Increase of Regional Cerebral Blood Volume during REM-Sleep in Man l

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1 Free Communications: E. Phenomenology of Sleep in Man 384 References BELL, A. 1.; STROEBEL, C. F., and PRIOR, D. D.: Interdisciplinary study. Scrotal sac and testes psychophysiological and psychological observations. Psychoanalyt. quart. 40: (1971). GOTISCHALK, L. A.; WINGATE, C. N., and GLESER, G. C.: Manual of instructions for using the Gottschalk-GIeser content analysis scales. Anxiety, hostility, and social alienation-personal disorganization. University of California Press, Berkely (1969). RECHTSCHAFFEN, A. and KALES, A.: A manual of standardized terminology, techniques and scoring system for sleep stages of human subjects. (Public Health Service, US Government Printing Office, Washington 1968). Author's address: Dr. A. 1. BELL, M.D., 960 Park Avenue, New York, NY 28 (USA) Sleep: Physiology, Biochemistry, Psychology, Pharmacology, Clinical Implications. 1st Europ. Congr. Sleep Res., Basel 1972, pp (Karger, Basel 1973) Increase of Regional Cerebral Blood Volume during -Sleep in Man l J. RISBERG and D. H. INGVAR Department of Clinical Neurophysiology, University Hospital, Lund Introduction Studies of brain blood flow and oxygen metabolism during sleep have not shown any consistent differences between slow-wave sleep and relaxed wakefulness [MANGOLD et ai., 1955]. During rapid eye movement () sleep, however, an increase of cerebral blood flow has been reported both in relation to wakefulness and to slow-wave sleep [KANzOW et ai., 1962; REIVICH et ai., 1968]. In a preliminary study by the present authors, regional cerebral blood volume (), which is a relative measure of blood flow, was measured during paradoxical sleep in normals [RISBERG et ai., 1969b]. The results showed a regional 'pattern ' of increases during 1 This study was supported by the Swedish Medical Research Council (project No. B73-14X-84-09A), by the Swedish Council for Social Science Research and by the Wallenberg Foundation, Stockholm.

2 RISBERG Increase of Blood Volume during -Sleep 385 sleep and a positive correlation between the density and the cerebral blood volume. The present investigation is an extension of the previous study. Material and Methods The measurements were made in 7 healthy, slightly sleep-deprived young volunteers who slept in the laboratory for a single night without any medication. The measurements were made by means of a y-emitting intravascular indicator, JLCi of 13II-labeled human serum albumin, injected intravenously [RISBERG and INGVAR, 1968]. The subjects slept 4-8 h in a specially constructed bed which enabled a mild fixation of the subject's head in relation to 8 scintillation detectors mounted within the headrest in lead collimators. Relative blood volume was measured during the night by continuous recording of the radiation from different regions of the head by means of the 8 scintillation detectors. The impulses from the detectors were accumulated during I-min epochs in 8 registers and then stored in a magnetic core memory. The main problem during the measurements was to keep a constant position of the subject's head in relation to the detectors during the recordings, a prerequisite of the method. Movements of the head terminated usable recording periods. In three cases, the transition from slow-wave sleep to sleep was accompanied by head movements; thus, data concerning differences between these sleep stages were obtained only from four recordings. In addition to the measurements, EEG and polygraphic recordings were made for classification of different sleep stages. Results The results from four transitions from orthodox sleep to paradoxical sleep are shown in figure 1. The level during tonic (no s) paradoxical sleep is used as a reference level ( ), and it is seen that the level is slightly lower during slow-wave sleep. The difference is, however, not statistically significant. During phasic paradoxical sleep <with s) the cerebral blood volume is increased especially in frontal regions (1 and 2) and parieto-occipital regions (7 and 8), significant at the 1- to 5-percent levels. It is evident from figure 1 that the mean level is increased in periods of high density. This is shown in more detail in figure 2 for four of the recordings. Discussion It has been shown in animal experiments that a linear relationship exists between changes of cerebral blood flow and cerebral blood volume

3 Free Communications: E. Phenomenology of Sleep in Man 386 ORTHO PARA no 1-8REIM/n,i~> 8 l/minl mean Fig. 1. Regional differences in cerebral blood volume () during sleep in 7 normals. Note the increases over frontal and parieto-occipital regions during paradoxical (para.) sleep with high frequency of. Ortho. = orthodox sleep. [RISBERG et ai., 1969a]. The changes demonstrated in this study are thus most likely to reflect changes of regional cerebral blood flow. The experimental results also show that volume changes are of much smaller magnitude than the flow changes (approximate relation 1 : 7). The small changes of demonstrated in the present study have, thus, to be interpreted in view of these data, and the variations recorded (up to 5 ) indicate flow changes of about 30. Such changes are of the same size as changes reported during mental activity in awake man [INGVAR and RISBERG, 1967; RISBERG and INGVAR, 1968]. The cranial skin, muscle and bone blood volume is also 'seen ' by the detectors during the measurements. There is, however, considerable evidence indicating that the extracranial blood pool is by and large constant during the present experimental conditions [RISBERG and INGVAR, 1968]. Increases in orbital and temporal muscle blood volume might, however, contribute to the increases found during

4 RISBERG Increase of Blood Volume during -Sleep 387 Mean 8 regions Case PARA SL., nr r<" ~... - I----ORTHO SL., PARA SL., """ V'... OS PARA SL...-~-.W '<UY PARA SL I I I ~ m," " Fig. 2. Changes of mean regional cerebral blood volume (, mean of 8 regions) during sleep in four normal subjects. Note the relationship between the frequency and the height of the increase. Para = paradoxical sleep, Ortho = orthodox sleep. sleep in the fronto-orbital region. The other significant increases found were, however, situated in regions where the extracranial contamination must have been very small. Respiratory and systemic circulatory changes may cause alterations of the cerebral blood flow and cerebral blood volume. Such factors have probably not been of importance for the present results. During sleep there is often a slight hypocapnia [BULOW, 1963], which should lead to a general reduction and not regional increases of the cerebral blood flow and volume. The increase in heart rate and blood pressure which might occur during paradoxical sleep should also, due to vasoconstriction, cause a general decrease of. The present results thus confirm the results from previous studies showing increase of cerebral blood flow and metabolism during sleep (see above). However, with the present technique it has been shown

5 Free Communications: E. Phenomenology of Sleep in Man 388 for the first time that brain circulation changes markedly within the sleep period in accordance with the appearance of phasic events (). The changes also show a regional pattern with the largest increases in frontal and parieto-occipital regions. Similar patterns have been found in the awake man during mental activity [RISBERG and INGVAR, 1968]. References BULOW, K.: Respiration and wakefulness in man. Acta physiol. scand. 59: supp!. 209, pp. 1- (1963). INGVAR, D. H. and RISBERG, J.: Increase of regional cerebral blood flow during mental effort in normals and in patients with focal brain disorders. Exp. Brain Res. 3: (1967). KANZOW, E.; KRAUSE, D. und KUHNEL, H.: Die Vasomotorik der Hirnrinde in den Phasen desynchronisierter EEG-Aktivitat im natiirlichen Schlaf der Katze. Pfiiigers Arch. ges. Physio!. 274: (1962). MANGOLD, R.; SOKOLOFF, L.; CONNER, E.; KLEINERMAN, J.; THERMAN, P., and KETY, S. S. The effects of sleep and lack of sleep on the cerebral circulation and metabolism in normal young men. J. din. Invest. 34: (1955). REIVICH, M.; ISAACS, G.; EVARTS, E., and KETY, S. S.: The effect of slow wave sleep and sleep on regional cerebral blood flow in cats. J. Neurochem. 15: (1968). RISBERG, J.; ANCRI, D., and INGVAR, D. H.: Correlation between cerebral blood volume and cerebral blood flow in the cat. Exp. Brain Res. 8: (1969a). RISBERG, J.; GUSTAFSON, L., and INGVAR, D. H.: Regional cerebral blood volume during paradoxical sleep: in BROCK et al. (Eds.) Cerebral blood flow, pp (Springer, Berlin 1969b). RISBERG, J. and INGV AR, D. H.: Regional changes in cerebral blood volume during mental activity. Exp. Brain Res. 5: (1968). Authors' address: Dr. J. RISBERG and Dr. D. H. INGVAR, Department of Clinical Neurophysiology, University Hospital, Lund (Sweden)