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Biomedical subjects

C Cajochen

Publications and source records attributed to C Cajochen.

At least 19 recordsLinked to original sources

[Sleep and circadian rhythms in ageing].

With age, the consolidation of nocturnal sleep decreases, daytime napping increases, and sleep occurs earlier. Sleep regulation is dependent on the interaction between a circadian pacemaker (biological clock) and the sleep homeostat (sleep pressure increasing with duration of time awake). We have shown that in the healthy elderly, the amplitude of circadian rhythms (e. g. melatonin secretion) declines, as does slow wave sleep, parallel with an increase in afternoon sleepiness and a tendency to fall asleep in the early evening when younger subjects do not. Light is the major zeitgeber to stabilise the biological clock: older subjects require sufficient light exposure during daytime and in the evening, and should take no or only brief naps during the day to improve sleep.

Aged, 80 and over↗

Role of melatonin in the regulation of human circadian rhythms and sleep.

The circadian rhythm of pineal melatonin is the best marker of internal time under low ambient light levels. The endogenous melatonin rhythm exhibits a close association with the endogenous circadian component of the sleep propensity rhythm. This has led to the idea that melatonin is an internal sleep "facilitator" in humans, and therefore useful in the treatment of insomnia and the readjustment of circadian rhythms. There is evidence that administration of melatonin is able: (i) to induce sleep when the homeostatic drive to sleep is insufficient; (ii) to inhibit the drive for wakefulness emanating from the circadian pacemaker; and (iii) induce phase shifts in the circadian clock such that the circadian phase of increased sleep propensity occurs at a new, desired time. Therefore, exogenous melatonin can act as soporific agent, a chronohypnotic, and/or a chronobiotic. We describe the role of melatonin in the regulation of sleep, and the use of exogenous melatonin to treat sleep or circadian rhythm disorders.

Body Temperature Regulation↗

Separation of circadian and wake duration-dependent modulation of EEG activation during wakefulness.

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.

Adult↗

Homeostatic control of slow-wave and spindle frequency activity during human sleep: effect of differential sleep pressure and brain topography.

The impact of a 40 h sleep deprivation versus a 40 h multiple nap paradigm on topographic and temporal aspects of electroencephalographic (EEG) activity during the subsequent recovery sleep was investigated in 10 young volunteers in a controlled 'constant posture' protocol. The accumulation of sleep pressure with extended wakefulness could be significantly attenuated by intermittent naps. The differential sleep pressure conditions induced frequency- and topographic-specific changes in the EEG slow wave range (0.5-5 Hz) and in the low (LSFA, 12.25-13.25 Hz) and high spindle frequency activity range (HSFA, 13.75-16.5 Hz) during non-REM sleep. The observed increase of EEG slow-wave activity (SWA) after high sleep pressure was significantly more pronounced in the fronto-central (Fz, Cz) than in the parieto-occipital (Pz, Oz) derivations. Low sleep pressure after the nap paradigm decreased SWA with an occipital predominance. Spindle frequency activity showed a dissimilar homeostatic regulation: HSFA was significantly decreased after high sleep pressure and increased after low sleep pressure, exclusively in the centro-parietal brain region (Cz, Pz). LSFA was significantly enhanced after both manipulations. The data indicate that EEG activity, in particular frontal SWA and centro-parietal HSFA, are under a clear sleep-wake-dependent homeostatic control and imply a reciprocal relationship in the homeostatic regulation of SWA and HSFA, which however shows different spatio-temporal aspects.

Adult↗

Dynamics of frontal EEG activity, sleepiness and body temperature under high and low sleep pressure.

The impact of sleep deprivation (high sleep pressure) vs sleep satiation (low sleep pressure) on waking EEG dynamics, subjective sleepiness and core body temperature (CBT) was investigated in 10 young volunteers in a 40 h controlled constant posture protocol. The differential sleep pressure induced frequency-specific changes in the waking EEG from 1-7 Hz and 21-25 Hz. Frontal low EEG activity (FLA, 1-7 Hz) during sleep deprivation exhibited a prominent increase as time awake progressed, which could be significantly attenuated by sleep satiation attained with intermittent naps. Subjective sleepiness exhibited a prominent circadian regulation during sleep satiation, with virtually no homeostatic modulation. These extremely different sleep pressure conditions were not reflected in significant changes of the CBT rhythm. The data demonstrate that changes in FLA during wakefulness are to a large extent determined by the sleep-wake dependent process with little circadian modulation, and reflect differential levels of sleep pressure in the awake subject.

Adult↗

Cold feet and prolonged sleep-onset latency in vasospastic syndrome.

People with vasospastic syndrome have cold hands and feet and abnormal vasoconstriction after local cold exposure. Normally there is a circadian rhythm of distal vasodilation, with onset in the early evening, which directly influences ability to fall asleep. We gave a sleep questionnaire to 32 patients with primary vasospastic syndrome and 31 healthy controls. People with vasospasticity had significantly prolonged sleep-onset latency both at onset of night-time sleep and after nocturnal disturbance. This prolonged latency could be associated with impaired capacity for distal vasodilation.

Adult↗

Early morning melatonin administration impairs psychomotor vigilance.

The acute soporific effect of melatonin in humans has been demonstrated in a range of studies. How alertness and performance are changed after melatonin given in the morning is not yet known. In a double-blind, placebo-controlled study of nine healthy young men, melatonin was given at 0700 h under controlled conditions of a modified constant routine protocol lasting 56 h (2 days, 3 nights with sleep). A clear decrement in neurobehavioral functions as measured by the Psychomotor Vigilance Test lasted for 6 h after melatonin administration (particularly in the lapse domain and median of the reaction time) without any effect on a letter cancellation task. A subjective soporific effect was present but less pronounced. Thus, melatonin taken in the morning requires caution in situations where high attention is needed.

Adult↗

Disturbed circadian rest-activity cycles in schizophrenia patients: an effect of drugs?

The circadian rest-activity cycle of schizophrenia patients stabilized for more than a year on monotherapy with a "classical" neuroleptic (haloperidol, flupentixol) or with the atypical neuroleptic clozapine was documented by continuous activity monitoring for 3-7 weeks. In this pilot study, the three patients treated with clozapine had remarkably highly ordered restactivity cycles, whereas the four patients on classical neuroleptics had minor to major circadian rhythm abnormalities. This is the first documentation of circadian rest-activity cycle disturbances in schizophrenia related to class of drug.

Antipsychotic Agents↗

EEG and subjective sleepiness during extended wakefulness in seasonal affective disorder: circadian and homeostatic influences.

BACKGROUND: Seasonal affective disorder (SAD) may reflect a disturbance of circadian phase relationships or a disturbance of sleep-wake dependent processes, both of which change daytime energy and sleepiness levels. METHODS: Under the unmasking conditions of a 40-hour constant routine protocol (CR), self-rated sleepiness and waking electroencephalogram (EEG) power density were assessed in women with SAD (n = 8) and in age-matched healthy control subjects (n = 9). RESULTS: There was no significant effect of season or light treatment in any of the measures. The time course of subjective sleepiness was characterized by a circadian modulation and an overall increase during extended wakefulness in both SAD patients and control subjects. A prominent circadian rhythm of subjective sleepiness was not different in SAD patients and control subjects; however, the progressive buildup of sleepiness, as quantified by nonlinear regression analysis, was significantly reduced in SAD patients, mainly because they were sleepier than control subjects during the first 12 hours of the CR. The time course of waking EEG theta-alpha activity showed a more rapid increase during the first 10 hours of the CR in SAD patients. In contrast to control subjects who showed a progressive increase in the course of the 40-hour episode of extended wakefulness, EEG theta-alpha activity in SAD patients did not further increase over the remainder of the CR. CONCLUSIONS: The data suggest that SAD patients may have a trait (rather than state) deficiency in the homeostatic buildup of sleep pressure during extended wakefulness as indexed by subjective sleepiness and EEG theta-alpha activity.

Adult↗

Dose-response relationship for light intensity and ocular and electroencephalographic correlates of human alertness.

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 <3 lux for several hours. Light exerted an acute alerting response as assessed by a reduction in the incidence of slow-eye movements, a reduction of EEG activity in the theta-alpha frequencies (power density in the 5-9 Hz range) as well as a reduction in self-reported sleepiness. This alerting response was positively correlated with the degree of melatonin suppression by light. In accordance with the dose response function for circadian resetting and melatonin suppression, the responses of all three indices of alertness to variations in illuminance were consistent with a logistic dose response curve. Half of the maximum alerting response to bright light of 9100 lux was obtained with room light of approximately 100 lux. This sensitivity to light indicates that variations in illuminance within the range of typical, ambient, room light (90-180 lux) can have a significant impact on subjective alertness and its electrophysiologic concomitants in humans during the early biological night.

Adolescent↗

Phase advance after one or three simulated dawns in humans.

A specially designed apparatus that can simulate the waveform of the dawn or dusk signal at any latitude and any day of the year has been shown to phase shift the circadian pacemaker in rodents and primates at a fraction of the illuminance previously used. Until recently, it was considered that rather high illuminances or rather long exposure episodes to room light were necessary to phase shift human circadian rhythms. This experiment shows that, under controlled conditions of a modified constant routine protocol, a single dawn signal is sufficient to phase advance the timing of the onset of secretion of the pineal hormone melatonin. The significant phase advance of salivary melatonin of 20 minutes, which is enhanced to 34 minutes after three consecutive dawn signals, is small, but appears to be of sufficient magnitude to entrain the human circadian pacemaker, which has an endogenous period of about 24.2h.

Adult↗

Functional link between distal vasodilation and sleep-onset latency?

Thermoregulatory processes have long been implicated in initiation of human sleep. The purpose of this study was to evaluate the role of heat loss in sleep initiation, under the controlled conditions of a constant-routine protocol modified to permit nocturnal sleep. Heat loss was indirectly measured by means of the distal-to-proximal skin temperature gradient (DPG). A stepwise regression analysis revealed that the DPG was the best predictor variable for sleep-onset latency (compared with core body temperature or its rate of change, heart rate, melatonin onset, and subjective sleepiness ratings). This study provides evidence that selective vasodilation of distal skin regions (and hence heat loss) promotes the rapid onset of sleep.

Adult↗

A rapid-cycling bipolar patient treated with long nights, bedrest, and light.

BACKGROUND: Stabilization of rapid-cycling bipolar disorder is extremely difficult. METHODS: A refractory bipolar I rapid-cycling patient on valproate was treated with long "nights" (extended sleep in darkness) and daytime light therapy. RESULTS: Rapid cycling immediately stopped on initiation of a 10 hour dark/rest period. This was extended to 14 hours (plus a self-selected 1 hour midday nap) without problems. Depression gradually improved when midday light therapy was added; near-euthymia was attained after light therapy was shifted to the morning. CONCLUSIONS: Nonpharmacological chronobiological treatments may be a means to interrupt rapid cycling.

Activity Cycles↗

EEG and ocular correlates of circadian melatonin phase and human performance decrements during sleep loss.

The aim of this study was to quantify the associations between slow eye movements (SEMs), eye blink rate, waking electroencephalogram (EEG) power density, neurobehavioral performance, and the circadian rhythm of plasma melatonin in a cohort of 10 healthy men during up to 32 h of sustained wakefulness. The time course of neurobehavioral performance was characterized by fairly stable levels throughout the first 16 h of wakefulness followed by deterioration during the phase of melatonin secretion. This deterioration was closely associated with an increase in SEMs. Frontal low-frequency EEG activity (1-7 Hz) exhibited a prominent increase with time awake and little circadian modulation. EEG alpha activity exhibited circadian modulation. The dynamics of SEMs and EEG activity were phase locked to changes in neurobehavioral performance and lagged the plasma melatonin rhythm. The data indicate that frontal areas of the brain are more susceptible to sleep loss than occipital areas. Frontal EEG activity and ocular parameters may be used to monitor and predict changes in neurobehavioral performance associated with sleep loss and circadian misalignment.

Adult↗

Frontal predominance of a relative increase in sleep delta and theta EEG activity after sleep loss in humans.

The effect of sleep deprivation (40 h) on topographic and temporal aspects of electroencephalographic (EEG) activity during sleep was investigated by all night spectral analysis in six young volunteers. The sleep-deprivation-induced increase of EEG power density in the delta and theta frequencies (1-7 Hz) during nonREM sleep, assessed along the antero-posterior axis (midline: Fz, Cz, Pz, Oz), was significantly larger in the more frontal derivations (Fz, Cz) than in the more parietal derivations (Pz, Oz). This frequency-specific frontal predominance was already present in the first 30 min of recovery sleep, and dissipated in the course of the 8-h sleep episode. The data demonstrate that the enhancement of slow wave EEG activity during sleep following extended wakefulness is most pronounced in frontal cortical areas.

Adult↗

Evening administration of melatonin and bright light: interactions on the EEG during sleep and wakefulness.

Both the pineal hormone melatonin and light exposure are considered to play a major role in the circadian regulation of sleep. In a placebo- controlled balanced cross-over design, we investigated the acute effects of exogenous melatonin (5 mg p.o. at 20.40 hours) with or without a 3-h bright light exposure (5000 lux from 21.00 hours-24.00 hours) on subjective sleepiness, internal sleep structure and EEG power density during sleep and wakefulness in healthy young men. The acute effects of melatonin, bright light and their interaction were measured on the first day (treatment day), possible circadian phase shifts were assessed on the post-treatment day. On the treatment day, the evening rise in subjective sleepiness was accelerated after melatonin and protracted during bright light exposure. These effects were also reflected in specific changes of EEG power density in the theta/alpha range during wakefulness. Melatonin shortened and bright light increased sleep latency. REMS latency was reduced after melatonin administration but bright light had no effect. Slow-wave sleep and slow-wave activity during the first non-rapid eye movement (NREMS) episode were suppressed after melatonin administration and rebounded in the second NREMS episode, independent of whether light was co-administered or not. Self rated sleep quality was better after melatonin administration whereas the awakening process was rated as more difficult after bright light. On the post-treatment day after evening bright light, the rise in sleepiness and the onset of sleep were delayed, independent of whether melatonin was co-administered or not. Thus, although acute bright light and melatonin administration affected subjective sleepiness, internal sleep structure and EEG power density during sleep and wakefulness in a additive manner, the phase shifting effect of a single evening bright light exposure could not be blocked by exogenous melatonin.

Adult↗

A schizophrenic patient with an arrhythmic circadian rest-activity cycle.

A haloperidol-treated patient with chronic schizophrenia had a near-arrhythmic circadian rest-activity cycle, whereas rhythms of 6-sulphatoxy-melatonin and core body temperature were of normal amplitude and phase-advanced. Sleep electroencephalography measured throughout a 31-h 'constant-bedrest' protocol revealed a phase-delayed sleep-wake propensity cycle, low sleep continuity (ultradian 'bouts'), and very little slow-wave sleep and slow-wave activity (0.75-4.5 Hz). Switching treatment to the atypical neuroleptic clozapine improved both the circadian organization of the rest-activity cycle and the patient's clinical state. This observation can be conceptualized in terms of the two-process model of sleep regulation. High-dose haloperidol treatment may have lowered the circadian alertness threshold, whereas clozapine augmented circadian amplitude (perhaps through its high affinity to dopamine D4 and serotonin 5HT7 receptors in the suprachiasmatic nuclei). Measurement of the circadian rest-activity cycle may be a useful non-invasive method to follow functional consequences of neuroleptic treatment.

Adult↗