on meta-analyses, systematic reviews and randomized controlled trials where available, plus updates on current clinical practice. Each presentation was followed by discussion, aimed to reach consensus where the evidence and/or clinical experience was considered adequate or otherwise to flag the area as a direction for future research. A draft of the proceedings was then circulated to all participants for comment. Key subsequent publications were added by the writer and speakers at draft stage. All comments were incorporated as far as possible in the final document, which represents the views of all participants although the authors take final responsibility for the document.
Wulff K, Joyce EM, Middleton B, Foster RG, Dijk D (2008) Sleep and rest/activity cycle disturbances in schizophrenia patients in comparison to unemployed healthy controls, JOURNAL OF SLEEP RESEARCH 17 pp. 76-77 WILEY-BLACKWELL PUBLISHING, INC
Franken P, Dijk DJ, Tobler I, Borbély AA (1994) High-frequency components of the rat electrocorticogram are modulated by the vigilance states., Neurosci Lett 167 (1-2) pp. 89-92
In view of the reports that in the human magnetoencephalogram, 40-Hz oscillations are more abundant in waking and REM sleep than in non-REM sleep, we performed a 24-h broad-band (0.25-64 Hz) spectral analysis of the electrocorticogram in unrestrained rats. Spectral power above 33 Hz was higher in waking and REM sleep than in non-REM sleep, and in the range of 6-38 Hz it was higher in REM sleep than in waking. Consistent frequency-specific changes in spectral power marked the transitions between vigilance states. The study demonstrates that the rat EEG exhibits state- and frequency-specific changes over a large frequency range.
Groeger JA, Viola AU, Lo JCY, von Schantz M, Archer SN, Dijk D-J (2008) Early morning executive functioning during sleep deprivation is compromised by a PERIOD3 polymorphism, SLEEP 31 (8) pp. 1159-1167 AMER ACAD SLEEP MEDICINE
Price LLA, Khazova M, Ohagan JB, Santhi N, Dijk D-J (2012) Developing an architectural dosimetry protocol for residential properties in circadian sleep research, JOURNAL OF SLEEP RESEARCH 21 pp. 199-199 WILEY-BLACKWELL
Dijk D-J (2010) Slow-wave sleep deficiency and enhancement: Implications for insomnia and its management, WORLD JOURNAL OF BIOLOGICAL PSYCHIATRY 11 pp. 22-28 TAYLOR & FRANCIS LTD
Van den Hoofdakker RH, Beersma DG, Dijk DJ (1986) Sleep disorders in depression., Eur Neurol 25 Suppl 2 pp. 66-70
Recently some hypotheses explaining sleep disturbances in depression have been proposed. One hypothesis assumes an advanced phase position of the circadian pacemaker controlling a.o. REM sleep (REMS) production. In another a deficiency of process S is proposed. In this paper the sleep of depressed patients and healthy subjects is compared with respect to REMS production and EEG power density (a possible reflection of process S). Data were derived from the literature and from own experiments. The results provide support only for the S deficiency hypothesis.
Dijk DJ (2014) Subjective sleepiness: an undervalued early sign of insufficient sleep?, J Sleep Res 23 (3)
Duffy JF, Zeitzer JM, Rimmer DW, Klerman EB, Dijk DJ, Czeisler CA (2002) Peak of circadian melatonin rhythm occurs later within the sleep of older subjects., Am J Physiol Endocrinol Metab 282 (2) pp. E297-E303
We investigated the relationship between sleep timing and the timing of the circadian rhythm of plasma melatonin secretion in a group of healthy young and older subjects without sleep complaints. The timing of sleep and the phase of the circadian melatonin rhythm were earlier in the older subjects. The relationship between the plasma melatonin rhythm and the timing of sleep was such that the older subjects were sleeping and waking earlier relative to their nightly melatonin secretory episode. Consequently, the older subjects were waking at a time when they had higher relative melatonin levels, in contrast with younger subjects, whose melatonin levels were relatively lower by wake time. Our findings indicate that aging is associated not only with an advance of sleep timing and the timing of circadian rhythms but also with a change in the internal phase relationship between the sleep-wake cycle and the output of the circadian pacemaker. In healthy older subjects, the relative timing of the melatonin rhythm with respect to sleep may not play a causal role in sleep disruption.
Wang D, Piper AJ, Yee BJ, Wong KK, Kim JW, D'Rozario A, Rowsell L, Dijk DJ, Grunstein RR (2014) Hypercapnia is a key correlate of EEG activation and daytime sleepiness in hypercapnic sleep disordered breathing patients, Journal of Clinical Sleep Medicine 10 (5) pp. 517-522
Background: The key determinants of daytime drowsiness in sleep disordered breathing (SDB) are unclear. Hypercapnia has not been examined as a potential contributor due to the lack of reliable measurement during sleep. To overcome this limitation, we studied predominantly hypercapnic SDB patients to investigate the role of hypercapnia on EEG activation and daytime sleepiness. Methods: We measured overnight polysomnography (PSG), arterial blood gases, and Epworth Sleepiness Scale in 55 severe SDB patients with obesity hypoventilation syndrome or overlap syndrome (COPD+ obstructive sleep apnea) before and
Kronauer RE, Wang W, Duffy JF, Czeisler CA, Wyatt JK, Dijk D, Klerman EB (2009) SURVIVAL ANALYSES OF SLEEP AND WAKE BOUTS REVEAL DIFFERENTIAL REGULATION OF THE MAINTENANCE OF NREM AND REM SLEEP, SLEEP 32 pp. A22-A22 AMER ACAD SLEEP MEDICINE
Dijk DJ (2014) Sleep and cognition in ageing: how to measure what?, J Sleep Res 23 (5) pp. 487-488
Brunner DP, Kräuchi K, Dijk DJ, Leonhardt G, Haug HJ, Wirz-Justice A (1996) Sleep electroencephalogram in seasonal affective disorder and in control women: effects of midday light treatment and sleep deprivation., Biol Psychiatry 40 (6) pp. 485-496
The role of sleep regulation in Seasonal Affective Disorder (SAD) was studied in 11 female SAD patients and eight controls in winter before and after light treatment (LT, 6000 lux, 10-14h, 5 days). The sleep electroencephalogram (EEG) was recorded at baseline and after the total sleep deprivation (TSD) of a 40-h constant routine. The well-known effects of TSD on sleep parameters and on EEG power spectra were replicated, indicating normal homeostatic sleep regulation in SAD. Sleep improved after LT in both groups. Since the condition following LT was the second session, these improvements may be an order effect and/or an effect of LT itself. After LT, sleep EEG spectra of SAD patients, but not of controls, showed modifications resembling those of recovery sleep. Since only SAD patients curtailed their sleep while remitting during the LT period, these EEG modifications can be explained by normal sleep regulation alone. We conclude that the robust antidepressant effect of LT in SAD is unlikely to be mediated by changes in sleep, and that sleep regulatory mechanisms are not a crucial factor in the pathogenesis of winter depression.
Dijk DJ (2015) Falling asleep at the wheel across Europe., J Sleep Res 24 (3)
Driver HS, Dijk DJ, Werth E, Biedermann K, Borbély AA (1996) Sleep and the sleep electroencephalogram across the menstrual cycle in young healthy women., J Clin Endocrinol Metab 81 (2) pp. 728-735
Cyclic changes in hormones, body temperature, and metabolic rate characterize the menstrual cycle. To investigate whether these changes are associated with changes in sleep and the sleep electroencephalogram (EEG), a total of 138 sleep episodes from 9 women with no premenstrual syndrome symptoms were recorded every second night throughout one ovulatory menstrual cycle and analyzed in relation to menstrual phase. Ovulation and menstrual cycle stage were confirmed by measurements of temperature, urinary LH, and midluteal plasma levels of estrogen and progesterone. No significant variation across the menstrual cycle was observed for subjective ratings of sleep quality and mood as well as for objective measures of total sleep time, sleep efficiency, sleep latency, rapid eye movement sleep latency, and slow wave sleep. In nonrapid eye movement sleep, EEG power density in the 14.25-15.0 hertz band, which corresponds to the upper frequency range of the sleep spindles, exhibited a large variation across the menstrual cycle, with a maximum in the luteal phase. The data show that in healthy young women, sleep spindle frequency activity varies in parallel with core body temperature, whereas homeostatic sleep regulatory mechanisms, as indexed by the time course of EEG slow wave activity are not substantially affected by the menstrual cycle.
Groeger JA, Dijk DJ (2005) Consolidating consolidation? Sleep stages, memory systems, and procedures, BEHAV BRAIN SCI 28 (1) pp. 73-+ CAMBRIDGE UNIV PRESS
We argue that by neglecting the fact that procedural memory may also have episodic qualities, and by considering only a systems approach to memory, Walker's account of consolidation of learning during subsequent sleep ignores alternative accounts of how sleep stages may be interdependent. We also question the proposition that sleep-based consolidation largely bypasses hippocampal structures.
Dijk DJ (2013) Sleep in children, sleep spindles, and the metrics of memory., J Sleep Res 22 (2) pp. 119-120
Dijk DJ, Duffy JF, Riel E, Shanahan TL, Czeisler CA (1999) Ageing and the circadian and homeostatic regulation of human sleep during forced desynchrony of rest, melatonin and temperature rhythms., J Physiol 516 ( Pt 2) pp. 611-627
1. The circadian timing system has been implicated in age-related changes in sleep structure, timing and consolidation in humans. 2. We investigated the circadian regulation of sleep in 13 older men and women and 11 young men by forced desynchrony of polysomnographically recorded sleep episodes (total, 482; 9 h 20 min each) and the circadian rhythms of plasma melatonin and core body temperature. 3. Stage 4 sleep was reduced in older people. Overall levels of rapid eye movement (REM) sleep were not significantly affected by age. The latencies to REM sleep were shorter in older people when sleep coincided with the melatonin rhythm. REM sleep was increased in the first quarter of the sleep episode and the increase of REM sleep in the course of sleep was diminished in older people. 4. Sleep propensity co-varied with the circadian rhythms of body temperature and plasma melatonin in both age groups. Sleep latencies were longest just before the onset of melatonin secretion and short sleep latencies were observed close to the temperature nadir. In older people sleep latencies were longer close to the crest of the melatonin rhythm. 5. In older people sleep duration was reduced at all circadian phases and sleep consolidation deteriorated more rapidly during the course of sleep, especially when the second half of the sleep episode occurred after the crest of the melatonin rhythm. 6. The data demonstrate age-related decrements in sleep consolidation and increased susceptibility to circadian phase misalignment in older people. These changes, and the associated internal phase advance of the propensity to awaken from sleep, appear to be related to the interaction between a reduction in the homeostatic drive for sleep and a reduced strength of the circadian signal promoting sleep in the early morning.
Möller-Levet CS, Archer SN, Bucca G, Laing EE, Slak A, Kabiljo R, Lo JC, Santhi N, von Schantz M, Smith CP, Dijk DJ (2013) Effects of insufficient sleep on circadian rhythmicity and expression amplitude of the human blood transcriptome., Proc Natl Acad Sci U S A 110 (12) pp. E1132-E1141
Insufficient sleep and circadian rhythm disruption are associated with negative health outcomes, including obesity, cardiovascular disease, and cognitive impairment, but the mechanisms involved remain largely unexplored. Twenty-six participants were exposed to 1 wk of insufficient sleep (sleep-restriction condition 5.70 h, SEM = 0.03 sleep per 24 h) and 1 wk of sufficient sleep (control condition 8.50 h sleep, SEM = 0.11). Immediately following each condition, 10 whole-blood RNA samples were collected from each participant, while controlling for the effects of light, activity, and food, during a period of total sleep deprivation. Transcriptome analysis revealed that 711 genes were up- or down-regulated by insufficient sleep. Insufficient sleep also reduced the number of genes with a circadian expression profile from 1,855 to 1,481, reduced the circadian amplitude of these genes, and led to an increase in the number of genes that responded to subsequent total sleep deprivation from 122 to 856. Genes affected by insufficient sleep were associated with circadian rhythms (PER1, PER2, PER3, CRY2, CLOCK, NR1D1, NR1D2, RORA, DEC1, CSNK1E), sleep homeostasis (IL6, STAT3, KCNV2, CAMK2D), oxidative stress (PRDX2, PRDX5), and metabolism (SLC2A3, SLC2A5, GHRL, ABCA1). Biological processes affected included chromatin modification, gene-expression regulation, macromolecular metabolism, and inflammatory, immune and stress responses. Thus, insufficient sleep affects the human blood transcriptome, disrupts its circadian regulation, and intensifies the effects of acute total sleep deprivation. The identified biological processes may be involved with the negative effects of sleep loss on health, and highlight the interrelatedness of sleep homeostasis, circadian rhythmicity, and metabolism.
Dijk DJ, Czeisler CA (1995) Contribution of the circadian pacemaker and the sleep homeostat to sleep propensity, sleep structure, electroencephalographic slow waves, and sleep spindle activity in humans., J Neurosci 15 (5 Pt 1) pp. 3526-3538
The role of the endogenous circadian pacemaker in the timing of the sleep-wake cycle and the regulation of the internal structure of sleep, including REM sleep, EEG slow-wave (0.75-4.5 Hz) and sleep spindle activity (12.75-15.0 Hz) was investigated. Eight men lived in an environment free of time cues for 33-36 d and were scheduled to a 28 hr rest-activity cycle so that sleep episodes (9.33 hr each) occurred at all phases of the endogenous circadian cycle and variations in wakefulness preceding sleep were minimized. The crest of the robust circadian rhythm of REM sleep, which was observed throughout the sleep episode, was positioned shortly after the minimum of the core body temperature rhythm. Furthermore, a sleep-dependent increase of REM sleep was present, which, interacting with the circadian modulation, resulted in highest values of REM sleep when the end of scheduled sleep episodes coincided with habitual wake-time. Slow-wave activity decreased and sleep spindle activity increased in the course of all sleep episodes. Slow-wave activity in non-REM sleep exhibited a low amplitude circadian modulation which did not parallel the circadian rhythm of sleep propensity. Sleep spindle activity showed a marked endogenous circadian rhythm; its crest coincident with the beginning of the habitual sleep episode. Analyses of the (nonadditive) interaction of the circadian and sleep-dependent components of sleep propensity and sleep structure revealed that the phase relation between the sleep-wake cycle and the circadian pacemaker during entrainment promotes the consolidation of sleep and wakefulness and facilitates the transitions between these vigilance states.
Duffy JF, Dijk DJ (2002) Getting through to circadian oscillators: why use constant routines?, J Biol Rhythms 17 (1) pp. 4-13
Overt 24-h rhythmicity is composed of both exogenous and endogenous components, reflecting the product of multiple (periodic) feedback loops with a core pacemaker at their center. Researchers attempting to reveal the endogenous circadian (near 24-h) component of rhythms commonly conduct their experiments under constant environmental conditions. However, even under constant environmental conditions, rhythmic changes in behavior, such as food intake or the sleep-wake cycle, can contribute to observed rhythmicity in many physiological and endocrine variables. Assessment of characteristics of the core circadian pacemaker and its direct contribution to rhythmicity in different variables, including rhythmicity in gene expression, may be more reliable when such periodic behaviors are eliminated or kept constant across all circadian phases. This is relevant for the assessment of the status of the circadian pacemaker in situations in which the sleep-wake cycle or food intake regimes are altered because of external conditions, such as in shift work or jet lag. It is also relevant for situations in which differences in overt rhythmicity could be due to changes in either sleep oscillatory processes or circadian rhythmicity, such as advanced or delayed sleep phase syndromes, in aging, or in particular clinical conditions. Researchers studying human circadian rhythms have developed constant routine protocols to assess the status of the circadian pacemaker in constant behavioral and environmental conditions, whereas this technique is often thought to be unnecessary in the study of animal rhythms. In this short review, the authors summarize constant routine methodology and what has been learned from constant routines and argue that animal and human circadian rhythm researchers should (continue to) use constant routines as a step on the road to getting through to central and peripheral circadian oscillators in the intact organism.
Ly JQM, Gaggioni G, Chellappa SL, Papachilleos S, Brzozowski A, Borsu C, Archer SN, Rosanova M, Sarrasso S, Dijk D-J, Phillips C, Maquet P, Massimini M, Vandewalle G (2014) Human cortical excitability depends on time awake and circadian phase, JOURNAL OF SLEEP RESEARCH 23 pp. 9-10 WILEY-BLACKWELL
Nocturnal sleep and daytime napping facilitate memory consolidation for semantically related and unrelated word pairs. We contrasted forgetting of both kinds of materials across a 12-hour interval involving either nocturnal sleep or daytime wakefulness (experiment 1) and a 2-hour interval involving either daytime napping or wakefulness (experiment 2). Beneficial effects of post-learning nocturnal sleep and daytime napping were greater for unrelated word pairs (Cohen's d=0.71 and 0.68) than for related ones (Cohen's d=0.58 and 0.15). While the size of nocturnal sleep and daytime napping effects was similar for unrelated word pairs, for related pairs, the effect of nocturnal sleep was more prominent. Together, these findings suggest that sleep preferentially facilitates offline memory processing of materials that are more susceptible to forgetting.
Santhi N, Thorne HC, van der Veen DR, Johnsen S, Mills SL, Hommes V, Schlangen LJ, Archer SN, Dijk DJ (2011) The spectral composition of evening light and individual differences in the suppression of melatonin and delay of sleep in humans., J Pineal Res
The effect of light on circadian rhythms and sleep is mediated by a multi-component photoreceptive system of rods, cones and melanopsin-expressing intrinsically photosensitive retinal ganglion cells. The intensity and spectral sensitivity characteristics of this system are to be fully determined. Whether the intensity and spectral composition of light exposure at home in the evening is such that it delays circadian rhythms and sleep also remains to be established. We monitored light exposure at home during 6-8?wk and assessed light effects on sleep and circadian rhythms in the laboratory. Twenty-two women and men (23.1?±?4.7?yr) participated in a six-way, cross-over design using polychromatic light conditions relevant to the light exposure at home, but with reduced, intermediate or enhanced efficacy with respect to the photopic and melanopsin systems. The evening rise of melatonin, sleepiness and EEG-assessed sleep onset varied significantly (P?0.01) across the light conditions, and these effects appeared to be largely mediated by the melanopsin, rather than the photopic system. Moreover, there were individual differences in the sensitivity to the disruptive effect of light on melatonin, which were robust against experimental manipulations (intra-class correlation?=?0.44). The data show that light at home in the evening affects circadian physiology and imply that the spectral composition of artificial light can be modified to minimize this disruptive effect on sleep and circadian rhythms. These findings have implications for our understanding of the contribution of artificial light exposure to sleep and circadian rhythm disorders such as delayed sleep phase disorder.
Dijk DJ, Beersma DG, Daan S, Lewy AJ (1989) Bright morning light advances the human circadian system without affecting NREM sleep homeostasis., Am J Physiol 256 (1 Pt 2) pp. R106-R111
Eight male subjects were exposed to either bright light or dim light between 0600 and 0900 h for 3 consecutive days each. Relative to the dim light condition, the bright light treatment advanced the evening rise in plasma melatonin and the time of sleep termination (sleep onset was held constant) for an average approximately 1 h. The magnitude of the advance of the plasma melatonin rise was dependent on its phase in dim light. The reduction in sleep duration was at the expense of rapid-eye-movement (REM) sleep. Spectral analysis of the sleep electroencephalogram (EEG) revealed that the advance of the circadian pacemaker did not affect EEG power densities between 0.25 and 15.0 Hz during either non-REM or REM sleep. The data show that shifting the human circadian pacemaker by 1 h does not affect non-REM sleep homeostasis. These findings are in accordance with the predictions of the two-process model of sleep regulation.
Vandewalle G, Schwartz S, Grandjean D, Wuillaume C, Balteau E, Degueldre C, Schabus M, Phillips C, Luxen A, Dijk DJ, Maquet P (2010) Spectral quality of light modulates emotional brain responses in humans, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 107 (45) pp. 19549-19554 NATL ACAD SCIENCES
Herron K, Dijk D, Ellis J, Sanders J, Sterr A (2008) Sleep actigraphy in brain injured patients with chronic low functioning upper limb hemiparesis,
Sleep actigraphy in brain injured patients with chronic low
functioning upper limb hemiparesis
K. HERRON1, D. DIJK2, J. ELLIS3, J. SANDERS1 and
1Department of Psychology, University of Surrey, Guildford, United
Kingdom, 2Surrey Sleep Research Centre, University of Surrey,
Guildford, United Kingdom and 3Section of Psychological Medicine,
University of Glasgow, Glasgow, United Kingdom
Introduction: Few studies have used actigraphy to examine sleep
behaviour in brain injured patients with chronic hemiparesis. This
is possibly due to suggestions that actigraphy recordings in those
with motor difficulties are likely to produce inaccurate sleep/wake
detection (Sadeh and Acebo, 2002). However, actigraphy provides
a favourable alternative to PSG when observing long term sleep
behaviour. Therefore, we aimed to further validate the use of
actigraphy in low functioning hemiparetic patients by comparing
subjective sleep diaries (SD) with actigraphy recordings to examine:
1) concordance between SD and actigraphy, and 2) the relationship
between motor deficits and activity.
Method: Twelve patients with chronic upper limb hemiparesis
(412 months) completed SDs and wore an actiwatch (Cambridge
Neurotechnology Ltd.) on the non-affected wrist for two weeks.
Residual motor ability was assessed through a series of neurobehavioural
Results: Comparison of SD and actigraphy revealed significant
dissociations between final wake time, sleep efficiency, number and
duration of night awakenings. Good concordance between SD
and actigraphy was found for retiring time, get up time, time in
bed, total sleep time and sleep onset latency. Mean activity
counts, during the day or night, were not associated with residual
Discussion and Conclusion: Actigraphy of the non-affected wrist, in
conjunction with SDs, are a valid apparatus for assessing long term
sleep behaviour in patients with hemiparesis. The results are in line
with previous studies in healthy persons without motor difficulties
whereby SDs and actigraphy correlate well, apart from parameters
which rely on subjective night time awakenings (Lockley et al. 1999). The latter can only be determined by PSG studies.
Jaspar M, Meyer C, Muto V, Shaffii-LeBourdiec A, Chellappa SL, Kussee C, Vandewalle G, Collette F, Middleton B, Archer S, Dijk DJ, Maquet P (2014) Sleep loss changes executive brain responses in the wake maintenance zone, JOURNAL OF SLEEP RESEARCH 23 pp. 61-61 WILEY-BLACKWELL
Dijk DJ, Larkin W (2004) Fatigue and performance models: general background and commentary on the circadian alertness simulator for fatigue risk assessment in transportation., Aviat Space Environ Med 75 (3 Suppl) pp. A119-A121
Mathematical models of fatigue and performance are potentially powerful tools to predict the effects of duty-rest schedules in many situations. Most current models, including the Circadian Alertness Simulator (CAS), derive from the two-process theory of sleep regulation. In these models, performance and fatigue are determined by a homeostatic process that depends solely on sleep/wake history, and a circadian process, driven by the biological clock. These models assume: 1) performance capability recovers in an exponential manner during sleep; 2) the homeostatic and circadian processes are additive. Current evidence suggests that both assumptions require modification. An attractive feature of the CAS is that it computes alertness curves for individuals, based on individual sleep/wake histories and other data. However, statistical evaluation is usually based on group data, with few performance metrics. As in other models, there is no substantive theory to connect the alertness computation with specific cognitive or psychomotor functions.
Meyer C, Muto V, Jaspar M, Kusse C, Lambot E, Chellappa SL, Degueldre C, Balteau E, Luxen A, Middleton B, Archer SN, Collette F, Dijk D-J, Phillips C, Maquet P, Vandewalle G (2016) Seasonality in human cognitive brain responses, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 113 (11) pp. 3066-3071 NATL ACAD SCIENCES
Laing EE, Johnston JD, Möller-Levet CS, Bucca G, Smith CP, Dijk D-J, Archer SN (2015) Exploiting human and mouse transcriptomic data: Identification of circadian genes and pathways influencing health, BioEssays
The power of the application of bioinformatics across multiple publicly available transcriptomic data sets was explored. Using 19 human and mouse circadian transcriptomic data sets, we found that NR1D1 and NR1D2 which encode heme-responsive nuclear receptors are the most rhythmic transcripts across sleep conditions and tissues suggesting that they are at the core of circadian rhythm generation. Analyzes of human transcriptomic data show that a core set of transcripts related to processes including immune function, glucocorticoid signalling, and lipid metabolism is rhythmically expressed independently of the sleep-wake cycle. We also identify key transcripts associated with transcription and translation that are disrupted by sleep manipulations, and through network analysis identify putative mechanisms underlying the adverse health outcomes associated with sleep disruption, such as diabetes and cancer. Comparative bioinformatics applied to existing and future data sets will be a powerful tool for the identification of core circadian- and sleep-dependent molecules.
Kouchaki S, Sanei S, Arbon E, Dijk DJ (2014) Tensor based Singular Spectrum Analysis for Automatic Scoring of Sleep EEG., IEEE Trans Neural Syst Rehabil Eng
A new supervised approach for decomposition of single channel signal mixtures is introduced in this paper. The performance of the traditional singular spectrum analysis (SSA) algorithm is significantly improved by applying tensor decomposition instead of traditional singular value decomposition (SVD). As another contribution to this subspace analysis method, the inherent frequency diversity of the data has been effectively exploited to highlight the subspace of interest. As an important application, sleep EEG has been analysed and the stages of sleep for the subjects in normal condition, with sleep restriction, and with sleep extension have been accurately estimated and compared with the results of sleep scoring by clinical experts.
Nollet M, Stenson G, Martynhak B, Wafford K, Dijk D-J, Winsky-Sommerer R (2014) Characterisation of the development of sleep disturbances in the unpredictable chronic mild stress murine model of major depression, JOURNAL OF SLEEP RESEARCH 23 pp. 78-78 WILEY-BLACKWELL
Herron K, Dijk D, Ellis J, Sanders J, Sterr A (2008) Sleep correlates of motor recovery in chronic stroke: a pilot study using sleep diaries and actigraphy,
Introduction: Sleep facilitates neuroplasticity (Tononi & Cirelli,
2006), an important process for post-stroke recovery, particularly
when re-learning motor skills. Associations between poor sleep and
poorer recovery during the acute phase have been reported (Good
et al. 1996; Gottselig et al. 2002). In addition, increased subjective
sleep needs have been associated with poorer outcome during the
chronic phase (Hermann, et al. 2008). However motor recovery,
which is of particular relevance for sleep dependent neuroplasticity,
has not been addressed. We aimed to investigate sleep behaviour in
the context of motor recovery within a homogenous stroke patient
sample during the chronic phase.
Method: Twelve patients with chronic upper limb hemiparesis
(412 months) completed sleep diaries (SD) and wore an actiwatch
(Cambridge Neurotechnology Ltd.) for two weeks. The SD
included twice daily Karolinska Sleepiness Scale (KSS) and Daily
Fatigue Scale (D-FIS) measures. Residual motor ability was
assessed through a series of neurobehavioural motor tests.
Results: Increasing daytime nap length (SD and actigraphy)
significantly correlated, or by near significant trend with better
motor ability on all neurobehavioural tests. Age was not associated
with napping behaviour or residual motor ability. Chronicity,
psychological adjustment, health, or nocturnal sleep did not
correlate with napping behaviour (SD and actigraphy) or motor
ability. Furthermore, increased subjective fatigue was associated
with increased napping behaviour.
Discussion and Conclusion: Patients who habitually napped had
better residual movement ability at least one year after stroke. It
may be that the benefits of napping facilitate performance as well as
consolidating motor learning. This has been shown in healthy
persons (Backhaus & Junghanns, 2006; Nishida & Walker, 2007)
which may translate into motor skill re-learning during stroke
recovery. Although the data is suggestive, previous rehabilitation
and medical care will contribute to residual motor ability in addition to the reported napping behaviour, therefore further clarification is required.
James LM, Iannone R, Palcza J, Renger JJ, Calder N, Cerchio K, Gottesdiener K, Hargreaves R, Murphy MG, Boyle J, Dijk DJ (2011) Effect of a novel histamine subtype-3 receptor inverse agonist and modafinil on EEG power spectra during sleep deprivation and recovery sleep in male volunteers., Psychopharmacology (Berl) 215 (4) pp. 643-653
Histamine and dopamine contribute to the maintenance of wakefulness.
This study aims to conduct an exploratory analysis of the effects of 10 and 50 mg of MK-0249, a novel histamine subtype-3 receptor inverse agonist, and 200 mg of modafinil, a presumed dopaminergic compound, on EEG power spectra during sleep deprivation and subsequent recovery sleep.
A total of 25 healthy men were recruited to a double-blind, placebo-controlled cross-over design. EEG power spectra, an electrophysiological marker of changes in sleepiness and vigilance, were obtained at the beginning of wake maintenance tests at two-hourly intervals throughout a night and day of sleep deprivation, which is an established model of excessive sleepiness.
After placebo, sleep deprivation was associated with enhancements in delta and theta and reductions in alpha and beta activity. Following dosing at 02:00 h, MK-0249 and modafinil reduced delta and theta activity and enhanced alpha and beta activity, compared to placebo. During recovery sleep initiated at 21:00 h, latency to sleep onset and number of awakenings were not different from placebo for any of the active treatments. Wake after sleep onset and stage 1% was increased and total sleep time, SWS% and REM% were reduced after both doses of MK-0249. Compared to placebo, MK-0249, the 50-mg dose in particular, reduced activity in some delta and theta/alpha frequencies and enhanced beta activity during NREM sleep and REM sleep. After modafinil, no changes were observed for power spectra during sleep.
Both MK-0249 and modafinil exert effects on the EEG which are consistent with wake promotion.
Trachsel L, Dijk DJ, Brunner DP, Klene C, Borbély AA (1990) Effect of zopiclone and midazolam on sleep and EEG spectra in a phase-advanced sleep schedule., Neuropsychopharmacology 3 (1) pp. 11-18
Midazolam (15 mg), a benzodiazepine (BDZ) hypnotic, and zopiclone (7.5 mg), a non-BDZ hypnotic, were administered to young, healthy subjects prior to bedtime. They went to bed at 2300 hours after taking placebo (PL-23), and then on three occasions at 1900 hour after taking placebo (PL-19) or one of the hypnotics. Advancing bedtime by 4 hour increased the combined value of waking, stage 1, and movement time. Compared to PL-19, both drugs reduced sleep latency and stage 3, and increased stage 2. Spectral analysis of the EEG in non-rapid-eye-movement sleep revealed a declining trend of power density in the low-frequency range in the course of the night. Activity in the 1 to 10 Hz range was markedly depressed by the two hypnotics, whereas activity in the spindle range (11 to 14 Hz) was augmented. The former changes persisted throughout the 12-hour recording period. The fact that both hypnotics bind to BDZ receptors could be responsible for the similar effects on the EEG spectra.
Perrin F, Peigneux P, Fuchs S, Verhaeghe S, Laureys S, Middleton B, Degueldre C, Del Fiore G, Vandewalle G, Balteau E, Poirrier R, Moreau V, Luxen A, Maquet P, Dijk DJ (2004) Nonvisual responses to light exposure in the human brain during the circadian night., Curr Biol 14 (20) pp. 1842-1846
The brain processes light information to visually represent the environment but also to detect changes in ambient light level. The latter information induces non-image-forming responses and exerts powerful effects on physiology such as synchronization of the circadian clock and suppression of melatonin. In rodents, irradiance information is transduced from a discrete subset of photosensitive retinal ganglion cells via the retinohypothalamic tract to various hypothalamic and brainstem regulatory structures including the hypothalamic suprachiasmatic nuclei, the master circadian pacemaker. In humans, light also acutely modulates alertness, but the cerebral correlates of this effect are unknown. We assessed regional cerebral blood flow in 13 subjects attending to auditory and visual stimuli in near darkness following light exposures (>8000 lux) of different durations (0.5, 17, 16.5, and 0 min) during the biological night. The bright broadband polychromatic light suppressed melatonin and enhanced alertness. Functional imaging revealed that a large-scale occipito-parietal attention network, including the right intraparietal sulcus, was more active in proportion to the duration of light exposures preceding the scans. Activity in the hypothalamus decreased in proportion to previous illumination. These findings have important implications for understanding the effects of light on human behavior.
Dijk DJ, Duffy JF, Silva EJ, Shanahan TL, Boivin DB, Czeisler CA (2012) Amplitude reduction and phase shifts of melatonin, cortisol and other circadian rhythms after a gradual advance of sleep and light exposure in humans., PLoS One 7 (2)
The phase and amplitude of rhythms in physiology and behavior are generated by circadian oscillators and entrained to the 24-h day by exposure to the light-dark cycle and feedback from the sleep-wake cycle. The extent to which the phase and amplitude of multiple rhythms are similarly affected during altered timing of light exposure and the sleep-wake cycle has not been fully characterized.
Dijk D-J, Winsky-Sommerer R (2012) Sleep: Moving to a 24/7 society, New Scientist 213 (2850)
Hasan S, Santhi N, Lazar AS, Slak A, Lo J, von Schantz M, Archer SN, Johnston JD, Dijk DJ (2012) Assessment of circadian rhythms in humans: comparison of real-time fibroblast reporter imaging with plasma melatonin., FASEB J
We compared the period of the rhythm of plasma melatonin, driven by the hypothalamic circadian pacemaker, to in vitro periodicity in cultured peripheral fibroblasts to assess the effects on these rhythms of a polymorphism of PER3 (rs57875989), which is associated with sleep timing. In vitro circadian period was determined using luminometry of cultured fibroblasts, in which the expression of firefly luciferase was driven by the promoter of the circadian gene Arntl (Bmal1). The period of the melatonin rhythm was assessed in a 9-d forced desynchrony protocol, minimizing confounding effects of sleep-wake and light-dark cycles on circadian rhythmicity. In vitro periods (32 participants, 24.61±0.33 h, mean±sd) were longer than in vivo periods (31 participants, 24.16±0.17 h; P0.4). Analyses of replicate in vitro assessments demonstrated that circadian period was reproducible within individuals (intraclass correlation=0.62), but in vivo and in vitro period assessments did not correlate (P>0.9). In accordance with circadian entrainment theory, in vivo period correlated with the timing of melatonin (P
Lockley SW, Dijk D-J, Kosti O, Skene DJ, Arendt J (2008) Alertness, mood and performance rhythm disturbances associated with circadian sleep disorders in the blind, JOURNAL OF SLEEP RESEARCH 17 (2) pp. 207-216 WILEY-BLACKWELL
Archer SN, Dijk DJ (2006) Clock polymorphisms associated with human diurnal preference, pp. 197-207
© Cambridge University Press 2013.It would be extremely unusual, not to mention highly inconvenient, if everyone woke up and went about their daily routines at the same time. Fortunately this is not the case, and humans display a wide range of sleep?wake timing preferences. Some of us like to wake up and get things done in the morning (so-called larks, or morning types), others prefer to be active later in the day and night (owls, or evening types), and many are in between or a mixture of the two. The range in sleep?wake timing is considerable and differences in preferred bedtime and wake time can be as much as 2?3 The on average between morning and evening types , and in circadian rhythm sleep phase disorders, bedtimes can range from 7?9 p.m. (advanced) to 2?6 a.m. (delayed) . It has often been assumed that diurnal preference (morningness versus eveningness) is not an acquired characteristic but relates to biological factors involved in the circadian timing system that regulates the optimum times for waking performance and sleep?wake timing. However, current understanding of factors influencing variation in sleep?wake timing and optimal timing of waking performance emphasizes the interactive contribution of social factors, such as work schedules and leisure time, and biological factors. Underlying biological factors include the timing (phase of entrainment) of the endogenous circadian rhythmicity relative to clock time, and the light?dark cycle . The phase of entrainment is determined by the intrinsic period of the circadian clock, as well as sensitivity to the effects of light on the circadian clock. In addition, sleep homeostatic mechanisms also play an important role in sleep?wake timing. This implies that diurnal preference could be related to any of these three main factors: circadian period, light sensitivity, and sleep homeostasis.
Dijk DJ, Hayes B, Czeisler CA (1993) Dynamics of electroencephalographic sleep spindles and slow wave activity in men: effect of sleep deprivation., Brain Res 626 (1-2) pp. 190-199
Recent developments in the understanding of the neurophysiological mechanisms underlying electroencephalographic (EEG) slow waves and sleep spindles imply an inverse relationship between these two EEG activities. The interrelationship between slow wave activity (0.75-4.5 Hz) and sleep-spindle activity (12-15 Hz) in electroencephalograms recorded in nine male subjects, during nocturnal baseline sleep and during recovery sleep from 40 h of wakefulness, was analyzed by power spectral analysis based on the fast Fourier transform and by transient patterns detection algorithms. Both techniques revealed that spindle activity was highest in sleep stage 2, increased over consecutive non-rapid-eye-movement sleep (non-REM sleep) episodes and was suppressed during recovery sleep. In contrast, slow wave activity decreased over consecutive non-REM sleep episodes and was enhanced during recovery sleep. Analysis of the dynamics of spindle and slow-wave activity within non-REM sleep episodes demonstrated that in the initial 20% of these episodes both spindle activity and slow wave activity increased, whereafter slow wave activity continued to increase but the average amplitude of spindles and total spindle activity, but not spindle density, decreased. At the end of non-REM sleep episodes the reverse pattern was observed. Sleep deprivation induced a more rapid rise of both spindle and slow wave activity in the very beginning of sleep. These data demonstrate that when averaged per sleep episode or non-REM sleep episode an inverse relationship between SWA and spindle activity exists but that in the initial and final part of non-REM sleep episodes the association between these two activities is positive. This biphasic relationship is discussed with reference to the hypothesis that the transition from sleep spindles to slow waves is dependent on a progressive hyperpolarization of thalamo-cortical neurons.
Tobler I, Dijk DJ, Jaggi K, Borbély AA (1991) Effects on night-time motor activity and performance in the morning after midazolam intake during the night., Arzneimittelforschung 41 (6) pp. 581-583
The hypnotic action and residual effects of a single night-time dose of midazolam (Ro 21-3981, Dormicum, 7.5 mg; CAS 59467-70-8) were investigated in young, healthy adults. The subjects went to bed at the habitual time and were awakened 3 h later for drug or placebo intake. Then they were allowed to continue their sleep. Motor activity was continuously recorded by a wrist-worn activity monitor. In comparison to placebo, prolonged night-time immobility periods were more frequent after midazolam. Sleep tended to be perceived as more quiet and as less interrupted by awakenings. 15 min after awakening in the morning, the subjects felt more relaxed after midazolam than after placebo. Performance assessed 2 h after awakening by a psychomotor test showed no decrement. The results show that a 7.5-mg dose of midazolam taken in the first half of the night has a significant hypnotic action without impairing psychomotor performance in the morning.
Herring R, Knight R, Shojaee-Moradie F, Johnsen S, Umpleby AM, Jackson N, Jones R, Dijk D-J, Russell-Jones DL (2015) Effect of subcutaneous insulin detemir on glucose flux, lipolysis and electroencephalography in type 1 diabetes, DIABETES OBESITY & METABOLISM 17 (11) pp. 1100-1103 WILEY-BLACKWELL
Study Objectives: Individual sleep timing differs and is governed partly by
circadian oscillators, which may be assessed by hormonal markers, or by clock
gene expression. Clock gene expression oscillates in peripheral tissues, including
leukocytes. The study objective was to determine whether the endogenous phase
of these rhythms, assessed in the absence of the sleep-wake and light-dark
cycle, correlates with habitual sleep-wake timing.
Design: Observational, cross-sectional.
Setting: Home environment and Clinical Research Center.
Participants: 24 healthy subjects aged 25.0 ± 3.5 (SD) years.
Measurements: Actigraphy and sleep diaries were used to characterize sleep
timing. Circadian rhythm phase and amplitude of plasma melatonin, cortisol, and
BMAL1, PER2, and PER3 expression were assessed during a constant routine.
Results: Circadian oscillations were more robust for PER3 than for BMAL1 or PER2.
Average peak timings were 6:05 for PER3, 8:06 for PER2, 15:06 for BMAL1, 4:20 for
melatonin, and 10:49 for cortisol. Individual sleep-wake timing correlated with the
phases of melatonin and cortisol. Individual PER3 rhythms correlated significantly
with sleep-wake timing and the timing of melatonin and cortisol, but those of PER2
and BMAL1 did not reach significance. The correlation between sleep timing and
PER3 expression was stronger in individuals homozygous for the variant of the
PER3 polymorphism that is associated with morningness.
Conclusions: Individual phase differences in PER3 expression during a constant
routine correlate with sleep timing during entrainment. PER3 expression in
leukocytes represents a useful molecular marker of the circadian processes
governing sleep-wake timing.
Beersma DG, Dijk DJ (1992) Selective SWS suppression does not affect the time course of core body temperature in men., J Sleep Res 1 (3) pp. 201-204
In eight healthy middle-aged men, sleep and core body temperature were recorded under baseline conditions, during all-night SWS suppression by acoustic stimulation, and during undisturbed recovery sleep. SWS suppression resulted in a marked reduction of sleep stages 3 and 4 but did not affect the time course of core body temperature. These data suggest that sleep stages 3 and 4 of nonREM sleep (i.e. SWS) do not play a major role in the regulation of core body temperature in humans.
Dijk D-J (2008) Slow-wave sleep, diabetes, and the sympathetic nervous system, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 105 (4) pp. 1107-1108 NATL ACAD SCIENCES
Dijk DJ (2011) Phenotyping sleep., J Sleep Res 20 (4)
Dijk DJ, Beersma DG, Bloem GM (1989) Sex differences in the sleep EEG of young adults: visual scoring and spectral analysis., Sleep 12 (6) pp. 500-507
Baseline sleep of 13 men (mean age of 23.5 years) and 15 women (21.9 years) was analyzed. Visual scoring of the electroencephalograms (EEGs) revealed no significant differences between the sexes in the amounts of slow-wave sleep and rapid-eye-movement (REM) sleep. Spectral analysis, however, detected significantly higher power densities during non-REM sleep over a wide frequency range (0.25-11.0 Hz) in the female versus male subjects. Also, during REM sleep, power densities were higher in the females. Analysis of the time course of EEG power density during sleep revealed that the differences between males and females persisted throughout the sleep episode. Comparison of these differences with published data on the effects of sleep deprivation on EEG power spectra did not suggest a common mechanism underlying sleep deprivation effects and the sex difference in sleep EEGs. It is concluded that sex differences in EEG power spectra are not likely to be caused by sex differences in sleep regulatory mechanisms but may, for instance, be caused by sex differences in skull characteristics.
Zeitzer JM, Duffy JF, Lockley SW, Dijk D-J, Czeisler CA (2007) Plasma melatonin rhythms in young and older humans during sleep, sleep deprivation, and wake, SLEEP 30 (11) pp. 1437-1443 AMER ACAD SLEEP MEDICINE
Landolt HP, Dijk DJ, Achermann P, Borbély AA (1996) Effect of age on the sleep EEG: slow-wave activity and spindle frequency activity in young and middle-aged men., Brain Res 738 (2) pp. 205-212
The effect of age on sleep and the sleep EEG was investigated in middle-aged men (mean age: 62.0 years) and in young men (mean age: 22.4 years). Even though the older men reported a higher number of nocturnal awakenings, subjective sleep quality did not differ. Total sleep time, sleep efficiency, and slow wave sleep were lower in the middle-aged, while stage 1 and wakefulness after sleep onset were higher. The differences in wakefulness within nonREM-REM sleep cycles was most pronounced in the third and fourth cycle. In the older men, EEG power density in nonREM sleep was reduced in frequencies below 14.0 Hz, whereas in REM sleep age-related reductions were limited to he delta-theta (0.25-7.0 Hz) and low alpha (8.25-10.0 Hz) band. Slow-wave activity (SWA, power density in the 0.75-4.5 Hz range) decreased in the course of sleep in both age groups. The between-group difference in SWA diminished in the course of sleep, whereas the difference in activity in the frequency range of sleep spindles (12.25-14.0 Hz) increased. It is concluded that frequency and state specific changes occur as a function of age, and that sleep dependent decline in SWA and increase in sleep spindle activity are attenuated with age.
Duffy JF, Cain SW, Chang A, Phillips AJ, Munch MY, Gronfier C, Wyatt JK, Dijk D, Wright KP, Czeisler CA (2011) SEX DIFFERENCE IN INTRINSIC CIRCADIAN PERIOD IN HUMANS, SLEEP 34 pp. A307-A307
van den Hoofdakker RH, Beersma DG, Dijk DJ (1987) The significance of sleep physiological disturbances in depression., Acta Psychiatr Belg 87 (3) pp. 302-316
Since the discovery of the antidepressant effects of interventions in the sleep-wake cycle, a number of hypotheses have emerged according to which disturbances in sleep physiology are not merely expressions but essential components of the pathophysiology of depression. Three hypotheses are presented, the "Phase-advance", the "S-deficiency" and the "ACh-hypersensitivity" hypotheses. They explain the therapeutic effects of total, partial and selective sleep deprivation as consequences of the normalization of disturbed sleep regulation. The question is dealt with whether there are indications that the hypothesized sleep regulatory disturbances exist and whether there is a relationship between the effects of sleep deprivation on sleep regulation and clinical state. None of the hypotheses is totally supported, none can be fully rejected.
Dijk DJ, Lockley SW (2002) Integration of human sleep-wake regulation and circadian rhythmicity., J Appl Physiol (1985) 92 (2) pp. 852-862
The human sleep-wake cycle is generated by a circadian process, originating from the suprachiasmatic nuclei, in interaction with a separate oscillatory process: the sleep homeostat. The sleep-wake cycle is normally timed to occur at a specific phase relative to the external cycle of light-dark exposure. It is also timed at a specific phase relative to internal circadian rhythms, such as the pineal melatonin rhythm, the circadian sleep-wake propensity rhythm, and the rhythm of responsiveness of the circadian pacemaker to light. Variations in these internal and external phase relationships, such as those that occur in blindness, aging, morning and evening, and advanced and delayed sleep-phase syndrome, lead to sleep disruptions and complaints. Changes in ocular circadian photoreception, interindividual variation in the near-24-h intrinsic period of the circadian pacemaker, and sleep homeostasis can contribute to variations in external and internal phase. Recent findings on the physiological and molecular-genetic correlates of circadian sleep disorders suggest that the timing of the sleep-wake cycle and circadian rhythms is closely integrated but is, in part, regulated differentially.
Beersma DG, Dijk DJ, Blok CG, Everhardus I (1990) REM sleep deprivation during 5 hours leads to an immediate REM sleep rebound and to suppression of non-REM sleep intensity., Electroencephalogr Clin Neurophysiol 76 (2) pp. 114-122
Nine healthy male subjects were deprived of REM sleep during the first 5 h after sleep onset. Afterwards recovery sleep was undisturbed. During the deprivation period the non-REM EEG power spectrum was reduced when compared to baseline for the frequencies up to 7 Hz, despite the fact that non-REM sleep was not experimentally disturbed. During the recovery interval a significant rebound of REM sleep was observed, which was only accompanied by a very slight increase of power in the lower non-REM EEG frequencies. In order to control for intermittent wakefulness, the same subjects were subjected to non-REM sleep interruption during the first 5 h after sleep onset 2 weeks later. Again subsequent recovery sleep was undisturbed. The interventions resulted in a similar amount of wakefulness in both conditions. During the intervention period, the non-REM EEG power spectrum was only marginally reduced in the delta frequency range. REM sleep duration was only slightly reduced. During the recovery interval, however, a substantial increase in EEG power in the delta frequency range was noted, without notable changes in REM time. It is concluded that an increased pressure for REM sleep results in longer REM episodes and a reduced intensity of non-REM sleep.
Landolt HP, Werth E, Borbély AA, Dijk DJ (1995) Caffeine intake (200 mg) in the morning affects human sleep and EEG power spectra at night., Brain Res 675 (1-2) pp. 67-74
Adenosine has been implicated in the physiological regulation of sleep propensity. The adenosine-receptor-antagonist, caffeine (100 mg), administered immediately prior to a nocturnal sleep episode, has previously been shown to lower sleep propensity as indexed by a reduced sleep efficiency, a reduced EEG power density in low delta frequencies and enhanced power density in the frequency range of sleep spindles. To further investigate the role of adenosine in sleep regulation we administered 200 mg of caffeine at 07.10 h and analyzed the sleep stages and EEG power spectra during the subsequent night in nine healthy men. Caffeine levels in saliva decreased from a maximum of 17 mumol/l one hour after intake, to 3 mumol/l immediately prior to the sleep episode starting at 23.00 h. Compared to placebo, sleep efficiency and total sleep time were significantly reduced. EEG power density in nonREM sleep was suppressed in the 0.25-0.5 Hz band and enhanced in the frequency range of sleep spindles (11.25-12.0 Hz and 13.25-14.0 Hz). In REM sleep EEG power density was suppressed in the frequency range of 0.75-4.5 and 5.25-6.0 Hz. The data indicate that a saliva level of caffeine as low as 3 mumol/l directly affects sleep propensity or, alternatively, that the presence of caffeine in the central nervous system during the waking episode reduces the progressive increase of sleep propensity associated with wakefulness.
Walsh JK, Deacon S, Dijk D-J, Lundahl J (2007) The selective extrasynaptic GABA(A) agonist, gaboxadol, improves traditional hypnotic efficacy measures and enhances slow wave activity in a model of transient insomnia, SLEEP 30 (5) pp. 593-602 AMER ACADEMY SLEEP MEDICINE
Dijk DJ, Duffy JF (1999) Circadian regulation of human sleep and age-related changes in its timing, consolidation and EEG characteristics., Ann Med 31 (2) pp. 130-140
The light-entrainable circadian pacemaker located in the suprachiasmatic nucleus of the hypothalamus regulates the timing and consolidation of sleep by generating a paradoxical rhythm of sleep propensity; the circadian drive for wakefulness peaks at the end of the day spent awake, ie close to the onset of melatonin secretion at 21.00-22.00 h and the circadian drive for sleep crests shortly before habitual waking-up time. With advancing age, ie after early adulthood, sleep consolidation declines, and time of awakening and the rhythms of body temperature, plasma melatonin and cortisol shift to an earlier clock hour. The variability of the phase relationship between the sleep-wake cycle and circadian rhythms increases, and in old age sleep is more susceptible to internal arousing stimuli associated with circadian misalignment. The propensity to awaken from sleep advances relative to the body temperature nadir in older people, a change that is opposite to the phase delay of awakening relative to internal circadian rhythms associated with morningness in young people. Age-related changes do not appear to be associated with a shortening of the circadian period or a reduction of the circadian drive for wake maintenance. These changes may be related to changes in the sleep process itself, such as reductions in slow-wave sleep and sleep spindles as well as a reduced strength of the circadian signal promoting sleep in the early morning hours. Putative mediators and modulators of circadian sleep regulation are discussed.
Cropley M, Dijk D, Stanley N (2003) The effects of rumination about work issues during leisure time on sleep: A two day diary study, SLEEP 26 pp. A305-A305 AMER ACADEMY SLEEP MEDICINE
Franken P, Dijk DJ, Tobler I, Borbély AA (1991) Sleep deprivation in rats: effects on EEG power spectra, vigilance states, and cortical temperature., Am J Physiol 261 (1 Pt 2) pp. R198-R208
Vigilance states, electroencephalogram (EEG) power spectra (0.25-25.0 Hz), and cortical temperature (TCRT) of 10 rats were obtained during a baseline day, a 24-h sleep deprivation (SD) period, and 2 days of recovery (recoveries 1 and 2). EEG power density in waking gradually increased in most frequencies during the SD period. Non-rapid-eye-movement (NREM) sleep was enhanced on both recovery days, and rapid-eye-movement sleep was enhanced only on recovery 1. In the initial 4 h of recovery 1, EEG slow-wave activity (SWA; mean power density 0.75-4.0 Hz) in NREM sleep was elevated relative to baseline, and the number of brief awakenings (nBA) was reduced. In the dark period of recovery 1 and the light period of recovery 2, SWA was below baseline, and nBA was increased. During the entire recovery period, SWA and nBA, both expressed as deviation from baseline values, were negatively correlated. During the SD period, TCRT was above baseline, and in the initial 16 h of recovery 1 it was below baseline. Whereas TCRT was negatively correlated with NREM sleep, no significant correlation was found between TCRT and SWA within NREM sleep. It is concluded that SD causes a short-lasting intensification of sleep, as indicated by the enhanced SWA and the reduced nBA, and a long-lasting increase in sleep duration. The different time courses of SWA and TCRT suggest that variations in NREM sleep intensity are not directly related to changes in TCRT.
Dijk D-J (2011) Sleep highlights, JOURNAL OF SLEEP RESEARCH 20 (2) pp. 257-258 WILEY-BLACKWELL
Wright KP, Hughes RJ, Kronauer RE, Dijk DJ, Czeisler CA (2001) Intrinsic near-24-h pacemaker period determines limits of circadian entrainment to a weak synchronizer in humans., Proc Natl Acad Sci U S A 98 (24) pp. 14027-14032
Endogenous circadian clocks are robust regulators of physiology and behavior. Synchronization or entrainment of biological clocks to environmental time is adaptive and important for physiological homeostasis and for the proper timing of species-specific behaviors. We studied subjects in the laboratory for up to 55 days each to determine the ability to entrain the human clock to a weak circadian synchronizing stimulus [scheduled activity-rest cycle in very dim (approximately 1.5 lux in the angle of gaze) light-dark cycle] at three approximately 24-h periods: 23.5, 24.0, and 24.6 h. These studies allowed us to test two competing hypotheses as to whether the period of the human circadian pacemaker is near to or much longer than 24 h. We report here that imposition of a sleep-wake schedule with exposure to the equivalent of candle light during wakefulness and darkness during sleep is usually sufficient to maintain circadian entrainment to the 24-h day but not to a 23.5- or 24.6-h day. Our results demonstrate functionally that, in normally entrained sighted adults, the average intrinsic circadian period of the human biological clock is very close to 24 h. Either exposure to very dim light and/or the scheduled sleep-wake cycle itself can entrain this near-24-h intrinsic period of the human circadian pacemaker to the 24-h day.
Archer SN, Laing EE, Möller-Levet CS, van der Veen DR, Bucca G, Lazar AS, Santhi N, Slak A, Kabiljo R, von Schantz M, Smith CP, Dijk DJ (2014) Mistimed sleep disrupts circadian regulation of the human transcriptome., Proc Natl Acad Sci U S A
Circadian organization of the mammalian transcriptome is achieved by rhythmic recruitment of key modifiers of chromatin structure and transcriptional and translational processes. These rhythmic processes, together with posttranslational modification, constitute circadian oscillators in the brain and peripheral tissues, which drive rhythms in physiology and behavior, including the sleep-wake cycle. In humans, sleep is normally timed to occur during the biological night, when body temperature is low and melatonin is synthesized. Desynchrony of sleep-wake timing and other circadian rhythms, such as occurs in shift work and jet lag, is associated with disruption of rhythmicity in physiology and endocrinology. However, to what extent mistimed sleep affects the molecular regulators of circadian rhythmicity remains to be established. Here, we show that mistimed sleep leads to a reduction of rhythmic transcripts in the human blood transcriptome from 6.4% at baseline to 1.0% during forced desynchrony of sleep and centrally driven circadian rhythms. Transcripts affected are key regulators of gene expression, including those associated with chromatin modification (methylases and acetylases), transcription (RNA polymerase II), translation (ribosomal proteins, initiation, and elongation factors), temperature-regulated transcription (cold inducible RNA-binding proteins), and core clock genes including CLOCK and ARNTL (BMAL1). We also estimated the separate contribution of sleep and circadian rhythmicity and found that the sleep-wake cycle coordinates the timing of transcription and translation in particular. The data show that mistimed sleep affects molecular processes at the core of circadian rhythm generation and imply that appropriate timing of sleep contributes significantly to the overall temporal organization of the human transcriptome.
Dijk DJ, Kronauer RE (1999) Commentary: models of sleep regulation: successes and continuing challenges., J Biol Rhythms 14 (6) pp. 569-573
Quantitative models have been developed to describe salient aspects of human sleep regulation. The two-process model of sleep regulation and the thermoregulatory model of sleep control highlight the interaction between sleep homeostasis and circadian rhythmicity and the association between sleep and temperature regulation, respectively. These models have been successful and inspiring, but continuing progress remains dependent on rigorous testing of some of their basic assumptions. Whereas it has been established that EEG slow-wave activity is a marker of sleep homeostasis, its causal role in regulating the timing of sleep and wakefulness remains to be demonstrated conclusively. Likewise, the causal role of the temperature regulatory system in sleep timing requires further investigation. In both models, many parameters have yet to be associated with specific physiologic processes. This makes it challenging, at least within the framework of these models, to account for interindividual differences or age-related changes in such features as sleep duration and sleep timing, as well as changes in the phase angle between the sleep-wake cycle and accepted markers of the circadian pacemaker, such as the body temperature or melatonin rhythm. Although the models may describe adequately global sleep patterns and their circadian modulation, detailed modeling of the frequent short awakenings from, and the subsequent transitions back to, sleep, as well as the variation of the propensity to awaken across the ultradian non-REM-REM cycle, is not addressed. Incoporation of these aspects of sleep in mathematical models of sleep regulation may further our understanding of a key aspect of sleep regulation, that is, its timing.
The contribution of the circadian timing system to the age-related advance of sleep-wake timing was investigated in two experiments. In a constant routine protocol, we found that the average wake time and endogenous circadian phase of 44 older subjects were earlier than that of 101 young men. However, the earlier circadian phase of the older subjects actually occurred later relative to their habitual wake time than it did in young men. These results indicate that an age-related advance of circadian phase cannot fully account for the high prevalence of early morning awakening in healthy older people. In a second study, 13 older subjects and 10 young men were scheduled to a 28-h day, such that they were scheduled to sleep at many circadian phases. Self-reported awakening from scheduled sleep episodes and cognitive throughput during the second half of the wake episode varied markedly as a function of circadian phase in both groups. The rising phase of both rhythms was advanced in the older subjects, suggesting an age-related change in the circadian regulation of sleep-wake propensity. We hypothesize that under entrained conditions, these age-related changes in the relationship between circadian phase and wake time are likely associated with self-selected light exposure at an earlier circadian phase. This earlier exposure to light could account for the earlier clock hour to which the endogenous circadian pacemaker is entrained in older people and thereby further increase their propensity to awaken at an even earlier time.
In organisms as diverse as single-celled algae and humans, light is the primary stimulus mediating entrainment of the circadian biological clock. Reports that some totally blind individuals appear entrained to the 24-h day have suggested that nonphotic stimuli may also be effective circadian synchronizers in humans, although the nonphotic stimuli are probably comparatively weak synchronizers, because the circadian rhythms of many totally blind individuals "free run" even when they maintain a 24-h activity-rest schedule. To investigate entrainment by nonphotic synchronizers, we studied the endogenous circadian melatonin and core body temperature rhythms of 15 totally blind subjects who lacked conscious light perception and exhibited no suppression of plasma melatonin in response to ocular bright-light exposure. Nine of these fifteen blind individuals were able to maintain synchronization to the 24-h day, albeit often at an atypical phase angle of entrainment. Nonphotic stimuli also synchronized the endogenous circadian rhythms of a totally blind individual to a non-24-h schedule while living in constant near darkness. We conclude that nonphotic stimuli can entrain the human circadian pacemaker in some individuals lacking ocular circadian photoreception.
Mazza M, Dijk D, Klerman EB (2004) Alertness and performance in older and younger adults during 16, 28, and 52 hours of sleep deprivation, SLEEP 27 pp. 154-155 AMER ACADEMY SLEEP MEDICINE
Emegbo S, Stanley N, Dijk D, Hindmarch I (2005) Differential effects of gender on sleep continuity during experimental fragmentation of sleep, SLEEP 28 pp. A144-A144 AMER ACADEMY SLEEP MEDICINE
DIJK DJ, CZEISLER CA (1994) BODY-TEMPERATURE IS ELEVATED DURING THE REBOUND OF SLOW-WAVE SLEEP FOLLOWING 40-H OF SLEEP-DEPRIVATION ON A CONSTANT ROUTINE (VOL 2, PG 117, 1993), JOURNAL OF SLEEP RESEARCH 3 (1) pp. 64-64 BLACKWELL SCIENCE LTD
Dijk D-J, Kronauer R (2000) Commentary: Models of sleep regulation: Successes and continuing challenges (Journal of Biological Rhythms 14:6 (569-576)), Journal of Biological Rhythms 15 (2) pp. 186-186
Campbell SS, Terman M, Lewy AJ, Dijk DJ, Eastman CI, Boulos Z (1995) Light treatment for sleep disorders: consensus report. V. Age-related disturbances., J Biol Rhythms 10 (2) pp. 151-154
Sleep maintenance insomnia is a major complaint among the elderly. As a result, an inordinate proportion of sleeping pill prescriptions go to individuals over 65 y of age. Because of the substantial problems associated with use of hypnotics in older populations, efforts have been made to develop nondrug treatments for age-related sleep disturbance, including timed exposure to bright light. Such bright light treatments are based on the assumption that age-related sleep disturbance is the consequence of alterations in the usual temporal relationship between body temperature and sleep. Although studies are limited, results strongly suggest that evening bright light exposure is beneficial in alleviating sleep maintenance insomnia in healthy elderly subjects. Less consistent, but generally positive, findings have been reported with regard to bright light treatment of sleep and behavioral disturbance in demented patients. For both groups, it is likely that homeostatic factors also contribute to sleep disturbance, and these may be less influenced by bright light interventions.
Vandewalle G, Gais S, Schabus M, Balteau E, Albouy G, Sterpenich V, Dijk D, Maquet P (2006) Superiority of blue (470 nm) light in eliciting non-image forming brain responses during auditory working memory in humans: a fMRI study, JOURNAL OF SLEEP RESEARCH 15 pp. 54-54 BLACKWELL PUBLISHING
Aeschbach D, Cajochen C, Tobler I, Dijk DJ, Borbély AA (1994) Sleep in a sitting position: effect of triazolam on sleep stages and EEG power spectra., Psychopharmacology (Berl) 114 (2) pp. 209-214
The effect of triazolam (0.25 mg) and placebo was investigated in healthy, male subjects who slept in a sitting position. After the intake of placebo, sleep efficiency, rapid eye movement (REM) sleep and subjective sleep quality were lower than in the preceding sleep episode in bed, while stage 1 and REM sleep latency were higher. Triazolam did not prevent this impairment of sleep. However, in comparison with the placebo condition, the percentage of slow wave sleep was higher in the first third of the night, and in the morning sleep was rated as more quite. EEG power density in nonREM sleep was reduced in the frequency range of 1.25-10.0 Hz and enhanced in the range of sleep spindles (12.25-13.0 Hz). These changes were still present in the last third of the night. In REM sleep, triazolam reduced spectral activity in some frequency bins between 4.25 and 10.0 Hz. The sitting position itself affected the nonREM sleep spectra, since the placebo level in the 2.25-21.0-Hz range exceeded the baseline level. We conclude that a 0.25 mg dose of triazolam does not effectively counteract a posture-induced sleep disturbance, but induces changes in the EEG spectra which are typical for benzodiazepine receptor agonists.
Klerman EB, Davis JB, Duffy JF, Dijk DJ, Kronauer RE (2004) Older people awaken more frequently but fall back asleep at the same rate as younger people, SLEEP 27 (4) pp. 793-798 AMER ACADEMY SLEEP MEDICINE
Duffy JF, Winkelman JW, Riel E, Dijk DJ, Czeisler CA (2001) Circadian modulation of PLMS, SLEEP 24 pp. A100-A101 AMER ACAD SLEEP MEDICINE
Dijk D-J (2000) Reply to technical note: Nonlinear interactions between circadian and homeostatic processes: Models or metrics? (Journal of Biological Rhythms 14:6 (604-608)), Journal of Biological Rhythms 15 (2) pp. 186-186
Sleepiness is common after stroke, but in contrast to its importance for rehabilitation, existing studies focus primarily on the acute state and often use subjective sleepiness measures only. We used quantitative electroencephalography (qEEG) to extract physiological sleepiness, as well as subjective reports, in response to motor-cognitive demand in stroke patients and controls. We hypothesised that (a) slowing of the EEG is chronically sustained after stroke; (b) increased power in lower frequencies and increased sleepiness are associated; and (c) sleepiness is modulated by motor-cognitive demand. QEEGs were recorded in 32 chronic stroke patients and 20 controls using a Karolinska Drowsiness Test protocol administered before and after a motor priming task. Subjective sleepiness was measured using the Karolinska Sleepiness Scale.The findings showed that power density was significantly increased in delta and theta frequency bands over both hemispheres in patients which were not associated with subjective sleepiness ratings. This effect was not observed in controls.The motor priming task induced differential hemispheric effects with greater increase in low-frequency bands and presumably compensatory increases in higher frequency bands. The results indicate sustained slowing in the qEEG in chronic stroke, but in contrast to healthy controls, these changes are not related to perceived sleepiness.
Van Someren EJW, Cirelli C, Dijk D-J, Van Cauter E, Schwartz S, Chee MWL (2015) Disrupted Sleep: From Molecules to Cognition, JOURNAL OF NEUROSCIENCE 35 (41) pp. 13889-13895 SOC NEUROSCIENCE
Aeschbach D, Lockyer BJ, Dijk D-J, Lockley SW, Nuwayser ES, Nichols LD, Czeisler CA (2009) Use of Transdermal Melatonin Delivery to Improve Sleep Maintenance During Daytime, CLINICAL PHARMACOLOGY & THERAPEUTICS 86 (4) pp. 378-382 NATURE PUBLISHING GROUP
Duffy JF, Cain SW, Chang AM, Phillips AJ, Münch MY, Gronfier C, Wyatt JK, Dijk DJ, Wright KP, Czeisler CA (2011) Quantification of Behavior Sackler Colloquium: Sex difference in the near-24-hour intrinsic period of the human circadian timing system., Proc Natl Acad Sci U S A
The circadian rhythms of melatonin and body temperature are set to an earlier hour in women than in men, even when the women and men maintain nearly identical and consistent bedtimes and wake times. Moreover, women tend to wake up earlier than men and exhibit a greater preference for morning activities than men. Although the neurobiological mechanism underlying this sex difference in circadian alignment is unknown, multiple studies in nonhuman animals have demonstrated a sex difference in circadian period that could account for such a difference in circadian alignment between women and men. Whether a sex difference in intrinsic circadian period in humans underlies the difference in circadian alignment between men and women is unknown. We analyzed precise estimates of intrinsic circadian period collected from 157 individuals (52 women, 105 men; aged 18-74 y) studied in a month-long inpatient protocol designed to minimize confounding influences on circadian period estimation. Overall, the average intrinsic period of the melatonin and temperature rhythms in this population was very close to 24 h [24.15 ± 0.2 h (24 h 9 min ± 12 min)]. We further found that the intrinsic circadian period was significantly shorter in women [24.09 ± 0.2 h (24 h 5 min ± 12 min)] than in men [24.19 ± 0.2 h (24 h 11 min ± 12 min); P
Wulff K, Joyce EM, Middleton B, Dijk DJ, Foster RG (2007) Sleep in schizophrenia, EUROPEAN NEUROPSYCHOPHARMACOLOGY 17 pp. S136-S137 ELSEVIER SCIENCE BV
Groeger JA, Lo JC, Dijk D (2008) Dissociable effects of recent and enduring sleep quality on reported everyday affect and function: a structural equation modeling approach, JOURNAL OF SLEEP RESEARCH 17 pp. 236-236 WILEY-BLACKWELL PUBLISHING, INC
Vandewalle G, Archer SN, Wuillaume C, Balteau E, Degueldre C, Luxen A, Dijk D, Maquet P (2009) MODULATION OF FMRI ASSESSED BRAIN RESPONSES TO BLUE AND GREEN LIGHT BY SLEEP HOMFOSTASIS, CIRCADIAN PHASE AND PER3 POLYMORPHISM, SLEEP 32 pp. A1-A1 AMER ACAD SLEEP MEDICINE
Dijk DJ, Lockley SW (2002) Invited review: Integration of human sleep-wake regulation and circadian rhythmicity, Journal of Applied Physiology 92 (2) pp. 852-862
The human sleep-wake cycle is generated by a circadian process, originating from the suprachiasmatic nuclei, in interaction with a separate oscillatory process: the sleep homeostat. The sleep-wake cycle is normally timed to occur at a specific phase relative to the external cycle of light-dark exposure. It is also timed at a specific phase relative to interal circadian rhythms, such as the pineal melatonin rhythm, the circadian sleep-wake propensity rhythm, and the rhythm of responsiveness of the circadian pacemaker to light. Variations in these internal and external phase relationships, such as those that occur in blindness, aging, morning and evening, and advanced and delayed sleep-phase syndrome, lead to sleep disruptions and complaints. Changes in ocular circadian photoreception, interindividual variation in the near-24-h intrinsic period of the circadian pacemaker, and sleep homeostasis can contribute to variations in external and internal phase. Recent findings on the physiological and molecular-genetic correlates of circadian sleep disorders suggest that the timing of the sleep-wake cycle and circadian rhythms is closely integrated but is, in part, regulated differentially.
Klerman EB, Dijk D-J (2008) Age-related reduction in the maximal capacity for sleep - Implications for insomnia, CURRENT BIOLOGY 18 (15) pp. 1118-1123 CELL PRESS
Dijk D-J (2006) Sleep of aging women and men: Back to basics, SLEEP 29 (1) pp. 12-13 AMER ACADEMY SLEEP MEDICINE
Dijk D-J (2013) Why do we sleep so late?, Journal of Sleep Research 22 (6) pp. 605-606
Mccarthy A, Edgar DM, Dijk D-J (2012) Defining rat and human sleep bout parameters using distribution fit statistics, JOURNAL OF SLEEP RESEARCH 21 pp. 197-197 WILEY-BLACKWELL
Iannone R, Palcza J, Renger JJ, Calder N, Cerchio K, Gottesdiener K, Hargreaves R, Dijk DJ, Boyle J, Murphy MG (2010) Acute Alertness-Promoting Effects of a Novel Histamine Subtype-3 Receptor Inverse Agonist in Healthy Sleep-Deprived Male Volunteers, CLINICAL PHARMACOLOGY & THERAPEUTICS 88 (6) pp. 831-839 NATURE PUBLISHING GROUP
Kattler H, Dijk DJ, Borbély AA (1994) Effect of unilateral somatosensory stimulation prior to sleep on the sleep EEG in humans., J Sleep Res 3 (3) pp. 159-164
The hypothesis that local activation of brain regions during wakefulness affects the EEG recorded from these regions during sleep was tested by applying vibratory stimuli to one hand prior to sleep. Eight subjects slept in the laboratory for five consecutive nights. During a 6-h period prior to night 3, either the left or the right hand was vibrated intermittently (20 min on-8 min off), while prior to night 5 the same treatment was applied to the contralateral hand. The sleep EEG was recorded from frontal, central, parietal and occipital derivations and subjected to spectral analysis. The interhemispheric asymmetry index (IAI) was calculated for spectral power in nonREM sleep in the frequency range 0.25-25.0 Hz for 0.5-Hz or 1-Hz bins. In the first hour of sleep following right-hand stimulation, the IAI of the central derivation was increased relative to baseline, which corresponds to a shift of power towards the left hemisphere. This effect was most prominent in the delta range, was limited to the first hour of sleep and was restricted to the central derivation situated over the somatosensory cortex. No significant changes were observed following left-hand stimulation. Although the effect was small, it is consistent with the hypothesis that the activation of specific neuronal populations during wakefulness may have repercussions on their electrical activity pattern during subsequent sleep.
Cropley M, Dijk DJ, Stanley N (2004) The effects of ruminative thinking about work on sleep, Psychology and Health 19 (SUPPL. 1)
Background: Sleep is one of the most important recovery mechanisms available to humans, allowing for recovery from daily strains, and therefore a prerequisite for health. Many workers complain that they are unable to get to sleep at night, and report poor sleep maintenance due to unwanted, ruminative thoughts and concerns about work-related issues. The present study investigated the effects of ruminative thinking on sleep, using self-reported diaries. Method: One-hundred and seven school teachers were asked to keep a diary record of their thoughts about work over a workday evening and were monitored hourly from 17.00 hrs until bedtime. Each individual also completed a diary assessment of their sleep patterns over the same night. Using information obtained from the diaries the sample was divided into high ruminators (those who thought about work issues a lot at bedtime) and low ruminators (those who thought about work issues little at bedtime) using tertile splits. Only individuals who did not work in the hour before bedtime were included in the analysis. Results: Logistic regression analysis revealed (after adjusting for age and gender), that high compared to low ruminators were: 3.5 time more likely to report 'difficulty falling asleep', 4.7 time more likely to report 'difficulty waking up', 5.7 times more likely to report 'difficulty getting back to sleep if awoken during the night', 6.8 times more likely to report 'restless sleep' and 3.4 times more likely to 'feel unrefreshed after awaking'. Relative to the low ruminators, high ruminators also reported that they had thought about work related issues - while trying to fall asleep (p
Dijk DJ, Lazar AS (2012) The Regulation of Human Sleep and Wakefulness: Sleep Homeostasis and Circadian Rhythmicity,
© 2012 by Oxford University Press, Inc. All rights reserved.The alternation of sleep and wakefulness is a major determinant of the structure and quality of our lives. The sleep- wake cycle is regulated by a fine-tuned balance between two physiological processes: sleep homeostasis, which measures sleep debt, and circadian rhythmicity, which determines the optimal internal (biological) time for sleep and wakefulness. Sleep homeostasis and circadian rhythmicity together influence many aspects of sleep, such as the time it takes to fall asleep, the timing of awakening and the interruptions of sleep, as well as the duration of rapid eye movement sleep, slow-wave sleep and specific brainwaves during sleep, such as sleep spindles. Alterations in the balance between sleep homeostasis and circadian rhythmicity contribute to sleep phenotypes such as morningness-eveningness and short-long sleepers as well as sleep disturbances. Emerging insights into the environmental, behavioral, physiological, neurochemical and molecular-genetic determinants of sleep homeostasis and circadian rhythmicity provide new avenues for the understanding and improvement of the sleep- wake cycle.
Jewett ME, Wyatt JK, Ritz-De Cecco A, Khalsa SB, Dijk DJ, Czeisler CA (1999) Time course of sleep inertia dissipation in human performance and alertness., J Sleep Res 8 (1) pp. 1-8
Alertness and performance on a wide variety of tasks are impaired immediately upon waking from sleep due to sleep inertia, which has been found to dissipate in an asymptotic manner following waketime. It has been suggested that behavioural or environmental factors, as well as sleep stage at awakening, may affect the severity of sleep inertia. In order to determine the time course of sleep inertia dissipation under normal entrained conditions, subjective alertness and cognitive throughput were measured during the first 4 h after habitual waketime from a full 8-h sleep episode on 3 consecutive days. We investigated whether this time course was affected by either sleep stage at awakening or behavioural/environmental factors. Sleep inertia dissipated in an asymptotic manner and took 2-4 h to near the asymptote. Saturating exponential functions fitted the sleep inertia data well, with time constants of 0.67 h for subjective alertness and 1.17 h for cognitive performance. Most awakenings occurred out of stage rapid eye movement (REM), 2 or 1 sleep, and no effect of sleep stage at awakening on either the severity of sleep inertia or the time course of its dissipation could be detected. Subjective alertness and cognitive throughput were significantly impaired upon awakening regardless of whether subjects got out of bed, ate breakfast, showered and were exposed to ordinary indoor room light (approximately 150 lux) or whether subjects participated in a constant routine (CR) protocol in which they remained in bed, ate small hourly snacks and were exposed to very dim light (10-15 lux). These findings allow for the refinement of models of alertness and performance, and have important implications for the scheduling of work immediately upon awakening in many occupational settings.
Boyle J, Groeger JA, Paska W, Cooper JA, Rockett C, Jones S, Gandhi P, Scott J, Atzori G, Dijk DJ (2012) A method to assess the dissipation of residual hypnotics: eszopiclone versus zopiclone., J Clin Psychopharmacol 32 (5) pp. 704-709
Lippincott, Williams & Wilkins
Next-day residual effects of single evening doses of 3 mg of eszopiclone, 7.5 mg of zopiclone, and placebo were assessed in a randomized, double-blind, placebo-controlled, 3-way crossover study that used a mild sleep restriction protocol (sleep duration, 7 hours). During each period, 91 healthy volunteers spent 2 consecutive nights in the laboratory with time in bed restricted to 7 hours. Volunteers completed the Continuous Tracking Test, Critical Flicker Fusion task, Digit Symbol Substitution Test, N-back tasks, and Linear Analogue Rating Scales every half-hour from 7.5 to 11.5 hours after dose, commencing 15 minutes after awakening. Nighttime dosing of both eszopiclone (3 mg) and racemic zopiclone (7.5 mg) was associated with next-day performance impairment, and these residual effects dissipated over time. Eszopiclone did not differ from zopiclone on the primary end point, mean Continuous Tracking Test tracking error averaged from 7.5 to 9.5 hours after dose; however, a prespecified post hoc parametric analysis of reciprocal-transformed data favored eszopiclone over racemic zopiclone (P = 0.026).
Dijk DJ (2015) Dreaming, memory, insomnia and the exploding attention for sleep, Journal of Sleep Research 24 (4)
Eastell R, Dijk D-J, Small M, Greenwood A, Sharpe J, Yamada H, Yuba M, Tanimoto M, Deacon S (2015) Morning vs evening dosing of the cathepsin K inhibitor ONO-5334: effects on bone resorption in postmenopausal women in a randomized, phase 1 trial, OSTEOPOROSIS INTERNATIONAL 27 (1) pp. 309-318 SPRINGER LONDON LTD
Whittlef C, Smith MR, Pilsworth SN, Dijk DJ, Mahowald MW (2003) Do we practice what we preach? Shiftwork and sleepiness in the Association of Polysomnographic Technologists (APT), SLEEP 26 pp. A95-A95 AMER ACADEMY SLEEP MEDICINE
Dijk D-J, Skeldon AC (2015) BIOLOGICAL RHYTHMS Human sleep before the industrial era, NATURE 527 (7577) pp. 176-177 NATURE PUBLISHING GROUP
Klerman EB, Wang W, Duffy JF, Dijk DJ, Czeisler CA, Kronauer RE (2012) Survival analysis indicates that age-related decline in sleep continuity occurs exclusively during NREM sleep., Neurobiol Aging
A common complaint of older persons is disturbed sleep, typically characterized as an inability to return to sleep after waking. As every sleep episode (i.e., time in bed) includes multiple transitions between wakefulness and sleep (which can be subdivided into rapid eye movement [REM] sleep and non-REM [NREM] sleep), we applied survival analysis to sleep data to determine whether changes in the "hazard" (duration-dependent probability) of awakening from sleep and/or returning to sleep underlie age-related sleep disturbances. The hazard of awakening from sleep-specifically NREM sleep-was much greater in older than in young adults. We found, however, that when an individual had spontaneously awakened, the probability of falling back asleep was not greater in young persons. Independent of bout length, the number of transitions between NREM and REM sleep stages relative to number of transitions to wake was approximately 6 times higher in young than older persons, highlighting the difficulty in maintaining sleep in older persons. Interventions to improve age-related sleep complaints should thus target this change in awakenings.
Lazar AS, Santhi N, Hasan S, Lo JC, Johnston JD, Von Schantz M, Archer SN, Dijk DJ (2012) Circadian period and the timing of melatonin onset in men and women: predictors of sleep during the weekend and in the laboratory., J Sleep Res
Sleep complaints and irregular sleep patterns, such as curtailed sleep during workdays and longer and later sleep during weekends, are common. It is often implied that differences in circadian period and in entrained phase contribute to these patterns, but few data are available. We assessed parameters of the circadian rhythm of melatonin at baseline and in a forced desynchrony protocol in 35 participants (18 women) with no sleep disorders. Circadian period varied between 23 h 50 min and 24 h 31 min, and correlated positively (n = 31, r(s) = 0.43, P = 0.017) with the timing of the melatonin rhythm relative to habitual bedtime. The phase of the melatonin rhythm correlated with the Insomnia Severity Index (n = 35, r(s) = 0.47, P = 0.004). Self-reported time in bed during free days also correlated with the timing of the melatonin rhythm (n = 35, r(s) = 0.43, P = 0.01) as well as with the circadian period (n = 31, r(s) = 0.47, P = 0.007), such that individuals with a more delayed melatonin rhythm or a longer circadian period reported longer sleep during the weekend. The increase in time in bed during the free days correlated positively with circadian period (n = 31, r(s) = 0.54, P = 0.002). Polysomnographically assessed latency to persistent sleep (n = 34, r(s) = 0.48, P = 0.004) correlated with the timing of the melatonin rhythm when participants were sleeping at their habitual bedtimes in the laboratory. This correlation was significantly stronger in women than in men (Z = 2.38, P = 0.017). The findings show that individual differences in circadian period and phase of the melatonin rhythm associate with differences in sleep, and suggest that individuals with a long circadian period may be at risk of developing sleep problems.
Dijk DJ, Strijkstra A, Daan S, Beersma DG, Van den Hoofdakker RH (1991) Effect of clomipramine on sleep and EEG power spectra in the diurnal rodent Eutamias sibiricus., Psychopharmacology (Berl) 103 (3) pp. 375-379
Sleep was recorded in the diurnal rodent Eutamias sibiricus, chronically implanted with EEG and EMG electrodes. The tricyclic antidepressant drug clomipramine suppressed the duration of REM sleep and EEG power density in the frequencies between 1.5 and 13.5 Hz in nonREM sleep. During the administration of clomipramine, 24 h of sleep deprivation by forced locomotion significantly reduced the duration of waking and increased the duration of nonREM sleep. During the first 2 h of recovery sleep, EEG power density of the frequencies between 2.5 and 6 Hz was enhanced. These effects of sleep deprivation were to a large extent similar to those of sleep deprivation under drug free conditions. It is concluded that clomipramine affects the EEG in nonREM sleep but does not interfere substantially with nonREM sleep regulatory processes, which are activated by sleep deprivation.
Hartmann JA, Thorne HC, Groeger JA, Dijk D (2009) EFFECTS OF SLEEP LOSS AND CIRCADIAN MISALIGNMENT ON PERFORMANCE AND ALERTNESS: A COMPARISON OF OBJECTIVE AND SUBJECTIVE MEASURES, SLEEP 32 pp. A60-A60 AMER ACAD SLEEP MEDICINE
Kamphuis J, Dijk DJ, Spreen M, Lancel M (2013) The relation between poor sleep, impulsivity and aggression in forensic psychiatric patients, Physiology and Behavior 123 pp. 168-173
Psychiatric disorders are often associated with disturbed sleep. Poor sleep can attenuate emotional control, including the regulation of aggression, and thus, may increase the risk of impulsive, aggressive acts. This cross-sectional study aimed to investigate the potential contribution of sleep problems to subjective and objective aggressiveness and impulsivity in a forensic psychiatric population. Questionnaires on sleep quality (Pittsburgh Sleep Quality Index), chronic severe insomnia (Sleep Diagnosis List), aggressiveness (Aggression Questionnaire) and impulsivity (Barratt Impulsiveness Scale-11) were completed by 96 forensic psychiatric inpatients, admitted to two forensic facilities in the Netherlands. To obtain more objective measurements of aggression and impulsivity, observational scores on a professional instrument to assess the risk of future aggression (Historical Clinical Future-30) and reported aggressive incidents were collected from files. Results showed that a worse sleep quality and higher insomnia scores were significantly associated with self-reported aggression and impulsivity, clinician-rated hostility and involvement in aggressive incidents within the facility. Whether a participant was professionally judged as impulsive could not be predicted by sleep quality or the insomnia score. To a large extent the results of this study support the hypothesis that poor sleep is related to impulsive, aggressive behavior in forensic psychiatric patients. It is worthwhile to examine the protective effect of treatment of sleep difficulties on aggressive reactivity in (forensic) psychiatric populations. © 2013 Elsevier Inc.
Dijk DJ (1999) Circadian variation of EEG power spectra in NREM and REM sleep in humans: dissociation from body temperature., J Sleep Res 8 (3) pp. 189-195
In humans, EEG power spectra in REM and NREM sleep, as well as characteristics of sleep spindles such as their duration, amplitude, frequency and incidence, vary with circadian phase. Recently it has been hypothesized that circadian variations in EEG spectra in humans are caused by variations in brain or body temperature and may not represent phenomena relevant to sleep regulatory processes. To test this directly, a further analysis of EEG power spectra - collected in a forced desynchrony protocol in which sleep episodes were scheduled to a 28-h period while the rhythms of body temperature and plasma melatonin were oscillating at their near 24-h period - was carried out. EEG power spectra were computed for NREM and REM sleep occurring between 90-120 and 270-300 degrees of the circadian melatonin rhythm, i.e. just after the clearance of melatonin from plasma in the 'morning' and just after the 'evening' increase in melatonin secretion. Average body temperatures during scheduled sleep at these two circadian phases were identical (36.72 degrees C). Despite identical body temperatures, the power spectra in NREM sleep were very different at these two circadian phases. EEG activity in the low frequency spindle range was significantly and markedly enhanced after the evening increase in plasma melatonin as compared to the morning phase. For REM sleep, significant differences in power spectra during these two circadian phases, in particular in the alpha range, were also observed. The results confirm that EEG power spectra in NREM and REM sleep vary with circadian phase, suggesting that the direct contribution of temperature to the circadian variation in EEG power spectra is absent or only minor, and are at variance with the hypothesis that circadian variations in EEG power spectra are caused by variations in temperature.
Skeldon A, Dijk D-J, Derks G (2014) Changes in sleep across the lifespan: using mathematical models to explore hypotheses to explain sleep timing, JOURNAL OF SLEEP RESEARCH 23 pp. 169-170 WILEY-BLACKWELL
Vandewalle G, Archer S, Wuillaume C, Balteau E, Degueldre C, Luxen A, Maquet P, Dijk D (2008) Polymorphism in period3 predicts fMRI-assessed inter-individual differences in the effects of sleep deprivation, JOURNAL OF SLEEP RESEARCH 17 pp. 38-38 WILEY-BLACKWELL PUBLISHING, INC
Lo JC, Groeger JA, Santhi N, Arbon EL, Lazar AS, Hasan S, Von Schantz M, Archer SN, Dijk DJ (2012) Effects of circadian phase and prior partial sleep deprivation on executive functions during total sleep deprivation are modulated by PER3 polymorphism, JOURNAL OF SLEEP RESEARCH 21 pp. 41-41 WILEY-BLACKWELL
Dijk D-J, Winsky-Sommerer R (2012) Sleep: How much we need and what keeps us awake, New Scientist 213 (2850) pp. iv-v
Light is considered the most potent synchronizer of the human circadian system and exerts many other non-image-forming effects, including those that affect brain function. These effects are mediated in part by intrinsically photosensitive retinal ganglion cells that express the photopigment melanopsin. The spectral sensitivity of melanopsin is greatest for blue light at approximately 480 nm. At present, there is little information on how the spectral composition of light to which people are exposed varies over the 24 h period and across seasons. Twenty-two subjects, aged 22±4 yrs (mean±SD) participated during the winter months (November?February), and 12 subjects aged 25±3 yrs participated during the summer months (April?August). Subjects wore Actiwatch-RGB monitors, as well as Actiwatch-L monitors, for seven consecutive days while living in England. These monitors measured activity and light exposure in the red, green, and blue spectral regions, in addition to broad-spectrum white light, with a 2 min resolution. Light exposure during the day was analyzed for the interval between 09:00 and 21:00 h. The time course of white-light exposure differed significantly between seasons (p = 0.0022), with light exposure increasing in the morning hours and declining in the afternoon hours, and with a more prominent decline in the winter. Overall light exposure was significantly higher in summer than winter (p = 0.0002). Seasonal differences in the relative contribution of blue-light exposure to overall light exposure were also observed (p = 0.0006), in particular during the evening hours. During the summer evenings (17:00?21:00 h), the relative contribution of blue light was significantly higher (p
The sensitivity of the human circadian system to light has been the subject of considerable debate. Using computer simulations of a recent quantitative model for the effects of light on the human circadian system, we investigated these effects of light during different experimental protocols. The results of the simulations indicate that the nonuniform distribution over the circadian cycle of exposure to ordinary room light seen in classical free-run studies, in which subjects select their exposure to light and darkness, can result in an observed period of approximately 25 h, even when the intrinsic period of the subject's endogenous circadian pacemaker is much closer to 24 h. Other simulation results suggest that accurate assessment of the true intrinsic period of the human circadian pacemaker requires low ambient light intensities (approximately 10-15 lx) during scheduled wake episodes, desynchrony of the imposed light-dark cycle from the endogenous circadian oscillator, and a study length of at least 20 days. Although these simulations await further experimental substantiation, they highlight the sensitivity to light of the human circadian system and the potential confounding influence of light on the assessment of the intrinsic period of the circadian pacemaker.
Dijk D-J (2012) Sleep restriction and emotion, electroencephalography (EEG) and dream recall, and insomnia and punctuality, Journal of Sleep Research 21 (3) pp. 233-234
Muto V, Jaspar M, Meyer C, LeBourdiec AS, Kussee C, Chellappa SL, Vandewalle G, Degueldre C, Luxen A, Collette F, Phillips C, Middleton B, Archer SN, Dijk D-J, Maquet P (2014) Neural correlates of sustained attention under sleep deprivation during a constant routine: circadian and homeostatic interaction, JOURNAL OF SLEEP RESEARCH 23 pp. 61-61 WILEY-BLACKWELL
Dijk DJ, Czeisler CA (1993) Body temperature is elevated during the rebound of slow-wave sleep following 40-h of sleep deprivation on a constant routine., J Sleep Res 2 (3) pp. 117-120
EEG, EMG, EOG and core body temperature were recorded during baseline sleep and during recovery sleep from a 40-h constant routine in 9 male subjects. Slow-wave sleep and slow-wave activity (SWA, EEG power density 0.75-4.5 Hz) were enhanced in the first two nonREM sleep episodes of recovery sleep. Core body temperature was not significantly different in the last 30 minutes before lights out but was significantly higher during recovery sleep in the interval between lights out and sleep onset and during the first nonREM sleep episode. The data demonstrate that an enhancement of SWA/SWS is not necessarily accompanied by lower values of core body temperature, and therefore challenge the notion that SWS is the primary factor responsible for the steep decline of body temperature that occurs at the onset of the nightly sleep episode.
Pugin F, Viola AU, Chellappa SL, Archer S, Dijk DJ, Cajochen C (2009) Can Per3 Length Polymorphism Predict Sleep Duration in Older Individuals?, NEUROPSYCHOBIOLOGY 59 (4) pp. 255-255 KARGER
Dijk DJ (2012) Sleep research: observing dreams and inducing hypnagogic images., J Sleep Res 21 (1) pp. 1-2
Dijk DJ (2009) Electrophysiological characteristics and regulation of SWS, EUROPEAN NEUROPSYCHOPHARMACOLOGY 19 pp. S716-S716 ELSEVIER SCIENCE BV
Wulff K, Dijk DJ, Middleton B, Foster RG, Joyce EM (2012) Sleep and circadian rhythm disruption in schizophrenia., Br J Psychiatry 200 (4) pp. 308-316
Sleep disturbances comparable with insomnia occur in up to 80% of people with schizophrenia, but very little is known about the contribution of circadian coordination to these prevalent disruptions.
Brunner DP, Dijk DJ, Tobler I, Borbély AA (1990) Effect of partial sleep deprivation on sleep stages and EEG power spectra: evidence for non-REM and REM sleep homeostasis., Electroencephalogr Clin Neurophysiol 75 (6) pp. 492-499
The effect of repeated partial sleep deprivation on sleep stages and sleep EEG parameters was investigated in young subjects. After 2 baseline nights (B1, B2) of 7.5 h, sleep was restricted for 2 nights (D1, D2) to the first 4 h of the habitual bedtime period. Two recovery nights (R1, R2) with 7.5 h sleep followed. During the deprivation nights, stages 1 and 2 and REM sleep were reduced, while slow wave sleep (SWS; stages 3 and 4) was not significantly affected. However, the time integral of EEG power density in the range of 0.75-4.5 Hz (slow wave energy) was reduced. In the recovery period, SWS showed an enhancement in R1, and REM sleep showed a rebound in R1 and R2. An increase of REM sleep in the early part of the sleep period was evident in R1. Sleep latency was reduced in D2, R1 and R2. In accordance with the 2-process model of sleep regulation, EEG power density in non-REM sleep in the range of 0.75-4.5 Hz (slow wave activity) was only slightly higher in D2 and R1 than in baseline. An enhancement of slow wave activity in REM sleep was present in D2. Power density in the frequency range of 13-16 Hz was reduced in non-REM sleep (R1), SWS (R2) and stage 2 (R1). The results show (1) that the moderate reduction of slow wave energy in the deprivation nights induces only a minor enhancement of slow wave activity during recovery sleep; and (2) that a REM sleep deficit gives rise to an immediate rebound when 'slow wave pressure' is low.(ABSTRACT TRUNCATED AT 250 WORDS)
Klerman EB, Rimmer DW, Dijk DJ, Kronauer RE, Rizzo JF, Czeisler CA (1998) Erratum: Nonphotic entrainment of the human circadian pacemaker (American Journal of Physiology (R991-R996)), American Journal of Physiology - Renal Physiology 275 (6 44-6)
Dijk DJ, Beersma DG, Daan S (1987) EEG power density during nap sleep: reflection of an hourglass measuring the duration of prior wakefulness., J Biol Rhythms 2 (3) pp. 207-219
The relation between the duration of prior wakefulness and EEG power density during sleep in humans was assessed by means of a study of naps. The duration of prior wakefulness was varied from 2 to 20 hr by scheduling naps at 1000 hr, 1200 hr, 1400 hr, 1600 hr, 1800 hr, 2000 hr, and 0400 hr. In contrast to sleep latencies, which exhibited a minimum in the afternoon, EEG power densities in the delta and theta frequencies were a monotonic function of the duration of prior wakefulness. The data support the hypothesis that EEG power density during non-rapid eye movement sleep is only determined by the prior history of sleep and wakefulness and is not determined by clock-like mechanisms.
Klerman EB, Dijk DJ (2005) Interindividual variation in sleep duration and its association with sleep debt in young adults, SLEEP 28 (10) pp. 1253-1259 AMER ACAD SLEEP MEDICINE
Lázár AS, Slak A, Lo JC, Santhi N, von Schantz M, Archer SN, Groeger JA, Dijk DJ (2012) Sleep, diurnal preference, health, and psychological well-being: a prospective single-allelic-variation study., Chronobiol Int 29 (2) pp. 131-146
Individual differences in sleep and diurnal preference associate with physical and mental health characteristics, but few genetic determinants of these differences have been identified. A variable number tandem repeat (VNTR) polymorphism in the PERIOD3 (PER3) gene (rs57875989) has been reported to associate with diurnal preference, i.e., preferred timing of waking and sleep. Here, the authors investigate in a prospective single-candidate genetic variant study whether allelic variation for this polymorphism associates also with reported actual sleep timing and sleep duration, as well as psychological and health measures. Six hundred and seventy-five subjects, aged 20 to 35 yrs, completed questionnaires to assess sleep and psychological and health characteristics and were genotyped for the PER3 VNTR. Homozygosity for the longer allele (PER3(5/5)) of the VNTR was associated with increased morning preference, earlier wake time and bedtime, and reduced daytime sleepiness. Separate analyses of work and rest days demonstrated that the increase in time in bed during rest days was greatest in PER3(5/5) homozygotes. PER3 genotype modified the effects of sleep timing and duration on fluid intelligence and body mass index. Genotype was not associated with physical or psychological characteristics as assessed by the SF-36 Health Questionnaire, the General Health Questionnaire, the Big Five Inventory, the Behavioral Inhibition System-Behavioral Activation System scales, and the Positive and Negative Affect Scale, even though these measures varied significantly with diurnal preference as assessed by the Morningness-Eveningness Questionnaire. Whereas diurnal preference also predicts mental health and psychological characteristics, as well as sleep timing, the PER3 VNTR specifically affects measures of sleep timing and may also modify the effects of sleep on health outcome measures.
Wyatt JK, Dijk DJ, Ritz-De Cecco A, Ronda JM, Czeisler CA (2006) Sleep-facilitating effect of exogenous melatonin in healthy young men and women is circadian-phase dependent, SLEEP 29 (5) pp. 609-618 AMER ACADEMY SLEEP MEDICINE
Aeschbach D, Dijk DJ, Trachsel L, Brunner DP, Borbély AA (1994) Dynamics of slow-wave activity and spindle frequency activity in the human sleep EEG: effect of midazolam and zopiclone., Neuropsychopharmacology 11 (4) pp. 237-244
Electroencephalographic slow-wave activity (SWA; power density in the 0.75 to 4.5 Hz band) and spindle frequency activity (SFA; 11.25 to 15.0 Hz) exhibit a typical time course and a distinct mutual relationship during sleep. Because benzodiazepines (BDZ) suppress SWA and enhance SFA, we investigated the effect of two BDZ-receptor agonists on the dynamics of these EEG parameters. A single dose of midazolam (15 mg), zopiclone (7.5 mg), or placebo was administered before bedtime to healthy young men. Although the two drugs reduced SWA and enhanced SFA, their time course across and within sleep cycles as well as their mutual relationship were little affected. The results constitute further evidence that hypnotics acting as BDZ-receptor agonists do not substantially interfere with the homeostatic aspect of sleep regulation.
Dijk DJ, Cajochen C (1997) Melatonin and the circadian regulation of sleep initiation, consolidation, structure, and the sleep EEG., J Biol Rhythms 12 (6) pp. 627-635
The endogenous circadian rhythm of melatonin, driven by the suprachiasmatic nucleus, exhibits a close association with the endogenous circadian component of the sleep propensity rhythm and the endogenous circadian component of the variation in electroencephalogram (EEG) oscillations such as sleep spindles and slow waves. This association is maintained even when the sleep-wake cycle is desynchronized from the endogenous circadian rhythm of melatonin. Administration of melatonin during the day increases daytime sleep propensity as indexed by both the latency to sleep onset and sleep consolidation. The EEG during daytime sleep after melatonin administration exhibits characteristics reminiscent of the nocturnal sleep EEG, that is, increased sleep spindle activity and reduced slow-wave sleep and slow-wave activity, as detected by quantitative EEG analysis. Administration of higher doses of melatonin (5 mg or more) prior to nocturnal sleep results in an increase in rapid eye movement (REM) sleep. These data demonstrate that melatonin exerts effects on the main characteristics of human sleep, that is, latency to sleep onset, sleep consolidation, slow waves, sleep spindles, and REM sleep. There is a need for further studies using physiological doses and delivery systems that generate physiological plasma melatonin profiles to firmly establish the role of the endogenous circadian rhythm of melatonin in the circadian regulation of sleep.
Vandewalle G, Archer SN, Wuillaume C, Balteau E, Degueldre C, Luxen A, Maquet P, Dijk D-J (2009) Functional Magnetic Resonance Imaging-Assessed Brain Responses during an Executive Task Depend on Interaction of Sleep Homeostasis, Circadian Phase, and PER3 Genotype, JOURNAL OF NEUROSCIENCE 29 (25) pp. 7948-7956
Orexins have a role in sleep regulation, and orexin receptor antagonists are under development for the treatment of insomnia. We conducted a randomised, double-blind, placebo-controlled, four-period crossover study to investigate the effect of single doses of the dual orexin receptor antagonist SB-649868 (10 or 30 mg) and a positive control zolpidem (10 mg), an allosteric modulator of GABA(A) receptors. Objective and subjective sleep parameters and next-day performance were assessed in 51 healthy male volunteers in a traffic noise model of situational insomnia. Compared with placebo, SB-649868 10 and 30 mg increased total sleep time (TST) by 17 and 31 min (p
Sleep is essential for the maintenance of human life, yet many features of sleep are poorly understood and mathematical models are an important tool for probing proposed biological mechanisms. The most well-known mathematical model of sleep regulation, the two-process model, models the sleep-wake cycle by two oscillators: a circadian oscillator and a homeostatic oscillator. An alternative, more recent, model considers the reciprocal interaction of sleep promoting neurons and the ascending arousal system regulated by homeostatic and circadian processes. Here we show there are fundamental similarities between these two models. The implications are illustrated with two important sleep-wake phenomena. Firstly, we show that in the two-process model, transitions between different numbers of daily sleep episodes can be classified as grazing bifurcations. This provides the theoretical underpinning for numerical results showing that the sleep patterns of many mammals can be explained by the reciprocal interaction model. Secondly, we show that when sleep deprivation disrupts the sleep-wake cycle, ostensibly different measures of sleepiness in the two models are closely related. The demonstration of the mathematical similarities of the two models is important because not only does it it allow some features of the two-process model to be interpreted physiologically but it also means that knowledge gained from the study of the two-process model can be used to inform understanding of the behaviour of the mutual inhibition model. This is important because the mutual inhibition model and its extensions are increasingly being used as a tool to understand a diverse range of sleep-wake phenomena sucah as the design of optimal shift-patterns, yet the values it uses for the parameters associated with the circadian and homeostatic processes are very different from those that have been experimentally measured in the context of the two-process model
James LM, Viola AU, Archer SN, Dijk D (2008) Topography of the effects of a PER3 polymorphism on alpha activity in REM sleep under baseline and recovery conditions, SLEEP 31 pp. A107-A107 AMER ACAD SLEEP MEDICINE
Cajochen C, Dijk DJ, Borbély AA (1992) Dynamics of EEG slow-wave activity and core body temperature in human sleep after exposure to bright light., Sleep 15 (4) pp. 337-343
In seven subjects sleep was recorded after a single 3-hour (2100-0000 hours) exposure to either bright light (BL, approx. 2,500 lux) or dim light (DL, approx. 6 lux) in a crossover design. The latency to sleep onset was increased after BL. Whereas rectal temperature before onset and during the first 4 hours of sleep was higher after BL than after DL, the time course of electroencephalographic (EEG) slow-wave activity (SWA, EEG power density in the range of 0.75-4.5 Hz) in nonrapid eye movement sleep (NREMS) differed only slightly between the conditions. After BL, SWA tended to be lower than after DL in the first NREMS-REMS cycle and was higher in the fourth cycle at the time when the rectal temperature did not differ. The differences in SWA may have been due to a minor sleep-disturbing aftereffect of BL, which was followed by a rebound. The data are not in support of a close relationship between SWA and core body temperature.
Cajochen C, Zeitzer JM, Czeisler CA, Dijk DJ (2000) Dose-response relationship for light intensity and ocular and electroencephalographic correlates of human alertness., Behav Brain Res 115 (1) pp. 75-83
Light can elicit both circadian and acute physiological responses in humans. In a dose response protocol men and women were exposed to illuminances ranging from 3 to 9100 lux for 6.5 h during the early biological night after they had been exposed to
Lazar AS, Lazar ZI, Dijk D-J (2015) Circadian regulation of slow waves in human sleep: Topographical aspects, NEUROIMAGE 116 pp. 123-134 ACADEMIC PRESS INC ELSEVIER SCIENCE
Viola AU, Archer SN, James LM, Groeger JA, Lo JCY, Skene DJ, von Schantz M, Dijk D-J (2007) PER3 polymorphism predicts sleep structure and waking performance, CURRENT BIOLOGY 17 (7) pp. 613-618 CELL PRESS
Dijk DJ, Brunner DP, Aeschbach D, Tobler I, Borbély AA (1992) The effects of ethanol on human sleep EEG power spectra differ from those of benzodiazepine receptor agonists., Neuropsychopharmacology 7 (3) pp. 225-232
A single dose of ethanol (0.60 g/kg of body weight) was administered to eight young healthy male subjects 35 minutes before bedtime. Compared to the average value of two baseline nights, subjective sleep and polysomnographically determined sleep parameters were not significantly affected. In the first 2 hours of sleep after ethanol intake, the combined value of wakefulness, stage 1, and movement time was reduced. In this interval, visually scored stage 4 sleep was increased, and electroencephalographic (EEG) power density in nonrapid-eye-movement (nonREM) sleep was enhanced in the lowest delta frequencies and reduced in the beta range. Computed for the entire sleep episode, power density in REM sleep was enhanced in some theta frequencies. In the sleep episode initiated 24 hours after ethanol intake, power density in nonREM and REM sleep was enhanced in delta and theta frequencies, and the subjectively perceived number of awakenings was reduced. The effects of ethanol on EEG power spectra during sleep differ from those published for benzodiazepine and nonbenzodiazepine hypnotics. This indicates that the effects of ethanol on the human sleep EEG are not mediated by the benzodiazepine receptor.
Wulff K, Joyce E, Middleton B, Foster R, Dijk D-J (2008) Circadian activity and sleep cycle disturbances in schizophrenia patients in comparison to unemployed healthy controls, INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY 11 pp. 150-150 CAMBRIDGE UNIV PRESS
Groeger JA, Lo JC, Santhi N, Arbon EL, Lazar A, Hasan S, Von Schantz M, Archer SN, Dijk DJ (2012) 'Trait-like' susceptibility to sleep loss varies with circadian phase and the task used to index vulnerable-resilient sleep-deprived performance, JOURNAL OF SLEEP RESEARCH 21 pp. 36-37 WILEY-BLACKWELL
Landolt HP, Moser S, Wieser HG, Borbély AA, Dijk DJ (1995) Intracranial temperature across 24-hour sleep-wake cycles in humans., Neuroreport 6 (6) pp. 913-917
The 24 h time course of intracranial temperature, recorded subdurally at the parahippocampal gyrus in six patients (19 24 h periods), exhibited a prominent 24 h rhythm with its crest located at 20-21 h. The declining trend of intracranial temperature between lights off and sleep onset persisted in the first nonREM sleep episode (studied in two patients, seven sleep episodes). The correlation between EEG slow-wave activity (SWA) in nonREM sleep and the change in temperature explained
Muto V, Meyer C, Jaspar M, Shaffii-Le Bourdiec A, Kusse C, Foret A, Vandewalle G, Collette F, Archer S, Dijk D-J, Maquet P (2012) Influence of sleep homeostasis and circadian rhythm on waking EEG oscillations during a constant routine, JOURNAL OF SLEEP RESEARCH 21 pp. 327-328 WILEY-BLACKWELL
Schwarz JF, Ingre M, Anund A, Fors C, Karlsson JG, Kecklund G, Van der Veen DR, Archer SN, Dijk D, Akerstedt T (2012) PERIOD3 VNTR POLYMORPHISM MODIFIES SLEEPINESS DURING REAL ROAD DRIVING, SLEEP 35 pp. A109-A109 AMER ACAD SLEEP MEDICINE
Phipps-Nelson J, Redman JR, Dijk DJ, Rajaratnam SM (2003) Daytime exposure to bright light, as compared to dim light, decreases sleepiness and improves psychomotor vigilance performance., Sleep 26 (6) pp. 695-700
STUDY OBJECTIVES: This study examined the effects of bright light exposure, as compared to dim light, on daytime subjective sleepiness, incidences of slow eye movements (SEMs), and psychomotor vigilance task (PVT) performance following 2 nights of sleep restriction. DESIGN: The study had a mixed factorial design with 2 independent variables: light condition (bright light, 1,000 lux; dim light,
Cropley M, Dijk D-J, Stanley N (2006) Job strain, work rumination, and sleep in school teachers, EUROPEAN JOURNAL OF WORK AND ORGANIZATIONAL PSYCHOLOGY 15 (2) pp. 181-196 PSYCHOLOGY PRESS
Herron K, Dijk D, Ellis J, Sanders J, Sterr AM (2008) Sleep actigraphy in brain injured patients with chronic low functioning upper limb hemiparesis, Journal of Sleep Research 17 pp. 102-102
Wyatt JK, Ritz-De Cecco A, Czeisler CA, Dijk DJ (1999) Circadian temperature and melatonin rhythms, sleep, and neurobehavioral function in humans living on a 20-h day., Am J Physiol 277 (4 Pt 2) pp. R1152-R1163
The interaction of homeostatic and circadian processes in the regulation of waking neurobehavioral functions and sleep was studied in six healthy young subjects. Subjects were scheduled to 15-24 repetitions of a 20-h rest/activity cycle, resulting in desynchrony between the sleep-wake cycle and the circadian rhythms of body temperature and melatonin. The circadian components of cognitive throughput, short-term memory, alertness, psychomotor vigilance, and sleep disruption were at peak levels near the temperature maximum, shortly before melatonin secretion onset. These measures exhibited their circadian nadir at or shortly after the temperature minimum, which in turn was shortly after the melatonin maximum. Neurobehavioral measures showed impairment toward the end of the 13-h 20-min scheduled wake episodes. This wake-dependent deterioration of neurobehavioral functions can be offset by the circadian drive for wakefulness, which peaks in the latter half of the habitual waking day during entrainment. The data demonstrate the exquisite sensitivity of many neurobehavioral functions to circadian phase and the accumulation of homeostatic drive for sleep.
Brunner DP, Dijk DJ, Borbély AA (1993) Repeated partial sleep deprivation progressively changes in EEG during sleep and wakefulness., Sleep 16 (2) pp. 100-113
The effect of repeated partial sleep deprivation on sleep stages and electroencephalogram (EEG) power spectra during sleep and wakefulness was investigated in nine healthy young subjects. Three baseline nights of 8 hours (2300-0700 hours) were followed by four nights with 4 hours of sleep (2300-0300 hours) and three recovery nights of 8 hours (2300-0700 hours). Sleep restriction curtailed sleep stages 1 and 2 as well as rapid eye movement (REM) sleep, but left slow wave sleep largely unaffected. In the first two recovery nights, total sleep time and REM sleep were enhanced, and sleep latency was shortened. Slow wave sleep was increased only in the first recovery night. In accordance with the prediction of the two-process model of sleep regulation, slow wave activity (SWA; spectral power density in the 0.75-4.5-Hz range) in nonrapid eye movement (NREM) sleep increased by approximately 20% in the first night following sleep restriction, remained at this level in the subsequent 3 nights and decreased immediately after the first recovery night. In contrast to these immediate changes, progressive and more persistent changes were seen in the EEG activity of higher frequencies. Thus, activity in the upper delta band tended to gradually increase from night to night during the sleep restriction period, whereas after an initial increase, activity in the theta-alpha band changed in the opposite direction. The progressive changes were also present in the EEG spectra of REM sleep and wakefulness. Because the time course of these changes paralleled the cumulative deficit in REM sleep, they may represent a correlate of REM sleep pressure.
Jones KHS, Ellis J, Von Schantz M, Skene DJ, Dijk D-J, Archer SN (2007) Age-related change in the association between a polymorphism in the PER3 gene and preferred timing of sleep and waking activities, JOURNAL OF SLEEP RESEARCH 16 (1) pp. 12-16 BLACKWELL PUBLISHING
Vandewalle G, Maquet P, Dijk D-J (2009) Light as a modulator of cognitive brain function, TRENDS IN COGNITIVE SCIENCES 13 (10) pp. 429-438 ELSEVIER SCIENCE LONDON
Muto V, Mascetti L, Matarazzo L, Kussé C, Foret A, Shaffii-Le Bourdiec A, Vandewalle G, Dijk DJ, Maquet P (2011) Reciprocal Interactions between Wakefulness and Sleep Influence Global and Regional Brain Activity., Curr Top Med Chem
Reciprocal interactions between wakefulness and sleep substantially influence human brain function in both states of vigilance. On the one hand, there is evidence that regionally-specialized brain activity during wakefulness is modulated by the interaction between a local use-dependent buildup of homeostatic sleep pressure and circadian signals. On the other hand, brain activity during sleep, although mainly constrained by genuine sleep oscillations, shows wake-dependent regionally-specific modulations, which are involved in the dissipation of local homeostatic sleep pressure and memory consolidation.
Vandewalle G, Balteau E, Phillips C, Degueldre C, Moreau V, Sterpenich V, Albouy G, Darsaud A, Desseilles M, Dang-Vu TT, Peigneux P, Luxen A, Dijk D-J, Maquet P (2006) Daytime light exposure dynamically enhances brain responses, CURRENT BIOLOGY 16 (16) pp. 1616-1621 CELL PRESS
Borsu C, Gaggioni G, Ly JQM, Papachilleos S, Brzozowski A, Rosanova M, Sarasso S, Archer SN, Dijk D-J, Phillips C, Maquet P, Massimini M, Chellappa SL, Vandewalle G (2014) Cortical excitability dynamics during extended wakefulness set PVT performance, JOURNAL OF SLEEP RESEARCH 23 pp. 176-176 WILEY-BLACKWELL
Thorne HC, Jones KH, Archer AN, Dijk D (2008) Spectral composition of daily light exposure in young adults in summer and winter, JOURNAL OF SLEEP RESEARCH 17 pp. 115-115 WILEY-BLACKWELL PUBLISHING, INC
Light is a powerful modulator of cognition through its long-term effects on circadian rhythmicity and direct effects on brain function as identified by neuroimaging. How the direct impact of light on brain function varies with wavelength of light, circadian phase, and sleep homeostasis, and how this differs between individuals, is a largely unexplored area. Using functional MRI, we compared the effects of 1 minute of low-intensity blue (473 nm) and green light (527 nm) exposures on brain responses to an auditory working memory task while varying circadian phase and status of the sleep homeostat. Data were collected in 27 subjects genotyped for the PER3 VNTR (12 PER3(5/5) and 15 PER3(4/4) ) in whom it was previously shown that the brain responses to this task, when conducted in darkness, depend on circadian phase, sleep homeostasis, and genotype. In the morning after sleep, blue light, relative to green light, increased brain responses primarily in the ventrolateral and dorsolateral prefrontal cortex and in the intraparietal sulcus, but only in PER3(4/4) individuals. By contrast, in the morning after sleep loss, blue light increased brain responses in a left thalamofrontoparietal circuit to a larger extent than green light, and only so in PER3(5/5) individuals. In the evening wake maintenance zone following a normal waking day, no differential effect of 1 minute of blue versus green light was observed in either genotype. Comparison of the current results with the findings observed in darkness indicates that light acts as an activating agent particularly under those circumstances in which and in those individuals in whom brain function is jeopardized by an adverse circadian phase and high homeostatic sleep pressure.
Klerman E, Wang W, Kronauer RE, Dijk D (2009) EFFECTS OF AGING AND SLEEP EXTENSION ON SLEEP MAINTENANCE QUANTIFIED USING SURVIVAL ANALYSES OF SLEEP AND WAKE BOUTS, SLEEP 32 pp. A115-A115 AMER ACAD SLEEP MEDICINE
Klerman EB, Dijk D (2012) ASSESSMENT OF THE ABILITY TO RECOVER SLEEP AFTER SLEEP DEPRIVATION IN A SLEEP SATIATION PROTOCOL, SLEEP 35 pp. A60-A61 AMER ACAD SLEEP MEDICINE
Klerman EB, Hughes RJ, Dijk DJ (2001) Sleep debt in healthy young individuals is inversely related to habitual sleep duration and associated with excessive daytime sleepiness, SLEEP 24 pp. A122-A122 AMER ACAD SLEEP MEDICINE
Dijk D-J (2013) Sensitive to sleep loss or not: Neurons, working memory, insomnia and the heart, Journal of Sleep Research 22 (3) pp. 237-238
AMPA receptor modulation is a potential novel approach to enhance cognitive performance. CX717 is a positive allosteric modulator of the AMPA receptor that has shown efficacy in rodent and primate cognition models. CX717 (100 mg, 300 mg and 1000 mg) and placebo were studied in 16 healthy male volunteers (18-45 years) in a randomized, crossover study. Cognitive function, arousal and recovery sleep (by polysomnography) were assessed during the extended wakefulness protocol. Placebo condition was associated with significant decrements in cognition, particularly at the circadian nadir (between 03:00 and 05:00). Pre-specified primary and secondary analyses (general linear mixed modelling, GLMM) at each separate time point did not reveal consistent improvements in performance or objective alertness with any dose of CX717. Exploratory repeated measures analysis, a method used to take into account the influence of individual differences, demonstrated an improvement in attention-based task performance following the 1000 mg dose. Analysis of the recovery sleep showed that CX717 1000 mg significantly reduced stage 4 and slow-wave sleep (p d 0.05) with evidence of reduced electroencephalogram (EEG) slow-wave and spindle activity. The study suggests that CX717 only at the 1000 mg dose may counteract effects of sleep deprivation on attention-based tasks and that it may interfere with subsequent recovery sleep.
Walsh J, Lundahl J, Dijk D, Deacon S (2006) Gaboxadol improves traditional hypnotic efficacy measures and enhances slow wave activity in a model of transient insomnia, JOURNAL OF SLEEP RESEARCH 15 pp. 195-196 BLACKWELL PUBLISHING
Dijk D, Stanley N, Groeger J, Deacon S (2006) Selective SWS/SWA deprivation is associated with increased daytime sleep propensity in young, middle-aged and older men and women, JOURNAL OF SLEEP RESEARCH 15 pp. 250-251 BLACKWELL PUBLISHING
Dijk DJ, von Schantz M (2005) Timing and consolidation of human sleep, wakefulness, and performance by a symphony of oscillators, JOURNAL OF BIOLOGICAL RHYTHMS 20 (4) pp. 279-290 SAGE PUBLICATIONS INC
Elliott AR, Shea SA, Dijk DJ, Wyatt JK, Riel E, Neri DF, Czeisler CA, West JB, Prisk GK (2001) Microgravity reduces sleep-disordered breathing in humans., Am J Respir Crit Care Med 164 (3) pp. 478-485
To understand the factors that alter sleep quality in space, we studied the effect of spaceflight on sleep-disordered breathing. We analyzed 77 8-h, full polysomnographic recordings (PSGs) from five healthy subjects before spaceflight, on four occasions per subject during either a 16- or 9-d space shuttle mission and shortly after return to earth. Microgravity was associated with a 55% reduction in the apnea-hypopnea index (AHI), which decreased from a preflight value of 8.3 +/- 1.6 to 3.4 +/- 0.8 events/h inflight. This reduction in AHI was accompanied by a virtual elimination of snoring, which fell from 16.5 +/- 3.0% of total sleep time preflight to 0.7 +/- 0.5% inflight. Electroencephalogram (EEG) arousals also decreased in microgravity (by 19%), and this decrease was almost entirely a consequence of the reduction in respiratory-related arousals, which fell from 5.5 +/- 1.2 arousals/h preflight to 1.8 +/- 0.6 inflight. Postflight there was a return to near or slightly above preflight levels in these variables. We conclude that sleep quality during spaceflight is not degraded by sleep-disordered breathing. This is the first direct demonstration that gravity plays a dominant role in the generation of apneas, hypopneas, and snoring in healthy subjects.
Ma J, Dijk DJ, Svetnik V, Tymofyeyev Y, Ray S, Walsh JK, Deacon S (2011) EEG power spectra response to a 4-h phase advance and gaboxadol treatment in 822 men and women., J Clin Sleep Med 7 (5) pp. 493-501A
To explore the effect of gaboxadol on NREM EEG in transient insomnia using power spectral analysis and evaluate the response between men and women.
Groeger J, Deacon S, Stanley N, Snyder E, Legters A, Dijk D (2007) Sizing the effect of selective SWS/SWA disruption on objective and subjective daytime sleep propensity, mood, executive function, sustained attention, working memory and overnight memory consolidation, SLEEP 30 pp. A134-A134 AMER ACADEMY SLEEP MEDICINE
Dijk DJ, Czeisler CA (1994) Paradoxical timing of the circadian rhythm of sleep propensity serves to consolidate sleep and wakefulness in humans., Neurosci Lett 166 (1) pp. 63-68
The contribution of the circadian pacemaker and the sleep homeostat to sleep tendency and consolidation was quantified by forced desynchrony of the sleep-wake cycle from the circadian pacemaker in eight men who lived in time-isolation for 33-36 days. Analysis of 175 polygraphically recorded sleep episodes revealed that the circadian pacemaker and the sleep homeostat contribute about equally to sleep consolidation, and that the phase relationship between these oscillatory processes during entrainment to the 24-h day is uniquely timed to facilitate the ability to maintain a consolidated bout of sleep at night and a consolidated bout of wakefulness throughout the day.
Bolhuis JJ, Fitzgerald RE, Dijk DJ, Koolhaas JM (1984) The corticomedial amygdala and learning in an agonistic situation in the rat., Physiol Behav 32 (4) pp. 575-579
Social agonistic behaviour of intact male rats is strongly reduced by the experience of defeat by a dominant male conspecific. Small electrolytic lesions in the corticomedial amygdala strongly affected this behavioural change due to defeat. No effects of the lesions were observed before and during the defeat. Some learning is still possible in corticomedial amygdala lesioned animals. A comparison of the effects of lesions made before the defeat with lesions made after the defeat revealed that the lesions primarily produce a retention deficit in social learning.
Dijk D-J (2011) Risk-taking and other effects of sleep loss on brain function and behaviour, JOURNAL OF SLEEP RESEARCH 20 (3) pp. 375-376 WILEY-BLACKWELL
Dijk D (2006) Individual differences in habitual sleep duration and circadian sleep regulation, JOURNAL OF SLEEP RESEARCH 15 pp. 22-22 BLACKWELL PUBLISHING
Groeger JA, Lo JC, Dijk D (2009) DIFFERENTIAL DISRUPTION OF EXECUTIVE FUNCTION, ON WAKING FROM MORNING AND AFTERNOON NAPS, IN SLEEP RESTRICTED SUBJECTS, SLEEP 32 pp. A405-A405 AMER ACAD SLEEP MEDICINE
Dijk DJ, Boulos Z, Eastman CI, Lewy AJ, Campbell SS, Terman M (1995) Light treatment for sleep disorders: consensus report. II. Basic properties of circadian physiology and sleep regulation., J Biol Rhythms 10 (2) pp. 113-125
The rationale for the treatment of sleep disorders by scheduled exposure to bright light in seasonal affective disorder, jet lag, shift work, delayed sleep phase syndrome, and the elderly is, in part, based on a conceptual framework developed by nonclinical circadian rhythm researchers working with humans and other species. Some of the behavioral and physiological data that contributed to these concepts are reviewed, and some pitfalls related to their application to bright light treatment of sleep disorders are discussed. In humans and other mammals the daily light-dark (LD) cycle is a major synchronizer responsible for entrainment of circadian rhythms to the 24-h day, and phase response curves (PRCs) to light have been obtained. In humans, phase delays can be induced by light exposure scheduled before the minimum of the endogenous circadian rhythm of core body temperature (CBT), whereas phase advances are induced when light exposure is scheduled after the minimum of CBT. Since in healthy young subjects the minimum of CBT is located approximately 1 to 2 h before the habitual time of awakening, the most sensitive phase of the PRC to light coincides with sleep, and the timing of the monophasic sleep-wake cycle itself is a major determinant of light input to the pacemaker. The effects of light are mediated by the retinohypothalamic tract, and excitatory amino acids play a key role in the transduction of light information to the suprachiasmatic nuclei. LD cycles have direct "masking" effects on many variables, including sleep, which complicates the assessment of endogenous circadian phase and the interpretation of the effects of light treatment on sleep disorders. In some rodents motor activity has been shown to affect circadian phase, but in humans the evidence for such a feedback of activity on the pacemaker is still preliminary. The endogenous circadian pacemaker is a major determinant of sleep propensity and sleep structure; these, however, are also strongly influenced by the prior history of sleep and wakefulness. In healthy young subjects, light exposure schedules that do not curtail sleep but induce moderate shifts of endogenous circadian phase have been shown to influence the timing of sleep and wakefulness without markedly affecting sleep structure.
Warman VL, Dijk DJ, Warman GR, Arendt J, Skene DJ (2003) Phase advancing human circadian rhythms with short wavelength light, NEUROSCIENCE LETTERS 342 (1-2) pp. 37-40 ELSEVIER SCI IRELAND LTD
Kelly TL, Neri DF, Grill JT, Ryman D, Hunt PD, Dijk DJ, Shanahan TL, Czeisler CA (1999) Nonentrained circadian rhythms of melatonin in submariners scheduled to an 18-hour day., J Biol Rhythms 14 (3) pp. 190-196
The human circadian timing system has previously been shown to free run with a period slightly longer than 24 h in subjects living in the laboratory under conditions of forced desynchrony. In forced desynchrony, subjects are shielded from bright light and periodic time cues and are required to live on a day length outside the range of circadian entrainment. The work schedule used for most personnel aboard American submarines is 6 h on duty alternating with 12 h off duty. This imposed 18-h cycle is too short for human circadian synchronization, especially given that there is no bright-light exposure aboard submarines. However, crew members are exposed to 24-h stimuli that could mediate synchronization, such as clocks and social contacts with personnel who are living on a 24-h schedule. The authors investigated circadian rhythms of salivary melatonin in 20 crew members during a prolonged voyage on a Trident nuclear submarine. The authors found that in crew members living on the 18-h duty cycle, the endogenous rhythm of melatonin showed an average period of 24.35 h (n = 12, SD = 0.18 h). These data indicate that social contacts and knowledge of clock time are insufficient for entrainment to a 24-h period in personnel living by an 18-h rest-activity cycle aboard a submarine.
Landolt HP, Dijk DJ (2010) Genetic Basis of Sleep in Healthy Humans, pp. 175-183
Dijk DJ (2000) Age, rhythm and bedroom lamps, RECHERCHE pp. 44-45 SOC ED SCIENTIFIQUES
Vandewalle G, Middleton B, Rajaratnam SMW, Stone BM, Thorleifsdottir B, Arendt J, Dijk D-J (2007) Robust circadian rhythm in heart rate and its variability: influence of exogenous melatonin and photoperiod, JOURNAL OF SLEEP RESEARCH 16 (2) pp. 148-155 BLACKWELL PUBLISHING
Wyatt JK, Cajochen C, Ritz-De Cecco A, Czeisler CA, Dijk DJ (2004) Low-dose repeated caffeine administration for circadian-phase-dependent performance degradation during extended wakefulness, SLEEP 27 (3) pp. 374-381 AMER ACADEMY SLEEP MEDICINE
Dijk DJ (2013) Adolescents' sleep rhythms, stress and sleepiness: be it residual or not., J Sleep Res 22 (4) pp. 363-364
Bliwise DL, Dijk DJ, Juul KV (2015) Nocturia is associated with loss of deep sleep independently from sleep apnea., Neurourol Urodyn 34 (4)
Lo JC, Dijk D, Groeger JA (2009) THE EFFECTS OF AN IMMEDIATE NAP VERSUS A DELAYED NAP ON DECLARATIVE MEMORY CONSOLIDATION, SLEEP 32 pp. A409-A409 AMER ACAD SLEEP MEDICINE
Driver HS, Werth E, Dijk DJ, Borbély AA (2008) The Menstrual Cycle Effects on Sleep, Sleep Medicine Clinics 3 (1) pp. 1-11
Women with ovulatory cycles have a biphasic change in body temperature, reduced subjective sleep quality premenstrually and at menstruation, while sleep homeostatic mechanisms, as reflected by slow wave sleep (SWS), are unaltered. The mid-luteal phase increase in body temperature is associated with more stage 2 sleep, higher spindle frequency activity, reduced REM sleep, and elevated heart rates during sleep when compared to the mid-follicular phase. Based on a few studies the effects of oral contraceptives (OC) appear small: women taking OCs have more stage 2 compared to naturally cycling women but less SWS than naturally cycling women in the luteal phase. © 2008 Elsevier Inc. All rights reserved.
Arbon EL, Knurowska M, Dijk DJ (2015) Randomised clinical trial of the effects of prolonged-release melatonin, temazepam and zolpidem on slow-wave activity during sleep in healthy people., J Psychopharmacol 29 (7) pp. 764-776
Current pharmacological treatments for insomnia include benzodiazepine and non-benzodiazepine hypnotics targeting ³-aminobutyric acid (GABA)A receptors, as well as agonists of the melatonin receptors MT1 and MT2. Melatonin, temazepam and zolpidem are thought to exert their effect through different mechanisms of action, but whether this leads to differential effects on electroencephalogram (EEG) power spectra during sleep in middle-aged people is currently not known. To establish whether the effects of prolonged-release melatonin (2 mg) on the nocturnal sleep EEG are different to those of temazepam (20 mg) and zolpidem (10 mg). Sixteen healthy men and women aged 55-64 years participated in a double-blind, placebo-controlled, four-way cross-over trial. Nocturnal sleep was assessed with polysomnography and spectral analysis of the EEG. The effects of single oral doses of prolonged-release melatonin, temazepam and zolpidem on EEG slow-wave activity (SWA, 0.75-4.5 Hz) and other frequencies during nocturnal non-rapid eye movement (NREM) sleep were compared. In an entire night analysis prolonged-release melatonin did not affect SWA, whereas temazepam and zolpidem significantly reduced SWA compared with placebo. Temazepam significantly reduced SWA compared with prolonged-release melatonin. Prolonged-release melatonin only reduced SWA during the first third of the night compared with placebo. These data show that the effects of prolonged-release melatonin on the nocturnal sleep EEG are minor and are different from those of temazepam and zolpidem; this is likely due to the different mechanisms of action of the medications.
Dijk DJ, Stanley N, Lundahl J, Groeger JA, Legters A, Trap Huusom AK, Deacon S (2011) Enhanced slow wave sleep and improved sleep maintenance after gaboxadol administration during seven nights of exposure to a traffic noise model of transient insomnia., J Psychopharmacol
Slow wave sleep (SWS) has been reported to correlate with sleep maintenance, but whether pharmacological enhancement of SWS also leads to improved sleep maintenance is not known. Here we evaluate the time-course of the effects of gaboxadol, an extra-synaptic gamma-aminobutyric acid (GABA) agonist, on SWS, sleep maintenance, and other sleep measures in a traffic noise model of transient insomnia. After a placebo run-in, 101 healthy subjects (20-78 y) were randomized to gaboxadol (n = 50; 15 mg in subjects
Krystal A, Walsh J, Cooper J, Schaefer K, Dijk D (2008) Efficacy of eszopiclone relative to zolpidem in patients with primary insomnia: a responder analysis of objective sleep outcomes, JOURNAL OF SLEEP RESEARCH 17 pp. 210-210 WILEY-BLACKWELL PUBLISHING, INC
Bettica P, Squassante L, Groeger JA, Gennery B, Winsky-Sommerer R, Dijk DJ (2012) Differential effects of a dual orexin receptor antagonist (SB-649868) and zolpidem on sleep initiation and consolidation, SWS, REM sleep, and EEG power spectra in a model of situational insomnia, Neuropsychopharmacology 37 (5) pp. 1224-1233
Orexins have a role in sleep regulation, and orexin receptor antagonists are under development for the treatment of insomnia. We conducted a randomised, double-blind, placebo-controlled, four-period crossover study to investigate the effect of single doses of the dual orexin receptor antagonist SB-649868 (10 or 30 mg) and a positive control zolpidem (10 mg), an allosteric modulator of GABA A receptors. Objective and subjective sleep parameters and next-day performance were assessed in 51 healthy male volunteers in a traffic noise model of situational insomnia. Compared with placebo, SB-649868 10 and 30 mg increased total sleep time (TST) by 17 and 31 min (p
Hasan S, van der Veen DR, Winsky-Sommerer R, Dijk DJ, Archer SN (2011) Altered sleep and behavioral activity phenotypes in PER3-deficient mice., Am J Physiol Regul Integr Comp Physiol
Sleep homeostasis and circadian rhythmicity interact to determine the timing of behavioral activity. Circadian clock genes contribute to circadian rhythmicity centrally and in the periphery, but some also have roles within sleep regulation. The clock gene Period3 (Per3) has a redundant function within the circadian system and is associated with sleep homeostasis in humans. This study investigated the role of PER3 in sleep/wake activity and sleep homeostasis in mice by recording wheel running activity under baseline conditions in wild-type (WT; n = 54) and in PER3-deficient (Per3(-/-); n = 53) mice, as well as EEG-assessed sleep before and after 6 hours of sleep deprivation in WT (n = 7) and Per3(-/-) (n = 8) mice. Whereas total activity and vigilance states did not differ between the genotypes, the temporal distribution of wheel running activity, vigilance states, and EEG delta activity was affected by genotype. In Per3(-/-) mice, running wheel activity was increased and REM sleep and NREM sleep were reduced in the middle of the dark phase, and delta activity was enhanced at the end of the dark phase. At the beginning of the baseline light period, there was less wakefulness and more REM and NREM in Per3(-/-) mice. Per3(-/-) mice spent less time in wakefulness and more time in NREM sleep in the light period immediately after sleep deprivation and REM sleep accumulated more slowly during the recovery dark phase. These data confirm a role for PER3 in sleep/wake timing and sleep homeostasis.
Laing EE, Johnston JD, Moller-Levet CS, Bucca G, Smith CP, Dijk DJ, Archer SN (2015) Exploiting human and mouse transcriptomic data: identification of circadian genes and pathways influencing health, BioEssays 36 10.1002/bies.201400193
Boivin DB, Czeisler CA, Dijk DJ, Duffy JF, Folkard S, Minors DS, Totterdell P, Waterhouse JM (1997) Complex interaction of the sleep-wake cycle and circadian phase modulates mood in healthy subjects., Arch Gen Psychiatry 54 (2) pp. 145-152
BACKGROUND: Several studies of healthy volunteers have revealed that subjective mood may vary with the duration of prior wakefulness and with the time of day. However, in these studies, the effects of extended wakefulness and circadian phase remained confounded, and the interaction of these 2 processes could not be assessed quantitatively. METHODS: In the present study, a total of 24 healthy young subjects (16 men, 8 women) lived on a 30-hour sleep-wake schedule for 19 to 23 days or on a 28-hour sleep-wake schedule for 33 to 36 days; both schedules induced desynchrony between the subjects' sleep-wake cycle and their endogenous circadian pacemaker. Subjective mood was assessed by 2 types of visual analog scales, which were administered twice every 2 hours and every 20 minutes, respectively, during all scheduled wakefulness episodes. A circadian phase and an interval elapsed since awakening were attributed to each data point, and circadian and wake-dependent fluctuations of mood were assessed. RESULTS: A significant variation of mood with circadian phase was observed, but no reliable main effect of the duration of prior wakefulness was found. A statistically significant interaction of circadian and wake-dependent fluctuations was evident; when the analysis was restricted to specific circadian phases, mood improved, deteriorated, or remained stable with the duration of prior wakefulness. CONCLUSIONS: These results indicate that, in healthy young subjects, subjective mood is influenced by a complex and nonadditive interaction of circadian phase and duration of prior wakefulness. The nature of this interaction is such that moderate changes in the timing of the sleep-wake cycle may have profound effects on subsequent mood.
Vandewalle G, Schmidt C, Albouy G, Sterpenich V, Darsaud A, Rauchs G, Berken P-Y, Balteau E, Degueldre C, Luxen A, Maquet P, Dijk D-J (2007) Brain Responses to Violet, Blue, and Green Monochromatic Light Exposures in Humans: Prominent Role of Blue Light and the Brainstem, PLOS ONE 2 (11) ARTN e1247
PUBLIC LIBRARY SCIENCE
Cajochen C, Wyatt JK, Czeisler CA, Dijk DJ (2002) Separation of circadian and wake duration-dependent modulation of EEG activation during wakefulness., Neuroscience 114 (4) pp. 1047-1060
The separate contribution of circadian rhythmicity and elapsed time awake on electroencephalographic (EEG) activity during wakefulness was assessed. Seven men lived in an environmental scheduling facility for 4 weeks and completed fourteen 42.85-h 'days', each consisting of an extended (28.57-h) wake episode and a 14.28-h sleep opportunity. The circadian rhythm of plasma melatonin desynchronized from the 42.85-h day. This allowed quantification of the separate contribution of circadian phase and elapsed time awake to variation in EEG power spectra (1-32 Hz). EEG activity during standardized behavioral conditions was markedly affected by both circadian phase and elapsed time awake in an EEG frequency- and derivation-specific manner. The nadir of the circadian rhythm in alpha (8-12 Hz) activity in both fronto-central and occipito-parietal derivations occurred during the biological night, close to the crest of the melatonin rhythm. The nadir of the circadian rhythm of theta (4.5-8 Hz) and beta (20-32 Hz) activity in the fronto-central derivation was located close to the onset of melatonin secretion, i.e. during the wake maintenance zone. As time awake progressed, delta frequency (1-4.5 Hz) and beta (20-32 Hz) activity rose monotonically in frontal derivations. The interaction between the circadian and wake-dependent increase in frontal delta was such that the intrusion of delta was minimal when sustained wakefulness coincided with the biological day, but pronounced during the biological night. Our data imply that the circadian pacemaker facilitates frontal EEG activation during the wake maintenance zone, by generating an arousal signal that prevents the intrusion of low-frequency EEG components, the propensity for which increases progressively during wakefulness.
James LM, Dijk D, Boyle J, Calder N, Iannone R, Palcza J, Renger J (2008) Effects of a single dose of modafinil on EEG during the MWT during acute sleep deprivation, JOURNAL OF SLEEP RESEARCH 17 pp. 206-206 WILEY-BLACKWELL PUBLISHING, INC
Klein T, Martens H, Dijk DJ, Kronauer RE, Seely EW, Czeisler CA (1993) Circadian sleep regulation in the absence of light perception: chronic non-24-hour circadian rhythm sleep disorder in a blind man with a regular 24-hour sleep-wake schedule., Sleep 16 (4) pp. 333-343
Sleep disturbances and the failure to entrain circadian rhythms to the 24-hour day have been reported in the majority of totally blind subjects. The present case study of a totally blind man with a well-documented recurring sleep disturbance was designed to investigate the mutual relationship between sleep and the circadian timing system. The 63-year-old subject, a high school teacher with a regular work schedule, had suffered from cyclically recurring insomnia for the past 28 years. Analysis of a sleep log that he had kept for the past 15 years suggested that his circadian rhythms were not entrained to the 24-hour day. During a 3-month inpatient study, the period of the endogenous circadian pacemaker was assessed by analysis of ambulatory core body temperature, urinary excretion and a series of estimates of the phase of core body temperature cycles and plasma cortisol levels during constant routines. All circadian markers revealed periods in the range of 24.22-24.27 hours, with no evidence for a modulation of the observed periods by the sleep-wake cycle. During this 3-month inpatient study, a complete cycle of the subject's sleep disturbance and remission was polysomnographically documented while the subject lived on a regular 24-hour schedule. Because the subject's circadian rhythms were free-running and his sleep times were fixed, sleep occurred at virtually all circadian phases. Analysis of sleep latency, REM sleep latency, sleep duration, wake in sleep episode and REM sleep during sleep episode revealed a strong modulation by circadian phase. These findings in this blind man suggest that: 1) the period of his cyclically recurring sleep disturbance is directly related to the nonentrained period of an endogenous circadian pacemaker that drives circadian variation in core body temperature, urinary excretion, plasma cortisol and sleep propensity; 2) both his sleep structure and the severity of his daily sleep disruption are directly related to circadian phase and 3) his circadian pacemaker, which has an endogenous period that deviates only 0.2-0.3 hours from 24 hours, cannot be entrained by periodic daily exposure to nonphotic time cues, including a very regular 24-hour sleep-wake schedule.
Vassalli A, Dijk D-J (2009) Sleep function: current questions and new approaches, EUROPEAN JOURNAL OF NEUROSCIENCE 29 (9) pp. 1830-1841 WILEY-BLACKWELL PUBLISHING, INC
Dijk DJ, Brunner DP, Beersma DG, Borbély AA (1990) Electroencephalogram power density and slow wave sleep as a function of prior waking and circadian phase., Sleep 13 (5) pp. 430-440
Human sleep electroencephalograms, recorded in four experiments, were subjected to spectral analysis. Waking prior to sleep varied from 12 to 36 h and sleep was initiated at different circadian phases. Power density of delta and theta frequencies in rapid-eye-movement (REM) sleep and non-REM (NREM) sleep increased monotonically as a function of prior waking. The increase of power density in the theta frequencies contrasts with the reported decrease of theta activity as detected by period-amplitude analysis. Slow wave activity (power density, 0.25-4.0 Hz) in NREM sleep during the first 3 h of sleep did not deviate significantly from the homeostatic process S of the two-process model of sleep regulation. In contrast, visually scored slow wave sleep, stages 3 and 4, deviated from this prediction at some circadian phases. It is concluded that, in accordance with the two-process model of sleep regulation, slow wave activity in NREM sleep depends on prior waking and is not significantly influenced by circadian phase.
Dijk DJ (2009) Regulation and functional correlates of slow wave sleep., J Clin Sleep Med 5 (2 Suppl) pp. S6-15
Franken P, Dijk D-J (2009) Circadian clock genes and sleep homeostasis, EUROPEAN JOURNAL OF NEUROSCIENCE 29 (9) pp. 1820-1829 WILEY-BLACKWELL PUBLISHING, INC
In humans, sleep and wakefulness and the associated cognitive processes are regulated through interactions between sleep homeostasis and the circadian system. Chronic disruption of sleep and circadian rhythmicity is common in our society and there is a need for a better understanding of the brain mechanisms regulating sleep, wakefulness and associated cognitive processes. This review summarizes recent investigations which provide first neural correlates of the combined influence of sleep homeostasis and circadian rhythmicity on cognitive brain activity. Markers of interindividual variations in sleep-wake regulation, such as chronotype and polymorphisms in sleep and clock genes, are associated with changes in cognitive brain responses in subcortical and cortical areas in response to manipulations of the sleep-wake cycle. This review also includes recent data showing that cognitive brain activity is regulated by light, which is a powerful modulator of cognition and alertness and also directly impacts sleep and circadian rhythmicity. The effect of light varied with age, psychiatric status, PERIOD3 genotype and changes in sleep homeostasis and circadian phase. These data provide new insights into the contribution of demographic characteristics, the sleep-wake cycle, circadian rhythmicity and light to brain functioning.
Dijk DJ, Cajochen C, Tobler I, Borbély AA (1991) Sleep extension in humans: sleep stages, EEG power spectra and body temperature., Sleep 14 (4) pp. 294-306
In eight male subjects the electroencephalogram (EEG) and core body temperature (Tcore) were recorded during long sleep episodes from 0000 to 1,500 hr. EEGs were visually scored and subjected to spectral analysis by fast Fourier transform. Slow-wave sleep [SWS, i.e. stages 3 + 4 of non-rapid eye movement (NREM) sleep and slow wave activity (SWA, mean EEG power density in the range of 0.75-4.5 Hz)] in NREM sleep attained highest values in the first 3 hr of sleep and lowest values in the morning hours when rapid eye movement (REM) sleep was at its maximum. Wakefulness was significantly enhanced in the last 3 hr of the recording period. Occasional NREM episodes containing SWS were observed in the late morning and early afternoon. However, no significant increase in SWS or SWA in the last 3 hr of the sleep episode over any of the preceding 3-hr intervals was present and SWA in this interval was significantly below the values observed at the beginning of sleep. The duration of NREM episodes varied significantly over the sleep episode. Analysis of the dynamics of SWA within NREM episodes revealed that SWA gradually rose during the episode. Consequently, SWA averaged per episode was positively correlated with episode duration. Tcore dropped in the initial part of sleep, rose during the morning hours and reached values in the afternoon that were higher than at the beginning of sleep. Thus the time course of Tcore dissociated from the time course of SWA. This indicates that SWA in NREM sleep is not directly related to the variation in core body temperature.
Wulff K, Joyce E, Middleton B, Dijk DJ, Foster RG (2006) The suitability of actigraphy, diary data, and urinary melatonin profiles for quantitative assessment of sleep disturbances in schizophrenia: A case report, CHRONOBIOLOGY INTERNATIONAL 23 (1-2) pp. 485-495 TAYLOR & FRANCIS INC
Eastman CI, Boulos Z, Terman M, Campbell SS, Dijk DJ, Lewy AJ (1995) Light treatment for sleep disorders: consensus report. VI. Shift work., J Biol Rhythms 10 (2) pp. 157-164
The unhealthy symptoms and many deleterious consequences of shift work can be explained by a mismatch between the work-sleep schedule and the internal circadian rhythms. This mismatch occurs because the 24-h zeitgebers, such as the natural light-dark cycle, keep the circadian rhythms from phase shifting to align with the night-work, day-sleep schedule. This is a review of studies in which the sleep schedule is shifted several hours, as in shift work, and bright light is used to try to phase shift circadian rhythms. Phase shifts can be produced in laboratory studies, when subjects are kept indoors, and faster phase shifting occurs with appropriately timed bright light than with ordinary indoor (dim) light. Bright light field studies, in which subjects live at home, show that the use of artificial nocturnal bright light combined with enforced daytime dark (sleep) periods can phase shift circadian rhythms despite exposure to the conflicting 24-h zeitgebers. So far, the only studies on the use of bright light for real shift workers have been conducted at National Aeronautics and Space Administration (NASA). In general, the bright light studies support the idea that the control of light and dark can be used to overcome many of the problems of shift work. However, despite ongoing practical applications (such as at NASA), much basic research is still needed.
Chellappa SL, Ly JQM, Gaggioni G, Papachilleos S, Borsu C, Brzozowski A, Archer SN, Rosanova M, Sarasso S, Dijk D-J, Maquet P, Massimini M, Phillips C, Moran RJ, Vandewalle G (2014) Dynamics of human cortical ensembles are set by circadian system and sleep homeostasis, JOURNAL OF SLEEP RESEARCH 23 pp. 79-79 WILEY-BLACKWELL
VANOORTMERSSEN GA, BENUS I, DIJK DJ (1985) STUDIES IN WILD HOUSE MICE - GENOTYPE-ENVIRONMENT INTERACTIONS FOR ATTACK LATENCY, NETHERLANDS JOURNAL OF ZOOLOGY 35 (1-2) pp. 155-169 E J BRILL
D'Rozario AL, Kim JW, Wong KKH, Bartlett DJ, Marshall NS, Dijk DJ, Robinson PA, Grunstein RR (2013) A new EEG biomarker of neurobehavioural impairment and sleepiness in sleep apnea patients and controls during extended wakefulness, Clinical Neurophysiology 124 (8) pp. 1605-1614
Objective: To explore the use of detrended fluctuation analysis (DFA) scaling exponent of the awake electroencephalogram (EEG) as a new alternative biomarker of neurobehavioural impairment and sleepiness in obstructive sleep apnea (OSA). Methods: Eight patients with moderate-severe OSA and nine non-OSA controls underwent a 40-h extended wakefulness challenge with resting awake EEG, neurobehavioural performance (driving simulator and psychomotor vigilance task) and subjective sleepiness recorded every 2-h. The DFA scaling exponent and power spectra of the EEG were calculated at each time point and their correlation with sleepiness and performance were quantified. Results: DFA scaling exponent and power spectra biomarkers significantly correlated with simultaneously tested performance and self-rated sleepiness across the testing period in OSA patients and controls. Baseline (8am) DFA scaling exponent but not power spectra were markers of impaired simulated driving after 24-h extended wakefulness in OSA (. r=. 0.738, p=. 0.037). OSA patients had a higher scaling exponent and delta power during wakefulness than controls. Conclusions: The DFA scaling exponent of the awake EEG performed as well as conventional power spectra as a marker of impaired performance and sleepiness resulting from sleep loss. Significance: DFA may potentially identify patients at risk of neurobehavioural impairment and assess treatment effectiveness. © 2013 International Federation of Clinical Neurophysiology.
D'Rozario AL, Kim JW, Wong KK, Bartlett DJ, Marshall NS, Dijk DJ, Robinson PA, Grunstein RR (2013) A new EEG biomarker of neurobehavioural impairment and sleepiness in sleep apnea patients and controls during extended wakefulness., Clin Neurophysiol
OBJECTIVE: To explore the use of detrended fluctuation analysis (DFA) scaling exponent of the awake electroencephalogram (EEG) as a new alternative biomarker of neurobehavioural impairment and sleepiness in obstructive sleep apnea (OSA). METHODS: Eight patients with moderate-severe OSA and nine non-OSA controls underwent a 40-h extended wakefulness challenge with resting awake EEG, neurobehavioural performance (driving simulator and psychomotor vigilance task) and subjective sleepiness recorded every 2-h. The DFA scaling exponent and power spectra of the EEG were calculated at each time point and their correlation with sleepiness and performance were quantified. RESULTS: DFA scaling exponent and power spectra biomarkers significantly correlated with simultaneously tested performance and self-rated sleepiness across the testing period in OSA patients and controls. Baseline (8am) DFA scaling exponent but not power spectra were markers of impaired simulated driving after 24-h extended wakefulness in OSA (r=0.738, p=0.037). OSA patients had a higher scaling exponent and delta power during wakefulness than controls. CONCLUSIONS: The DFA scaling exponent of the awake EEG performed as well as conventional power spectra as a marker of impaired performance and sleepiness resulting from sleep loss. SIGNIFICANCE: DFA may potentially identify patients at risk of neurobehavioural impairment and assess treatment effectiveness.
Vandewalle G, Gais S, Schabus M, Balteau E, Carrier J, Darsaud A, Sterpenich V, Albouy G, Dijk DJ, Maquet P (2007) Wavelength-dependent modulation of brain responses to a working memory task by daytime light exposure, CEREBRAL CORTEX 17 (12) pp. 2788-2795 OXFORD UNIV PRESS INC
Dijk D-J (2013) Sleep credit and debit: Grey matter and emotional intelligence in the balance?, Journal of Sleep Research 22 (5) pp. 480-481
Campbell SS, Eastman CI, Terman M, Lewy AJ, Boulos Z, Dijk DJ (1995) Light treatment for sleep disorders: consensus report. I. Chronology of seminal studies in humans., J Biol Rhythms 10 (2) pp. 105-109
Examination of the influence of the light-dark cycle on circadian rhythmicity has been a fundamental aspect of chronobiology since its inception as a scientific discipline. Beginning with Bünning's hypothetical phase response curve in 1936, the impact of timed light exposure on circadian rhythms of literally hundreds of species has been described. The view that the light-dark cycle was an important zeitgeber for the human circadian system, as well, seemed to be supported by early studies of blind and sighted subjects. Yet, by the early 1970s, based primarily on a series of studies conducted at Erling-Andechs, Germany, the notion became widely accepted that the light-dark cycle had only a weak influence on the human circadian system and that social cues played a more important role in entrainment. In 1980, investigators at the National Institute of Mental Health reported that bright light could suppress melatonin production in humans, thereby demonstrating unequivocally the powerful effects of light on the human central nervous system. This finding led directly to the use of timed bright light exposure as a tool for the study and treatment of human circadian rhythms disorders.
Wang D, Yee BJ, Wong KK, Kim JW, Dijk DJ, Duffin J, Grunstein RR (2015) Comparing the effect of hypercapnia and hypoxia on the electroencephalogram during wakefulness, Clinical Neurophysiology 126 (1) pp. 103-109
© 2014 International Federation of Clinical Neurophysiology.Objective: Hypoxia has been postulated as a key mechanism for neurocognitive impairment in sleep-disordered breathing. However, the effect of hypoxia on the electroencephalogram (EEG) is not clear. Methods: We examined quantitative EEG recordings from 20 normal volunteers under three 5-min ventilatory control protocols: progressive hypercapnia with iso-hyperoxia (pO2=150mmHg) (Protocol 1), progressive hypercapnia with iso-hypoxia (pO2=50mmHg) (Protocol 2), and progressive hypoxia with a CO2 scrubber in the circuit (Protocol 3). Each protocol started with a 5-min session of breathing room air as baseline. Results: In Protocol 1, compared to its baseline, iso-hyperoxia hypercapnia led to a lower Alpha% and higher Delta/Alpha (D/A) ratio. Similarly, in Protocol 2, the iso-hypoxia hypercapnia induced a higher Delta%, a lower Alpha% and higher D/A ratio. No difference was found in any EEG spectral band including the D/A ratio when Protocols 1 & 2 were compared. In Protocol 3, the Delta%, Alpha% and D/A ratio recorded during hypoxia were not significantly different from baseline. Conclusions: We found that hypercapnia, but not hypoxia, may play a key role in slowing of the EEG in healthy humans. Significance: Hypercapnia may be a greater influence than hypoxia on brain neuroelectrical activities.
Klerman EB, Rimmer DW, Dijk DJ, Kronauer RE, Rizzo JF, Czeisler CA (1998) Erratum: Nonphotic entrainment of the human circadian pacemaker (American Journal of Physiology - Regulatory and Integrative Physiology (April 1998) 274:43 (R991-R996)), American Journal of Physiology - Regulatory Integrative and Comparative Physiology 275 (2 44-2)
Dijk DJ (1996) Internal rhythms in humans, SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY 7 (6) pp. 831-836 ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
Background and purpose: In work with chronic stroke patients the authors observed that patients frequently appear sleepy and often comment on their poor sleep. Sleep difficulties are frequently reported and indeed clinically recognized in the acute phase post-stroke, but little is known about the sleep and daytime sleepiness of chronic stroke patients with sustained disabilities. The latter, however, deserves clarification because sleep is a critical modulator of health, daytime performance and wellbeing. The present study therefore explored the sleep and sleepiness in a chronic stroke population with sustained physical deficits. Methods: An opportunity sample of 20 patients with chronic low-functioning hemiplegia (12 months) completed the Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index, Medical Outcome Study Short Form 36 and Hospital Anxiety and Depression Scale. Results: Compared to a normative healthy population, long-term stroke survivors reported poorer sleep and greater daytime sleepiness. Increased levels of sleepiness were associated with longer chronicity, whereas nocturnal sleep parameters were not. Conclusions: In line with clinical observations, stroke survivors with sustained physical disabilities report poorer sleep and experience greater levels of sleepiness. Further research in a larger cohort and including objective sleep measures is necessary to investigate the nature and scale of sleep difficulties and daytime sleepiness in more detail so that care and treatment strategies can be developed in due course.
Ly J, Gaggioni G, Chellappa S, Papachilleos S, Brzozowski A, Borsu C, Rosanova M, Sarasso S, Middleton BA, Luxen A, Archer S, Phillips C, Dijk D, Maquet P, Massimini M, Vandewalle G (2016) Circadian regulation of human cortical excitability, Nature Communications 11828
Nature Publishing Group
Prolonged wakefulness alters cortical excitability, which is essential for proper brain function and cognition. However, besides prior wakefulness, brain function and cognition are also affected by circadian rhythmicity. Whether the regulation of cognition involves a circadian impact on cortical excitability is unknown. Here, we assessed cortical excitability from scalp EEG-responses to transcranial magnetic stimulation in 22 participants during 29-h of wakefulness under constant conditions. Data reveal robust circadian dynamics of cortical excitability that were strongest in those individuals with highest endocrine markers of circadian amplitude. In addition, the time course of cortical excitability correlated with changes in EEG synchronization and cognitive performance. These results demonstrate that the crucial factor for cortical excitability, and basic brain function in general, is the balance between circadian rhythmicity and sleep need, rather than sleep homeostasis alone. These findings have implications for clinical applications such as noninvasive brain stimulation in neurorehabilitation.
Objectives: Evidence for a causal relationship between sleep-loss and metabolism is derived primarily from short-term sleep deprivation studies in the laboratory. The objective of this study was to investigate whether small changes in sleep duration over a three week period while participants are living in their normal environment lead to changes in insulin sensitivity and other metabolic parameters. Methods: Nineteen healthy, young, normal-weight men were randomised to either sleep restriction (habitual bedtime minus 1.5 h) or a control condition (habitual bedtime) for three weeks. Weekly assessments of insulin sensitivity by hyperinsulinaemic-euglycaemic clamp, anthropometry, vascular function, leptin and adiponectin were made. Sleep was assessed continuously using actigraphy and diaries. Results: Assessment of sleep by actigraphy confirmed that the intervention reduced daily sleep duration by 01:19 ± 00:15 (SE; p
The power of the application of bioinformatics across multiple publicly available transcriptomic data sets was explored. Using 19 human and mouse circadian transcriptomic data sets, we found that NR1D1 and NR1D2 which encode heme-responsive nuclear receptors are the most rhythmic transcripts across sleep conditions and tissues suggesting that they are at the core of circadian rhythm generation. Analyzes of human transcriptomic data show that a core set of transcripts related to processes including immune function, glucocorticoid signalling, and lipid metabolism is rhythmically expressed independently of the sleep-wake cycle. We also identify key transcripts associated with transcription and translation that are disrupted by sleep manipulations, and through network analysis identify putative mechanisms underlying the adverse health outcomes associated with sleep disruption, such as diabetes and cancer. Comparative bioinformatics applied to existing and future data sets will be a powerful tool for the identification of core circadian- and sleep-dependent molecules.
Diagnosis and treatment of circadian rhythm sleep-wake disorders requires assessment of circadian phase of the brain?s circadian pacemaker. The gold-standard univariate method is based on collection of a 24 h time series of plasma melatonin, a suprachiasmatic nucleus driven pineal hormone. We developed and validated a multivariate whole-blood mRNA based predictor of melatonin phase which requires few samples. Transcriptome data were collected under normal, sleep-deprivation and abnormal sleep-timing conditions to assess robustness of the predictor. Partial least square regression (PLSR), applied to the transcriptome, identified a set of 100 biomarkers primarily related to glucocorticoid signaling and immune function. Validation showed that PLSR-based predictors outperform published blood-derived circadian phase predictors. When given one sample as input, the R2 of predicted vs observed phase was 0.74, whereas for two samples taken 12 h apart, R2 was 0.90. This blood transcriptome based model enables assessment of circadian phase from a few samples.
Why do we go to sleep late and struggle to wake up on time? Historically, light-dark cycles were dictated by the solar day, but now humans can extend light exposure by switching on artificial lights. We use a mathematical model incorporating effects of light, circadian rhythmicity and sleep homeostasis to provide a quantitative theoretical framework to understand effects of modern patterns of light consumption on the human circadian system. The model shows that without artificial light humans wake-up at dawn. Artificial light delays circadian rhythmicity and preferred sleep timing and compromises synchronisation to the solar day when wake-times are not enforced. When wake-times are enforced by social constraints, such as work or school, artificial light induces a mismatch between sleep timing and circadian rhythmicity (?social jet-lag?). The model implies that developmental changes in sleep homeostasis and circadian amplitude make adolescents particularly sensitive to effects of light consumption. The model predicts that ameliorating social jet-lag is more effectively achieved by reducing evening light consumption than by delaying social constraints, particularly in individuals with slow circadian clocks or when imposed wake-times occur after sunrise. These theory-informed predictions may aid design of interventions to prevent and treat circadian rhythm-sleep disorders and social jet-lag.
Most antidepressants suppress rapid eye movement (REM) sleep, which is thought to be important to brain function, yet the resulting REM sleep restriction is well tolerated. This study investigated the impact of antidepressants with different mechanisms of action, such as selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCA), on the regulation of REM sleep in rats. REM sleep was first demonstrated to be homeostatically regulated using 5, 8 and 10 hours of REM-sleep specific restriction through EEG-driven triggered arousals, with an average of 91 ± 10% of lost REM sleep recovered following a 26-29 -hour recovery period. Acute treatment with the antidepressants paroxetine, citalopram and imipramine inhibited REM sleep by 84 ± 8, 84 ± 8 and 69 ± 9% respectively relative to vehicle control. The pharmacologically-induced REM sleep deficits by citalopram and paroxetine were not fully recovered, whereas, after imipramine the REM sleep deficit was fully compensated. Given the marked difference between REM sleep recovery following the administration of paroxetine, citalopram, imipramine and REM sleep restriction, the homeostatic response was further examined by pairing REM sleep specific restriction with the three antidepressants. Surprisingly, the physiologically-induced REM sleep deficits incurred prior to suppression of REM sleep by all antidepressants was consistently recovered. The data indicate that REM sleep homeostasis remains operative following subsequent treatment with antidepressants and is unaffected by additional pharmacological inhibition of REM sleep.
Chellappa S, Gaggioni G, Ly J, Papachilleos S, Borsu C, Brzozowski A, Rosanova M, Sarasso S, Luxen A, Middleton BA, Archer S, Dijk D, Massimini M, Maquet P, Phillips C, Moran R, Vandewalle G (2016) Circadian dynamics in measures of cortical excitation and inhibition balance, Scientific Reports 6 33661
Nature Publishing Group
Several neuropsychiatric and neurological disorders have recently been characterized as dysfunctions arising from a ?final common pathway? of imbalanced excitation to inhibition within cortical networks. How the regulation of a cortical E/I ratio is affected by sleep and the circadian rhythm however, remains to be established. Here we addressed this issue through the analyses of TMS-evoked responses recorded over a 29h sleep deprivation protocol conducted in young and healthy volunteers. Spectral analyses of TMS-evoked responses in frontal cortex revealed non-linear changes in gamma band evoked oscillations, compatible with an influence of circadian timing on inhibitory interneuron activity. In silico inferences of cell-to-cell excitatory and inhibitory connectivity and GABA/Glutamate receptor time constant based on neural mass modeling within the Dynamic causal modeling framework, further suggested excitation/inhibition balance was under a strong circadian influence. These results indicate that circadian changes in EEG spectral properties, in measure of excitatory/inhibitory connectivity and in GABA/glutamate receptor function could support the maintenance of cognitive performance during a normal waking day, but also during overnight wakefulness. More generally, these findings demonstrate a slow daily regulation of cortical excitation/inhibition balance, which depends on circadian-timing and prior sleep-wake history.
A common complaint of older persons is disturbed sleep, typically characterized as an inability to return to sleep after waking. As every sleep episode (i.e., time in bed) includes multiple transitions between wakefulness and sleep (which can be subdivided into rapid eye movement [REM] sleep and non-REM [NREM] sleep), we applied survival analysis to sleep data to determine whether changes in the "hazard" (duration-dependent probability) of awakening from sleep and/or returning to sleep underlie age-related sleep disturbances. The hazard of awakening from sleep-specifically NREM sleep-was much greater in older than in young adults. We found, however, that when an individual had spontaneously awakened, the probability of falling back asleep was not greater in young persons. Independent of bout length, the number of transitions between NREM and REM sleep stages relative to number of transitions to wake was approximately 6 times higher in young than older persons, highlighting the difficulty in maintaining sleep in older persons. Interventions to improve age-related sleep complaints should thus target this change in awakenings. © 2013 Elsevier Inc.
Common cold sufferers frequently report sleep disruption during the symptomatic
period of infections. We examined the effects of treatment with a
topical aromatic pharmaceutical ointment (Vicks VapoRub®), on associated
sleep disturbances. The effects of Vicks VapoRub® versus placebo (petrolatum
ointment) on subjective and objective measured sleep parameters were assessed
in an exploratory study of 100 common cold patients, in a randomized,
single blind, controlled, two-arm, parallel design study. The primary efficacy
variable was subjective sleep quality measured with the SQSQ (Subjective
Quality of Sleep Questionnaire). Additional measures included, ease of falling
asleep and depth of sleep (measured with a post-sleep Visual Analog Scale),
total sleep time, sleep onset latency, activity score, percentage of sleep, sleep
efficiency (measured with actigraphy and SQSQ) and sleep quality index
measured with a modified Karolinska Sleep Diary (KSD). The primary endpoint,
?How was the quality of your sleep last night?? showed a statistically
significant difference in change from baseline in favour of VapoRub treatment
(p = 0.0392) versus placebo. Positive effects of VapoRub versus placebo were
also observed for ?How refreshed did you feel upon waking up?? (p = 0.0122)
(SQSQ), ?Did you get enough sleep?? (p = 0.0036) (KSD), ?How was it to get
up?? (p = 0.0120) (KSD) and ?Do you feel well-rested?? (p = 0.0125) (KSD).
No statistically significant changes from baseline versus placebo were detected
in the Actiwatch endpoints. Vicks VapoRub®when applied before retiring to bed can reduce subjective sleep disturbances during a common cold. The results
of this exploratory study support the belief among patients that the use
of VapoRub improves subjective sleep quality during common cold which was
associated with more refreshing sleep.
Hughes M, Abruzzi K, Allada R, Anafi R, Arpat A, Asher G, Baldi P, de Bekker C, Bell-Pedersen D, Blau J, Brown S, Ceriani M, Chen Z, Chiu J, Cox J, Crowell A, DeBruyne J, Dijk D, DiTacchio L, Doyle F, Duffield G, Dunlap J, Eckel-Mahan K, Esser K, FitzGerald G, Forger D, Francey L, Fu Y, Gachon F, Gatfield D, de Goede P, Golden S, Green C, Harer J, Harmer S, Haspel J, Hastings M, Herzel H, Herzog E, Hoffmann C, Hong C, Hughey J, Hurley J, de la Iglesia H, Johnson C, Kay S, Koike N, Kornacker K, Kramer A, Lamia K, Leise T, Lewis S, Li J, Li X, Liu A, Loros J, Martino T, Menet J, Merrow M, Millar A, Mockler T, Naef F, Nagoshi E, Nitabach M, Olmedo M, Nusinow D, Ptá
ek L, Rand D, Reddy A, Robles M, Roenneberg T, Rosbash M, Ruben M, Rund S, Sancar A, Sassone-Corsi P, Sehgal A, Sherrill-Mix S, Skene D, Storch K, Takahashi J, Ueda H, Wang H, Weitz C, Westermark P, Wijnen H, Xu Y, Wu G, Yoo S, Young M, Zhang E, Zielinski T, Hogenesch J (2017) Guidelines for Genome-Scale Analysis of Biological Rhythms, Journal of Biological Rhythms 32 (5) pp. 380-393
Genome biology approaches have made enormous contributions to our understanding of biological rhythms, particularly in identifying outputs of the clock, including RNAs, proteins, and metabolites, whose abundance oscillates throughout the day. These methods hold significant promise for future discovery, particularly when combined with computational modeling. However, genome-scale experiments are costly and laborious, yielding ?big data? that are conceptually and statistically difficult to analyze. There is no obvious consensus regarding design or analysis. Here we discuss the relevant technical considerations to generate reproducible, statistically sound, and broadly useful genome-scale data. Rather than suggest a set of rigid rules, we aim to codify principles by which investigators, reviewers, and readers of the primary literature can evaluate the suitability of different experimental designs for measuring different aspects of biological rhythms. We introduce CircaInSilico, a web-based application for generating synthetic genome biology data to benchmark statistical methods for studying biological rhythms. Finally, we discuss several unmet analytical needs, including applications to clinical medicine, and suggest productive avenues to address them.
Sleep is regulated by a homeostatic process which in the two-process model of human sleep
regulation is represented by EEG slow-wave activity (SWA). Many studies of acute
manipulation of wake duration have confirmed the precise homeostatic regulation of SWA in
rodents and humans. However, some chronic sleep restriction studies in rodents show that the
sleep homeostatic response, as indexed by SWA, is absent or diminishes suggesting
adaptation occurs. Here, we investigate the response to 7 days of sleep restriction (6 h time in
bed) and extension (10 h time in bed) as well as the response to subsequent total sleep
deprivation in 35 healthy participants in a cross-over design. The homeostatic response was
quantified by analyzing sleep structure and SWA measures. Sleep restriction resulted
primarily in a reduction of REM sleep. SWA and accumulated SWA (slow-wave energy)
were not much affected by sleep extension/restriction. The SWA responses did not diminish
significantly in the course of the intervention and did not deviate significantly from the
predictions of the two-process model. The response to total sleep deprivation consisted of an
increase in SWA, rise rate of SWA and SWE and did not differ between the two conditions.
The data show that changes in sleep duration within an ecologically relevant range, have a
marked effect on REM sleep and that SWA responds in accordance with predictions based on
a saturating exponential increase during wake and an exponential decline in sleep of
homeostatic sleep pressure during both chronic sleep restriction and extension.
Sleep and its sub-states are assumed to be important for brain function across the lifespan but which aspects of sleep associate with various aspects of cognition, mood and self-reported sleep quality has not yet been established in detail. Sleep was quantified by polysomnography, quantitative Electroencephalogram (EEG) analysis and self-report in 206 healthy men and women, aged 20?84 years, without sleep complaints. Waking brain function was quantified by five assessments scheduled across the day covering objectively assessed performance across cognitive domains including sustained attention and arousal, decision and response time, motor and sequence control, working memory, and executive function as well as self-reports of alertness, mood and affect. Controlled for age and sex, self-reported sleep quality was negatively associated with number of awakenings and positively associated with the duration of Rapid Eye Movement (REM) sleep, but no significant associations with Slow Wave Sleep (SWS) measures were observed. Controlling only for age showed that associations between objective and subjective sleep quality were much stronger in women than in men. Analysis of 51 performance measures demonstrated that, after controlling for age and sex, fewer awakenings and more REM sleep were associated significantly with better performance on the Goal Neglect task, which is a test of executive function. Factor analysis of the individual performance measures identified four latent variables labeled Mood/Arousal, Response Time, Accuracy, and Visual Perceptual Sensitivity. Whereas Mood/Arousal improved with age, Response Times became slower, while Accuracy and Visual perceptual sensitivity showed little change with age. After controlling for sex and age, nominally significant association between sleep and factor scores were observed such that Response Times were faster with more SWS, and Accuracy was reduced where individuals woke more often or had less REM sleep. These data identify a positive contribution of SWS to processing speed and in particular highlight the importance of sleep continuity and REM sleep for subjective sleep quality and performance accuracy across the adult lifespan. These findings warrant further investigation of the contribution of sleep continuity and REM sleep to brain function.
Acute and chronic insufficient sleep are associated with adverse health outcomes and risk of accidents.
There is therefore a need for biomarkers to monitor sleep debt status. None are currently available. We
applied Elastic-net and Ridge regression to entire and pre-filtered transcriptome samples collected in
healthy young adults during acute total sleep deprivation and following 1 week of either chronic
status. The size of identified panels ranged from 9-74 biomarkers. Panel performance, assessed by
leave-one-subject-out cross-validation and independent validation, varied between sleep debt
conditions. Using between-subject assessments based on one blood sample, the accuracy of classifying
?Acute sleep loss? was 92%, but only 57% for classifying ?Chronic sleep insufficiency?. A reasonable
accuracy for classifying ?chronic sleep insufficiency? could only be achieved by a within-subject
comparison of blood samples. Biomarkers for sleep debt status showed little overlap with previously
identified biomarkers for circadian phase. Biomarkers for acute and chronic sleep loss also showed little
overlap but were associated with common functions related to the cellular stress response, such as heat
shock protein activity, the unfolded protein response, protein ubiquitination and endoplasmic reticulum
associated protein degradation, and apoptosis. This characteristic response of whole blood to sleep loss
can further aid our understanding of how sleep insufficiencies negatively affect health. Further
development of these novel biomarkers for research and clinical practice requires validation in other
protocols and age groups.
Human and rodent vigilance states have evolutionarily conserved control mechanisms, which suggests that measures of sleep can translate from the laboratory to the clinic. Continuity is an essential aspect of sleep architecture that facilitates the restoration of both body and mind. Current measures of vigilance state continuity do not align well between species and this prevents accurate translation. Throughout this thesis, survival and transition probability analyses were evaluated for their ability to quantify vigilance state continuity in humans and rats. These techniques produced more effective quantification of sleep architecture than metrics such as wake after sleep onset, number of awakenings and average bout lengths.
Two methods for defining a bout were first investigated. In both humans and rats, statistical properties of bouts were characterized using different bout-duration thresholds. It was found that bouts are best modelled with distributions that include a time component. Biological relevance of sleep continuity was also investigated in rats, where bouts of NREM sleep as short as 20 seconds reduced the homeostatic pressure, yet awakenings as short as 10 seconds were enough to disrupt the restorative processes of sleep. Short bouts were therefore an important component of sleep architecture and must be considered when evaluating continuity. Continuity metrics were next used to evaluate sleep restriction in rats and circadian rhythmicity in humans. Both homeostatic and circadian influences exerted significant control of NREM sleep continuity, whilst REM continuity was mostly unaffected. Finally, pharmacological agents were tested and their impact on state continuity effectively translated between species. NREM sleep continuity was not altered by the REM sleep inhibition of SSRI?s which differed to the deficits induced by REM sleep restriction. The main contribution of this thesis is to demonstrate that accurate quantification of vigilance state continuity can improve understanding of sleep architecture and the evaluation of pharmacological agents to deliver better patient outcomes.