Sleep, 16(7):603-609
© 1993 American Sleep Disorders Association and Sleep Research Society
Fundamental Research
Middle Cerebral Artery Blood Flow Velocity in
Healthy Persons During Wakefulness and Sleep:
A Transcranial Doppler Study
*D. W. Droste, *W. Berger, *E. Schuler and
*Department of Neurology and t Department of Neurosurgery,
tJ. K. Krauss
University of Freiburg i.Br., Germany
Summary: In 10 normal young adults, middle cerebral artery blood flow velocity was measured continuously over
one night by transcranial Doppler sonography. Polysomnography was used to assess the different sleep stages and
waking state. During rapid eye movement (REM) sleep, middle cerebral artery blood flow velocity was higher than
in any other sleep stage and wakefulness. During the waking state the velocity was higher than in sleep stage 2.
Spontaneous rhythmic oscillations of cerebral blood flow velocity were found related to different stages of sleep. A
fast Fourier's transformation of the Doppler wave forms revealed a periodicity of 20-75 seconds, which was most
prominent during REM sleep and to a lesser degree during sleep stages 1, 2 and 3 and the waking state. These
waves may correspond to intracranial pressure changes referred to as B-waves. Key Words: Sleep-Cerebral blood
flow- Transcranial Doppler sonography-B-waves.
It is generally accepted that, compared to the waking
state, cerebral blood flow increases during REM (rapid
eye movement) sleep and decreases during slow-wave
sleep (1-5). Using transcranial Doppler sonography
(TCD) it is possible to measure noninvasively the blood
flow velocity in the large basal cerebral arteries (6). The
diameters of these large arteries are assumed to remain
more or less constant (7), changes in cerebral blood
flow are caused by constriction or dilatation of the
smaller resistance vessels. Therefore, cerebral blood
flow velocity changes in the large basal arteries correlate with changes in cerebral blood flow. Transcranial
Doppler sonography is a useful to describe changes in
cerebral blood flow, not absolute values (8).
Hajak et al. (9) found an increase of middle cerebral
artery (MCA) blood flow velocity in adults during REM
sleep and a decrease during slow-wave sleep. Fischer
et al. (10) also found a decrease of MCA blood flow
velocity during slow-wave sleep, as compared to the
waking state, in both adults and children.
Rhythmic changes of middle cerebral artery blood
flow velocity with a wavelength of about 1 minute have
been described in healthy persons (11-13), in patients
with carotid artery disease (12) and closed head injury
Accepted for publication July 1993.
Address correspondence and reprint requests to Dr. D. W. Droste,
Neurologische Universitatsklmik Hansastr. 9, D-79104 Freiburg i.
Br., Germany.
(13) and in patients with normal pressure hydrocephalus (14). These waves correlate with the rhythmic
changes of intracranial pressure (ICP) known as
B-waves (13-15).
The following study was designed to measure cerebral blood flow velocity in MeA in the waking state
and during different sleep stages in healthy persons.
We were particularly interested in the detection of
spontaneous oscillations in blood flow velocity and in
their relation to different sleep stages.
MATERIALS AND METHODS
Ten young adults with no signs of cerebrovascular
disease participated in the study after having given
informed consent (Table 1).
We used the TC 2000S transcranial Doppler (Eden
Medizinische Elektronik GmbH, Uberlingen, Germany). The highest MCA blood flow velocity was
sought at a depth of 45-55 mm through the temporal
window. The lowest ultrasound intensity giving a good
signal was used (26-39%, i.e. less than 100 mW/cm 2
in situ spatial peak temporal average intensity). We
recorded the envelope curve of the Doppler spectrum
with a sample rate of 41 Hz on the hard disc of the
TC 2000S. Continuous measurement was made possible by securing the probe in a head ribbon and with
sticky tape and collodium.
603
D. W DROSTE ET AL.
604
TABLE 1.
Subject
no.
Age
(years)
1
2
3
4
5
6
7
8
9
10
28
28
29
25
28
30
26
27
31
28
28
Mean
m = male, f = female.
Sex a
Side
measured
m
m
m
f
f
m
f
m
m
m
left
left
right
right
left
right
left
right
left
right
Characteristics of subjects and recorded sleep
Total time
recorded
(hours.
Time awake
minutes)
(minutes)
6.10
5.39
6.01
5.45
6.00
7.00
7.11
7.18
8.14
6.17
6.33
38
28
21
129
43
56
36
34
29
5
42
Time spent in sleep stage (minutes)
2
75
32
23
23
18
24
46
46
67
67
42
176
136
178
128
201
167
175
176
209
134
168
3
40
33
56
15
31
35
67
67
38
53
43
4
REM
10
64
49
37
49
61
73
74
46
65
53
35
40
38
18
18
20
42
42
91
93
53
a
For polysomnography we used the Respisomnograph (Madaus Medizin-Elektronik, Gundelfingen,
Germany) with computerized registration of bipolar
electroencephalogram (C4-A2 and C3-A1, sample rate
64 Hz), electrooculogram (sample rate 64 Hz), envelope electromyogram (mentalis muscle, sample rate 16
Hz) and electrocardiogram (sample rate 64 Hz). The
sleep stages were assessed visually every 10 seconds,
following the criteria of Rechtschaffen and Kales (16).
An observer was present continuously and noted
movements and refixed the Doppler probe and electrodes if necessary. Temporal comparability of the two
systems was achieved by adjusting the time of the two
computers in the evening before each measurement.
to sleep stage 2 (=100.0%) were 5.9, 1.3, 3.0, 2.4 and
13.9% for the waking state, sleep stages 1, 3, 4 and
REM sleep, respectively. Analyzing results from each
hemisphere separately demonstrated differences as
compared to sleep stage 2 of 4.3% (waking state), -0.4%
(1),1.8% (3), 4.0% (4) and 11.1% (REM) for the left
side and 7.7%, 3.2%, 4.2%, 1.2% and 16.9% for the
right side, respectively.
We performed a fast Fourier transform (FFT) of the
Doppler values over the whole night for each subject.
With this method it is possible to detect periodicities
of different wavelengths. The term "spectral power" is
an indicator of relative frequency and amplitude of
these periodicities. There was a peak between 0.6 and
1.2 seconds wavelength with a spectral power of2,50027,000
(Fig. 2). There was a second lower peak with
RESULTS
half the wavelength of the above mentioned waveThe overnight measurement including polysomnog- length (0.3-0.6 seconds) with a spectral power of 400raphy and TCD was well tolerated in all subjects. No 7,000. Also, a small peak was observed consistently at
side effects such as headaches or skin alterations were a third of that wavelength (0.2-0.4 seconds).
Within the range of respiration (3-6 seconds of
observed. In all the subjects an MCA signal of sufficient
wavelength), peaks were visible in all patients; howquality was found.
All subjects showed a tendency toward lower Dopp- ever, the spectral power was low (1.5-105). An inconler values in the morning, independent from the sleep stant finding (5 subjects, spectral power 16-140) was
stages (Fig. 1). The REM phases were clearly distin- a small peak at a wavelength of about 10-20 seconds
guishable from the other phases by a marked increase (Fig. 3). All but four subjects showed a peak with a
in blood flow velocity.
wavelength between 20 and 72 seconds and a spectral
We performed ScheWe's test to detect relative changes power of 31 0-900. Two (subjects 7 and 9) had no clear
ofMCA blood flow velocity. As there was a significant peaks in this range, and two other subjects showed two
fluctuation of waking state blood flow velocity, de- peaks, at 27 seconds (spectral power 155) and 44 secpending on the position at the beginning or the end of onds (spectral power 155, subject 4, cf. Fig. 3) and 29
the registration (i.e. before falling asleep or after waking seconds (spectral power 310) and 67 seconds (spectral
up), we used the mean velocity of the longest sleep power 460, subject 8). Up to 12 minutes of wavelength
stage, i.e. sleep stage 2, in each subject as a reference no further peaks were observed (Fig. 4).
for calculations (=100.0%). Mean REM-phase blood
As we were especially interested in the frequency of
flow velocity was significantly (p < 0.05) higher than B-wave equivalents during different sleep stages, we
the mean velocities of any other phase. Waking state connected all the Doppler values of identical sleep
values were significantly (p < 0.05) higher than sleep phases of a single subject and performed an FFT of
phase 2 values. The relative differences as compared this period for 0-3-minute rhythms. Occasionally a
Sleep, Vol. 16, No.7, 1993
TeD AND SLEEP
605
MeA blood flow
velocity [cm/s]
90
80
70
60
50
40
30
7.0
10
7
8
time [h]
FIG. 1. TeD signal over one night, subject 8. For specific sleep stages, please note: lowest = awake, second lowest = stage 1, followed
in ascending order by stages 2, 3 and 4; highest (filled black) = REM. Note the tendency toward lower values in the morning and the
increase during REM phases.
peak at 75-85 seconds was present. This peak probably
represents an artifact (interval during which the machine saves on the hard disc and interrupts recording).
Only rhythms of a spectral power higher than 100 were
considered. During the waking state five subjects (1,
2, 5, 7 and 8) had peaks between 35 and 75 seconds
of a spectral power between 110 and 230. Seven subjects (all but 3,6 and 8) had peaks between 40 and 75
seconds of a spectral power between 104 and 260 during sleep stage 1. In sleep stage 2, subjects 2, 4, 5 and
7 had peaks between 40 and 60 seconds of a spectral
power between 100 and 370 (Fig. 5). Two subjects (5
and 8) showed peaks at 40 and 70 seconds ofa spectral
power of 140 and 220 in sleep stage 3. In subject 5
only, there was a rhythm of 42 seconds and spectral
power of 110 in sleep stage 4. All but two subjects (3
and 4) showed peaks between 45 and 70 seconds of a
spectral power of 110-1,100 during REM sleep (Fig.
6). As a last step we connected all Doppler values of
identical sleep stages of all 10 subjects to perform an
FFT. Peaks were found only for the waking state (47
seconds and 60 seconds, spectral power 130 and 200,
respectively), sleep stage 1 (45-55 seconds, spectral
power 170), sleep stage 2 (40-60 seconds, spectral power 190), sleep stage 3 (40 seconds, spectral power 105)
and REM sleep (25 seconds, spectral power 210; 4570 seconds, spectral power 380).
DISCUSSION
We found MeA blood flow velocity to be higher
during REM sleep and lower during slow-wave sleep
as compared to the waking state, which is consistent
with regional cerebral blood flow studies (1-5) and
TeD studies (9,10). A decrease of MeA blood flow
velocity over the night was observed as described by
Hajak et aI. (9) and Fischer et aI. (10). Further studies
should question the value of the waking state as a
frequently used reference, taking into consideration the
substantial differences of MeA blood flow velocity at
the beginning (higher) and the end (lower) of the night.
There was a tendency toward a higher MeA blood
flow velocity during REM sleep on the right side than
on the left side. Meyer et aI. (3) described a higher right
hemispheric blood flow in narcoleptics during REM
sleep and dreaming.
Sleep, Vol. 16, No.7, 1993
D. W DROSTE ET AL.
606
spectral power
wavelength [5]
FIG. 2.
FFT of TeD signal over one night in subject 8 showing the fast rhythm of heartbeat.
spectral power
1&0
1150
140
130
120
110
100
110
80
70
&0
150
40
30
20
10
0
0
wavelength [5]
FIG. 3. FFT ofTCD signal over one night in subject 4 showing a small peak at 10 seconds and two higher ones at 25 and 45 seconds.
Sleep. Vol. 16. No.7. 1993
607
TeD AND SLEEP
spectral power
wavelength [min]
FIG. 4.
FFT of TCD signal over one night in subject 1 with no further peaks in the minute range.
MeA blood flow
velocity [cm/s]
-,. ~=.~-- =:~~~=--==-=~~-_ =._== _ :_~=~~~~~=.=.~~-_=~-.==::-:-~_-_ _ : _ _ ~:--=-- ~~_ =:~:~ _ =-' ___~~-1Y:.J
~nfl·
22222222222222WWW~~~~~222222222
"'<IV
0- -'-"~"'r"" ,-~""-r"-' ·.··I.,~-r""r-I-rr~-~,··l"r.,~.-,-,.I-""T' '~.,. , .•... , .. ,
'T
• . , .. , - ,
,.
, .. ,
. -,...... --:l?
• • . ,.,.
"-,
,
,
time [min]
FIG. 5. The mean MCA blood flow velocity over almost 11 minutes in subject 5. The different sleep stages and the waking state are
indicated above. The rhythm with a wavelength of approximately 20-60 seconds is pronounced in sleep stage 2.
Sleep. Vol. 16. No.7. 1993
D. W. DROSTE ET AL.
608
MeA blood flow
velocity [cm/s]
...._________ . ____________ ._. _____ .... _. _____________ .. _________________ .. -',,--.'--'0- _________ ...
-"_.
2110-
__
.. _----".-.
__..- ------" .. _--_.. "---"_._---"-- - ..
"
--.--.~ ...
- ---- ... - ..
-
._._. __ .. ".-- ....
_-
-
~
..
_--'
REM REM REM REM REM REM REM REM
.LOO
time [min]
FIG. 6. The mean MeA blood flow velocity during almost II minutes of REM sleep in subject 8; fluctuations have a wavelength of 4080 seconds.
The marked FFf peak ofMCA blood flow velocity
between 0.6 and 1.2 seconds of wavelength corresponds to the heartbeat, and the rhythm with half the
wavelength is probably a result of the dicrotic Doppler
flow velocity curve or represents the harmonics as well
as the small peak at a third of the wavelength of the
heartbeat.
The rhythm of respiration was barely visible in the
FFf of the TCD signal. The small inconstant peak at
about 10 seconds of wavelength probably corresponds
to Hering-Traube-Mayer waves, rhythmic oscillations
of heartbeat and blood pressure, assumed to be triggered by the sympathetic nervous system (17-19).
Lundberg (15) considered C-waves ofICP to be identical with Hering-Traube-Mayer waves. A rhythm of
a wavelength between 20 and 72 seconds was visible
in eight subjects. Regarding the different sleep stages,
a rhythm between 20 and 75 seconds of wavelength
was marked especially during REM sleep, to a lesser
degree during wakefulness, sleep stages 1, 2 and 3, and
almost absent in sleep stage 4. Spontaneous rhythmic
oscillations within this range of wavelength are well
known from ICP recordings, where they are referred
to as B-waves (15). Auer and Sayama (20) (direct observation of animal pial vessels), Newell et al. (13) and
Droste and Krauss (14) (simultaneous TCD and ICP
recordings) have shown that these waves are mediated
by changes in intracranial vessel diameter. The site of
generation and the complex interactions with respiSleep. Vol. 16, No.7, 1993
ratory and cardiovascular oscillations are still controversial (20-23). A high relative frequency of B-waves
is one criterion taken as an indicator for shunt responsiveness in patients with normal pressure hydrocephalus (NPH) (24-25). Two studies (26,27) have
demonstrated that ICP raises during sleep stage 2 and
REM sleep, the sleep stages where we found higher
B-wave equivalent activity. Invasive ICP measurements in normal subjects are not performed. Thus, the
concept that B-waves are related to NPH is based on
examinations in patients. However, some of the subjects of our series (healthy young adults) also had frequent velocity oscillations in the frequency range of
B-waves (Fig. 5). It might be possible that B-wave
equivalents in healthy persons do not correspond to
marked ICP oscillations and that the phenomenon of
ICP B-waves in NPH patients is due to an impaired
transmission of physiological vascular oscillations.
Acknowledgements: We are very grateful to Prof. Dr.
Schulte-Monting for the biomathematical interpretation of
the data, to Eden Medizinische Elektronik GmbH, Uberlingen, Germany for technical support and to Madaus Medizin
Elektronik, Gundelfingen, Germany, for providing us with
the Respisomnograph.
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