A 1-year systematic diary was kept by an anonymous diarist in Hamburg in the year 1755-1756. Slee... more A 1-year systematic diary was kept by an anonymous diarist in Hamburg in the year 1755-1756. Sleep, activities, food intake, urine volume, and meteorological data were documented daily. The systematic recording of sleep and naps, with an accuracy of a quarter of an hour allowed analysis of the placement, duration, and consistency of sleep.
Sleep became a subject of scientific research in the second half of the 19th century. Since sleep... more Sleep became a subject of scientific research in the second half of the 19th century. Since sleep, unlike other physiological functions, cannot be attributed to a specific organ, there was no distinct method available to study sleep until then. With the development of physiology and psychology, and a rapidly increasing knowledge of the structure and functioning of the nervous system, certain aspects of sleep became accessible to objective study. A first step was to measure responsiveness to external stimuli systematically, during sleep, allowing a first representation of the course of sleep (Schlaftiefe = sleep depth). A second method was to register continuously the motor activity across the sleep–wake cycle, which allowed the documentation in detail of rest–activity patterns of monophasic and polyphasic sleep–wake rhythms, or between day or night active animals. The central measurement for sleep research, however, became the electroencephalogram in the 1930s, which allowed observation of the sleeping brain with high temporal resolution. Beside the development of instruments to measure sleep, prolonged sleep deprivation was applied to study physiological and psychological effects of sleep loss. Another input came from clinical and neuropathological observations of patients with pronounced disorders of the sleep–wake cycle, which for the first time allowed localisation of brain areas that are essentially involved in the regulation of sleep and wakefulness. Experimental brain stimulation and lesion studies were carried out with the same aim at this time. Many of these activities came to a halt on the eve of World War II. It was only in the early 1950s, when periods with rapid eye movements during sleep were recognised, that sleep became a research topic of itself. Jouvet and his team explored the brain mechanisms and transmitters of paradoxical sleep, and experimental sleep research became established in all European countries. Sleep medicine evolving simultaneously in different countries, with early centres in Italy and France. In the late 1960s sleep research and chronobiology began to merge. In recent decades, sleep research, dream research, and sleep medicine have benefited greatly from new methods in genetic research and brain imaging techniques. Genes were identified that are involved in the regulation of sleep, circadian rhythms, or sleep disorders. Functional imaging enabled a high spatial resolution of the activity of the sleeping brain, complementing the high temporal resolution of the electroencephalogram.
Geschichte der Schlafmedizin • Überblick über die Bedeutung des Schlafs in der Medizin von der An... more Geschichte der Schlafmedizin • Überblick über die Bedeutung des Schlafs in der Medizin von der Antike bis zur aktuellen Schlaff orschung • Entdeckung und Klassifi kation der unterschiedlichen Schlafstörungen im Verlauf der Jahrhunderte Kernaussagen 6.1 Einleitung Wissen über den Schlaf gehört seit der Antike zur ärztlichen Kunst. Hippocrates (c. 460-c. 375 v. Chr.) und Galen (c. 129-c. 199 n. Chr.) blieben mit ihrem Wissen und ihren Anschauungen bis in die frühe Neuzeit die verbindlichen Autoritäten auch für das Erkennen und Behandeln von Störungen des Schlafs und des Wachseins. Der große islamische Arzt und Gelehrte Al-Razi (Rhazes, c. 854-925 / 935 n. Chr.) kompilierte und verbreitete dieses Wissen, zusammen mit den ihm bekannten indischen und chinesischen Quellen. Der andere führende Mediziner und Philosoph des Orients war Ibn Sina, latinisiert Avicenna (c. 980-1037 n. Chr.). Sein "Canon Medicinae", der die Anatomie, Physiologie, Krankheits-und Arzneilehre umfasste, galt bis zum Ende des 15. Jahrhunderts als das vollständigste medizinische Lehrbuch. Angaben über den Schlaf und die Schlafstörungen Incubus und Wachsein der Kinder im Schlaf fi ndet sich in den Werken beider Ärzte. Die früheste und größte medizinische Schule des Mittelalters war die von Salerno. Hier wurde eine Gesundheitslehre entwickelt, die bis in die frühe Neuzeit ärztliches Handeln beeinfl usste. Von ganz unmittelbarem Interesse für die Medizin waren dabei die beiden Bücher des Aristoteles (384-322 v. Chr.) über den Schlaf und über die Träume. Das Wachsein (vigilia) ist bei Aristoteles durch die Fähigkeit zur Wahrnehmung gekennzeichnet, der Schlaf (somno) durch dessen Abwesenheit. Das Vermögen der Wahrnehmung hat seinen Sitz im
Measured and rated sleep differ in normal sleepers and even more in patients with sleep disorders.... more Measured and rated sleep differ in normal sleepers and even more in patients with sleep disorders. The study aimed to asses sleep/wake perception in electrophysiologically defined sleep in patients with sleep disorders. 117 consecutively referred patients (75 females), median age 50.3 years, range 20–73 years) with various sleep disorders were randomized for one induced waking, either out of stage 2 (S2) or REM sleep, as part of a clinical routine polysomnography. Patients were classified as either nonsleepy (Epworth Sleepiness Scale score ESS ≤ 10) or sleepy (ESS ≥ 11). The most frequent diagnoses of non-sleepy patients were insomnia and RLS, while sleepy patients suffered predominantly from OSAS, hypersomnia and insufficient sleep syndrome. Subjects were deliberately aroused once, either out of consolidated stage 2 sleep (n = 66) or REM sleep (n = 51) and asked for sleep/wake perception (sleep/wake and related questions). While 81 (69.2%) of the subjects estimated that they had been sleeping or dozing before they were aroused, 36 (30.8%) reported that they had been awake. Awake ratings were significantly more frequent for S 2 (45.5%) than for REM sleep (11.8%). The difference between sleep states was most pronounced for insomniacs (58.1% awake ratings in S2 vs. 5.3% in REM sleep). Mismatches between measured sleep and perceived state are quite frequent, with a greater disparity for S2 than for REM sleep, especially in insomniac patients. We suggest that state judgement is contingent not only on the state of the sleep regulating system but also on cognitive processes associated with processing of external and internal stimuli, and dreaming.
Hossain et al. (2005) have recently suggested that fatigue and sleepiness can be independent cons... more Hossain et al. (2005) have recently suggested that fatigue and sleepiness can be independent consequences of sleep disorders. They found that a majority (64%) of referred patients with sleep disorders had pathological fatigue scores without overlap of sleepiness, while only 4% had pathological sleepiness without overlapping fatigue. To clarify the relationship between fatigue and sleepiness is of general interest since fatigue is a frequently encountered symptom also in other diseases such as multiple sclerosis (MS), where fatigue is one of the most disabling symptoms. Here we present data on the relationship of fatigue and sleepiness in a sample of 53 patients (39 females, 14 males) with relapsing-remitting or secondary progressive MS from an ongoing study on fatigue and actimetry in MS patients. Patients had a mean age of 42 ± 11 years. Mean duration of the disease was 7.3 ± 6.7 years and the mean score on the Expanded Disability Status Scale (EDSS) was 2.8 ± 1.5. All patients were under treatment with Interferon-beta 1b (Beta-feron). Exclusion criteria were psychoactive medication or treatment with corticosteroids during the last 3 months. The patients completed different questionnaires, two of them addressing fatigue and sleepiness. As in the study by Hossain et al. (2005) fatigue was assessed by the Fatigue Severity Scale (FSS; Krupp et al., 1989) and sleepiness by the Epworth Sleepiness Scale (ESS; Johns, 1991). Mean (±SD) scores were 4.2 ± 1.6 for the FSS, and 8.3 ± 3.7 for the ESS. We adopted from Hossain et al. an FSS cutoff scores >3 for increased fatigue and an ESS cutoff score >10 for pathological sleepiness. As in the Hossain et al. analysis we classified the MS patients into four groups according to their FSS and ESS scores. Twenty-five patients (47.2%) were fatigued but not sleepy, 12 patients (22.6%) were both fatigued and sleepy while only three patients (5.7%) were not fatigued but sleepy. The remaining 13 patients (24.5%) were neither fatigued nor sleepy (Fig. 1). The observed proportions are close to those reported by Hossain et al. for patients with sleep disorders, 63.9% scored high on fatigue only, 19.1% on fatigue and sleepiness, 3.9% on sleepiness only and 13.1% neither on fatigue nor on sleepiness. The data from both samples suggest that self-rated fatigue and sleepiness are two dimensions, which vary independently to a large degree. However, while Hossain et al. reported a low correlation (r ¼ 0.18) between FSS and ESS total scores, this correlation was higher and significant (r ¼ 0.52, P < 0.001) for our sample of MS patients. To further explore the relationship between the two scales, we have performed a single-item analysis (chi-squared tests). Taking multiple testing into account, only P-values £ 0.01 were accepted as statistically significant. Four of eight ESS items were significantly related to one or more FSS items, namely the items ESS 1 (sitting and reading), ESS 2 (watching TV), ESS 3 (sitting, inactive in a public place, e.g. a theatre or a meeting) and ESS 4 (as a passenger in a car for an hour without a break). From the nine FSS items, only three (FSS 1, FSS 3 and FSS 4) were significantly related to single ESS items. The single-item analysis showed that there is limited overlap between both scales, and that the correlation between the FSS and ESS total scores depends essentially on a subset of items. The four ESS items, which were significantly related to FSS items describe situations where patients tend to fall asleep unintentionally while sitting more or less inactive. The four remaining ESS items, which did not correlate significantly with FSS items, describe situations where sleepiness is either intended or at least not clearly avoided, as in item 5 (ÔLying down to rest in the afternoon when circumstances permitÕ) and item 7 (ÔSitting quietly after a lunch without alcoholÕ), or situations, where sleepiness would be absolutely inappropriate as in items 6 (ÔSitting and talking to someoneÕ) and 8 (ÔIn a car, while stopped for a few minutes in trafficÕ). It would be of interest to see whether patients with sleep disorders show a
Fatigue is a frequent and disabling symptom in patients with multiple sclerosis (MS). The objecti... more Fatigue is a frequent and disabling symptom in patients with multiple sclerosis (MS). The objective of the study was to compare fatigue and sleepiness in MS, and their relationship to physical activity. Eighty patients with MS rated the extent of experienced fatigue (Fatigue Severity Scale, FSS) and sleepiness (Epworth Sleepiness Scale, ESS). The relationship between the scales was analysed for the scales as a whole and for single items. The clinical status of the patients was measured with the Extended Disability Status Scale (EDSS). In addition, physical activity was recorded continuously for 1 week by wrist actigraphy. The mean scores of fatigue and sleepiness were significantly correlated (FSS vs. ESS r = 0.42). Single item analysis suggests that fatigue and sleepiness converge for situations that demand self-paced activation, while they differ for situations in which external cues contribute to the level of activation. While fatigue correlated significantly with age (r = 0.40), disease severity (EDSS, r = 0.38), and disease duration (r = 0.25), this was not the case for sleepiness. Single patient analysis showed a larger scatter of sleepiness scores in fatigued patients (FSS [ 4) than in non-fatigued patients. Probably, there is a subgroup of MS patients with sleep disturbances that rate high on ESS and FSS. The amount of physical activity, which was measured actigraphically, decreased with disease severity (EDSS) while it did not correlate with fatigue or sleepiness.
Sleep disorders are frequently associated with impaired performance although the type and extent ... more Sleep disorders are frequently associated with impaired performance although the type and extent of cognitive deficits varies widely between different types of sleep disorders. Treatment is expected to ameliorate these deficits. However, cognitive functioning and its change with treatment depend on numerous factors. In this chapter we discuss methodological issues, including test selection, and personspecific, task-specific and environmental factors that influence cognitive functioning. In addition, features of study design and sampling strategies are discussed. The chapter ends with a short overview of routes by which treatment may affect cognition in sleep-disordered patients.
The 2-process model, initially put forward by Borbély in 1982, describes sleep-wake behavior as r... more The 2-process model, initially put forward by Borbély in 1982, describes sleep-wake behavior as regulated by the additive interaction of a circadian and a homeostatic process. The output of the model is dichotomous, either sleep or awake, and not a continuous function of sleep propensity (SP). The " distance " between the homeostatic component S and the circadian component C at a given time might be accepted as a continuous measure of SP, implying additive interaction of C and S. However, an additive interaction misses two abundantly described components of the sleep wake cycle, namely the afternoon nap (or performance dip) zone and the evening wake maintenance (or forbidden sleep) zone. We propose two modifications of the 2-process model, to include also these daytime variations. First, the modified model is based on the interaction of two main sleep drives, one for Slow-wave-and one for REM sleep. While we keep process S, we have replaced the circadian double-threshold process C by a single circadian sleep drive R, derived from REM sleep. Second, comparison between different modes of action between the two regulating processes strongly suggests that a model with a multiplicative interaction between S and R optimally describes the known variations of human SP. Multiplicative interaction of S with R implies that the two processes may either magnify or dampen each other at a given time. Under the condition of a normal phase and duration of nighttime sleep, our SxR model successfully displays four characteristics across 24 hours for SP: (a) a major peak at nighttime, (b) a secondary increase peaking post-noon, (c) a local minimum at sleep offset in the morning and (d) a second local minimum in the evening hours. Simulations with delayed or advanced night sleep times suggest that the magnitude of the post-noon SP depends on the phase of the preceding night sleep period. While post-noon SP attenuated or disappeared with phase delays of night sleep, phase advancing resulted in an increase of SP during daytime. In contrast, the evening local minimum of SP remained stable in all conditions. We conclude that a simple, straightforward multiplication of the intensities of two sleep drives, one circadian and the other homeostatic, appears to be sufficient to model the major aspects of the SP variations across 24 hours. Furthermore it is conceptually very attractive that in our model the two main constituents of sleep, REM sleep and non-REM sleep, both contribute to SP. Figure 1. The time courses for the homeostatic sleep drive S (filled circles) and the circadian sleep drive R (open circles) are represented in the lower panel. The scale is relative, running in arbitrary units (a.u.) from 0 (low) to 1 (high). The sleep propensity function (SP, open squares, upper panel) was computed by multiplying the values of S and R at each point in time. An eight hour sleep episode (hatched bar) is assumed to take place between 24:00h and 08:00h.
We have read with interest the recent article by Paech et al. 1 in this journal. The authors have... more We have read with interest the recent article by Paech et al. 1 in this journal. The authors have performed an important study with the aim to disentangle homeostatic and circadian influences on sleep under conditions of high sleep pressure, induced by severe sleep restriction with only 4.7 h of sleep per 28-hour sleep-wake cycle of a forced desynchrony protocol. 1,2 Their results show a strong homeostatic sleep drive, an attenuated circadian modulation in different sleep variables and most important, a loss of circadian modulation of sleep efficiency, which was found to be above 90% at any circadian phase. The latter result differs clearly from results of studies which had measured sleep efficiency in either forced desynchrony protocols with a 1:2 sleep-wake ratio 3,4 or ultra-short sleep-wake cycles for 24 hours. 5 In all these studies sleep efficiency displayed an explicit circadian modulation, with less sleep in the so-called forbidden zone of sleep 5 or wake maintenance zone, 6 which corresponds to the rising limb of core body temperature, near its circadian crest. Lavie et al. 5 observed a pronounced circadian modulation of sleep efficiency, sparing the wake maintenance zone, even after a preceding night without sleep.
SUMMARY While electrophysiologically measured sleep and perception of sleep generally concur, var... more SUMMARY While electrophysiologically measured sleep and perception of sleep generally concur, various studies have shown this is not always the case. The objective of the present study was to assess the perception of actual state during sleep by the technique of planned awakenings and interviewing subjects on the preawakening state. Sixty-eight (43 females, 25 males) young (mean age: 24.1, SD 5.1 years) normal sleeping subjects were deliberately awakened out of consolidated sleep, either stage 2 (S2), or REM sleep, during the first night in a non-clinical sleep laboratory. While the preawakening state was experienced as sleep in 48 cases (70.6%), it was experienced as wakefulness in 20 cases (29.4%). The percentage of awake judgements was somewhat, but not significantly, higher for awakenings out of S2 (38.2%), to REM sleep (20.6%). The proportion of mismatches between electrophysiologically defined sleep and state judgements was time-dependent with more awake judgements for REM sleep in the second half of the sleep period (41.7%) than in the first one (17.4%). Those subjects who made an awake judgement more frequently had a feeling of being aware of the situation and their surroundings than those who made a sleep judgement (80% versus 33%). Awareness during sleep may be a cognitive style, which favours mismatches between state perception and electrophysiologically defined sleep. Sleep periods with concordant or discordant state judgements did not differ in electrophysiologically defined sleep onset latency, sleep efficiency, or sleep state distribution. k e y w o r d s awakening, awareness, cognitive activity, sleep perception
SUMMAR Y Daytime tiredness or sleepiness and deficits in cognitive performance are common complai... more SUMMAR Y Daytime tiredness or sleepiness and deficits in cognitive performance are common complaints in sleep disordered patients. Till now there are few studies comparing patients from different diagnostic groups of sleep disorders in the same experimental protocol. We studied the time course of cognitive functions and subjective alertness in a parallel group design with four groups of patients [narcolepsy, untreated or treated obstructive sleep apnea (OSA), or psychophysiological insomnia] and a control group of subjects without sleep complaints. Each group consisted of 10 subjects, matched for age and gender. After a night with polysomnography, subjects were studied for 10 h from 08:00 hours to 18:00 hours at 20 min intervals under standardized environmental conditions. Four psychological tests were applied, (1) a critical flicker fusion (CFF) test to measure optical fusion threshold (alertness); (2) a paper-and-pencil visual line tracking test (selective attention); (3) a visual analog scale (VAS) for tiredness/ sleepiness; and (4) the Tiredness Symptoms Scale (TSS), a 14 items check list. Each test session lasted for 8 min, followed by a 12 min pause. The level and time course of cognitive performance and self-rating data were analysed with hierarchical linear mixed effects models. Cognitive tests showed decrements in alertness and selective attention in untreated patients with insomnia, narcolepsy, and sleep apnea. Narcoleptic patients and untreated OSA had a lower CFF threshold than controls, and for narcoleptic patients the time course differed from that of all other groups. In the visual tracking test the performance of all groups of patients was worse compared with normal controls. Self-rated tiredness/sleepiness was significantly more pronounced in the three groups of untreated patients than in control subjects. k e y w o r d s alertness, cognitive performance, critical flicker fusion, insomnia, narcolepsy, obstructive sleep apnea, selective attention, sleepiness, tiredness
Spontaneous awakenings from sleep were studied in a group of 20 infants whose sleep-waking patter... more Spontaneous awakenings from sleep were studied in a group of 20 infants whose sleep-waking patterns were recorded polygraphically for 24 h. While 10 infants were orally fed the other 10 underwent continuous feeding for various gastrointestinal diseases. Spontaneous awakening from sleep was analysed with regard to the prior sleep state, age and feeding condition. Infants awoke preferentially out of REM sleep and less often out of non-REM sleep. The feeding condition had no significant influence on the distribution of awakenings. The propensity for REM awakenings was significantly greater than would have been expected according to the REM sleep amount. This tendency was more pronounced for younger (__< 3 months) than for older (> 4 months) infants. REM sleep episodes which were interrupted by awakenings were significantly shorter than uninterrupted ones, since awakenings occurred predominantly shortly after REM sleep onset. It is proposed that the specific pattern of brain activity during REM sleep facilitates the transition from sleep into the waking state, particularly in the youngest infants.
A 1-year systematic diary was kept by an anonymous diarist in Hamburg in the year 1755-1756. Slee... more A 1-year systematic diary was kept by an anonymous diarist in Hamburg in the year 1755-1756. Sleep, activities, food intake, urine volume, and meteorological data were documented daily. The systematic recording of sleep and naps, with an accuracy of a quarter of an hour allowed analysis of the placement, duration, and consistency of sleep.
Sleep became a subject of scientific research in the second half of the 19th century. Since sleep... more Sleep became a subject of scientific research in the second half of the 19th century. Since sleep, unlike other physiological functions, cannot be attributed to a specific organ, there was no distinct method available to study sleep until then. With the development of physiology and psychology, and a rapidly increasing knowledge of the structure and functioning of the nervous system, certain aspects of sleep became accessible to objective study. A first step was to measure responsiveness to external stimuli systematically, during sleep, allowing a first representation of the course of sleep (Schlaftiefe = sleep depth). A second method was to register continuously the motor activity across the sleep–wake cycle, which allowed the documentation in detail of rest–activity patterns of monophasic and polyphasic sleep–wake rhythms, or between day or night active animals. The central measurement for sleep research, however, became the electroencephalogram in the 1930s, which allowed observation of the sleeping brain with high temporal resolution. Beside the development of instruments to measure sleep, prolonged sleep deprivation was applied to study physiological and psychological effects of sleep loss. Another input came from clinical and neuropathological observations of patients with pronounced disorders of the sleep–wake cycle, which for the first time allowed localisation of brain areas that are essentially involved in the regulation of sleep and wakefulness. Experimental brain stimulation and lesion studies were carried out with the same aim at this time. Many of these activities came to a halt on the eve of World War II. It was only in the early 1950s, when periods with rapid eye movements during sleep were recognised, that sleep became a research topic of itself. Jouvet and his team explored the brain mechanisms and transmitters of paradoxical sleep, and experimental sleep research became established in all European countries. Sleep medicine evolving simultaneously in different countries, with early centres in Italy and France. In the late 1960s sleep research and chronobiology began to merge. In recent decades, sleep research, dream research, and sleep medicine have benefited greatly from new methods in genetic research and brain imaging techniques. Genes were identified that are involved in the regulation of sleep, circadian rhythms, or sleep disorders. Functional imaging enabled a high spatial resolution of the activity of the sleeping brain, complementing the high temporal resolution of the electroencephalogram.
Geschichte der Schlafmedizin • Überblick über die Bedeutung des Schlafs in der Medizin von der An... more Geschichte der Schlafmedizin • Überblick über die Bedeutung des Schlafs in der Medizin von der Antike bis zur aktuellen Schlaff orschung • Entdeckung und Klassifi kation der unterschiedlichen Schlafstörungen im Verlauf der Jahrhunderte Kernaussagen 6.1 Einleitung Wissen über den Schlaf gehört seit der Antike zur ärztlichen Kunst. Hippocrates (c. 460-c. 375 v. Chr.) und Galen (c. 129-c. 199 n. Chr.) blieben mit ihrem Wissen und ihren Anschauungen bis in die frühe Neuzeit die verbindlichen Autoritäten auch für das Erkennen und Behandeln von Störungen des Schlafs und des Wachseins. Der große islamische Arzt und Gelehrte Al-Razi (Rhazes, c. 854-925 / 935 n. Chr.) kompilierte und verbreitete dieses Wissen, zusammen mit den ihm bekannten indischen und chinesischen Quellen. Der andere führende Mediziner und Philosoph des Orients war Ibn Sina, latinisiert Avicenna (c. 980-1037 n. Chr.). Sein "Canon Medicinae", der die Anatomie, Physiologie, Krankheits-und Arzneilehre umfasste, galt bis zum Ende des 15. Jahrhunderts als das vollständigste medizinische Lehrbuch. Angaben über den Schlaf und die Schlafstörungen Incubus und Wachsein der Kinder im Schlaf fi ndet sich in den Werken beider Ärzte. Die früheste und größte medizinische Schule des Mittelalters war die von Salerno. Hier wurde eine Gesundheitslehre entwickelt, die bis in die frühe Neuzeit ärztliches Handeln beeinfl usste. Von ganz unmittelbarem Interesse für die Medizin waren dabei die beiden Bücher des Aristoteles (384-322 v. Chr.) über den Schlaf und über die Träume. Das Wachsein (vigilia) ist bei Aristoteles durch die Fähigkeit zur Wahrnehmung gekennzeichnet, der Schlaf (somno) durch dessen Abwesenheit. Das Vermögen der Wahrnehmung hat seinen Sitz im
Measured and rated sleep differ in normal sleepers and even more in patients with sleep disorders.... more Measured and rated sleep differ in normal sleepers and even more in patients with sleep disorders. The study aimed to asses sleep/wake perception in electrophysiologically defined sleep in patients with sleep disorders. 117 consecutively referred patients (75 females), median age 50.3 years, range 20–73 years) with various sleep disorders were randomized for one induced waking, either out of stage 2 (S2) or REM sleep, as part of a clinical routine polysomnography. Patients were classified as either nonsleepy (Epworth Sleepiness Scale score ESS ≤ 10) or sleepy (ESS ≥ 11). The most frequent diagnoses of non-sleepy patients were insomnia and RLS, while sleepy patients suffered predominantly from OSAS, hypersomnia and insufficient sleep syndrome. Subjects were deliberately aroused once, either out of consolidated stage 2 sleep (n = 66) or REM sleep (n = 51) and asked for sleep/wake perception (sleep/wake and related questions). While 81 (69.2%) of the subjects estimated that they had been sleeping or dozing before they were aroused, 36 (30.8%) reported that they had been awake. Awake ratings were significantly more frequent for S 2 (45.5%) than for REM sleep (11.8%). The difference between sleep states was most pronounced for insomniacs (58.1% awake ratings in S2 vs. 5.3% in REM sleep). Mismatches between measured sleep and perceived state are quite frequent, with a greater disparity for S2 than for REM sleep, especially in insomniac patients. We suggest that state judgement is contingent not only on the state of the sleep regulating system but also on cognitive processes associated with processing of external and internal stimuli, and dreaming.
Hossain et al. (2005) have recently suggested that fatigue and sleepiness can be independent cons... more Hossain et al. (2005) have recently suggested that fatigue and sleepiness can be independent consequences of sleep disorders. They found that a majority (64%) of referred patients with sleep disorders had pathological fatigue scores without overlap of sleepiness, while only 4% had pathological sleepiness without overlapping fatigue. To clarify the relationship between fatigue and sleepiness is of general interest since fatigue is a frequently encountered symptom also in other diseases such as multiple sclerosis (MS), where fatigue is one of the most disabling symptoms. Here we present data on the relationship of fatigue and sleepiness in a sample of 53 patients (39 females, 14 males) with relapsing-remitting or secondary progressive MS from an ongoing study on fatigue and actimetry in MS patients. Patients had a mean age of 42 ± 11 years. Mean duration of the disease was 7.3 ± 6.7 years and the mean score on the Expanded Disability Status Scale (EDSS) was 2.8 ± 1.5. All patients were under treatment with Interferon-beta 1b (Beta-feron). Exclusion criteria were psychoactive medication or treatment with corticosteroids during the last 3 months. The patients completed different questionnaires, two of them addressing fatigue and sleepiness. As in the study by Hossain et al. (2005) fatigue was assessed by the Fatigue Severity Scale (FSS; Krupp et al., 1989) and sleepiness by the Epworth Sleepiness Scale (ESS; Johns, 1991). Mean (±SD) scores were 4.2 ± 1.6 for the FSS, and 8.3 ± 3.7 for the ESS. We adopted from Hossain et al. an FSS cutoff scores >3 for increased fatigue and an ESS cutoff score >10 for pathological sleepiness. As in the Hossain et al. analysis we classified the MS patients into four groups according to their FSS and ESS scores. Twenty-five patients (47.2%) were fatigued but not sleepy, 12 patients (22.6%) were both fatigued and sleepy while only three patients (5.7%) were not fatigued but sleepy. The remaining 13 patients (24.5%) were neither fatigued nor sleepy (Fig. 1). The observed proportions are close to those reported by Hossain et al. for patients with sleep disorders, 63.9% scored high on fatigue only, 19.1% on fatigue and sleepiness, 3.9% on sleepiness only and 13.1% neither on fatigue nor on sleepiness. The data from both samples suggest that self-rated fatigue and sleepiness are two dimensions, which vary independently to a large degree. However, while Hossain et al. reported a low correlation (r ¼ 0.18) between FSS and ESS total scores, this correlation was higher and significant (r ¼ 0.52, P < 0.001) for our sample of MS patients. To further explore the relationship between the two scales, we have performed a single-item analysis (chi-squared tests). Taking multiple testing into account, only P-values £ 0.01 were accepted as statistically significant. Four of eight ESS items were significantly related to one or more FSS items, namely the items ESS 1 (sitting and reading), ESS 2 (watching TV), ESS 3 (sitting, inactive in a public place, e.g. a theatre or a meeting) and ESS 4 (as a passenger in a car for an hour without a break). From the nine FSS items, only three (FSS 1, FSS 3 and FSS 4) were significantly related to single ESS items. The single-item analysis showed that there is limited overlap between both scales, and that the correlation between the FSS and ESS total scores depends essentially on a subset of items. The four ESS items, which were significantly related to FSS items describe situations where patients tend to fall asleep unintentionally while sitting more or less inactive. The four remaining ESS items, which did not correlate significantly with FSS items, describe situations where sleepiness is either intended or at least not clearly avoided, as in item 5 (ÔLying down to rest in the afternoon when circumstances permitÕ) and item 7 (ÔSitting quietly after a lunch without alcoholÕ), or situations, where sleepiness would be absolutely inappropriate as in items 6 (ÔSitting and talking to someoneÕ) and 8 (ÔIn a car, while stopped for a few minutes in trafficÕ). It would be of interest to see whether patients with sleep disorders show a
Fatigue is a frequent and disabling symptom in patients with multiple sclerosis (MS). The objecti... more Fatigue is a frequent and disabling symptom in patients with multiple sclerosis (MS). The objective of the study was to compare fatigue and sleepiness in MS, and their relationship to physical activity. Eighty patients with MS rated the extent of experienced fatigue (Fatigue Severity Scale, FSS) and sleepiness (Epworth Sleepiness Scale, ESS). The relationship between the scales was analysed for the scales as a whole and for single items. The clinical status of the patients was measured with the Extended Disability Status Scale (EDSS). In addition, physical activity was recorded continuously for 1 week by wrist actigraphy. The mean scores of fatigue and sleepiness were significantly correlated (FSS vs. ESS r = 0.42). Single item analysis suggests that fatigue and sleepiness converge for situations that demand self-paced activation, while they differ for situations in which external cues contribute to the level of activation. While fatigue correlated significantly with age (r = 0.40), disease severity (EDSS, r = 0.38), and disease duration (r = 0.25), this was not the case for sleepiness. Single patient analysis showed a larger scatter of sleepiness scores in fatigued patients (FSS [ 4) than in non-fatigued patients. Probably, there is a subgroup of MS patients with sleep disturbances that rate high on ESS and FSS. The amount of physical activity, which was measured actigraphically, decreased with disease severity (EDSS) while it did not correlate with fatigue or sleepiness.
Sleep disorders are frequently associated with impaired performance although the type and extent ... more Sleep disorders are frequently associated with impaired performance although the type and extent of cognitive deficits varies widely between different types of sleep disorders. Treatment is expected to ameliorate these deficits. However, cognitive functioning and its change with treatment depend on numerous factors. In this chapter we discuss methodological issues, including test selection, and personspecific, task-specific and environmental factors that influence cognitive functioning. In addition, features of study design and sampling strategies are discussed. The chapter ends with a short overview of routes by which treatment may affect cognition in sleep-disordered patients.
The 2-process model, initially put forward by Borbély in 1982, describes sleep-wake behavior as r... more The 2-process model, initially put forward by Borbély in 1982, describes sleep-wake behavior as regulated by the additive interaction of a circadian and a homeostatic process. The output of the model is dichotomous, either sleep or awake, and not a continuous function of sleep propensity (SP). The " distance " between the homeostatic component S and the circadian component C at a given time might be accepted as a continuous measure of SP, implying additive interaction of C and S. However, an additive interaction misses two abundantly described components of the sleep wake cycle, namely the afternoon nap (or performance dip) zone and the evening wake maintenance (or forbidden sleep) zone. We propose two modifications of the 2-process model, to include also these daytime variations. First, the modified model is based on the interaction of two main sleep drives, one for Slow-wave-and one for REM sleep. While we keep process S, we have replaced the circadian double-threshold process C by a single circadian sleep drive R, derived from REM sleep. Second, comparison between different modes of action between the two regulating processes strongly suggests that a model with a multiplicative interaction between S and R optimally describes the known variations of human SP. Multiplicative interaction of S with R implies that the two processes may either magnify or dampen each other at a given time. Under the condition of a normal phase and duration of nighttime sleep, our SxR model successfully displays four characteristics across 24 hours for SP: (a) a major peak at nighttime, (b) a secondary increase peaking post-noon, (c) a local minimum at sleep offset in the morning and (d) a second local minimum in the evening hours. Simulations with delayed or advanced night sleep times suggest that the magnitude of the post-noon SP depends on the phase of the preceding night sleep period. While post-noon SP attenuated or disappeared with phase delays of night sleep, phase advancing resulted in an increase of SP during daytime. In contrast, the evening local minimum of SP remained stable in all conditions. We conclude that a simple, straightforward multiplication of the intensities of two sleep drives, one circadian and the other homeostatic, appears to be sufficient to model the major aspects of the SP variations across 24 hours. Furthermore it is conceptually very attractive that in our model the two main constituents of sleep, REM sleep and non-REM sleep, both contribute to SP. Figure 1. The time courses for the homeostatic sleep drive S (filled circles) and the circadian sleep drive R (open circles) are represented in the lower panel. The scale is relative, running in arbitrary units (a.u.) from 0 (low) to 1 (high). The sleep propensity function (SP, open squares, upper panel) was computed by multiplying the values of S and R at each point in time. An eight hour sleep episode (hatched bar) is assumed to take place between 24:00h and 08:00h.
We have read with interest the recent article by Paech et al. 1 in this journal. The authors have... more We have read with interest the recent article by Paech et al. 1 in this journal. The authors have performed an important study with the aim to disentangle homeostatic and circadian influences on sleep under conditions of high sleep pressure, induced by severe sleep restriction with only 4.7 h of sleep per 28-hour sleep-wake cycle of a forced desynchrony protocol. 1,2 Their results show a strong homeostatic sleep drive, an attenuated circadian modulation in different sleep variables and most important, a loss of circadian modulation of sleep efficiency, which was found to be above 90% at any circadian phase. The latter result differs clearly from results of studies which had measured sleep efficiency in either forced desynchrony protocols with a 1:2 sleep-wake ratio 3,4 or ultra-short sleep-wake cycles for 24 hours. 5 In all these studies sleep efficiency displayed an explicit circadian modulation, with less sleep in the so-called forbidden zone of sleep 5 or wake maintenance zone, 6 which corresponds to the rising limb of core body temperature, near its circadian crest. Lavie et al. 5 observed a pronounced circadian modulation of sleep efficiency, sparing the wake maintenance zone, even after a preceding night without sleep.
SUMMARY While electrophysiologically measured sleep and perception of sleep generally concur, var... more SUMMARY While electrophysiologically measured sleep and perception of sleep generally concur, various studies have shown this is not always the case. The objective of the present study was to assess the perception of actual state during sleep by the technique of planned awakenings and interviewing subjects on the preawakening state. Sixty-eight (43 females, 25 males) young (mean age: 24.1, SD 5.1 years) normal sleeping subjects were deliberately awakened out of consolidated sleep, either stage 2 (S2), or REM sleep, during the first night in a non-clinical sleep laboratory. While the preawakening state was experienced as sleep in 48 cases (70.6%), it was experienced as wakefulness in 20 cases (29.4%). The percentage of awake judgements was somewhat, but not significantly, higher for awakenings out of S2 (38.2%), to REM sleep (20.6%). The proportion of mismatches between electrophysiologically defined sleep and state judgements was time-dependent with more awake judgements for REM sleep in the second half of the sleep period (41.7%) than in the first one (17.4%). Those subjects who made an awake judgement more frequently had a feeling of being aware of the situation and their surroundings than those who made a sleep judgement (80% versus 33%). Awareness during sleep may be a cognitive style, which favours mismatches between state perception and electrophysiologically defined sleep. Sleep periods with concordant or discordant state judgements did not differ in electrophysiologically defined sleep onset latency, sleep efficiency, or sleep state distribution. k e y w o r d s awakening, awareness, cognitive activity, sleep perception
SUMMAR Y Daytime tiredness or sleepiness and deficits in cognitive performance are common complai... more SUMMAR Y Daytime tiredness or sleepiness and deficits in cognitive performance are common complaints in sleep disordered patients. Till now there are few studies comparing patients from different diagnostic groups of sleep disorders in the same experimental protocol. We studied the time course of cognitive functions and subjective alertness in a parallel group design with four groups of patients [narcolepsy, untreated or treated obstructive sleep apnea (OSA), or psychophysiological insomnia] and a control group of subjects without sleep complaints. Each group consisted of 10 subjects, matched for age and gender. After a night with polysomnography, subjects were studied for 10 h from 08:00 hours to 18:00 hours at 20 min intervals under standardized environmental conditions. Four psychological tests were applied, (1) a critical flicker fusion (CFF) test to measure optical fusion threshold (alertness); (2) a paper-and-pencil visual line tracking test (selective attention); (3) a visual analog scale (VAS) for tiredness/ sleepiness; and (4) the Tiredness Symptoms Scale (TSS), a 14 items check list. Each test session lasted for 8 min, followed by a 12 min pause. The level and time course of cognitive performance and self-rating data were analysed with hierarchical linear mixed effects models. Cognitive tests showed decrements in alertness and selective attention in untreated patients with insomnia, narcolepsy, and sleep apnea. Narcoleptic patients and untreated OSA had a lower CFF threshold than controls, and for narcoleptic patients the time course differed from that of all other groups. In the visual tracking test the performance of all groups of patients was worse compared with normal controls. Self-rated tiredness/sleepiness was significantly more pronounced in the three groups of untreated patients than in control subjects. k e y w o r d s alertness, cognitive performance, critical flicker fusion, insomnia, narcolepsy, obstructive sleep apnea, selective attention, sleepiness, tiredness
Spontaneous awakenings from sleep were studied in a group of 20 infants whose sleep-waking patter... more Spontaneous awakenings from sleep were studied in a group of 20 infants whose sleep-waking patterns were recorded polygraphically for 24 h. While 10 infants were orally fed the other 10 underwent continuous feeding for various gastrointestinal diseases. Spontaneous awakening from sleep was analysed with regard to the prior sleep state, age and feeding condition. Infants awoke preferentially out of REM sleep and less often out of non-REM sleep. The feeding condition had no significant influence on the distribution of awakenings. The propensity for REM awakenings was significantly greater than would have been expected according to the REM sleep amount. This tendency was more pronounced for younger (__< 3 months) than for older (> 4 months) infants. REM sleep episodes which were interrupted by awakenings were significantly shorter than uninterrupted ones, since awakenings occurred predominantly shortly after REM sleep onset. It is proposed that the specific pattern of brain activity during REM sleep facilitates the transition from sleep into the waking state, particularly in the youngest infants.
For centuries the scope of sleep disorders in medical writings was limited to those disturbances ... more For centuries the scope of sleep disorders in medical writings was limited to those disturbances which were either perceived by the sleeper him-or herself as troublesome, such as insomnia, or which were recognized by an observer as strange behavioral acts during sleep, such as sleepwalking or sleep terror. Awareness of other sleep disorders, which are caused by malfunction of a physiological system during sleep, such as sleep-related respiratory disorders, were widely unknown or ignored before sleep monitoring techniques became available, mainly in the second half of the 20 th century. Finally, circadian sleep-wake disorders were recognized as a group of disturbances by its own only when chronobiology and sleep research began to interact extensively in the last two decades of the 20 th century. Sleep medicine as a medical specialty with its own diagnostic procedures and therapeutic strategies could be established only when key findings in neurophysiology and basic sleep research allowed a breakthrough in the understanding of the sleeping brain, mainly since the second half of the last century.
Uploads
Papers by Hartmut Schulz
accessible to objective study. A first step was to measure responsiveness to external stimuli systematically, during sleep, allowing a first representation of the course of sleep (Schlaftiefe = sleep depth). A second method was to register continuously the motor activity across the sleep–wake cycle, which allowed the documentation in detail of rest–activity patterns of monophasic and polyphasic sleep–wake rhythms, or between day or night active animals. The central measurement for sleep research,
however, became the electroencephalogram in the 1930s, which allowed observation
of the sleeping brain with high temporal resolution. Beside the development of instruments to measure sleep, prolonged sleep deprivation was applied to study physiological and psychological effects of sleep loss. Another input came from clinical and neuropathological observations of patients with pronounced disorders of the sleep–wake cycle, which for the first time allowed localisation of brain areas that are
essentially involved in the regulation of sleep and wakefulness. Experimental brain stimulation and lesion studies were carried out with the same aim at this time. Many of these activities came to a halt on the eve of World War II. It was only in the early 1950s, when periods with rapid eye movements during sleep were recognised, that sleep became a research topic of itself. Jouvet and his team explored the brain mechanisms and transmitters of paradoxical sleep, and experimental sleep research became established in all European countries. Sleep medicine evolving simultaneously in different countries, with early centres in Italy and France. In the late 1960s sleep research and chronobiology began to merge. In recent decades, sleep research, dream research, and sleep medicine have benefited greatly from new methods in genetic research and brain imaging techniques. Genes were identified that are involved in the regulation of sleep, circadian rhythms, or sleep disorders.
Functional imaging enabled a high spatial resolution of the activity of the sleeping brain, complementing the high temporal resolution of the electroencephalogram.
accessible to objective study. A first step was to measure responsiveness to external stimuli systematically, during sleep, allowing a first representation of the course of sleep (Schlaftiefe = sleep depth). A second method was to register continuously the motor activity across the sleep–wake cycle, which allowed the documentation in detail of rest–activity patterns of monophasic and polyphasic sleep–wake rhythms, or between day or night active animals. The central measurement for sleep research,
however, became the electroencephalogram in the 1930s, which allowed observation
of the sleeping brain with high temporal resolution. Beside the development of instruments to measure sleep, prolonged sleep deprivation was applied to study physiological and psychological effects of sleep loss. Another input came from clinical and neuropathological observations of patients with pronounced disorders of the sleep–wake cycle, which for the first time allowed localisation of brain areas that are
essentially involved in the regulation of sleep and wakefulness. Experimental brain stimulation and lesion studies were carried out with the same aim at this time. Many of these activities came to a halt on the eve of World War II. It was only in the early 1950s, when periods with rapid eye movements during sleep were recognised, that sleep became a research topic of itself. Jouvet and his team explored the brain mechanisms and transmitters of paradoxical sleep, and experimental sleep research became established in all European countries. Sleep medicine evolving simultaneously in different countries, with early centres in Italy and France. In the late 1960s sleep research and chronobiology began to merge. In recent decades, sleep research, dream research, and sleep medicine have benefited greatly from new methods in genetic research and brain imaging techniques. Genes were identified that are involved in the regulation of sleep, circadian rhythms, or sleep disorders.
Functional imaging enabled a high spatial resolution of the activity of the sleeping brain, complementing the high temporal resolution of the electroencephalogram.