Basic Rest-Activity Cycle-22 Years Later

Transcription

1 Sleep, 5(4) Raven Press, New York Basic Rest-Activity Cycle-22 Years Later Nathaniel Kleitman Santa Monica, California, US.A. Summary: This review furnishes data in support of the suggestion that an ultradian basic rest-activity cycle is involved in the functioning of the central nervous system and manifests itself in the alternation of non-rem and REM sleep and a similar periodicity in wakefulness. Key Words: Sleep Wakefulness-Basic rest-activity cycle-dreaming. The original suggestion of a basic rest-activity cycle (BRAC), advanced in ), was based on the manifestation of a periodicity in the interfeeding intervals in infants on a self-demand schedule. These intervals were integers of a 40 to 45-min cyclicity throughout the 24 h of day and night (four cycles during the day and five at night). The reports to be reviewed dealt with the periodicity of motor performance, sensory acuity, and a variety of visceral functions in man and animals during wakefulness; most affirm, but some question or even deny, the existence of basic rest-activity cyclicity. Friedman and Fisher (2) were among the first to report oral activity cycles (eating, drinking, smoking) of normal human adults, during their waking hours, with a mean length of 96 min. Later Friedman observed a similar cyclicity in mild chronic schizophrenics (3) and in obesity-bulimics (4). Orr et al. (5) monitored performance on a complex vigilance test continuously for 48 h, and noted a cycle of about 90 min. They followed it up with an assessment of time-dependent changes in human performance (6). Sterman and Hoppenbrouwers (7) followed the development of sleep-waking and rest-activity patterns from fetus to adult in man. Meier-Koll et al. (8) observed a 90-min periodicity, similar to the sleep stages cycle, in stereotyped hand waving of a mentally defective child. Sterman et al. (9,10) established a self-feeding cycle in the cat that is about 23 min, and that corresponds to the eat's non rapid eye movement (NREM)-rapid eye movement (REM) cycle during sleep; the authors concluded that "the waking cat spent the same proportion of time in performance as the sleeping cat in REM." Delgado-Garcia et al. (11) noted the presence of an uitradian rhythmicity in the spontaneous and instrumental behavior of rhesus monkeys, with a cycle average Accepted for publication July Address correspondence and reprint requests to Nathaniel Kleitman, 222 Washington Avenue, Santa Monica, CA 90403, U.S.A. 311

2 312 N.KLEITMAN of 72 min. Lewis et al. (12) measured three hand-mouth activities of the rhesus monkey: nondigestivc, fceding, and drinking. All thiee were rhythri1ic, w-ith peaks every min. Several publications on the cyclicity of sensory functions were authored by Lavie and associates. A differential response to beta movement apparent motion (an illusion "produced by alternately flashing on and off two nearby lights; when the frequency of alternation is optimal, the observer sees only one light moving across the field"), tested on subjects after they were awakened from REM or NREM sleep, was noted by Lavie and Sutter (13). Ultradian rhythms in the perception of the spiral aftereffect were found by Lavie et al. (14,15), and discussed by Lavie (16). Kripke and Sonnenschein (17) described an ultradian cycle of min in fantasy, reported by subjects who were tested every 5 min during 1O-h isolation. Ultradian cyclicity of other physiological systems was reported by several authors. Othmer et al. (18), on the basis of 24-h polygraphic tracings, inferred that "the so-called sleep-dream cycle of human sleep is not specific to sleep, but is a general activity pattern of the brain." Bailey et al. (19) found regular oscillations, with periods of 1-2 h, in their subjects' oxygen consumption. Orr et al. (5) noted that their subjects' heart rates showed the same cyclicity as performance of a complex vigilance task; the period was about 90 min. Hiatt and Kripke (20) reported 90- to 120-min ultradian rhythms in gastric motility. Lavie and Kripke (21) discerned a cycle of min in urine flow of waking subjects. However, the urine flow rhythm was clearly out of phase with electrolyte concentrations and osmolarity rhythms. Lavie and Scherson (22) observed "rhythmic variations in subjects' ability to fall asleep throughout the day." Conversely, one should expect to detect a variation in vigilance, and that was reported by Okawa et al. (23), who tested nine subjects by following their electroencephalographs (EEG) from 8 a.m. to 8 p.m.; the ultradian rhythms in vigilance had periods of min. Lavie (24) also noted an ultradian 75- to 125-min rhythm in alertness, on the basis of pupillary diameter, light reflex, and motility. As with urinary flow, variations in pupillary motility were out of phase with those of size and light reflex. Earlier, Globus et al. (25) tested subjects, awakened at varying times after their first REM periods, and found that performances on three different tests were not synchronized. In discussing the functions of the two cerebral hemispheres in relation to BRAC, Broughton (26) stated that "a seemingly important issue is whether the waking verbal-intellectual and the fantasy-intuitive dominant activities tend to increase together during activity peaks in the daytime or, like in NREM and REM sleep, continue to peak out of phase with each other within the min cycle," and predicted that "this alternation will prove to be the case." Broughton's prediction was confirmed by Klein and Armitage (27), who assessed performance of verbal and spatial matching tasks by eight subjects every 15 min for 8 h. The authors found significant 90- to 100-min oscillations for each task, but found also that the oscillations were out of phase. Another complicating feature is the possible existence of a multiplicity of cycles. Horne and Whitehead (28), studying ultradian rhythms in human respiration, Sleep. Vol. 5, No

3 BASIC REST-ACTIVITY CYCLE-22 YEARS LATER 313 ' " " noted 30- and 60-min periodicities in addition to the 90-min one. Tsuji et al. (29) detected several kinds of ultradian rhythms, with cycles of 1.5, , and 6.5 h, in the alpha wave activity of seven young healthy subjects. Concurrently, variations in mood had a rhythm of 4-6 h. Honma and Hiroshiga (30) measured locomotor activity, body temperature, and plasma corticosterone in rats exposed to prolonged continuous light, and found ultradian well-synchronized rhythms of 4-6 h superimposed on circadian rhythms. After 3 months of exposure, the circadian rhythms disappeared and the ultradian rhythms were reduced to 1-2 h. In reviewing the beginnings of behavior in the animal kingdom, Corner (31) postulated that, instead of one BRAC, there may be at least two or three sets of fundamental rhythms, ranging from 1 min to 1-2 h. Hiatt et al. (32), and later Lavie (33), also suggested the presence of several ultradian oscillators. The question whether REM sleep represents the activity phase of the BRAC is related to its being sleep dependent or not. Moses et al. (34,35) concluded that "the min cycle found in some waking activities is not an expression of the REM cycle found in sleep, but is a separate neurophysiological process." This was later modified by Johnson (36), who stated that "acceptance of the REM-cycle as a sleep-dependent rhythm does not lead to a denial of the basic rest-activity cycle." McPartland and Kupfer (37) suggested that REM sleep is determined by two clocks, one sleep-dependent and the other related to the rest-activity cycle. This was confirmed with respect to the first REM episode, which usually occurs min after the sleep onset. Subsequent REMs, however, as was beautifully demonstrated in longitudinal studies by Schulz et al. (38,39), occur progressively later on successive nights of sleep, reflecting the circadian rhythm which is slightly longer than 24 h. This finding establishes beyond doubt that the REM cycles-after the first one-represent successive activity phases of the BRAC. The dependence of REM cycling on the BRAC does not preclude its vulnerability to external and internal influences. As noted above, the first such influence is the cessation of wakefulness-sleep onset. Other disruptive influences are sleep deprivation, as reported by Moses et al. (35); interruptions of sleep, which were found by Brezinova et al. (40) to lengthen or shorten subsequent sleep cycles; awakenings for testing purposes, which also affected subsequent cycles, as noted by Schulz et al. (41). REM appearance shortly after the onset of sleep in narcoleptics was indicated in a review by Rechtschaffen et al. (42), and was noted also by Carskadon and Dement (43) in normal subjects and narcoleptics who followed a 90-min schedule of 60 min of enforced wakefulness and 30 min of allowable sleep. Nakagawa (44) kept 20 subjects under observation for 21 h. Though "asked not to fall asleep," they did so from time to time, with REM episodes occurring at the onset of sleep. Further, Sitaram et al. (45) were able to reduce the NREM-REM cycle from 104 to 56 min by repeated infusions of arecholine, a cholinergic muscarinic agonist, and to lengthen the cycle by scopolamine, a cholinergic muscarinic antagonist. Kripke et al. (46), by keeping monkeys on a strict schedule of 12 h of light and 12 h of darkness, revealed 24 cycles/day during darkness, when the animals slept, and 12 cycles/day when the lights were on and they were awake. The conclusion: "group averaged curves suggested that the lights-off and lights-on Sleep. Vol. 5. No

4 314 N. KLEITMAN events had temporary phase-resetting effects on the ultradian cycles." This was followed by a report by Bowden et ai. (47) on the behavior of monkeys during wakefulness. Of the variables recorded-ingestion, locomotion, exploration, self-grooming, and resting-self-grooming was not significantly related to the orality-locomotion-exploration complex. A similar dissociation among variables was observed by Levin et al. (48), who determined that there was a 90-min rhythm for plasma noradrenaline-a reliable indicator of sympathetic nervous activity-in the rhesus monkey, but that this periodicity was "unassociated with levels of arousal or feeding behavior." Lucas and Harper (49) prepared cats for chronic sleep recording and placed electrodes in the mesencephalic reticular formation, with drowsiness leading to self-stimulation. The rate of stimulation required to maintain wakefulness revealed not only a prominent rhythm of min but also that "peaks in spectral estimates of the data correspond closely to the reported cycle lengths of the circadian and polycyclic sleep-wake cycles, and the REM sleep cycle." They concluded that "the tendency to sleep is modulated in the cat by at least three periodic factors during prolonged wakefulness." A similar triple regulation of sleep-waking behavior was postulated by Meier-Koll (50), on the basis of data obtained on a young infant, with the three endogenous rhythms constituting a system of interacting oscillators, rather than running independently. Lavie (51) noted the "nonstationarity" in human perceptual ultradian rhythms, where differences may be found in figures for morning and afternoon testing, or even in the course of one testing period. To study the mechanism responsible for driving the BRAe, Lucas and Sterman (52) produced bilateral lesions in the basal forebrains of cats trained to produce an operant EEG response for food. "These lesions significantly shortened the mean periodicity of the polyphasic sleep-wake cycle, but not that of the basic restactivity cycle"-a negative finding with respect to location of the BRAe controlling mechanism. A possible involvement of the pineal gland was revealed in the work of Kavaliers (53) on the lake chub, which showed short-term ultradian activities ( h) with a significant ultradian frequency of 1.5 h. Pinealectomyeliminated ultradian frequencies, suggesting that the pineal gland may playa part in the generation of these frequencies. Objections to the use of "activity" as a component of the BRAe were made by Kripke (54,55), who asserted that activity was confined to the eyes and the EEG. Actually, this phase of the cycle involves gastric hunger contractions and sexual excitement-processes concerned with self-preservation and preservation of the species-which led to the designation of the cycle as basic. As brought out in previous reviews (56-58), the surge of cortical activity during the REM phase of the 90-min NREM-REM cycle leads-with phylogenetic and ontogenetic development-to the hallucinatory experience of dreaming, which involves the analysis of externally and internally generated impulses in the light of one's previous experience, and the elaboration of appropriate responses (although innervation of peripheral effectors may be blocked). Because of the low level of cortical function during sleep-perhaps related to a paucity of proprioceptive and other sensory stimulation-both analysis and integration are inferior to the performance Sleep, Vol. 5, No.4, 1982

5 BASIC REST-ACTIVITY CYCLE-22 YEARS LATER 315 of the waking brain. They may be likened to the quickly forgotten waking experiences of very young children, senile persons, and normal adults under the influence of an appropriate dose of alcohol. The highest cortical functioning often relates to projection of events into the future, and leads to act inhibition (8 of the 10 Commandments begin with "Thou shalt not"), and the low level of cortical activity in dreaming often results in antisocial "acts." It would perhaps be as productive to interview sufficiently drunken persons, as to have them report the contents of poorly recalled dreams. Dreaming, as cortical activity during the REM periods, is as inevitable in sleep as thinking is in wakefulness, and no particular function needs to be ascribed to it. To quote an apt analogy with Hans Andersen's fairly tale of The Emperor's New Clothes, invoked by Ullman (59), "The emperor in this case was our real knowledge of dreams and the illusory fine clothes he wore were elaborately spun but expendable psychoanalytic notions concerning the source and function of the dream." It will be recalled that it was a small child who was bold enough to state that the emperor was naked. Of course, the absence of a distinct purpose in dreaming does not preclude its utilization for diagnostic or therapeutic ends. In humans, crying at first and speech later are applications of the expiratory phase of breathing, but that does not make phonation a function of respiration. The majority of investigators cited in this review explicitly or implicitly supported, or found their data to be in accord with, the postulated operation of the basic rest-activity cycle in both sleep and wakefulness. Two studies that appear to be most convincing in that respect are those by Schulz and associates (38,39,41) on sleeping humans, and by Sterman and his group (9,10) on waking cats. They alone would clinch the argument in favor of the BRAe. In conclusion, it should be pointed out that findings on the physiology of sleep and wakefulness may be mutually beneficial. The establishment of the 90-min NREM-REM periodicity in human sleep led to the suggestion of the operation of a basic rest-activity cycle during both sleep and wakefulness, and conversely, dreaming appears to be a component of the activity phase of the same periodicity during sleep, thus requiring no teleological explanation. REFERENCES 1. Kleitman N. The nature of dreaming. In: Wolstenholme GEW, O'Connor M, eds, The nature of sleep. London: Churchill, 1961: Friedman S, Fisher C. On the presence of a rhythmic, diurnal, oral instinctual drive cycle in man. JAm Psychoanal Assoc 1967;15: Friedman S. Oral activity cycles in mild chronic schizophrenia. Am J Psychiatry 1968;125: Friedman S. On the presence of a variant form of instinctual regression: oral drive cycles in obesity-bulimia. Psychoanal Q 1972;41: Orr WC, Hoffman HJ, Hegge FW. U1tradian rhythms in extended performance. Aerosp Med 1974;45: Orr WC, Hoffman HJ, Hegge FW. The assessment of time-dependent changes in human performance. Chronobiologia 1976;3: Sterman MB, Hoppenbrouwers T. The development of sleep-waking and rest-activity patterns from fetus to adult in man. In: Sterman MB, McGinty DJ, Adinolfi AM, eds, Brain development and behavior. New York: Academic Press, 1971: Meier-Koll A, Fels T, Kofler B, Schulz-Weber U, Thiessen M. Basic rest activity cycle and stereotyped behavior of a mentally defective child. Neuropaediatrie 1977;8: Sleep, Vol. 5, No.4, 1982

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