The Development of Sleep Medicine: A Historical Sketch.

ABSTRACT: 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 terrors. 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.

Sleep-readiness signals in insomniacs and good sleepers.

Sleep is preceded by physiological and behavioural events that inform the subject that it is time to sleep. Our hypothesis is that insomniacs do not adequately recognize such signals, thus missing the best time to go to bed. Eighty-seven chronic insomniac participants and 76 age-matched good sleeper controls were recruited. Semi-structured interviews focused on three aspects of nocturnal sleep: features, habitual activities and signals that they usually rely on in order to decide their readiness to sleep. The results showed that insomniacs relied more than good sleepers on external signals (time) than on bodily ones to decide to go to sleep.

Daytime course of sleepiness in de novo Parkinson's disease patients.

Normal subjects show an increase of sleepiness in the morning, early afternoon and before sleep. In the advanced stages of Parkinson's disease (PD) the mean level of sleepiness is quite high, while with respect to healthy subjects it seems to be unchanged in the early stages. The aim of this study was to evaluate the time-course of the sleepiness level during the wakefulness period in untreated patients with early-stage Parkinson's disease. Eighteen Parkinson's disease patients who had never been treated before with dopaminergic drugs (male = 9, female = 9, age: 68.39 ± 1.89, mean ± standard error) and 18 healthy subjects (male = 9, female = 9, age: 67.22 ± 1.98) were recruited for this study. All subjects underwent continuous actigraphic recording for three consecutive days, during which they also completed the Karolinska Sleepiness Scale (KSS) once an hour throughout wakefulness. Our results showed a higher level of sleepiness in the patients than the controls in the hours following awakening and in the early afternoon, specifically at 08:00 and 14:00 hours (08:00 hours, PD patients, KSS: 3 ± 0.3 versus healthy subjects, KSS: 2 ± 0.2, P < 0.05; 14:00 hours, PD patients, KSS: 4.4 ± 0.5 versus healthy subjects, KSS: 3 ± 0.3, P < 0.05). We suggest that some daytime hours are sensitive windows showing the first increase of sleepiness which will spread later to the whole daytime.

Forerunners of REM sleep.

The development of sleep research can be divided into two main periods. The first one was initiated in 1863 by the first systematic measurement of the depth of sleep, the second in 1953 by the discovery of recurrent episodes of rapid eye movements in sleep. The main methodological procedure in the first of these two periods was the measurement of a single physiological variable, while beginning with long-term measurements of the electroencephalogram (EEG) in sleep, multi-channel, polygraphic recording became the method of choice for sleep studies. Although rhythmic changes in the ultradian frequency range of one to 2 h were observed early in many variables during sleep (movements, autonomic functions, penile erections), the recognition of the existence of two different states of sleep (rapid eye movement (REM) and non-rapid eye movement (NREM sleep)) was contingent upon a 'synthetic' view, which focus on the coalescence of multiple variables. The dual concept of sleep organization evolved stepwise in parallel to the rapid growth of neurophysiological knowledge and techniques in the first half of the 20th century, culminating in the discovery of REM sleep.

Factors involved in sleep satisfaction in the elderly.

BACKGROUND: In healthy aged subjects, subjective complaints of poor sleep are not as frequent as one would expect from the notable objective age-related sleep impairments. This discrepancy could depend on the sleep characteristics they require to feel satisfied about their sleep, which could be different from younger subjects. In order to verify this hypothesis, our study aims to identify changes in sleep satisfaction predictors as a function of age. METHODS: Sleep features, both quantitative (sleep latency, sleep duration, frequency and duration of night-time awakenings) and qualitative (calmness of sleep, ease of falling asleep, satisfaction with sleep, ease of awakening, freshness after awakening and sufficient sleep), as well as afternoon nap habits were investigated throughout a pre-arranged interview in healthy individuals: 117 elderly subjects (47 men, 70 women, 65-99 years) and 120 young adults (48 men, 72 women, 19-28 years). RESULTS: Quantitative sleep features worsen with age, whereas qualitative ones are equivalent or even improved in the aged group; only "calmness of sleep" decreases with age. Afternoon nap habits increase in elderly subjects, but they do not appear to be linked to sleep satisfaction. Predictors of sleep satisfaction differ between age groups: freshness after awakening but not frequency of night-time awakenings were relevant for elderly subjects, whereas the opposite was observed in young adults. CONCLUSIONS: These findings point out that sleep satisfaction is preserved in healthy elderly individuals despite the worsening of quantitative night-time sleep features, reflected by the increase of afternoon naps. This discrepancy could be explained by changes in sleep satisfaction determinants, towards which a spontaneous adaptive adjustment is likely to occur in aged subjects. In contrast with young adults, elderly subjects heed the freshness perceived after the awakening and pay little attention to frequent night-time awakenings.

Body movements during night sleep and their relationship with sleep stages are further modified in very old subjects.

The night sleep of 12 healthy subjects aged 76-98 was polygraphically investigated in order to analyse body movements and their association with sleep stages at very old age; this group was compared with 11 healthy old subjects aged 61-75 years. In very old subjects sleep is less punctuated by body movements and the association of body movements with each sleep stage is further modified compared to less old subjects. Short-lasting movements emerge indifferently from stage 1, stage 2 and REM sleep, but are significantly less frequent in SWS. Furthermore, in very old subjects the probability of awakening after body movements is higher than in old subjects, suggesting that sleep is more vulnerable to the occurrence of body movements than at previous ages. The difficulty in the elderly to maintain a stable state expresses the inability to sustain and coordinate stable physiological activities characteristic of the old age. In addition, the presence of numerous awakenings, not preceded by movements, supports the hypothesis that the awakening in the very old people may be a sudden event, as should be confirmed by the study of other behavioural and physiological activities preceding awakening.

Yawning in morning and evening types.

Yawning occurs more frequently in the early morning and in the late evening, close to sleep onset and after the awakening, and it might be linked to sleep propensity. We aimed to study yawning and its temporal distribution in morning and evening subjects who display different sleep-wake and sleepiness rhythms. Sixteen healthy young adults (8 evening-types and 8 morning-types, matched for age and gender) have been selected and instructed to keep their habitual sleep schedules and to signal every yawning occurrence for three consecutive days. Results show that evening-types yawn more frequently than morning-types, particularly during morning hours. Yawning frequency decreases across daytime in evening-types reaching its lowest level in the early evening and increases thereafter. Instead, in morning-types, yawning frequency remains quite low during daytime and increases in the evening. Moreover, both morning and evening types show a progressive increase of yawning frequency in the hours preceding sleep onset, whereas they differ after the awakening. Evening-types show a higher yawning frequency that remains quite stable in the hours following the awakening, while morning-types display a decline in yawning frequency. Our findings show that the temporal distribution of yawning frequency differs between chronotypes, supporting the hypothesis that differences in sleep-wake rhythm affect yawning, which could represent a behavioural sign of sleep propensity.

Yawning frequency and distribution in preterm and near term infants assessed throughout 24-h recordings.

Yawning has been observed in foetuses and preterm infants. The aim of this study was to assess the frequency and the 24 h distribution of yawning in preterm infants. Twelve low-risk infants between 31 and 40 weeks of post-conceptional age (PCA) were continuously video-recorded for 24 h in their incubator. Spontaneous yawning was defined as opening of the mouth to its full extension in a dramatic stretch movement. The results showed that the rate of yawning across the 24-h period was 1.10/h. The highest incidence of yawns was in the waking motility pattern when compared to active sleep or quiet sleep motility patterns. Between 31 and 40 weeks, yawn incidence significantly decreased mainly during the day. The marked decrease in yawn frequency with age may be related to the development of circadian and homeostatic control of sleep and wake.

Spontaneous awakenings in preterm and term infants assessed throughout 24-h video-recordings.

The study aimed to evaluate the development of awakenings during preterm and term age in 12 low-risk infants observed between 33 and 40 weeks of post-conceptional age. Waking was been detected through the analysis of body motility. Gross generalized body movements with prolonged startles, marked stretching and writhing was considered as waking, whereas vigorous, forceful abrupt body movements with high frequency tremor sometimes superimposed upon movements were considered as corresponding to crying. Total number of awakenings in the 24 h does not show significant changes with age, whereas the mean duration increases significantly, which is accounted for mainly by those awakenings starting with crying, in particular, during the day. These data suggest a developmental gap between the ability to sustain the waking state, which already starts to increase before term age, and the ability to maintain prolonged sleep episodes, which has been shown to develop later. Furthermore, the developmental difference between awakenings starting with crying and awakenings starting with wakefulness suggests that two kinds of awakenings might be modulated by different factors.

Music in dreams.

Music in dreams is rarely reported in scientific literature, while the presence of musical themes in dreams of famous musicians is anecdotally reported. We did a systematic investigation to evaluate whether the occurrence of musical dreams could be related to musical competence and practice, and to explore specific features of dreamt pieces. Thirty-five professional musicians and thirty non-musicians filled out a questionnaire about the characteristics of their musical activity and a structured dream log on the awakening for 30 consecutive days. Musicians dream of music more than twice with respect to non-musicians; musical dreams frequency is related to the age of commencement of musical instruction, but not to the daily load of musical activity. Nearly half of the recalled music was non-standard, suggesting that original music can be created in dreams.

Body movements during night sleep in healthy elderly subjects and their relationships with sleep stages.

In order to enlighten the profile of body movements during sleep at old age, the night sleep of twelve elderly subjects was polygraphically investigated; seven young healthy subjects were the control group. Significantly less body movements during sleep were found in the elderly compared to young subjects, meaning that the decrease in the number of body movements observed from infancy to childhood up to adulthood also continues at later ages. Differently from young adult, whose sleep body movements mainly occur in stage REM, no specific sleep state and/or stage was preferentially associated with the occurrence of body movements in the elderly. These data may point to an age-related modification in the interaction between motor cortex control and subcortical circuits. Furthermore, when body movements occur in elderly individuals, they are significantly more often followed in the next 60 s by a sleep stage change or by a spontaneous behavioural awakening. This might reflect a peculiar inability of elderly subjects to sustain stable states, and could also suggest that body movements may act as a co-factor in a process, comprising other physiological changes, leading to state shifts.

What in sleep is for memory.

Since the seminal research by Jenkins and Dallenbach in the 1920s, it has been well proven that sleep has a major effect on the memory of pre-sleep material. However, there is still sparse knowledge about exactly which features of sleep have the most impact. Studies which examined separately the role of non-rapid eye movement (NREM) sleep and rapid eye movement (REM) sleep provided largely controversial results and aroused harsh scientific debate, and the investigation of the link of specific sleep patterns to different memory systems (e.g. declarative vs. procedural) did not fully reconcile these inconsistencies. New research perspectives have been proposed in recent years to overcome the limits of the previous 'single state' approach. Psychological, neurophysiological and neuroanatomical data have recently suggested that NREM and REM sleep both play a part in memory consolidation. We here present the hypothesis that NREM and REM are complementary for memory processes during sleep, thanks to their close interaction within the NREM-REM cycle, and discuss experimental data which prove the critical role of the sleep cycle for the morning recall of verbal material.

Time course of EEG background activity level before spontaneous awakening in the second semester of human life.

This research aimed at investigating the time course of the EEG background activity level before spontaneous awakening out of rapid eye movement (REM) sleep, and non-rapid eye movement sleep with and without slow wave sleep (NREMSWS+, NREMSWS-) in the second semester of life. Twelve infants from 25 to 54 weeks of life were continuously monitored by polygraphic recording and behavioural observation during the night, and the EEG activity was analyzed by a method of automatic analysis. The EEG activation level increased before the awakening out of NREMSWS+ sleep, and was always high both in REM sleep and in NREMSWS-.

Time course of EEG background activity level before spontaneous awakening in infants.

This research aimed to investigate the time course of the cortical activity level preceding spontaneous awakening as a function of age and state. Two groups of infants (1-4 and 9-14 weeks of age) were continuously monitored by polygraphic recording and behavioural observation during the night. The electroencephalographic (EEG) activity recorded by the C3-O1 lead was analysed through an automatic analysis method which provides, for each 30-s epoch, a single measure, time domain based, of the EEG synchronization. The EEG parameter values were computed in the 6 min preceding each awakening out of non-rapid eye movement (NREM) sleep and out of rapid eye movement (REM) sleep. The EEG background activity level did not change in the minutes preceding awakening out of REM sleep. Awakening out of NREM sleep was preceded by a change of EEG activity level in the direction of higher activation with different time course according to the age. Both REM and NREM sleep results suggest that a high level of EEG activity is a prerequisite for the occurrence of a spontaneous awakening.

Yawning and behavioral states in premature infants.

Low risk, premature infants between 30 to 35 weeks post-conceptual age (PCA) residing in an neonatal intensive care unit environment were observed in the home incubator for spontaneous yawning from 2400 to 0500 hr. Videorecordings were analyzed for the behavioral states of quiet sleep (QS), active sleep (AS), wake (W), and drowse (D) in 3-min epochs as well as the contextual behaviors before and after yawn events using a 1-min window. Yawning periods predicted higher levels of motoric activation than nonyawn periods. Sequence analysis of preceding and following states with or without yawns were examined for stability or change. All states with or without yawn events had state stability for the preceding and following epochs, with two exceptions: 1) D state with yawning was associated with state change in the preceding 3-min epoch (most often W), and 2) D state without yawning was associated with state change in the following epoch (W or AS). Yawns were not present in QS. The results suggest that yawning is associated with increased behavioral arousal that is not state-specific. However, yawning in D state predicts state transitions in the preceding, but not the following, epoch. It is proposed that D may be an unstable state that becomes more stable when yawning is present.

Awakening from sleep.

Awakening is a crucial event for the organism. The transition from sleep to waking implies physiological processes which lead to a new behavioural state. Spontaneous awakenings have varying features which may change as a function of several factors. The latter include intrasleep architecture, circadian phase, time awake, age, or disordered sleep. Despite its clear theoretical and clinical importance, the topic of awakening (in humans) has received little attention so far. This contribution focuses on major issues which relate to awakening from both basic (experimental) and clinical research. Recent knowledge on neurophysiological mechanisms is reported. The experimental data which provide in the human suggestions on the regulation of awakening are discussed, mainly those concerning sleep architecture and homeostatic/circadian factors also in a life-span perspective, since age is a powerful factor which may influence awakening. Clinical contributions will examine two main sleep disorders: insomnia and hypersomnia. Daytime functioning is shown in insomniac patients and compared to other pathologies like sleep apnea. A final section evokes links between some types of night waking and psychological factors.

Early steps of awakening process.

This paper summarizes the main aspects of sleep and waking development and shows results about awakening as a function of age. Awakenings come mainly from active sleep and their number decreases with age. Understanding the awakening process should take into account the development of sleep and waking states and of circadian rhythms and homeostatic processes.