Biomedical subjects

Christian Cajochen

Publications and source records attributed to Christian Cajochen.

28 records · Page 2Linked to original sources

PubMed2004

Waking up properly: is there a role of thermoregulation in sleep inertia?

We assume that alertness should be highest at the end of a sleep episode: it is not. There is always sleep inertia upon awakening, which can last minutes to hours, and whose underlying physiological mechanisms are largely unknown. Previously, we had found a functional relationship between the degree of distal vasodilatation (as measured by the distal-proximal skin temperature gradient (DPG) and sleepiness (as measured by subjective ratings), promoting rapid sleep onset. This led us to hypothesize that the dissipation of sleep inertia (sleepiness) would be associated with reverse thermoregulatory mechanisms, i.e. distal vasoconstriction. In two sets of experiments with either a nocturnal sleep episode (study 1) or an afternoon nap (study 2) we could show that vasodilatation of hands and feet increased after lights off and that this was reversed after lights on. The time course of the DPG was significantly and positively correlated with subjective sleepiness (KSS), reflecting similar temporal relationships in both studies 1 and 2. The extremities cooled at a rate very closely parallel to the decay of sleepiness [time constants for the exponential decline calculated for study 2: DPG, 0.286 +/- 0.048 h versus KSS, 0.332 +/- 0.050 h; NS], indicating redistribution of heat from the shell to the core during dissipation of sleepiness. There was no statistical evidence that the time course of sleep inertia and its thermophysiological correlates depend on sleep structure prior to awakening. The symmetry between the thermoregulatory processes initiating sleepiness and those dissipating it is striking. In order to directly test our hypothesis, further studies with thermophysiological interventions (e.g. cooling the extremities) are needed.

Body Temperature Regulation↗

PubMed2004

The frontal predominance in human EEG delta activity after sleep loss decreases with age.

Sleep loss has marked and selective effects on brain wave activity during subsequent recovery sleep. The electroencephalogram (EEG) responds to sleep deprivation with a relative increase in power density in the delta and theta range during non-rapid eye movement sleep. We investigated age-related changes of the EEG response to sleep deprivation along the antero-posterior axis (Fz, Cz, Pz, Oz) under constant routine conditions. Both healthy young (20-31 years) and older (57-74 years) participants manifested a significant relative increase in EEG power density in the delta and theta range after 40 h of sleep deprivation, indicating a sustained capacity of the sleep homeostat to respond to sleep loss in ageing. However, the increase in relative EEG delta activity (1.25-3.75 Hz) following sleep deprivation was significantly more pronounced in frontal than parietal brain regions in the young, whereas such a frontal predominance was diminished in the older volunteers. This age-related decrease of frontal delta predominance was most distinct at the beginning of the recovery sleep episode. Furthermore, the dissipation of homeostatic sleep pressure during the recovery night, as indexed by EEG delta activity, exhibited a significantly shallower decline in the older group. Activation of sleep regulatory processes in frontal brain areas by an extension of wakefulness from 16 to 40 h appears to be age-dependent. These findings provide quantitative evidence for the hypothesis that frontal brain regions are particularly vulnerable to the effects of elevated sleep pressure ('prefrontal tiredness') and ageing ('frontal ageing').

Adult↗

PubMed2004

Evening melatonin and bright light administration induce additive phase shifts in dim light melatonin onset.

In healthy young men, administration of a single light pulse (5000 lux for 3 hr) or a single melatonin pill (5 mg) at 20:40 hr under controlled constant routine conditions of <10 lux, yielded a phase delay and a phase advance, respectively, in the circadian marker of dim light melatonin onset 24 hr later. Phase shifts after combining the two interventions were additive. Melatonin suppression is not necessary for a phase shift by light, and melatonin is not a 'weak' Zeitgeber relative to bright light when ambient lighting is strictly controlled.

Adult↗

PubMed2003

A phase response curve to single bright light pulses in human subjects.

The circadian pacemaker is differentially sensitive to the resetting effects of retinal light exposure, depending upon the circadian phase at which the light exposure occurs. Previously reported human phase response curves (PRCs) to single bright light exposures have employed small sample sizes, and were often based on relatively imprecise estimates of circadian phase and phase resetting. In the present study, 21 healthy, entrained subjects underwent pre- and post-stimulus constant routines (CRs) in dim light (approximately 2-7 lx) with maintained wakefulness in a semi-recumbent posture. The 6.7 h bright light exposure stimulus consisted of alternating 6 min fixed gaze (approximately 10 000 lx) and free gaze (approximately 5000-9000 lx) exposures. Light exposures were scheduled across the circadian cycle in different subjects so as to derive a PRC. Plasma melatonin was used to determine the phase of the onset, offset, and midpoint of the melatonin profiles during the CRs. Phase shifts were calculated as the difference in phase between the pre- and post-stimulus CRs. The resultant PRC of the midpoint of the melatonin rhythm revealed a characteristic type 1 PRC with a significant peak-to-trough amplitude of 5.02 h. Phase delays occurred when the light stimulus was centred prior to the critical phase at the core body temperature minimum, phase advances occurred when the light stimulus was centred after the critical phase, and no phase shift occurred at the critical phase. During the subjective day, no prolonged 'dead zone' of photic insensitivity was apparent. Phase shifts derived using the melatonin onsets showed larger magnitudes than those derived from the melatonin offsets. These data provide a comprehensive characterization of the human PRC under highly controlled laboratory conditions.

Adult↗

PubMed2003

Human sleep spindle characteristics after sleep deprivation.

OBJECTIVE: Sleep spindles (12-15 Hz oscillations) are one of the hallmarks of the electroencephalogram (EEG) during human non-rapid eye movement (non-REM) sleep. The effect of a 40 h sleep deprivation (SD) on spindle characteristics along the antero-posterior axis was investigated. METHODS: EEGs during non-REM sleep in healthy young volunteers were analyzed with a new method for instantaneous spectral analysis, based on the fast time frequency transform (FTFT), which yields high-resolution spindle parameters in the combined time and frequency domain. RESULTS: FTFT revealed that after SD, mean spindle amplitude was enhanced, while spindle density was reduced. The reduction in spindle density was most prominent in the frontal derivation (Fz), while spindle amplitude was increased in all derivations except in Fz. Mean spindle frequency and its variability within a spindle were reduced after SD. When analyzed per 0.25 Hz frequency bin, amplitude was increased in the lower spindle frequency range (12-13.75 Hz), whereas density was reduced in the high spindle frequency range (13.5-14.75 Hz). CONCLUSIONS: The observed reduction in spindle density after SD confirms the inverse homeostatic relationship between sleep spindles and slow waves whereas the increase in spindle amplitude and the reduction in intra-spindle frequency variability support the hypothesis of a higher level of synchronization in thalamocortical cells when homeostatic sleep pressure is enhanced.

Adult↗

PubMed2003

Human circadian melatonin rhythm phase delay during a fixed sleep-wake schedule interspersed with nights of sleep deprivation.

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.

Biological Clocks↗

PubMed2003

Regional differences in the circadian modulation of human sleep spindle characteristics.

Electroencephalographic oscillations in the sleep spindle frequency range (11-16 Hz) are a key element of human nonrapid eye movement sleep. In the present study, sleep spindle characteristics along the anterior-posterior axis were analysed during and outside the circadian phase of melatonin secretion. Sleep electroencephalograms were recorded during naps distributed over the entire circadian cycle and analysed with two different methodological approaches, the classical fast Fourier transform in the frequency-domain and a new method for instantaneous spectral analysis, the fast time frequency transform that yields high-resolution parameters in the combined time-frequency-domain. During the phase of melatonin secretion, spindle density was generally increased and intraspindle frequency variation reduced. Furthermore, lower spindle frequencies were promoted: peak frequencies shifted towards the lower end of the spindle frequency range, and spindle amplitude was enhanced in the low-frequency range (11-14.25 Hz) and reduced in the high-frequency range (approximately 14.5-16 Hz). The circadian variation showed a clear dependence on brain topography such that it was maximal in the parietal and minimal in the frontal derivation. Our data provide evidence that the circadian pacemaker actively promotes low-frequency sleep spindles during the biological night with a parietal predominance.

Adult↗

PubMed2003

Is sleep per se a zeitgeber in humans?

It is not clear whether shifting of sleep per se, without a concomitant change in the light-dark cycle, can induce a phase shift of the human circadian pacemaker. Two 9-day protocols (crossover, counterbalanced order) were completed by 4 men and 6 women (20-34 years) after adherence to a 2330 to 0800 h sleep episode at home for 2 weeks. Following a modified baseline constant routine (CR) protocol on day 2, they remained under continuous near-darkness (< 0.2 lux, including sleep) for 6 days. Four isocaloric meals were equally distributed during scheduled wakefulness, and their timing was held constant. Subjects remained supine inbed from 2100 to 0800 h on all days; sleep was fixed from 2330 to 0800 h in the control condition and was gradually advanced 20 min per day during the sleep advance condition until a 2-h difference had been attained. On day 9, a 25 to 27 h CR protocol (approximately 0.1 lux) was carried out. Phase markers were the evening decline time of the core body temperature (CBT) rhythm and salivary melatonin onset (3 pg/ml threshhold). In the fixed sleep condition, the phase drift over 7 days ranged from +1.62 to -2.56 h (for both CBT and melatonin rhythms, which drifted in parallel). The drifts were consistently advanced in the sleep advance schedule by +0.66 +/- 0.23 (SEM) h for CBT (p = 0.02) and by 0.27 +/- 0.14 h for melatonin rhythms (p = 0.09). However, this advance was small to medium according to effect size. Sleep per se may feed back onto the circadian pacemaker, but it appears to be a weak zeitgeber in humans.

Adult↗

PubMed2002

Alteration of internal circadian phase relationships after morning versus evening carbohydrate-rich meals in humans.

The effects of a single morning and evening carbohydrate-rich meal for 3 consecutive days on circadian phase of core body temperature (CBT), heart rate, and salivary melatonin rhythms were compared under controlled constant routine conditions. In 10 healthy young men entrained to a natural light-dark cycle with regular sleep timing, CBT and heart rate were significantly elevated for approximately 8 h after the last evening carbohydrate-rich meal (EM), and nocturnal melatonin secretion (as measured by salivary melatonin and urinary 6-sulphatoxymelatonin levels) was reduced, compared to the morning carbohydrate-rich meal (MM) condition. Thus, circadian phase could not be measured until the following day due to this acute masking effect. The day after the last meal intervention, MM showed a significant advanced circadian phase position in CBT (+59+/-12 min) and heart rate (+43+/-18 min) compared to EM. However, dim-light melatonin onset was not significantly changed (+15+/-13 min). The results are discussed with respect to central (light-entrainable) and peripheral (food-entrainable) oscillators. Food may be a zeitgeber in humans for the food-entrainable peripheral oscillators, but melatonin data do not support such a conclusion for the light-entrainable oscillator in the suprachiasmatic nucleus.

Adult↗

PubMedDate not supplied

Dawn-dusk simulation light therapy of disturbed circadian rest-activity cycles in demented elderly.

We investigated whether low intensity dawn-dusk simulation (DDS), a 'naturalistic' form of light therapy designed to embed sleep in its accustomed phase, could improve the disturbed circadian rest-activity cycle, nocturnal sleep and and/or cognitive functions in dementia. A protocol of 3 weeks each of baseline, treatment and follow-up was completed by 13 patients (85yr old+/-5yr, MMSE 14+/-5; n=9 DDS versus n=4 'placebo' dim red light) who wore an activity/lux monitor throughout. There were no significant changes in clinical or cognitive status, nor modification of circadian stability or amplitude characteristics of the rest-activity cycle. However, two aspects of sleep responded to DDS but not to dim red light. The main sleep episode was 1:14h earlier during treatment (p=0.03) compared with before and after DDS. With respect to actimetry-determined sleep variables, the DDS group tended to have shortened 'sleep latency', longer 'sleep duration', more nocturnal immobility and less nocturnal activity than the dim red group (p<0.1). In parallel, nighttime light exposure tended to be reduced (p=0.07). These promising findings-after only 3 weeks of light treatment in elderly patients with advanced dementia-suggest that the circadian timing system remains functionally responsive even to low intensity DDS light. Increasing zeitgeber strength is an important strategy for improving sleep quality and timing in dementia, and DDS light therapy may provide one of the appropriate means to do so.

Aged↗