eriodic sleepiness is a nearly
universal experience which only recently has received serious scientific study.
Among the developments that spurred scientific interest in sleepiness was the
recognition that persistent excessive daytime sleepiness is a medical symptom
that is indicative of various serious life-threatening conditions.
Clinical necessity then hastened the generation of valid and reliable methods of
quantifying sleepiness. With a means of measuring sleepiness and a recognition
of its importance, there now is a rapidly growing base of scientific and clinical
information on the nature and determinants of sleepiness.
Sleepiness is a basic physiological need state which can be likened to hunger or thirst. As with hunger or thirst, the deprivation of sleep induces sleepiness and sleep reverses this need state (Figure 1). The presence and intensity of sleepiness, like hunger or thirst, are inferred by how readily its onset occurs, how easily it is disrupted, and how long it endures Normally, severe deprivation states do not routinely regulate eating, drinking, or sleeping. Other factors (i.e., taste, smell, time-of-day, social and other biological variables) modulate these behaviors before severe deprivation states develop.
Repeated attempts to fall asleep during the day, after long sleep, normal sleep, and a sleepless night. The subjects lie down at two-hour intervals between 9:30 a.m. and 7:30 p.m. If they fall asleep, they are immediately awakened. The amount of time required to fall asleep is used as a measure of sleep propensity. After an extended sleep during the preceding night, the participants take a longer time to fall asleep; after a night without sleep, the time is greatly reduced.
The experience of physiological sleepiness, however, does not become evident until it is most severe and persistent. But even when it is severe, the subjective experience of sleepiness and its behavioral indicators (nodding, yawning or eye rubbing) can be reduced under conditions of high motivation, excitement, or competing needs (e.g., hunger or thirst). Within a conventional 24-hour sleep-waking schedule, maximal sleepiness occurs in the middle of the night. When forced to be awake in the middle of the night, one experiences fatigue, weariness, difficulty in concentrating and memory lapses. Similar symptoms can be experienced during the day when physiological sleepiness becomes severe enough to intrude on waking activity. When one is alert (sleepiness and alertness are used as antonyms), sleepiness is not experienced even in "soporific" situations (e.g., in warm rooms, during looong, monotonous automobile trips or boring lectures).
Sleepiness is assumed to be a central nervous system phenomenon, although the physiological substrates of sleepiness have yet to be determined. Several electrophysiological events have been identified as potential indicators of sleepiness. Humans deprived or restricted of sleep show increased amounts of EEG alpha and theta activity while behaviorally awake and show identifiable episodes of microsleep. These physiological events seem to indicate the presence of sleepiness, but the substates underlying these events are not known.
The examination of the neuronal and neurochemical mechanisms that are responsible for sleepiness and alertness involve a number of complex issues. First, it is not clear whether or not sleepiness and alertness have underlying and neurobiological mechanisms that are different from that of sleep, per se. Additionally, sleepiness and alertness may each be controlled by separate substances or systems. The relation of the neuronal and chemical mechanisms of sleepiness and alertness to circadian mechanisms is also not known.
Most of the peptides, neurotransmitters, and neuromodulators described in Part F. (Chemical and Neuronal Mechanisms of Sleep and Wakefulness) as being involved in sleep and waking states also seem to be involved in sleepiness and alertness. Similarly, those neuronal systems described as controlling sleep and wakefulness probably are also important in sleepiness and alertness (see Part E., Brain and Mechanisms of Sleep and Wakefulness). Thus, while it is widely assumed that sleepiness is a physiological state, its substrates are unknown.
It was noted above that a number of factors such as motivation, stimulation, and competing needs may mask the expression of the physiological state of sleepiness. Early in the history of the study of the daytime consequences of sleep loss it became evident that it was difficult to accurately assess sleepiness. Most performance tasks used to assess the effects of sleep loss were found to be insensitive. Only long, monotonous tasks were shown to be reliable indicators of changes in nocturnal sleep time. Various self-report measures of mood, which include sleepiness among the factors (i.e., factor analytic scales) or measures which singularly assess sleepiness (i.e., visual analog measures), are used with some success. However, inconsistencies in results have led to questions regarding the use of performance tasks and subjective assessments as measures of sleepiness.
A direct, objective measure of sleepiness, the Multiple Sleep Latency Test (MSLT), is now widely used as the standard method of quantifying physiological sleepiness. The basic assumption of the test is that if all competing motives are minimized, one's tendency to fall asleep will reflect the state of physiological sleepiness. Consequently, at 2-hr intervals throughout the day, individuals are permitted to fall asleep while lying in a quiet, dark bedroom and their tendency to fall asleep is measured repeatedly using standard polysomnographic procedures. The reliability and validity of this measure have been documented in a variety of experimental and clinical situations.
In using the MSLT, several characteristics of the test and the parameter it yields must be recognized. First, the test requires a multiple assessment of sleep tendency; its reliability drops appreciably when only one or two tests of sleep tendency are conducted. Also, each sleep latency test is terminated after 20 min duration, which under some circumstances could produce a "ceiling effect." More problematic is the lower limit of the test; it is not possible to measure latencies of less than 30 sec (i.e., a "basement effect").
The relation of the MSLT to other measures of a person's mood and capacity to function is not direct. Under normal circumstances, direct correlations of MSLT test scores with measures of performance or mood are not robust. But when sleepiness is maximal (i.e., after deprivation or sedating drugs), correlations between the MSLT and various other measures of functional capacity are very strong. The discrepancies among the various measures have led some to postulate the existence of several types or aspects of sleepiness. Another view is that performance and MSLT are affected differently by other variables such as age, education, and motivation, which may be what account for the discrepancies among measures when sleep drive is less intense.
The degree of daytime sleepiness is directly related to the quantity of previous sleep. Total sleep deprivation and even modest sleep restriction reduces the average sleep latency in a systematic manner. Also, the effects of sleep restriction accumulate over successive days. Conversely, the extension of nocturnal sleep time or increasing sleep time with daytime naps increases the average sleep latency on the MSLT. Furthermore, the extension of sleep time by giving various drugs also produces an increased sleep latency on the MSLT. Again, the effects of the sleep extension will accumulate over successive days leading to progressive increases in daytime alertness.
The quality and continuity of sleep also affects daytime sleepiness. In several clinical conditions, and in some elderly individuals, the sleep process is disrupted by frequent, brief arousals of 3-15 sec duration. The arousals are characterized by bursts of EEG alpha activity or EEG desynchronization (low voltage fast activity); sometimes skeletal muscle tone increases. Typically, these arousals do not result in wakefulness by sleep stage scoring criteria or behavioral indicators. Sleep is not shortened, per se, but rather fragmented and disrupted. The amount of Stage 1 sleep and/or the frequency of shifts between sleep stages are increased. Correlational studies in patients with sleep disorders have linked sleep fragmentation to daytime sleepiness. The successful treatment of the sleep disorder involves the restoration of sleep continuity and reversal of the sleepiness. Likewise, experimental fragmentation of the sleep of healthy normals with strong audio tones has also been shown to produce daytime sleepiness.
A biphasic pattern of sleep tendency over the 24-hr day has been well-documented, suggesting there is a strong circadian component to sleepiness (see Part VII, Temporal Regulation of Sleep and Wakefulness). Two elevations in sleepiness (troughs in alertness) are found over the day, the greater occurring during the nocturnal hours (about 2 a.m. to 6 a.m.) and the lessor during the daytime hours (2 p.m. to 6 p.m.). This circadian rhythm in sleepiness parallels the circadian variation in body temperature, with shortened latencies occurring in conjunction with temperature reductions. Sleepiness and temperature, however, are not mirror images and become dissociated under free-running conditions (see Part G., Temporal Regulation of Sleep and Wakefulness).
Drugs have profound effects on sleepiness and alertness. The central nervous system depressant drugs increase sleepiness, which is their desired therapeutic effect. The benzodiazepines, barbiturates and ethanol all have been shown to decrease sleep latency. Each of these classes of drugs has been shown to facilitate the actions of GABA, which is a major inhibitory neurotransmitter system in the central nervous system (see Part F., Chemical and Neuronal Mechanisms of Sleep and Wakefulness).
With other drug classes, sleepiness is an undesired side effect. A commonly reported side effect of the H1 antihistamines is daytime sleepiness. Objective studies using the MSLT have confirmed these sedating effects relate to their differential liposolubility and penetrance into the central nervous system. Histamine is now recognized as an active central nervous system substance; it is thought to have a role in the central control of wakefulness (see Part F., Chemical and Neuronal Mechanisms of Sleep and Wakefulness). Among antihypertensive agents, particularly the beta adrenoceptor blockers, there are differences in liposolubility and central nervous system side effects that have been reported. Several studies have now documented the sedating effects of some of the beta blockers. Presumably, these effects are due to a blocking of the diffuse forebrain noradrenergic system which maintains cortical activation (see Part F., Chemical and Neuronal Mechanisms of Sleep and Wakefulness).
Predictably, stimulant drugs reduce sleepiness and increase alertness. Amphetamine, methylphenidate and pemoline, which are given to treat the excessive sleepiness of narcolepsy, have been found to reduce sleepiness. These drugs are known to facilitate catecholaminergic activity and thereby enhance and prolong wakefulness. Caffeine is a commonly used stimulant found widely in beverages and foods; it also has been shown to increase alertness as measured by the MSLT (Figure 2). Caffeine is an adenosine antagonist; adenosine, as some have shown, promotes the onset of sleep.
Lastly, an unknown central nervous system pathology is assumed to be the determinant of the daytime sleepiness associated with two specific sleep disorders-narcolepsy and idiopathicu central nervous system hypersomnolenceu. While the pathophysiologies of these disorders are unknown, the excessive sleepiness has been well documented using the MSLT. However, the nature of the sleepiness in these conditions probably differs from that of other causes of sleepiness. For example, patients with narcolepsy and sleep-deprived normals respond quite differently to napping (earlier it was noted sleep reverses sleepiness). Clearly, understanding the neurobiology of these conditions will further our understanding of the neurobiology of sleepiness.
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