Kurt Kräuchi

Warm feet promote the rapid onset of sleep

Even healthy people occasionally have difficulty falling asleep. Psychological relaxation techniques, hot baths, soothing infusions of plant extracts, melatonin and conventional hypnotics are all invoked in the search for a good nights sleep. Here we show that the degree of dilation of blood vessels in the skin of the hands and feet, which increases heat loss at these extremities, is the best physiological predictor for the rapid onset of sleep. Our findings provide further insight into the thermoregulatory cascade of events that precede the initiation of sleep.

Physiology: Warm feet promote the rapid onset of sleep

Even healthy people occasionally have difficulty falling asleep. Psychological relaxation techniques, hot baths, soothing infusions of plant extracts, melatonin and conventional hypnotics are all invoked in the search for a good nights sleep. Here we show that the degree of dilation of blood vessels in the skin of the hands and feet, which increases heat loss at these extremities, is the best physiological predictor for the rapid onset of sleep. Our findings provide further insight into the thermoregulatory cascade of events that precede the initiation of sleep.

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.

Circadian and wake-dependent modulation of fastest and slowest reaction times during the psychomotor vigilance task

Performance on the psychomotor vigilance task (PVT) sensitively reflects a circadian modulation of neurobehavioral functions, as well as the effect of sleep pressure developing with duration of time awake, without being confounded by a learning curve. Sixteen healthy volunteers underwent two 40-h constant posture protocols in a balanced crossover design. During these protocols, either low sleep pressure conditions were attained by an alternating cycle of 150 min of wakefulness and 75 min of sleep (NAP) protocol, or high sleep pressure conditions were achieved by total sleep deprivation (SD) protocol. During scheduled wakefulness in both protocols, the PVT was carried out every 225 min. Quantitative analysis of the lapses, slowest (90th percentile) and fastest (10th percentile) reaction times (RTs) during the protocols, indicated that the lapses and slowest RTs were sensitive to changes in homeostatic sleep pressure. Our data indicate that the difference between the fastest and slowest RTs (interpercentile range 10th-90th percentile) was particular sensitive to detect very early effects of growing sleep pressure. On the other hand, decrements in PVT performance which were related to circadian phase did not depend significantly on any categorization (such as percentiles of the RTs).

Circadian Clues to Sleep Onset Mechanisms

Thermoregulatory processes have long been implicated in initiation of human sleep. A meta-analysis of studies carried out under the controlled conditions of a constant routine protocol followed by nocturnal sleep revealed that heat loss, indirectly measured by the distal-proximal skin temperature gradient, 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). The cognitive signal of “lights out” induced relaxation, with a consequent shift in heat redistribution from the core to the periphery (as measured by an abrupt increase in skin temperatures and a rapid fall in heart rate). These thermoregulatory changes took place before sleep onset: sleep itself had minor further effects. Thus, when the confounding, long-lasting masking effects of lying down are controlled for, circadian thermoregulation initiates sleep, but does not appear to play a major role in its maintenance.

‘Natural’ light treatment of seasonal affective disorder

Patients with seasonal affective disorder (SAD) were treated for 1 week either with a daily 1-h morning walk outdoors (natural light) or low-dose artificial light (0.5 h@2800 lux). The latter treatment (given under double-blind conditions) can be considered mainly placebo and did not improve any of the depression self-ratings, whereas natural light exposure improved all self-ratings. According to the Hamilton depression score, 25% remitted after low-dose artificial light and 50% after the walk. Sleep duration or timing were not crucial for the therapeutic response. The morning walk phase-advanced the onset and/or offset of salivary melatonin secretion, but individual clinical improvement could not be correlated with specific phase-shifts. Morning cortisol was decreased. Low-dose artificial light did not modify melatonin or cortisol patterns. This is the first study to provide evidence for the use of outdoor light exposure as a potential alternative or adjuvant to conventional artificial light therapy in SAD.

Daytime melatonin administration enhances sleepiness and theta/alpha activity in the waking EEG

It is still controversial whether the pineal hormone melatonin can be characterized as a hypnotic. We therefore measured subjective sleepiness and waking EEG power density in the range of 0.25-20 Hz after a single dose of melatonin (5 mg). During an 8 h mini-constant routine protocol, melatonin administered in a double blind cross-over design to healthy young men at 1300 h or 1800 h increased subjective sleepiness, as rated half-hourly on three different scales (Visual Analogue Scale, Akerstedt Sleepiness Symptoms Check List, Akerstedt Sleepiness Scale) and objective fatigue as evidenced by augmented waking EEG power density in the theta/alpha range (5.25-9 Hz). The increase in subjective sleepiness reached significance 40 min and 90 min after melatonin administration (at 1300 h and 1800 h, respectively) and lasted for 3 h (at 1300 h) and 5 h (at 1800 h). The increase in the theta/alpha frequencies of the waking EEG occurred immediately after melatonin ingestion and stayed significantly higher parallel to the higher sleepiness ratings. However, the EEG changes appeared before the subjective symptoms of sleepiness became manifest. There was a significant correlation between salivary melatonin levels and the timing of increased subjective sleepiness. Melatonin had no effects on mood.

Homeostatic versus Circadian Effects of Melatonin on Core Body Temperature in Humans

Evidence obtained in animals has suggested a link of the pineal gland and its hormone melatonin with the regulation of core body temperature (CBT). Depending on the species considered, melatonin intervenes in generating seasonal rhythms of daily torpor and hibernation, in heat stress tolerance, and in setting the CBT set point. In humans, the circadian rhythm of melatonin is strictly associated with that of CBT, the nocturnal decline of CBT being inversely related to the rise of melatonin. Whereas there is inconsistent evidence for the suggestion that the decline of CBT may prompt the release of melatonin, conversely, stringent data indicate that melatonin decreases CBT. Administration of melatonin during the day, when it is not normally secreted, decreases CBT by about 0.3 to 0.4°C, and suppression of melatonin at night enhances CBT by about the same magnitude. Accordingly, the nocturnal rise of melatonin contributes to the circadian amplitude of CBT. The mechanisms through which melatonin decreases CBT are unclear. It is known that melatonin enhances heat loss, but a reduction of heat production cannot be excluded. Besides actions on peripheral vessels aimed to favor heat loss, it is likely that the effect of melatonin to reduce CBT is exerted mainly in the hypothalamus, where thermoregulatory centers are located.Recentobservationshaveshownthattheacutethermoregulatoryeffects induced by melatonin and bright light are independent of their circadian phase-shifting effects. The effect of melatonin ultimately brings a saving of energy and is reduced in at least two physiological situations: aging and the luteal menstrual phase. In both conditions, melatonin does not exert its CBT-lowering effects. Whereas in older women this effect may represent an age-related alteration, in the luteal phase this modification may represent a mechanism of keeping CBT higher at night to promote a better embryo implantation and survival.

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

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’).