Chapter 13

Ultradian Cycles in Sleep Propensity: Or,

Kleitman's BRAC Revisited
P. Lavie

Kleitman's BRAe

In 1961, and then in 1963, Kleitman speculated that the cyclic variations in
brain activity during sleep manifested as the rapid eye movement-non-rapid
eye movement (REM-NREM) cycles are only a nocturnal fragment of an
ongoing 24-h cycle which he termed the "basic rest-activity cycle" (BRAC).
Although Kleitman was somewhat vague about the properties of the BRAC,
he predicted that it would be manifested in cyclic variations in alertness. In his
words: "This cycle is obscured during wakefulness by the great surge of cortical
activity, but suggestions of its presence may be discerned in daytime oscilla-
tions in alertness, the often irresistible drowsiness after a big meal, and the
relief that some persons get from brief catnaps" (Kleitman 1961, p. 361). No
doubt Kleitman's BRAC concept captured the imagination of many. This is
evident from the large number of studies searching for ca 1.5-h cycles, which is
the dominant periodicity of the REM-NREM sleep cycle in a variety of
physiological, behavioural and endocrine functions (for a review see Lavie
1982). A large number of these studies have shown ultradian cycles with
periodicities centred around this privileged periodicity, in support of Kleitman's
hypothesis. Such cycles were shown in various electroencephalographic (EEG)
frequency bands such as a (8-9 Hz; Kripke and Sonnenschein 1978; Gertz and
Lavie 1983) and J (0.5-3 Hz; Kripke 1972), or the total power of the EEG
(Manseau and Broughton 1984), in the tendency to fall asleep during the
day (Lavie and Scherson 1981), and in autonomic indices of arousal such as
pupillary diameter and reactivity to light (Lavie 1979), respiratory rate (Horne
and Whitehead 1976) and heart rate (Orr et al. 1976).
These findings were corroborated by findings of ultradian cycles with similar
periodicities in behavioural responses such as reaction time (Orr et al. 1976),
the intensity of visual illusions (Lavie et al. 1974), and in the accuracy of motor
coordination (Gopher and Lavie 1980).
However, there is as yet no firm evidence that the ultradian cycles observed
during wakefulness are regulated by the same underlying neural mechanism

D. Lloyd et al. (eds.), Ultradian Rhythms in Life Processes

© Springer-Verlag London Limited 1992
284 Ultradian Cycles in Sleep Propensity: Or, Kleitman's BRAC Revisited

that is responsible for the REM-NREM cycle. To further complicate the

picture, it has become evident that physiological functions unrelated to arousal
also show cyclicities of approximately 1.5 h. Such cycles were shown in urine
flow in humans (Lavie and Kripke 1977), and in gastric motility in waking
(Hiatt and Kripke 1975) and sleeping humans (Lavie et al. 1978), as well as in
other species (Grivel and Ruckebusch 1972). Elsewhere, Lavie and Kripke
(1981) and Lavie (1982) proposed that ultradian cycles of approximately 1.5 hi
cycle represent a multioscillatory phenomenon rather than the activity of a
single oscillator.
This chapter re-examines the sleep REM - NREM cycle and the ultradian
cycles in alertness during wakefulness in view of the experimental data
obtained in my laboratory in recent years. It will be argued that, in spite of the
fact that REM - NREM cycles and the waking cycles in alertness most probably
reflect independent processes, they nevertheless evolved along similar evolu-
tionary lines subserving similar regulatory functions which complement each
other.

REM-NREM Cycle: A Concerted Tide of Brain Activities

Although there is general agreement regarding the cyclic nature of the REM-
NREM sequences, the nocturnal component of the BRAC, actually this
cycle is far from being precise and stationary. Data accumulated over the
last 30 years have shown that the REM - NREM cycle represents intricate
and coordinated changes in multiple brain subsystems, all obeying the same
basic cyclicity of approximately 1.5 h/cycle. Occulomotor activity, muscle
tonus, EEG activities, autonomic dominance, brain energy utilization, and
the subjective experience of dreaming, all oscillate nightly in a concerted
cycle. Occasionally, however, disharmony occurs when some of the REM
components are "spilled over" to neighbouring sleep stages. The opposite may
also occur: occasionally REM sleep is fragmented by brain activities belonging
to NREM sleep stages. But these irregularities cannot refute the fact that
REM-NREM sequences alternate cyclically; moreover, in view of its com-
plexity, the regularity of the cycle is rather impressive.
An important feature of the REM - NREM cycle is its phase control. In
normals retiring to sleep around their habitual sleep time, the phase of the
REM - NREM cycle is determined to a great extent by the time of falling
asleep. Thus, the first REM period occurs approximately 90( ±20) min after
falling asleep. Subsequent REM periods recur every 90-80min thereafter.
Although there are some exceptions where the phase control of the REM-
NREM cycle is not functioning properly, such as in narcoleptics who have
REM periods at sleep onset, or in patients with major depression who also
have abnormally short REM latencies, ca 1.5 h REM latency is considered to
be a robust marker of adult sleep.
In 1975, McCarley and Hobson proposed a model of REM sleep that was
physiologically based on the activity of two neuronal populations: "REM-on"
cells, which appear to promote REM sleep; and "REM-off' cells, which
appear to inhibit REM sleep. They proposed that the periodic occurrence
of REM sleep might be a function of a reciprocal interaction between the
REM Sleep: A Single or Multioscillatory Phenomenon? 285

populations of these two cells. The Lotka- Volterra equations (see McCarley
and Hobson 1975) were used to describe this interaction. The model was later
refined by McCarley and Massaquoi (1986) as a limit cycle model which also
included a consideration of the circadian effects on the REM generator. It
should be pointed out, however, that this model relates only to the appearance
of the traditional markers of REM sleep, i.e. rapid eye movements, low
voltage fast EEG activity, loss of muscular tonus, and the appearance of high
voltage, monophasic ponto-geniculate-occipital waves (in the cat). As is
shown below, it is not at all clear that all REM components are generated
by the same oscillator.

REM Sleep: A Single or Multioscillatory Phenomenon?

As described above, REM sleep is manifested by a variety of physiological

phenomena all occurring in synchrony. Is the REM - NREM cycle run by a
single "clock" having different "hands", or does it reflect the activity of
multiple clocks all beating in synchrony? There is compelling evidence suggest-
ing that at least some of the REM components represent the temporal con-
fluence of multiple oscillations all sharing the same periodicity. The following
case history exemplifies the complexity of the control mechanisms of the
REM-NREM cyclicity and its heterogeneity.
Penile erection is one of the most prominent and marked changes associated
with REM sleep (Fisher et al. 1965). Erections accompanied some 80%-
90% of all REM periods and, when measured independently of other REM
variables, they clearly displayed a 90-min periodicity. In fact, the 90-min
periodicity in erections was described 9 years before the discovery of REM
sleep (Ohlmeyer et al. 1944). In spite of the near-perfect synchronization
between the REM - NREM cycle and the penile erection cycles, under certain
circumstances they may be completely dissociated from each other. In recent
years, in my laboratory, we have followed a unique patient who suffered
a highly localized brainstem lesion which damaged his executive REM mech-
anism (Lavie et al. 1984b; Lavie 1990). During multiple laboratory sleep
recordings, this patient was found to have astonishingly low amounts of REM
sleep (2%-4%). Nevertheless, the patient showed an intact 90-min periodicity
in penile erections (Fig. 13.1). Episodes of erections occurred at the expected
times of the REM periods without any concomitant REM components. It is
also interesting to note that this patient shows no behavioural deficits and
conducts a normal working life - in spite of the minute amounts of REM
sleep. This case clearly indicates that because two measures share the same
periodicity and are synchronized with each other it does not necessarily mean
that they are regulated by the same oscillatory mechanisms. Most probably
several neural generators participated in the regulation of the REM - NREM
cycles, all sharing the same dominant periodicity of ca 1.5 h.
Besides the problem of the singularity of the control mechanism of REM
sleep, there is a question concerning the nature of the REM-NREM cycle
which is of no lesser importance: is the REM-NREM cycle a sleep-dependent
or a sleep-independent cycle? Any attempt to examine the BRAC model must
deal first with this question.
286 Ultradian Cycles in Sleep Propensity: Or, Kleitman's BRAC Revisited

rn
w

~~ ~~
w
REM
1
~ W
rn

, , I I , ,

01 :00 02:00 03:00 04:00 05:00 06:00

CLOCK TIME Ihl
Fig. 13.1. Ultradian cyclicity in penile erections in a patient with almost total absence of REM
sleep. Note that each night the first episode of erection (stippled area) occurred at approximately
the same time that REM sleep would be expected i.e. 90 min after sleep onset. (Reproduced, with
permission, from Lavie 1989b.)

REM-NREM Cycle: A Sleep-Dependent or a Sleep-

I ndependent Phenomenon?

Whether the oscillator regulating REM sleep functions only during sleep and
ceases to function during wakefulness is the subject of an on-going debate in
the literature (Schulz et al. 1975; Moses et al. 1977; McPortland and Kupfer
1978; Ursin et al. 1983; Carmen et al. 1984; Lavie 1987). This question touches
up0n issues of the existence of a waking counterpart to the REM - NREM cycle
and upon the nature of the sleep cycle itself. Most studies attempting to
investigate this question did so by experimental interruptions of the sleep cycle
at different phases with respect to the REM-NREM cycle, and observing the
effects of the interruption on the appearance of subsequent REM periods.
Although it was shown that sleep interruptions lengthened subsequent REM-
NREM cycles (Brezinova 1974; Gaillard and Tuglular 1976), Schulz (1985)
demonstrated that the lengthening of the cycle is proportional to the length of
the NREM period before the interruption. Schulz interpreted these results
as indicating that a REM-inducing process is taking place inbetween two
REM Sleep - A Gating Mechanism 287

successive REM episodes. This process may be halted temporarily but not
destroyed by the sleep interruption.
Experimental results from our laboratory provided evidence that the oscil-
lator regulating REM periodicity during sleep is not halted by short periods of
wakefulness. In a series of studies we utilized ultrashort sleep-wake cycles in
order to investigate circadian and ultradian variations in sleep propensity
(Lavie and Scherson 1981; Lavie and Zomer 1984; Lavie 1986; Lavie and Segal
1989, Lavie and Weler 1989; Lavie and Zvuloni 1992). By this technique,
subjects were instructed to attempt either to fall asleep or to resist sleep for
5 or 7 min every 20 min. The total amount of sleep obtained in each trial
was used to construct the 24-h sleep propensity function (SPF). In recent
experiments we preferred the 7/13 sleep-wake ratio (see p. 289) because it is
close to what is considered to be the optimal sleep/wake ratio of 8/9, while at
the same time it does not allow a significant accumulation of sleep. Such an
accumulation could obscure the shape of the SPF.
Besides the information about the shape of the SPF and the occurrence of
ultradian cycles in sleep propensity obtained by the 7/13 paradigm which will
be described shortly, an unexpected experimental outcome of the studies
utilizing the 7/13 paradigm was the occurrence of multiple REM periods within
the 7-min trials. These occurred in about half of the subjects, particularly
during the late night-early morning period. Although there is no immediate
explanation of why sleep fragmentation induced REM periods resembling the
"sleep onset REM periods" in narcolepsy, analysis of the temporal distribution
of trials containing REM allowed examination of the properties of the REM
generator (Lavie 1987). Fig. 13.2 shows the occurrence of REM sleep under
such conditions in an "REM-prone" subject. As can be seen, the first REM
episode appeared at approximately 02:00 h, which was followed by two sub-
sequent REMs at 70-80-min intervals thereafter. Analysis of inter-REM
intervals of more than 42 series of data, each constructed from 72 consecutive
7-min trials, revealed a dominant 60-80-min periodicity. Identical periodicity
was also found in narcoleptic patients tested under a similar 7/13 paradigm
after a night of normal sleep in the laboratory (Lavie 1991).
These results led to the conclusion that the oscillator regulating REM con-
tinues to function during short periods of wakefulness. This lends credence
to the notion that under certain conditions there may be a continuation of
ultradian cycles across the sleep/wakefulness boundary.

REM Sleep - A Gating Mechanism

REM sleep, no doubt, is an outstanding physiological phenomenon. There is

no other comparable physiological phenomenon which has been described in
such great detail, and whose function is still an enigma. The possible function
of REM sleep has attracted the imagination of many. Memory consolidation,
regulation of effect and motivation, and genetic programming have all been
raised as possible candidates for REM function. However, none of these
theories is sufficiently comprehensive to account for all the diverse manifesta-
tions of this sleep state. Like the blind people who examined the elephant
and saw in it different animals depending on the part they were touching,
288 Ultradian Cycles in Sleep Propensity: Or, Kleitman's BRAC Revisited

8
• REM
.ST1 + 2
6

CLOCK TIME (h)

Fig. 13.2. Periodicity in the occurrence of REM sleep in a normal young adult tested under the
7/13 sleep-wake paradigm (raw data). ST, stages.

the proposed function of REM sleep is greatly dependent upon the specific
REM aspects that were examined. There is nothing wrong with finding several
functions of REM sleep which are seemingly independent of each other. In
many cases, evolutionary processes utilize existing structures in widely dis-
parate ways. I would like to propose that REM sleep has yet another function
which utilizes its unique physiological characteristics. This function, I believe is
linked with Kleitman's BRAe concept.
The periodic occurrence of REM provides the organism with privileged
gates which facilitate a smooth transition from sleep to waking. Elsewhere I
have elaborated some of the supportive evidence for this assertion (Lavie 1985,
1989a, 1992). Briefly, it was shown that subjects in isolation who rely only on
internal cues to wake up from sleep, woke up significantly more often from
REM sleep than from NREM sleep (Weitzman et al. 1980). Likewise, subjects
requested to wake up from sleep at predetermined times without the aid of an
alarm clock, significantly woke up more often from REM sleep (Lavie et al.
1979; Zepelin 1986). Furthermore, there is evidence that awakening from
REM sleep has a distinct evolutionary advantage over awakening from NREM
sleep, because it is associated with an activation of the right hemisphere's
orienting mechanisms (Gordon et al. 1982; Bertini et al. 1984; Lavie et al.
1984a). Thus, upon awakening from REM the organism can immediately
orient itself in space and avoid maladaptive behaviours. This view of REM
sleep as a gating mechanism to ensure a smooth transition from sleep to
wakefulness can be seen as an enlargement upon Snyder's (1966) sentinal
theory of REM sleep. Snyder viewed REM sleep as a privileged state during
which the organism can search the environment for possible predators. In the
following sections, I argue that the REM gating mechanism is complemented
by a similar mechanism during wakefulness which facilitates the transitions in
the reverse direction, from wakefulness to sleep.
Multiple Sleep Latency Tests and Sleep Propensity 289

"Sleep Gates"

Although we tend to disregard introspection and personal experience as un-

scientific, personal experience can, nevertheless, provide valuable information
about the nature of falling asleep. In spite of the fact that most people maintain
a 24-h sleep-wake cycle which in the adult comprises a single sleep episode
and a single waking episode, on many occasions sleepiness and readiness to
sleep are experienced more than once a day. Most people feel drowsy during
midafternoon and, if permitted, fall asleep much faster at that time of the day
than at any other. However, 2-3h later, readiness to sleep diminishes whether
or not one has slept. Such transient feelings of "being ready to sleep", which
rapidly disappear, may also come at other times of the day. Some people
describe it metaphorically as: "Once my sleep gate is open I must take a nap,
even a brief one. This charges me for hours." These brief "cat naps" - lasting
for no more than a few minutes but offsetting sleepiness and fatigue for
prolonged periods of time - were one of the clues that led Kleitman in 1961 to
the BRAC hypothesis. In contrast to nocturnal sleep periods, "cat naps" occur
abruptly without any preceding sensations of impending fatigue.
If sleep-wake cycles are regulated by a 24-h clock, why do these diurnal
sleepiness crises occur? I return to this question at the end of this chapter.

Multiple Sleep Latency Tests and Sleep Propensity

Experimental data support personal experience by demonstrating that sleep

propensity systematically varies across 24h (for a review, see Broughton 1989).
If prior wake-time is held constant, the 24-h course of sleep propensity (SPF)
can be plotted. This, in fact, has been attempted by a number of investigators
using a variety of experimental techniques. These included methods such as
continuous or frequent sampling of EEG and frequent measurements of sleep
latency during the day. The best known and most widely used method is the
multiple sleep latency test (MSLT), first introduced by Carskadon and Dement
in 1977. The MSLT measures the speed of falling asleep in a standard setting.
The first test of the MSLT is usually conducted 2 h after the subject has woken
up from nocturnal sleep, and then at 2-h intervals until 20:00 h. Although
the MSLT provides reliable data on diurnal sleep latencies, and its clinical
validity has been convincingly demonstrated (Carskadon and Dement 1979;
Richardson et al. 1978; Mitler et al. 1982), a sampling frequency of once every
2 h is too slow to provide an accurate description of the diurnal variations in
sleep propensity. The MSLT will miss any cycle in sleep propensity faster than
six per day.
Continuous recording techniques, on the other hand, lack standardization,
and their results are heavily dependent on subjects' activity and level of tonic
arousal (for further discussion, see Lavie 1989b). Furthermore, since in normal
subjects the act of falling asleep is under voluntary control, continuous record-
ing techniques usually rely on indirect measurements of sleep propensity.
To overcome these problems we have developed the ultrashort sleep-wake
paradigm, described above, which allows measurements of diurnal variations in
290 Ultradian Cycles in Sleep Propensity: Or, Kleitman's BRAC Revisited

I REM
St.3-4 AS
051.2
GlSl.1

(/)
W
I-
:J
Z
~
6

07:00 19:00 07:00 19:00 07:00

CLOCK TIME (h)
Fig. 13.3. Fony-elgm nour sleep propensity tunctlOns ot a normal young adult tested with the 7/13
sleep-wake paradigm under the attempting sleep (AS) and resisting sleep (RS) conditions. Note
the prominent ultradian cyclicities during the periods 07:00 to 19:00 h on both days of the
experimental periods and in both experimental conditions. St., stage.

sleep propensity directly. Testing subjects under this paradigm indeed showed
ultradian cycles in sleep propensity with a periodicity of approximately 90-
120min (Lavie and Scherson 1981; Lavie and Zvuloni 1992). Before these
cycles are described, it should be made clear that, in comparison with the
impressive changes in the state of brain activities associated with the circadian
sleep-wake cycle, the ultradian cycles in sleep propensity are of a relatively
low amplitude and on many occasions are unstable both with respect to fre-
quency and/or with respect to phase. Fig. 13.3 depicts examples of ultradian
cycles in sleep propensity obtained by the 7/13 paradigm.
The existence of sleep propensity cycles during the day, which is congruent
with Kleitman's proposal, leads to the discussion of the relationships between
the REM - NREM cycles and the sleep propensity cycles. Are they both part
of an ongoing cycle which continues uninterrupted from sleep to waking as
envisaged by Kleitman? Or, are perhaps the sleep and waking cycles regulated
independently? If, for instance, it could be shown that the phase of the waking
Living on a 20-Min "Day" 291

cycle is locked to the phase of the preceding REM-NREM cycle, then it would
support the possibility of an ongoing cycle, presumably with a common origin.
Preliminary experimental evidence indicated that the phase of the waking
ultradian rhythms may have a consistent phase relationship with the preceding
REM-NREM cycle (Lavie and Zomer 1984). Awakening from REM sleep
was shown to be associated with a higher level of arousal than awakening
from NREM sleep. These carry-over effects, however, were short-lasting and
became progressively unstable. Other studies showing differential effects of
awakening from REM and NREM sleep on alertness and performance were
carried out for periods that were too short to allow any conclusion concerning
the phase continuity of the sleep and waking cycles (Lavie 1974; Lavie and
Sutter 1975). Furthermore, the fact that awakening from REM and NREM
sleep was found to be associated with differential activation of the two cerebral
hemispheres (Gordon et al. 1982; Bertini et al. 1984; Lavie et al. 1984a)
placed these earlier observations within the context of REM sleep as a gating
mechanism.
Recent results from our laboratory have provided evidence, however, that
the phase of the ultradian cycles in sleep propensity may be determined by
the starting time of the experimental paradigm itself. These results are now
described in greater detail.

Living on a 20-Min "Day"

Evidence for the dependency of the phase of the ultradian cycles in sleep
propensity on the starting time of the experimental paradigm was obtained in a
study where subjects were tested with the 7/13 sleep-wake paradigm for 48
consecutive hours. Details about the design of this study can be found in
the article by Lavie and Zvuloni (1992), therefore they are described only
briefly here. Eight healthy young male adults who regularly slept 7-8 h per
day participated in two 48-h experimental periods. In each of them, subjects
arrived at the sleep laboratory at 21:00h on the evening before the start of the
7/13 sleep-wake paradigm. They were fitted with electrodes to measure EEG,
electrooculographic and electromyographic activity, and slept in the laboratory
from approximately 23:00 until 06:40 h. At 06:40 h, they were wakened up
from sleep, and at 07:00h they started a 7/13 sleep-wake paradigm that lasted
for 48 consecutive hours. As described before, under this paradigm, every
20 min subjects were instructed to lie in bed with eyes closed and to attempt
to fall asleep. In total, the experimental period comprised 144 cycles of
7-min sleep attempts followed by 13-min intervening wake periods outside the
bedroom.
The second experimental period was conducted at least 10 days after the
first. Here, too, subjects spent the night before the 7/13 paradigm asleep in the
laboratory. At 07:00 h they started a 48-h schedule of 7 min resisting sleep
attempts, 13 min awake outside the bedroom. The specific instructions to the
subjects were to lie quietly awake in bed for 7 min with eyes closed and to
resist sleep. Each 7-min trial of attempting or resisting sleep was scored for
sleep stages 1, 2, 3-4, REM and wake, according to conventional criteria.
292 Ultradian Cycles in Sleep Propensity: Or, Kleitman's BRAC Revisited

Synchronized Cycles in Sleep Propensity

All subjects successfully completed the two 48-h experimental periods. In both
the AS (attempting sleep) and RS (resisting sleep) conditions the temporal
structure of sleep propensity revealed a pronounced 24-h cycle, on which faster
variations were superimposed. A median smoothing procedure was used to
emphasize the 24-h cycles. This procedure is aimed at removing the fast
variations from the data (Figs. 13.4 and 13.5). It is evident from the Figures
that there was a great similarity between the 24-h structure of sleep propen-
sity in the AS and RS conditions. The nocturnal sleep "gates" i.e. the first
nocturnal trial during which subjects were able to initiate sleep very easily,
indicated in the Figures by a steep increase in sleep propensity, opened at
exactly the same times on both days of the study and in both experimental
conditions.
What about the ultradian variations? These are first exemplified in a single
subject and then for the entire group. Fig. 13.3 (see above) presents the 48-h
data of a single subject for the AS and RS conditions. In both conditions there
were prominent ultradian variations in sleep propensity during the first day

AS
6

11.
W
W
...J
en
o
~
o "
I ,_
r---",
,,
.
z 6
RS ,--' \
~
, ,
, I
, I

,, ,
, ""
"'I '
,,,
"

,, ""
,,
,,, ".'
3
" ,
, • I

, ,I
,,
, I
,
,
I

,"
\
,- __ J '. ________ -'
, , I

,,'- L_,'----'
,

o
07:00 19:00 07:00 19:00 07:00
CLOCK TIME (h)
Fig. 13.4. Forty-eight hour sleep propensity functions for the AS and RS conditions smoothed by a
median smoothing procedure.
Synchronized Cycles in Sleep Propensity 293

AS
6

c..
w
,---
W
...J
(J)
u.
0
, I'\." \""\ ,--,
,
,,
~
,,
1\
0
z 6
1 \_, \ _ _, \
,
~
RS
,
,
'-,
",
I
,
, I ,
I I I
, I I
3 " \ ' I ,
, ,-,' , I
, , ~-, ' I ,
I " I ,
I I 'I , I
~ I I, I I
'i I I I ,
o '--I '--'
07:00 19:00 07:00 19:00 07:00
CLOCK TIME (h)

Fig. 13.5. Forty-eight hour sleep propensity functions for the AS and RS conditions smoothed by a
median smoothing procedure.

(07 :00 to 19:00 h). These were mostly manifested in prominent increases in
sleep stage 2.
The ultradian variations were masked during the night period by the high
levels of sleepiness, but they reappeared during the second day of the study,
particularly during the period 09:00 to 19:00 h. The relationships between
the ultradian variations in sleep propensity in the AS and RS conditions
were investigated by a cross-correlation analysis. First, cross-correlations were
calculated for the first 12h of the experimental periods (36 data points), during
which the ultradian variations were most pronounced (Fig. 13.6). This revealed
a significant in-phase relationship between the two conditions, with a common
periodicity of 120 min. Fig. 13.7 presents the 72-h lag cross-correlation function
based on the entire 48-h time series of the same subject (144 data points). This
revealed both the 24-h component and the 2-h component which were both
in-phase across the two experimental conditions. A similar pattern emerged
when data from all eight subjects were averaged before the cross-correlational
analysis. Figs. 13.8 and 13.9 present the averaged SPFs for the two experi-
mental conditions and the corresponding cross-correlation function. Although
in comparison with the cross-correlation function of the single subject pre-
294 Ultradian Cycles in Sleep Propensity: Or, Kleitman's BRAC Revisited

0.5

!zw
U 0
u::
u..
w
8

-0.5

-1

-4 -2 o 2 4
TIME LAG (h)

Fig. 13.6. Cross-correlation function of the first 12 h of the RS and AS sleep propensity functions
presented in Fig. 13.3.

sented in Fig. 13.7 the magnitude of the ultradian component in the averaged
data is relatively small, it is nevertheless clearly evident.
The results of the cross-correlational analysis yield two important con-
clusions. First, in agreement with the visual impression, it shows that sleep
propensity under experimental conditions of AS and RS was modulated by
both a 24-h and a 2-h component and, second, that subjects were synchronized
with each other with respect to both components. The finding that subjects
were synchronized with respect to the 24-h component is hardly a surprise in
view of the fact that all were students having approximately the same daily
Synchronized Cycles in Sleep Propensity 295

- 0.5

- 1

- 80 - 40 o 40 80
TIME LAG (TRIAL)
Fig. 13.7. Cross-correlation function of the 48-h RS and AS sleep propensity functions presented
in Fig. 13.3.

routines. The synchronization among subjects with respect to the 2-h com-
ponent, however, is unexpected. As mentioned before, previous results did not
provide strong evidence for a consistent phase relationship between the REM-
NREM cycle and the ultradian variations in arousal. If such relationships
exist, then in order to explain the present findings it must be assumed that all
subjects woke up from sleep at precisely the same phase of the REM - NREM
cycle. But examination of the nocturnal sleep patterns revealed that this was
not the case; different subjects woke up from sleep at different phases of the
REM-NREM cycle.
296 Ultradian Cycles in Sleep Propensity : Or, Kleitman's BRAC Revisited

_AS
RS

rn
5z
2

01:00 19:00 01:00

CLOCK TIME (h)

Fig. 13.8. Average 48-h sleep propensity function (N = 8) for the AS and RS conditions.

At least two other possible explanations can be invoked for this surprising
finding. First, awakening from sleep itself, regardless of the specific sleep stage,
acted as the synchronizing trigger. This can be seen as analogous to the
synchronization of the REM-NREM cycle by the process of falling asleep.
Since subjects were awakened at the same time, their ultradian rhythms which
were triggered by the awakening process were synchronized. Second, the phase
of the ultradian cycles was determined by the start of the testing procedure
itself. In order to decide between these possibilities, data of subjects awakened
from sleep at different times should be analysed. Such a study had been
performed in our laboratory previously (Lavie and Scherson 1981). In that
study, which was the first to utilize an ultrashort sleep-wake cycle, subjects
were given 5-min sleep attempts every 20 min from 09:00 until 19:00 h. Since
subjects spent the night before the start of the study asleep at their homes,
wake-up time varied between subjects. Fig. 13.10 presents the mean of total
sleep time calculated across all subjects, and the same data after removing the
quadratic trend. The autocorrelation function of the de trended data revealed a
2-h component. The existence of a 2-h component in the average data indicates
that subjects were synchronized with each other. Otherwise, the phase dis-
persion among subjects would have resulted in the disappearance of the cycle
in the averaged data.
Increasing the Sleep Pressure 297

- 80 -40 o 40 80

TIME LAG (TRiAl)

Fig. 13.9. Cross-correlation function of the average 48-h RS and AS sleep propensity functions
presented in Fig. 13.8.

Increasing the Sleep Pressure

In both studies described above sleep pressure was low because subjects were
not sleep deprived before the start of the study. Increasing the sleep pressure
resulted in the disappearance of the 2-h cycle (Lavie 1986). This is exemplified
in Fig. 13.11, which depicts the averaged data of 36 subjects tested with
the 7/13 paradigm after a night of sleep deprivation. The important features
of this Figure are the midafternoon increase in sleepiness, the decrease in
298 Ultradian Cycles in Sleep Propensity: Or, Kleitman's BRAC Revisited

15 50

~ 11
c: 40
:.;.

'#.
CJ)

Inm
.. .1\/ /\
\.1 ..:.::
30
"tI
o
"'11
UI

20~

(\
z

J 10

-9 o
07:00 13:00 19:00
CLOCK TIME (h)

Fig, 13.10. Mean total sleep time of 11 subjects investigated with a 5 /15 sleep-wake paradigm
from 09:00 to 19:00 before (broken line) and after (continuous line) removing the quadratic trend.

.REM
6 .ST3-4
rlST2
en .ST1

~
z 4
~

19:00 07:00
CLOCK TIME (h)
Fig. l3.11. Average sleep propensity function of 36 subjects tested with the 7/13 sleep-wake
paradigm after an "overnight" sleep deprivation (smoothed by a three-point moving average). ST,
stage(s).
The Sleep and Waking Ultradian Cycles - A Unifying Concept 299

sleepiness during the evening hours ("forbidden zone" for sleep) and the steep
increase in sleepiness at approximately 23:00h (sleep gate). This general pat-
tern was found in more than 70 subjects tested with the 7/13 sleep-wake
paradigm after a night of sleep deprivation. It should be noted, however, that
in spite of the increasing sleep pressure, some individual subjects still showed
prominent ultradian cycles, but these were the exception rather than the rule.

The Sleep and Waking Ultradian Cycles - A Unifying

Concept

The existence of ultradian cyclicities in sleep propensity which appeared to

be synchronized across individuals takes us back to Kleitman's BRAC. To
recapitulate, Kleitman hypothesized that the ultradian REM-NREM sleep
cycles are only a fragment of a 24-h cycle which, during wakefulness, is
manifested as fluctuations in cortical alertness, and during sleep as the REM-
NREM cycle. Although the accumulated findings cannot attest to a common
origin for the sleep-wake cycles, they nevertheless support the existence of
orderly fluctuations in cortical alertness during sleep and wakefulness sub-
serving a similar function.
I propose that the ultradian cycles in sleep propensity can be best described
as reflecting cyclic fluctuations in the balance between arousal-producing
mechanisms and brainstem or diencephalic sleep-promoting structures. The
balance between the two opposing systems determines cortical alertness in
much the same way that the balance between "on" cells and "off" cells in
the brainstem determines the balance between REM and NREM sleep. The
function of the waking cycles is to provide multiple gates during which the
transition from waking to sleep is greatly facilitated. These are complementary
to the REM gating mechanism in sleep which facilitates transition in the
opposite direction and is described above. Such a system ensures that, if the
need should arise, sleep can be initiated at anyone of many times across
the day. Obviously, in order to be adaptive such a system should be highly
flexible and highly responsive to environmental stimuli. This dual gating
mechanism provides the sleep-wake system with great flexibility which is of
obvious adaptive value.
Although Kleitman was not so explicit about what determines the phase of
the BRAC, it appears from his writings that he envisaged, at least implicitly, a
continuation between the sleep and waking components of the cycle. The
present results indicate that the phase of the waking cycle was dependent upon
the start of the experiment. This was evident from the fact that different
subjects were synchronized with each other although testing occurred on dif-
ferent days. What could be the explanation for such a synchronization? It
is possible that the ultradian cycles in sleep propensity reflect an inherent
responsivity cycle of neural structures involving the regulation of sleep propen-
sity. Thus, when subjects repeatedly attempt to fall asleep, the recruitment of
sleep-promoting structures can be done only intermittently. Periods during
which somnogenic structures are activated are followed by refractory periods
during which the sleep-promoting structures are unresponsive. The fact that
the same cyclicity was observed under both the attempting and the resisting
300 Ultradian Cycles in Sleep Propensity: Or, Klcitman's BRAC Revisited

sleep conditions may indicate that such intermittent recruitment of somnogenic

structures can be done either actively or passively by sleep-inducing environ-
mental conditions,
It can be concluded therefore that the temporal structure of both sleep and
wakefulness has evolved evolutionarily in such a way that maximizes flexibility
of the sleep-wake cycle by ensuring smooth transitions from one state to
another. During both states of existence there is an ultradian gating mechanism
which facilitates these state transitions. This cyclic process rightfully deserves
to be termed the basic rest-activity cycle.

Summary
This chapter examines Kleitman's basic rest-activity cycle (BRAC) model in
view of data accumulated in recent years on the sleep REM - NREM cycles and
on the waking ultradian cycles in alertness. It is argued that the REM-NREM
cycles represent a temporal confluence of changes in diverse brain systems
which are potentially dissociable from each other. It is still unclear whether all
REM components sub serve the same function. Likewise, the l.S-h ultradian
periodicities during waking are a multioscillatory phenomenon which includes,
besides cycles in alertness, ultradian cycles in kidney excretions and gastro-
intestinal motility which appear to be independent of each other. The waking
ultradian cycles in alertness are shown in a variety of arousal-related indices
and can be best described as reflecting periodic variations in the balance
between the activity of brain structures concerned in sleep and waking. The
cycles disappear when sleep pressure increases. Analysis of the phase relation-
ships between the ultradian cycles in alertness of different individuals, or the
relationships between cycle phases of the same individual tested at different
times, led to the surprising conclusion that the phase of the ultradian cycles in
alertness is locked to the start of the testing period. This finding is interpreted
in the light of the proposal that the sleep and waking ultra dian cycles function
as a gating mechanism, providing the organism with smooth transitions from
sleep to wakefulness and vice versa.

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