Sleepiness: Its Measurement and Determinants

Sleep, 5:S128-S134 1982 Raven Press, New York Sleepiness: Its Measurement and Determinants T. Roth, T. Roehrs, and F. Zorick Sleep Disorders and Research Center, Henry Ford Hospital, Detroit, Michigan The relation of sleep and waking function has been a major focus of sleep researchers. Initially, this relation was of interest because it was thought that information about the functions of sleep would be gained. The basic experimental paradigm consisted of totally, partially, or selectively depriving subjects of sleep and then measuring subsequent decrements in daytime functioning. More recently, daytime distress-especially somnolence-has been recognized as a primary and disabling symptom of several important sleep-wake disorders. Consequently, daytime functioning has been assessed to gain further insight into the diagnosis and treatment of these sleep disorders. Research on the daytime sequelae of sleep loss and disturbed sleep has focused on three major aspects of waking function: performance, mood, and objective sleepiness. In the area of performance many different types of tasks have been evaluated. Not all performance tests are equally sensitive to manipulations of sleep. Although a comprehensive review of the sleep-performance literature (1) is beyond the scope of this paper, it is important to point out that tasks that are long and monotonous are typically the most sensitive to sleep changes (2). Similarly the sleep-mood literature reports the use of many different types of measures of subjective state, including factor analytic scales, visual analog scales, and scales for specific aspects of mood. These different measures have assessed various parameters of mood, such as depression, vigor, and lethargy. However, sleepiness is the only aspect of mood that is consistently and systematically affected by manipulations of sleep. Various types of mood scales have been used to assess subjective sleepiness. Two conclusions can be drawn from this research: (a) the various subjective measures of sleepiness are highly intercorrelated (3), and (b) they are sensitive to various manipulations of sleep length and sleep quality (4). Of the different subjective measures of sleepiness, the Stanford Sleepiness Scale is the best validated (5) and, consequently, the most frequently used. Unlike mood and performance, direct measures of daytime sleepiness do not have a long research history. In fact, only the Multiple Sleep Latency Test (MSLT) has been shown to give a reliable measure of the effects of different Address correspondence and reprint requests to T. Roth, Sleep Disorders and Research Center, Henry Ford Hospital, 2921 W. Grand Boulevard, Detroit, Michigan 48202. Key Words: Daytime sleepiness-mslt -Mood-Performance-Sleep loss-sleep fragmentation. S128

SLEEPINESS: MEASURES AND CAUSES S129 manipulations of sleep. Specifically, the MSLT has been shown to be sensitive to both sleep deprivation and sleep extension (6,7). A review of sleep literature has shown that five different variables affect these the aspects of daytime functioning: sleep loss, sleep fragmentation, circadian rhythms, CNS pathology, and CNS drugs. Although these variables interact with each other, the effects of each on the various aspects of daytime function will be discussed separately. Differentiations will be made between data collected from direct experimentation with subjects and clinical data collected from patients. Sleep loss The experimental data on sleep deprivation clearly show that both total and partial sleep deprivation lead to decrements in waking performance (2). In fact, as little as 2 h of sleep loss will produce waking decrements. The degree of impairment is dependent on the amount of sleep deprivation and the nature of the performance test. As was previously mentioned, the longer and the more monotonous the task, the greater the likelihood that sleep loss will disrupt performance. This suggests that motivation is an important variable. In fact, under conditions that optimize subjects' motivation, a decrease or even a disappearance of the performance decrement occurs (2). During experimental sleep deprivation, subjects also complain of increased sleepiness. Systematic research on the effects of sleep deprivation on mood has consistently shown a significant increase in sleepiness (4). No studies have assessed the effects of sleep loss on mood with varying motivational conditions. This type of study is necessary, as it is a common observation that the degree of experienced sleepiness associated with sleep loss is dependent on the cause of the sleep loss. Objective measures of sleepiness (MSLT), like performance evaluations, have shown effects with only 2 h of sleep loss (8), and further systematic increases with greater amounts of sleep loss. Unlike the case with performance, motivation does not seem to reduce the effect of the sleep loss as measured by MSLT. That is, after total sleep deprivation subjects can compensate for impaired performance, but they cannot stay awake for prolonged periods of time while in bed in a darkened room, even ifthey are instructed to do so (9). In clinical experience, chronic sleep loss has been isolated as one of the causes of patients' complaints of daytime sleepiness (10). These patients generally report sleeping longer on weekends than on weekdays, and, if allowed to sleep undisturbed in the laboratory, will show a total sleep time longer than their usual time in bed at home. When these patients are given the MSLT, they show a degree of sleepiness greater than that of controls. Further, unlike other patients with daytime sleepiness, they show a systematic decrease in sleep latency through the day. In summary, sleep loss occurring in patients, or experimentally produced in subjects, leads to clear changes in daytime functioning. Sleep fragmentation Sleep fragmentation refers to the disruption of nocturnal sleep without any actual sleep loss. There has been little systematic study of the effects of sleep fragmentation on waking function. One of the few experimental areas with data to

5130 T. ROTH ET AL. address this issue is research on the effects of noise on sleep (11). Although some decrements in performance and changes in mood have been reported with repeated noise presentations during sleep, the nature of this relationship is not well understood. The most compelling data on sleep fragmentation come from work with sleep disorders patients. Of the various sleep disorders associated with the complaint of excessive daytime sleepiness, sleep apnea and nocturnal myoclonus are two possible models of sleep fragmentation (12). In both of these conditions, nocturnal sleep is highly fragmented, and measurements of waking somnolence (MSLT) show significantly shorter latencies to sleep onset in these patients than in normal controls. For example, in sleep apnea patients arousals during sleep in association with respiratory changes can occur up to once every minute of sleep. On the MSLT these patients usually fall asleep within 2 to 3 min. One study of sleep apnea patients found that the best predictor of daytime sleepiness was the number of respiratory-related arousals (13). The correlation between these two variables was 0.67. Recently, we evaluated a group of apnea patients surgically treated with uvulopalatopharyngoplasty. These patients were divided into responders and nonresponders on the basis of pre- to posttreatment changes in nocturnal respiratory parameters. A responder was defined as a patient showing at least a 50% reduction in the number of apneas per hour of total sleep time. As might be expected, the responders also showed a significant reduction in the number of brief arousals. In terms of waking function, responders showed a significant improvement on the MSLT. The mean sleepiness index was 81.6 pre-surgery and 56.9 post-surgery. In contrast, nonresponders showed no significant change in their sleepiness index (76.2 pre-surgery and 84.7 post-surgery). These clinical data suggest that sleep fragmentation and waking function are related; that is, the continuity of sleep is important for maintenance of optimal waking function. However, much work needs to be done in this area. What is the minimal number of arousals during sleep necessary to produce a change in waking function? Are all arousals during sleep equivalent? Some arousals produce awakenings, some produce stage shifts, and some produce only transient effect. Do these different types of arousals have different effects on waking function? What is the normal range of number of arousals during sleep, and does this change with age? Finally, are the daytime effects of sleep fragmentation the same as those of sleep loss? These questions about sleep continuity must be answered if we are to understand fully the relation of sleep and waking function. Circadian rhythms A significant step in our understanding of human sleep-wake functioning has been the recognition of the importance of biological rhythms (14). Specifically, it has been shown that certain types of performance as well as mood follow a 24-h cycle which varies with the biological rhythm. Sleep tendency follows a similar rhythm. In a recent study evaluating sleep latency in subjects functioning on a 90-min sleep-wake schedule, it was found that subjects have short sleep latencies at their usual sleep periods and longer sleep latencies during their usual wake period (15). The importance of these rhythms is seen in the fact that they persist with

SLEEPINESS: MEASURES AND CAUSES Sl31 minor modifications, even when subjects are in a time-free environment. Additionally, when subjects are required to deviate from their normal sleep-wake schedules (e.g., 180 0 phase reversal, phase delay, or phase advance), decrements in performance have been found. On an applied level, the disruptive effects of phase shifting are most evident in shift workers. When these people are required to reverse their sleep-wake schedule, they show impaired performance and changes in mood, and report increased napping (16). Clinically, patients with circadian phase delays, phase advances, or simply irregular sleep-wake schedules complain of difficulty with sleep onset or with maintaining adequate wakefulness during the day (14). Circadian rhythms are a major determinant of our ability to function during the day. The effects of deviations from normal sleep-wake schedules have significant impact on all three aspects of waking function. Central nervous system pathology Obviously, many CNS pathologies affect waking function. However, there is no direct evidence of ens pathologies that involve sleep-wake mechanisms and that disturb waking functions directly rather than secondarily to the disruption of sleep. But the sleep disorders literature describes two conditions that suggest that such exist(s). Patients with narcolepsy and idiopathic ens hypersomnolence report disturbed daytime function; yet there is no consistent evidence of either sleep loss or sleep fragmentation (12). Extensive objective daytime evaluation has been done only on narcoleptics. Narcoleptic patients have been shown to suffer significant decrements in performance (17). Similarly, the MSL T shows that these patients fall asleep on daytime naps in 2-3 min (18). Although narcoleptic patients often show fragmented sleep, the daytime sleepiness of narcoleptic patients with disturbed sleep and without disturbed sleep is the same (19). Although sleep fragmentation in narcoleptics must be better understood, it is clearly not the major cause of their daytime distress. Thus, narcolepsy is seen as a ens dysfunction, not because of any specific ens findings, but because offailure so far to find any other established cause for the daytime impairment. Even though there is no direct evidence for a CNS dysfunction, one may speculate about a REM sleep dysfunction in these patients, based on the characteristic nature of their sleep onsets. All-night recordings of sleep indicate that narcoleptics frequently exhibit sleep onset REM periods (20). More recently it has been demonstrated that the MSL T is an ideal method of evaluating sleep onset in narcoleptic patients (21). Several studies have shown that narcoleptics, unlike normal or patient controls, show REM onsets in about 50% of their naps. Narcolepsy is one condition suggesting that a ens pathology of sleep-wake mechanisms has a direct and systematic effect on all three aspects of waking function. CNS drugs Two classes of drugs have been studied with respect to sleep and waking function. ens stimulants, when administered pre-sleep, have been shown to fragment sleep in normal controls (22). Although these drugs are used routinely in the treatment of narcolepsy, little objective and systematic work has been done to evaluate their effects on waking functioning in narcoleptic patients.

S132 T. ROTH ET AL. On the other hand, there is a very large literature on the effects of CNS depressants on waking function. Studies have shown that these drugs impair waking performance and decrease subjective alertness (23). Both mood and performance measures are sensitive to different dosages of these drugs and, generally, the duration of the decrement seen in these measures is longer with long-acting drugs than short-acting drugs. It is important to point out that the overwhelming majority of these studies have been done in normal volunteers. Studies with insomniac patients, who routinely take these medications, show similar but less consistent results (23). With the advent of the MSL T, the effects of these drugs on waking somnolence have been measured directly. As might be expected, the MSLT results reflect the performance results in normals (24). There is a significant increase in sleepiness during the day after the nighttime administration of long-acting drugs as compared with administration of placebo or short-acting drugs. The major difference between the MSLT and performance results is that the MSLT is equally sensitive to drug effects in normal subjects and in patients complaining 9f insomnia, whereas performance measures of drug effects are more sensitive in normal subjects than in insomniac patients. Clearly, CNS drugs have potentially significant effects on one's ability to function during the day. On a clinical basis, very few patients are seen in sleep clinics complaining of daytime distress in which the major cause is the use of CNS depressants. It must be emphasized that this does not imply that this does not occur; it simply means that patients do not go to sleep clinics for this problem. 1,. Interrelation of measures of daytime functioning This overview has shown that there is high level of consistency between performance, mood, and objectively measured sleepiness in response to a number of variables. Variables that cause a decrease in sleep latency on the MSLT also produce decrements in performance and increases in subjective estimates of sleepiness. Similarly, patient groups (e.g., narcoleptics and patients with apnea) that show short sleep latencies on the MSLT also complain of sleepiness during the day and show performance decrements. This consistency in both experimental and clinical data leads to the speculation that there is some physiological state of sleepiness that can be quantified by use of subjective estimates, certain performance tests, and direct measures of the propensity to fall asleep. The question then arises as to the degree of redundancy or overlap among these various measures. Several studies have sought to correlate two or more of these measures of daytime function in response to various experimental manipulations. In many ofthese studies all parameters are affected by the experimental manipulation, and yet there is a weak correlation between the parameters. A possible explanation for this apparent discrepancy is similar results due to the experimental manipulation, but a low intercorrelation. Although all the measures of daytime function are similarly affected by the experimental manipulation, they are differentially affected by other variables which are not controlled. In some ways this is quite obvious. Scores on performance tests, although shown to be affected by manipulations of sleep and wakefulness, are also influenced by such variables as intelligence, age, and other individual differences. It is quite

~ SLEEPINESS: MEASURES AND CAUSES SI33 likely that latency to fall asleep on a nap is less contaminated by these types of individual differences. For example, this may explain why performance tests are sensitive to hypnotic drug effects in a homogeneous group of normals. but are less sensitive to drug effects in a heterogeneous group of patients. In contrast, the MSL T is sensitive to drugs in both normal volunteer and patient studies. Similarly, motivation seems to be a variable that affects performance and mood more than it does the propensity to fall asleep in the nap test. As discussed previously, sleep-deprived subjects can overcome performance decrements by being highly motivated. Subjects are less able to postpone sleep onset after sleep deprivation, even if motivated to do so. In a sense, the MSLT is like a performance test constructed with the aim of optimizing performance decrements. The measurement of daytime functioning is of critical importance to our understanding the nature of sleep. It is becoming 'clear that an understanding of sleep variables requires an understanding of their effect on waking function. Just as the development of tests sensitive to the effects of sleep deprivation enhanced our knowledge of the effects of sleep loss, so the development and standardization of the MSLT provides us with a tool for the better understanding of normal variations in sleep and of the nature of sleep disorders. 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. II. 12. 13. 14. IS. REFERENCES Williams HL, Lubin A, Goodnow JJ. Impaired performance with acute sleep loss. Psychol Monog 1959; 73:313-7. Webb WB. Sleep deprivation: total, partial and selective. In: Chase MH, ed, The sleeping brain. Los Angeles: BIS/BRS, 1972:323-62. Lutz T, Roth T, Kramer M, Felson J. The relationship between sleepiness and performance. Sleep Res 1976; 5: 104. Roth T, Kramer M, Lefton W, Lutz T. The effects of sleep deprivation on mood. Sleep Res 1974; 3:154. Hoddes E, Zarcone V, Smythe H, Phillips R, Dement W. Quantification of sleepiness: a new approach. Psychophysiology 1973; 10:431-6. Carskadon M, Dement W. Effects of total sleep loss on sleep tendency. Percept Mot Skills 1979; 48:495-506. Carskadon M, Dement W. Sleep tendency during extension of noctu~nal sleep. Sleep Res 1979; 8:147. Carskadon M, Harvey K, Dement W. Acute restriction of nocturnal sleep in children. Percept Mot Skills 1981; 53:103-12. Hartse KM, Roth T, Zorick FJ. Daytime sleep tendency in normal and sleep-deprived subjects: implications for the evaluation of excessive daytime sleepiness. Electroencephalogr C/in Neurophysiol 1982; 53:23P. Sicklesteel J, Zorick FJ, Wittig R, Conway W, Roth T. Daytime somnolence and insufficient sleep: a case series. Sleep Res 1981; 10:233. Roth T, Kramer M, Trinder I. The effect of noise during sleep on the sleep patterns of different age groups. Can Psychiat Assoc J 1972; 17:197-201. Association of Sleep Disorder Centers. Diagnostic classification of sleep and arousal disorders, first edition, prepared by the Sleep Disorders Classification Committee, HP Roffwarg, Chairman. Sleep 1979; 2:1-137. Roth T, Hartse KM, Zorick F, Conway W. Multiple naps and the evaluation of daytime sleepiness in patients with upper airway sleep apnea. Sleep 1980; 3:425-39. Weitzman E, Czeisler CA, Zimmerman IC, Ronda JM, Knauer RS. Chronobiological disorders: analytic and therapeutic techniques. In: Guilleminault C, ed, Sleeping and waking disorders: indications and techniques. Menlo Park, California: Addison-Wesley, 1982:297-329. Carskadon M, Dement W. Sleepiness and sleep state on a 90-min schedule. Psychophysiology 1977; 14:127-33.

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