Disturbed sleep is among the most frequent health complaints physicians encounter. More than one-half of adults in the United States experience at least intermittent sleep disturbance. For most, it is an occasional night of poor sleep or daytime sleepiness. However, the Institute of Medicine has estimated that 50–70 million Americans suffer from a chronic disorder of sleep and wakefulness, which can lead to serious impairment of daytime functioning. In addition, such problems may contribute to or exacerbate medical or psychiatric conditions. Thirty years ago, many such complaints were treated with hypnotic medications without further diagnostic evaluation. Since then, a distinct class of sleep and arousal disorders has been identified.
Given the opportunity, most adults will sleep 7–8 h per night, although the timing, duration, and internal structure of sleep vary among healthy individuals and as a function of age. At the extremes, infants and the elderly have frequent interruptions of sleep. In the United States, adults tend to have one consolidated sleep episode per day, although in some cultures sleep may be divided into a mid-afternoon nap and a shortened night sleep. Two principal neural systems govern the expression of the sleep and wakefulness states within the daily cycle. The first potentiates sleep in proportion to the duration of wakefulness (the "sleep homeostat"), while the second rhythmically modulates sleep and wakefulness tendencies at appropriate phases of the 24-h day (the circadian clock). Intrinsic abnormalities in the function of either of these systems, or extrinsic disturbances (environmental, drug- or illness-related) that supersede their normal expression, can lead to clinically recognizable sleep disorders.
States and Stages of Sleep
States and stages of human sleep are defined on the basis of characteristic patterns in the electroencephalogram (EEG), the electrooculogram (EOG—a measure of eye-movement activity), and the surface electromyogram (EMG) measured on the chin and neck. The continuous recording of this array of electrophysiologic parameters to define sleep and wakefulness is termed polysomnography.
Polysomnographic profiles define two states of sleep: (1) rapid-eye-movement (REM) sleep and (2) non-rapid-eye-movement (NREM) sleep. NREM sleep is further subdivided into three stages, characterized by increasing arousal threshold and slowing of the cortical EEG. REM sleep is characterized by a low-amplitude, mixed-frequency EEG similar to that of NREM stage N1 sleep. The EOG shows bursts of REM similar to those seen during eyes-open wakefulness. Chin EMG activity is absent, reflecting the brainstem-mediated muscle atonia that is characteristic of that state.
Organization of Human Sleep
Normal nocturnal sleep in adults displays a consistent organization from night to night (Fig. 27-1). After sleep onset, sleep usually progresses through NREM stages N1–N3 sleep within 45–60 min. Slow-wave sleep (NREM stage N3 sleep) predominates in the first third of the night and comprises 15–25% of total nocturnal sleep time in young adults. The percentage of slow-wave sleep is influenced by several factors, most notably age (see below). Prior sleep deprivation increases the rapidity of sleep onset and both the intensity and amount of slow-wave sleep.
Stages of REM sleep (solid bars), the three stages of NREM sleep, and wakefulness over the course of the entire night for representative young and older adult men. Characteristic features of sleep in older people include reduction of slow-wave sleep, frequent spontaneous awakenings, early sleep onset, and early morning awakening. (From the Division of Sleep Medicine, Brigham and Women's Hospital.)
The first REM sleep episode usually occurs in the second hour of sleep. More rapid onset of REM sleep in an adult (particularly if <30 min) may suggest pathology such as endogenous depression, narcolepsy, circadian rhythm disorders, or drug withdrawal. NREM and REM alternate through the night with an average period of 90–110 min (the "ultradian" sleep cycle). Overall, REM sleep constitutes 20–25% of total sleep, and NREM stages N1 and N2 are 50–60%.
Age has a profound impact on sleep state organization (Fig. 27-1). Slow-wave sleep is most intense and prominent during childhood, decreasing sharply coincident with puberty and across the second and third decades of life. After age 30, there is a continued decline in the amount of slow-wave sleep, and the amplitude of delta EEG activity comprising slow-wave sleep is profoundly reduced. The depth of slow-wave sleep, as measured by the arousal threshold to auditory stimulation, also decreases with age. In the otherwise healthy older person, slow-wave sleep may be completely absent, particularly in males. Paradoxically, older people are better able to tolerate acute sleep deprivation than young adults, maintaining reaction time and sustaining vigilance with fewer lapses of attention.
A different age profile exists for REM sleep than for slow-wave sleep. In infancy, REM sleep may comprise 50% of total sleep time, and the percentage is inversely proportional to developmental age. The amount of REM sleep falls off sharply over the first postnatal year as a mature REM-NREM cycle develops; thereafter, REM sleep occupies a relatively constant percentage of total sleep time.
Experimental studies in animals have variously implicated the medullary reticular formation, the thalamus, and the basal forebrain in the generation of sleep, while the brainstem reticular formation, the midbrain, the subthalamus, the thalamus, and the basal forebrain have all been suggested to play a role in the generation of wakefulness or EEG arousal.
Current models suggest that the capacity for sleep and wakefulness generation is distributed along an axial "core" of neurons extending from the brainstem rostrally to the basal forebrain. A cluster of γ-aminobutyric acid (GABA) and galaninergic neurons in the ventrolateral preoptic (VLPO) hypothalamus is selectively activated coincident with sleep onset. These neurons project to and inhibit the multiple neural wakefulness centers that comprise the ascending arousal system, and selective cell-specific lesions of VLPO substantially reduce sleep time, indicating that the hypothalamic VLPO neurons play an executive role in sleep regulation. More recent data have identified another sleep center, the median preoptic nucleus (MnPOn) of the hypothalamus with similar activation patterns and projections, suggesting that, like that of wakefulness, executive control of ...