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Thalamo-cortical recruiting responses during sleep characterized by a low voltage fast EEG
412
Electroencephalography and Clinical Neurophysiology Elsevier Publishing Company, Amsterdam - Printed in The Netherlands
THALAMO-CORTICAL DURING
RECRUITING
SLEEP CHARACTERIZED
RESPONSES
BY A LOW VOLTAGE
FAST EEG 1
I. LEHTINEN AND P. VALLEALA
Department of Physiology, University of Turku, Turku (Finland) (Accepted for publication: January 3, 1969)
Low frequency repetitive electrical stimulation of "non-specific" thalamus can in certain circumstances elicit so-called recruiting responses in wide areas of the cerebral cortex. This finding, first described in anaesthetized preparations (Dempsey and Morison 1942a; Jasper 1949), could also be found in unrestrained animals during quiet wakefulness (Evarts and Magoun 1957) and during sleep characterized by EEG slow waves (Yamaguchi et al. 1963, 1964). By using a threshold intensity for recruiting responses, these responses decreased or were abolished when the mesencephalic reticular formation of the brainstem was simultaneously stimulated (Moruzzi and Magoun 1949). Recruiting responses were also decreased or absent when the animal was attentively awake (Evarts and Magoun 1957; Weinberger et al. 1968) or in sleep characterized by a low voltage fast EEG (Rossi et al. 1961; Yamaguchi et al. 1963, 1964; Allison 1965). In anaesthetized preparations and during slow wave sleep repetitive stimulation of "nonspecific" thalamus elicits recruiting responses at the threshold level as intermittently occurring groups which build up from the level of spontaneous activity, i.e., there are no distinct evoked potentials to be found in the electrocorticogram between successive recruiting response groups. On the other hand, during low voltage fast sleep (Yamaguchi et aL 1963) and alert wakefulness (Wells and Sutin 1964) the same type of repetitive thalamic stimulation evokes a cortical potential with every pulse and these potentials do not exhibit typical waxing and waning. The different types of evoked reactivity to 1 Aided by a grant from the Juselius Foundation, Finland.
repetitive stimulation of "non-specific" thalamus will here be denominated as follows: recruiting response will mean a series of evoked potentials in which the amplitude varies in the manner of spindling. To elicit such responses during low voltage fast sleep the intensity of repetitive thalamic stimulation has to be at a higher level than is needed to elicit recruiting responses during slow wave sleep. Recruiting wave will signify a single evoked potential of a recruiting response. Sustained waves refer to successive evoked potentials not showing waxing and waning. The general characteristics of the thalamocortical recruiting response during low voltage fast sleep and the relation of such a response to the occurrence of rapid eye movements (REMs) is the main theme of the present study. Furthermore, recruiting responses are related to the electrical activity of levator palpebrae superioris in that stage of sleep. METHODS
The experiments were performed on six adult, unanaesthetized, freely moving cats, carrying teflon-coated stainless steel electrodes previously implanted under barbiturate anaesthesia. Stimulating electrodes consisted of two wires, each 0.25 mm in diameter. They were insulated to their obliquely cut ends, cemented side by side and their tips were separated vertically by 1 mm. The stimulating electrodes were inserted at coordinates F 8.5-11.0, L 0-1.0, V 0 to + l, according to Snider and Niemer's atlas (1961), but the precise final localization was based on the observation of cortical recruiting responses to thalamic stimulation. The stimuli consisted in rectangular pulses Electroenceph. clin. NeurophysioL, 1969, 27:412--421
RECRUITING RESPONSESDURING SLEEP of 0.4-1.0 msec duration at 8/see and the peak current varied from 0.15 to 0.50 mA, except in one cat in which it amounted to 1.3 mA. The current was monitored on a CRO by measuring the voltage drop over a 0.5 k ~ resistor in series with the electrodes. Stimulation was provided by a Grass S-4 stimulator and an RF isolation unit. For recording of REMs and the movements of the upper eyelids, two wires 0.13 mm in diameter were inserted through the roof of each orbit into the levator palpebrae superioris muscles. The ends of the wires lying inside the muscles were denuded of insulation for a length of about 5 mm. These wires were used for recording the E M G and electro-oculogram (EOG). In the latter case the electrode pair consisted of one lead from each levator muscle. In a control animal a more conventional way of recording the EOG was used by placing the electrodes at the inner canthus of each eye. There were, however, no consistent differences in the temporal distribution of the EOG during low voltage fast sleep when recorded in these two ways. Cortical electrodes were placed on the dura within 0.5-2.0 mm lateral to the midline for recording electrical activity from both anterior sigmold gyri. A reference electrode was cemented in the frontal bone. All recording electrodes were fixed according to the technique of Sheatz (1961). Activity led off from the cortex and levator muscles was amplified by conventional techniques, displayed on a CRO and fed to magnetic tape. Concurrent tracings of EEO and EOG were recorded with an ink-writing oscillograph. To facilitate sleep the animal was kept on a slowly revolving drum during the night before the recording day. During experiments the animal was kept in a shielded sound-attenuated cage provided with a window. During sleep recordings the cage was completely dark. Wakefulness in this study means quiet wakefulness, i.e., the animal sat or was in the "sphinx" position, looking through the window of the cage. During low voltage fast sleep stimulation was performed as follows: in one part of the experiments the duration of stimulation and the interval between successive stimuli were varied, but an attempt was made to start the stimulation period either during strong REMs or absence of REMs. In another part a systematic scheme was used in
413
three animals; stimulation periods of 10 sec were continually alternated with pauses of the same duration. In this material the recordings obtained with an ink-writing oscillograph were divided into 200 msec parts. With respect to every 200 msec division a judgement was made as to which of the following three categories it belonged: "Only recruiting responses", "Only R E M " or " R E M and recruiting responses simultaneously". The total numbers of 200 msec periods in these three groups were then determined. In each animal such analyses comprised measurements from several low voltage fast sleep periods. After experimental series which could last several weeks the positions of the stimulating electrodes were marked by electrolytic deposits of iron. The points were then checked histologically in serial sections which were stained with cresyl violet (Nissl). The marked sites of the electrode tips were found in all cases to be in the general region of n. centralis medialis, within 1.0 mm from the midline. RESULTS
Recruiting responses during low voltage fast sleep compared with their occurrence during slow wave sleep and wakefulness When the intensity of repetitive stimulation of "non-specific" thalamus was gradually raised G35 mA 0.30
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Fig. 1 Thresholds for recruiting responses (large circles) and sustained waves (small circles). Measurements were made from one animal during the same recording session, including the stages of low voltage fast sleep (shaded columns), slow wave sleep (S) and wakefulness (W). Stimulation of "non-specific" thalamus: 8/see, 1 msec. Ordinate: stimulation current (mA). Abscissa: time (hours).
Electroenceph. clin. Neurophysiol., 1969, 27:412-421
414
I. LEHTINEN AND P. VALLEALA
during low voltage fast sleep, the sustained waves represented the first noticeable reaction in the electrocorticogram. The amplitude of the first wave at the start of stimulation was usually small-
er than that of the following waves. When stimulus strength was raised still further, recruiting responses started to appear as intermittent groups, and both recruiting, responses and sus-
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3 Fig. 2 Recruiting responses recorded during one session. In A a transition from slow wave sleep to low voltage fast sleep. Stimulus strength was liminal for recruiting responses during slow wave sleep. In the other samples stimulus strength was raised in order to provoke recruiting responses during low voltage fast sleep (B, C and D) and during wakefulness (D and F). 1 : ECoG of anterior sigmoid gyrus; 2: EOG; 3 : stimulus marker. Calibrations: 50/~V, 5 sec. Note the gradual appearance of sustained waves at the beginning of low voltage fast sleep (A).
Eleetroeneeph. elin. Neurophysiol., 1969, 27:412--421
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I
RECRUITING RESPONSES DURING SLEEP
tained waves were seen in the same record (e.g., Fig. 4). There was no considerable difference between the latencies of sustained and recruiting waves. In different animals these latencies varied from 12 to 20 msec, and the difference between their thresholds from 0.05 to 0.15 mA. Fig. 1 shows the threshold values corresponding to the first appearance of sustained waves (small circles) and of recruiting responses (large circles). Measurements were made during low voltage fast sleep (shaded columns in Fig. 1) and, for comparison, also during slow wave sleep and wakefulness. All the data shown in Fig. 1 were sampled from one animal in the course of one recording day, but the same general type of relationship between threshold levels was found in every animal. The thresholds in Fig. 1 are roughly grouped into two zones, upper and lower. In this figure all thresholds show a gradual rise as a function of time, and this change is about equivalent in the two zones. This kind of gradual rise of threshold was not a consistent finding in all animals and on all recording days and was not further investigated in this study. It can be seen in Fig. 1 that within the lower zone the threshold values for sustained waves during low voltage fast sleep and wakefulness and, on the other hand, for recruiting responses during slow wave sleep are about the same. These facts with respect to low voltage fast sleep and slow wave sleep can also be found in Fig. 2, A, but from another point of view. The figure shows a gradual transition from the latter to the former during the course of the same thalamic stimulation. The stimulus strength was chosen to be liminal for the appearance of recruiting responses. In the beginning of this recording the ongoing cortical activity is interrupted by recruiting response groups. Later the recruiting tendency decreases while the sustained waves start to appear. Eye movements typical of low voltage fast sleep emerge with these events. The threshold values composing the upper zone in Fig. 1 show more dispersion than in the lower one. It has to be remembered that in the present study we are dealing with quiet wakefulness; if the animal was restless the threshold for recruiting responses was much higher, or these phenomena could not be elicited at all. Measurements made during slow wave sleep
415
have been indicated in Fig. 1 with the same symbols as for other stages, although the meaning of the symbols is somewhat different: the large circles in Fig. 1 within S columns represent thresholds for eliciting recruiting responses without concomitant sustained waves and, on the other hand, the small circles in S columns indicate the first appearance of sustained waves in the intervening periods of successive recruiting response groups. Thus slow wave sleep with respect to the background of recruiting responses is clearly different from both low voltage fast sleep and wakefulness, which in this respect are quite similar. During the latter the recruiting responses never develop from a background of mere spontaneous cortical activity, as is the case when the animal is drowsy, in slow wave sleep or under barbiturate anaesthesia, but they are always connected with sustained waves coming up during the periods between successive recruiting responses. In addition, during the course of continuous repetitive stimulation the frequency of int~mittent recruiting response groups during slow wave sleep is higher and their temporal distribution more regular than in low voltage fast sleep and wakefulness.
The relationship between recruiting responses and rapid eye movements The investigation of the relationship between recruiting responses and REMs was always started by choosing the lowest intensity of repetitive thalamic stimulation which provoked intermittent recruiting responses, i. e., the level which within the shaded columns in Fig. 1 is indicated by large circles. For example, in Fig. 2, A the stimulus intensity was below the threshold level and was therefore raised until recruiting responses started (Fig. 2, B-D). This type of thalamic stimulation did not cause any clear temporary cessation of ongoing motor activity in awake animals and never produced any kind of repetitive twitching or obvious autonomic reactions. It has to be emphasized that, when long lasting, it did not prevent shifts from low voltage fast to slow wave sleep or vice versa, nor did it clearly activate such transitions. Fig. 2, B-D give examples of cases in which the stimulation periods were varied and attempts were made to start the stimulus either during Electroenceph. clin. Neurophysiol., 1969, 27:412-421
416
I. LEHTINEN AND P. VALLEALA REM
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Fig. 3 Temporal distribution of recruiting responses (RR) and rapid eye movements (REM) during one low voltage fast sleep period lasting about 3 min. The continuous recording should be read from left to right and from top to bottom. Stimulation periods of 10 sec alternated with pauses of the same duration. In only one case did recruiting responses and REMs overlap in this recording.
strong REMs or absence of REMs. Fig. 3 shows results from one low voltage fast sleep period during which a systematic stimulation schedule was used (see Methods). The data of Fig. 2 and 3 are from the same animal (Cat 1). In these figures, which are representative of all experiments of this kind, it can be seen that recruiting responses and REMs did not usually occur simultaneously. This was most consistent during the period corresponding to the culmination of recruiting
spindling. As shown in Table I the simultaneous occurrence of recruiting responses and REMs in a group of three animals was only of the order of 1%, whereas "Only R R " and "Only R E M " classes combined varied from 32.7% to 42.4% of the total stimulation time. On the other hand, the cortical evoked potentials not contributing to intermittent recruiting phenomena, i.e., sustained waves, could occur regularly with REMs. One low voltage fast sleep period lasting about 3 min is schematically shown in Fig. 3. In the final phase of this period the EEG is actually changing to that of slow wave sleep. This change is indicated by the paucity of REMs and the tendency for recruiting responses to occur with the start of stimulation, while their number during a 10 sec stimulation period tends to increase. In fact, the first spindles characteristic of slow wave sleep started immediately after the last recruiting response group depicted in the lowermost line of Fig. 3. In those exceptional cases in which recruiting response and REMs occurred simultaneously the waxing of the former was slower and their culmination in spindling was of smaller amplitude as compared with recruiting responses occurring without concurrent REMs. On the other hand, it was also very uncommon that EOG bursts of large amplitude occurred during such overlapping periods. Fig. 2, E and F represent experiments from the same recording session as that illustrated in Fig. 2, A-D, but in this case the animal was awake. The cat sat still and looked through the window of the cage, which was now partly illuminated. One can observe the same type of
TABLE I Occurrence of recruiting responses (RR) and rapid eye movements (RE M) during low voltage fast sleep in three animals. For analysis see Methods.
Cat (No.)
1 2 3
Number of 200 msec periods
7639 3050 2600
Stimulation
No stimulation
Only REM
Only RR.
R E M and R R simultaneously
Total REM
Total REM
%
%
%
%
%
25.5 27.5 20.0
12.8 14.9 12.7
0.93 1.15 0.62
26.5 28.7 20.6
32.8 30.2 28.3
Electroenceph. clin. Neurophysiol., 1969, 27:412~-21
RECRUITING RESPONSES DURING SLEEP
417
Fig. 4 Relation of recruiting responses to the electrical activity of left levator palpebrae superioris muscle during low voltage fast sleep (4 samples). Upper traces: ECoG of left anterior sigmoid gyrus. Lower traces: E M G of levator muscle. Stimulation is continuous in the second and fourth samples and its start in the first and third samples is indicated by an arrow. Calibrations: 50/zV (ECoG), 1 sec.
relationship between recruiting responses and the eye movements of visual inspection as that encountered in the same animal during low voltage fast sleep. Finally, the relation of recruiting responses to the electrical activity of levator palpebrae superioris was similar to that to REMs. Thus they did not usually occur concurrently during low voltage fast sleep (Fig. 4). It was sometimes found that the tonic component of the E M G burst which just preceded the recruiting response decreased in parallel with the waxing phase of recruitment (Fig. 4, A). DISCUSSION
in the present study recruiting responses during slow wave sleep and sustained waves
during low voltage fast sleep represented the first reactions in records from the anterior sigmoid gyrus when the strength of repetitive stimuli to "non-specific" thalamus was gradually raised. With further increase of stimulus strength during low voltage fast sleep, recruiting responses started as intermittent groups; in this situation the recruiting and sustained waves thus occurred in the same recording and were apparently quite closely related. Among the similarities between recruiting and sustained waves in this stage of sleep are the relatively long equal latencies, the similar type of minimal or absent initial positivity and the same general wave forms. On the other hand, such characteristics of sustained waves as the increase of the surface-negative component following the second thalamic stimulus as compared to Electroenceph. clin. Neurophysiol. , 1969, 27:412~-21
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I. LEHTINEN AND P. VALLEALA
that following the first stimulus (e.g., Fig. 4,C), and the lack of the typical spindling to continuous repetitive stimulation are reminiscent of the augmenting response (Dempsey and Morison 1942b; Brookhart and Zanchetti 1956). In the present study the intermingling of sustained waves, i.e., the "augmenting-like" component and the recruiting response varies essentially according to the state of the animal. It has to be remembered that in this study the thresholds for recruiting responses during slow wave sleep and for sustained waves during low voltage fast sleep were about the same, so that the appearance of sustained waves cannot be explained by the spread of stimulating current but rather by a change in transmission circumstances. It seems obvious that repetitive stimulation of "non-specific" thalamus will uncover one kind of periodic tendency which essentially would determine the frequency of recruiting response groups both during slow wave sleep and low voltage fast sleep. During slow wave sleep these groups often appear with rather regular intervals and at relatively high frequency. During low voltage fast sleep, on the other hand, their occurrence is lower and the intervening intervals between successive groups are irregular. It seems probable that during low voltage fast sleep there are some factors which can modulate and also totally inhibit the periodic tendency. A later discussion will indicate that the factors which are effective during low voltage fast sleep, and possibly strongly modify the influence of this kind of periodic tendency, are the phasic events concurrent with REMs. A tendency to sustained waves during slow wave sleep (Fig. 2, A) and that to recruiting responses during low voltage fast sleep would be a sensitive indication of an alteration in the actual sleep stage. Sensitivity of recruiting responses to reveal slight changes in arousal level has been emphasized by Weinberger et al. (1968). When stimulating "non-specific" thalamus during low voltage fast sleep at threshold intensity for recruiting responses, it was highly uncommon for the latter and REMs to occur concurrently. This finding, which confirms and extends the results obtained by Allison (1965), may be explained in two ways. First, the low voltage fast sleep mechanism itself and its phasic accentuations, being temporarily related to REMs, may
depress the so-called synchronizing thalamocortical system and thus prevent the appearance of recruiting responses during thalamic stimulation (Rossi et al. 1961; Yamaguchi et aL 1964; Allison 1965). Supporting this possibility is the higher threshold for recruiting responses during low voltage fast sleep than during slow wave sleep. Moreover, during low voltage fast sleep there is a varying delay to the first recruiting response from the start of stimulation, as can be seen in Fig. 3. During slow wave sleep, on the contrary, the first recruiting response tends to build up soon after the start of stimulation (See transition to slow wave sleep in lower part of Fig. 3). it is possible that REMs which sometimes filled up such a delay were also a causal factor for it, by preventing the appearance of recruiting responses. Secondly, the repetitive stimulation of "nonspecific" thalamus itself, and especially the events relating to recruiting responses during this kind of stimulation, might inhibit the mechanism responsible for REMs. A background to this assumption are the findings concerning the induction of recruiting responses in the mesencephalic and bulbar reticular formation (Schlag and Faidherbe 1961), as well as the changes in motor behaviour, e.g., in the form of an "arrest reaction" (Hunter and Jasper 1949) and the cessation of conditioned movement (Rougeul et al. 1967). The finding that recruiting responses and REMs usually did not occur concurrently could be stated in another way: it was highly uncommon for REMs to start during recruiting responses. This point of view indicates that the events caused by thalamic stimulation, being concurrent with recruiting responses, could inhibit the mechanism producing REMs. It is unlikely, however, that this kind of thalamic stimulation, in the present study, exerted any marked effect on the causal mechanism of REMs because of the small difference to be found in cats 1 and 2 in Table I between Total REM (Stimulation) and Total REM (No stimulation). It has to be remembered that the intensity of thalamic stimulation was no higher than was necessary to elicit recruiting responses. Naturally one can not exclude the possibility that such a stimulus could influence some other qualities of REMs than merely the temporal occurrence which was analysed in this study. Electroenceph. clin. Neurophysiol., 1969, 27:412~-21
419
RECRUITING RESPONSES DURING SLEEP
When dealing with the relationship between recruiting responses and REMs it thus seems probable that both factors, low voltage fast sleep with REMs and thalamic stimulation with recruiting responses, must be taken into account, although the influence of the former factor is assumed to be the more important and will be further discussed below. During low voltage fast sleep the generalized thalamo-cortical system can be inhibited by the descending influence mediated by the somatosensory and motor cortex (Krauthamer et al. 1968). This influence could explain findings made in the present study providing that its timing corresponds to that of REMs. Some studies could point to such a possibility, because during low voltage fast sleep phasic enhancements in the pyramidal discharge are often related in time with the bursts of REMs and originate from motor (Marchiafava and Pompeiano 1964) as well as from somato-sensory cortex (Morrison and Pompeiano 1965). Recent evidence suggests that the mechanism causing the spontaneous spindle burst probably is a necessary prerequisite for the presence of the recruiting response (Lehtinen and Valleala 1968). The so-called "spindle-tripping" (Jasper and Droogleever-Fortuyn 1947) can sometimes be demonstrated during the intervals of the REM bursts, thus indicating an increased susceptibility to spindle activity during these periods (Lehtinen and Valleala, in preparation). In the light of the present study and the findings mentioned above it seems that during low voltage fast sleep in the course of continual repetitive thalamic stimulation the occurrence of the recruiting response indicates a tendency to slow wave sleep. By stimulating the "non-specific" thalamus during this stage of sleep, and thus creating the possibility of the presence of recruiting responses, we are actually measuring the intensity of the mechanism maintaining the state of electrocortical desynchronization. Occasional decrease in this intensity, i.e., a tendency to spindle activity, will then afford the necessary prerequisite for the appearance of the recruiting response. SUMMARY
1. During sleep characterized by a low voltage
fast EEG, recruiting responses could be elicited in cats in the course of repetitive stimulation of "non-specific" thalamus by using a stimulus strength slightly supraliminal for recruiting responses during sleep characterized by EEG slow waves. 2. The occurrence of recruiting responses and "sustained waves" depended on the stimulus strength and the actual state of the animal. 3. In the same animal the thresholds for eliciting recruiting responses during slow wave sleep and "sustained waves" during low voltage fast sleep and quiet wakefulness were about the same. There was no remarkable difference between the latencies of the "sustained" and recruiting waves during low voltage fast sleep. 4. During low voltage fast sleep, recruiting responses and rapid eye movements (REMs) usually did not appear simultaneously; i.e., if stimulation was started during REMs the first recruiting response was often delayed. From another point of view, REMs did not usually start during recruiting responses. A similar relationship was found between recruiting responses and the electrical activity of the levator palpebrae superioris muscles. The decrease of the tonic component of the levator EMG was often parallel with the waxing phase of the recruiting response. In the waking state also the searching eye movements and recruiting responses did not usually occur concurrently. 5. It can be assumed that during low voltage fast sleep in the course of continual repetitive stimulation, the temporal distribution of recruiting response groups corresponds to fluctuations of the low voltage fast sleep level. These fluctuations might indicate an occasional tendency to slow wave sleep. R~SUM~ REPONSES
PAR
CALES PENDANT
RECRUTEMENT LE SOMMEIL
THALAMO-CORTICARACTERIfiE PAR
UN EEG RAPIDE DE BAS VOLTAGE
1. Pendant le sommeil caractCris¢ par un EEG rapide de bas voltage, des r~ponses par recrutement ont 6t6 obtenues chez des chats au cours de stimulations r6p6titives du thalamus "non sp6cifique",enutilisantune intensit6 de stimulation 16g~rement supraliminaire ~t l'intensit6 n6cessaire Electroenceph. clin. Neurophysiol., 1969, 27:412-421
420
I. LEHTINEN AND P. VALLEALA
p o u r o b t e n i r des r6ponses p a r r e c r u t e m e n t p e n d a n t le s o m m e i l caract6ris6 p a r des ondes E E G lentes. 2. L a survenue de r6ponses p a r r e c r u t e m e n t et d ' " o n d e s e n t r e t e n u e s " d6pend de l'intensit6 d u stimulus et de l'6tat actuel de l ' a n i m a l . 3. Chez le m~me animal, le seuil n6cessaire ~t l ' a p p a r i t i o n de r6ponses p a r r e c r u t e m e n t pend a n t le sommeil lent et d ' o n d e s entretenues p e n d a n t le sommeil r a p i d e et p e n d a n t l'6tat de veille tranquille, est sensiblement le m~me. I1 n ' y a p a s de diff6rence n o t a b l e entre les latences des ondes entretenues et des ondes p a r recrutem e n t p e n d a n t le s o m m e i l rapide. 4. P e n d a n t le s o m m e i l rapide, les r6ponses p a r r e c r u t e m e n t et les m o u v e m e n t s oculaires r a p i d e s n ' a p p a r a i s s e n t p a s h a b i t u e l l e m e n t de fa~on simultan6e, c'est-~t-dire que si la stimul a t i o n d6bute p e n d a n t les m o u v e m e n t s oculaires rapides, les premieres r6ponses p a r r e c r u t e m e n t sont souvent retard6es. D ' a u t r e part, les m o u v e m e n t s oculaires r a p i d e s ne d 6 b u t e n t p a s h a b i t u e l l e m e n t p e n d a n t les r6ponses p a r recrutement. U n e relation similaire s ' o b s e r v e entre r6ponses p a r r e c r u t e m e n t et activit6 61ectrique des muscles p a l p 6 b r a u x 616vateurs sup6rieurs. L a d i m i n u t i o n de la c o m p o s a n t e tonique de I ' E M G d u muscle 616vateur est souvent parall~le la p h a s e a s c e n d a n t e de la r6ponse p a r recrutement. A l'6tat de veille 6galement, les mouvements oculaires d ' e x p l o r a t i o n et les r6ponses p a r r e c r u t e m e n t ne surviennent h a b i t u e l l e m e n t p a s de faqon c o n c o m i t a n t e . 5. O n p e u t d o n c p o s t u l e r que p e n d a n t le sommeil rapide, a u cours d ' u n e s t i m u l a t i o n r6p6titive continue, la d i s t r i b m i o n t e m p o r e l l e des groupes de r6ponses p a r r e c r u t e m e n t corr e s p o n d aux fluctuations d u niveau de s o m m e i l rapide. Ces fluctuations p o u r r a i e n t i n d i q u e r une t e n d a n c e occasionnelle a u s o m m e i l lent.
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421
(Lond.), 1963,199: 186-187.
YAMAGUCHI,N., LING, G. M. and MARCZYNSKI,T. J.
(N. Y.), 1964, 116: 235-237. YAMAGUCm, N., LrNG, G. M. and MARCZYNSKI, T. J. Differences between cortical recruiting responses observed during wakefulness and natural sleep. Nature
Recruiting responses observed during wakefulness and sleep in unanesthetized chronic cats. Electroenceph. clin. Neurophysiol., 1964,17: 246-254.
Reference: LEHTINEN,I. and VALLEALA,P. Thalamo-cortical recruiting responses during sleep characterized by a low voltage fast EEG. Electroenceph. clin. Neurophysiol., 1969, 27:412-421.
ANNOUNCEMENTS THE
SOCIETY
OF BIOLOGICAL
The Society of Biological Psychiatry announces two awards to be given in May, 1970. The first is the Gold Medal Award to a distinguished senior scientist in the field of Biological Psychiatry. The second are two $750 awards: one for clinical research and one for basic research in the fields related to Biological Psychiatry.
PSYCHIATRY
These latter two awards are to be given to young men under 35 years of age. The deadlines for entries are February 1, 1970. For details please contact Williamina A. Himwich, Ph.D., Chairman, Committee on Research Awards, Society of Biological Psychiatry, Galesburg State Research Hospital, Galesburg, Illinois 61401, U.S.A.
Electroenceph. clin. Neurophysiol., 1969, 27:421
THE
SOCIETY
FOR
Following discussions and assessment of the response by interested scientists throughout the United States, a new society has been formed to promote better undecstanding of the functioning of nervous systems including the part they play in determining behavior. A steering group was organized by the Committee on Brain Sciences of the National Research Council, culminating in the formation of the Society for Neuroscience. The new group will foster interdisciplinary communication and investigation among scientists from the many fields involved and at all levels of biologic organization. It will also seek to attract potential investigators, to advance their education, and to inform the general public of
NEUROSCIENCE current research in this area and its implications. Specific activities envisioned for the society, in addition to national meetings, include sponsorship of local chapters to arrange meetings of scientists of differing backgrounds interested in nervous systems, and establishment of a central source of information on interdisciplinary curricula and training programs in neuroscience. The society will also produce nontechnical reports on new information in this broad area, underlining its relevance to the h u m a n condition. Inquiries should be addressed to the Society for Neuroscience, c/o Dr. Louise H. Marshall, 2101 Constitution Avenue, N.W., Washington, D.C. 20418, U.S.A.
Electroenceph. clin. Neurophysiol., 1969, 27:421
Electroencephalography and Clinical Neurophysiology Elsevier Publishing Company, Amsterdam - Printed in The Netherlands
THALAMO-CORTICAL DURING
RECRUITING
SLEEP CHARACTERIZED
RESPONSES
BY A LOW VOLTAGE
FAST EEG 1
I. LEHTINEN AND P. VALLEALA
Department of Physiology, University of Turku, Turku (Finland) (Accepted for publication: January 3, 1969)
Low frequency repetitive electrical stimulation of "non-specific" thalamus can in certain circumstances elicit so-called recruiting responses in wide areas of the cerebral cortex. This finding, first described in anaesthetized preparations (Dempsey and Morison 1942a; Jasper 1949), could also be found in unrestrained animals during quiet wakefulness (Evarts and Magoun 1957) and during sleep characterized by EEG slow waves (Yamaguchi et al. 1963, 1964). By using a threshold intensity for recruiting responses, these responses decreased or were abolished when the mesencephalic reticular formation of the brainstem was simultaneously stimulated (Moruzzi and Magoun 1949). Recruiting responses were also decreased or absent when the animal was attentively awake (Evarts and Magoun 1957; Weinberger et al. 1968) or in sleep characterized by a low voltage fast EEG (Rossi et al. 1961; Yamaguchi et al. 1963, 1964; Allison 1965). In anaesthetized preparations and during slow wave sleep repetitive stimulation of "nonspecific" thalamus elicits recruiting responses at the threshold level as intermittently occurring groups which build up from the level of spontaneous activity, i.e., there are no distinct evoked potentials to be found in the electrocorticogram between successive recruiting response groups. On the other hand, during low voltage fast sleep (Yamaguchi et aL 1963) and alert wakefulness (Wells and Sutin 1964) the same type of repetitive thalamic stimulation evokes a cortical potential with every pulse and these potentials do not exhibit typical waxing and waning. The different types of evoked reactivity to 1 Aided by a grant from the Juselius Foundation, Finland.
repetitive stimulation of "non-specific" thalamus will here be denominated as follows: recruiting response will mean a series of evoked potentials in which the amplitude varies in the manner of spindling. To elicit such responses during low voltage fast sleep the intensity of repetitive thalamic stimulation has to be at a higher level than is needed to elicit recruiting responses during slow wave sleep. Recruiting wave will signify a single evoked potential of a recruiting response. Sustained waves refer to successive evoked potentials not showing waxing and waning. The general characteristics of the thalamocortical recruiting response during low voltage fast sleep and the relation of such a response to the occurrence of rapid eye movements (REMs) is the main theme of the present study. Furthermore, recruiting responses are related to the electrical activity of levator palpebrae superioris in that stage of sleep. METHODS
The experiments were performed on six adult, unanaesthetized, freely moving cats, carrying teflon-coated stainless steel electrodes previously implanted under barbiturate anaesthesia. Stimulating electrodes consisted of two wires, each 0.25 mm in diameter. They were insulated to their obliquely cut ends, cemented side by side and their tips were separated vertically by 1 mm. The stimulating electrodes were inserted at coordinates F 8.5-11.0, L 0-1.0, V 0 to + l, according to Snider and Niemer's atlas (1961), but the precise final localization was based on the observation of cortical recruiting responses to thalamic stimulation. The stimuli consisted in rectangular pulses Electroenceph. clin. NeurophysioL, 1969, 27:412--421
RECRUITING RESPONSESDURING SLEEP of 0.4-1.0 msec duration at 8/see and the peak current varied from 0.15 to 0.50 mA, except in one cat in which it amounted to 1.3 mA. The current was monitored on a CRO by measuring the voltage drop over a 0.5 k ~ resistor in series with the electrodes. Stimulation was provided by a Grass S-4 stimulator and an RF isolation unit. For recording of REMs and the movements of the upper eyelids, two wires 0.13 mm in diameter were inserted through the roof of each orbit into the levator palpebrae superioris muscles. The ends of the wires lying inside the muscles were denuded of insulation for a length of about 5 mm. These wires were used for recording the E M G and electro-oculogram (EOG). In the latter case the electrode pair consisted of one lead from each levator muscle. In a control animal a more conventional way of recording the EOG was used by placing the electrodes at the inner canthus of each eye. There were, however, no consistent differences in the temporal distribution of the EOG during low voltage fast sleep when recorded in these two ways. Cortical electrodes were placed on the dura within 0.5-2.0 mm lateral to the midline for recording electrical activity from both anterior sigmold gyri. A reference electrode was cemented in the frontal bone. All recording electrodes were fixed according to the technique of Sheatz (1961). Activity led off from the cortex and levator muscles was amplified by conventional techniques, displayed on a CRO and fed to magnetic tape. Concurrent tracings of EEO and EOG were recorded with an ink-writing oscillograph. To facilitate sleep the animal was kept on a slowly revolving drum during the night before the recording day. During experiments the animal was kept in a shielded sound-attenuated cage provided with a window. During sleep recordings the cage was completely dark. Wakefulness in this study means quiet wakefulness, i.e., the animal sat or was in the "sphinx" position, looking through the window of the cage. During low voltage fast sleep stimulation was performed as follows: in one part of the experiments the duration of stimulation and the interval between successive stimuli were varied, but an attempt was made to start the stimulation period either during strong REMs or absence of REMs. In another part a systematic scheme was used in
413
three animals; stimulation periods of 10 sec were continually alternated with pauses of the same duration. In this material the recordings obtained with an ink-writing oscillograph were divided into 200 msec parts. With respect to every 200 msec division a judgement was made as to which of the following three categories it belonged: "Only recruiting responses", "Only R E M " or " R E M and recruiting responses simultaneously". The total numbers of 200 msec periods in these three groups were then determined. In each animal such analyses comprised measurements from several low voltage fast sleep periods. After experimental series which could last several weeks the positions of the stimulating electrodes were marked by electrolytic deposits of iron. The points were then checked histologically in serial sections which were stained with cresyl violet (Nissl). The marked sites of the electrode tips were found in all cases to be in the general region of n. centralis medialis, within 1.0 mm from the midline. RESULTS
Recruiting responses during low voltage fast sleep compared with their occurrence during slow wave sleep and wakefulness When the intensity of repetitive stimulation of "non-specific" thalamus was gradually raised G35 mA 0.30
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TIME
Fig. 1 Thresholds for recruiting responses (large circles) and sustained waves (small circles). Measurements were made from one animal during the same recording session, including the stages of low voltage fast sleep (shaded columns), slow wave sleep (S) and wakefulness (W). Stimulation of "non-specific" thalamus: 8/see, 1 msec. Ordinate: stimulation current (mA). Abscissa: time (hours).
Electroenceph. clin. Neurophysiol., 1969, 27:412-421
414
I. LEHTINEN AND P. VALLEALA
during low voltage fast sleep, the sustained waves represented the first noticeable reaction in the electrocorticogram. The amplitude of the first wave at the start of stimulation was usually small-
er than that of the following waves. When stimulus strength was raised still further, recruiting responses started to appear as intermittent groups, and both recruiting, responses and sus-
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3 Fig. 2 Recruiting responses recorded during one session. In A a transition from slow wave sleep to low voltage fast sleep. Stimulus strength was liminal for recruiting responses during slow wave sleep. In the other samples stimulus strength was raised in order to provoke recruiting responses during low voltage fast sleep (B, C and D) and during wakefulness (D and F). 1 : ECoG of anterior sigmoid gyrus; 2: EOG; 3 : stimulus marker. Calibrations: 50/~V, 5 sec. Note the gradual appearance of sustained waves at the beginning of low voltage fast sleep (A).
Eleetroeneeph. elin. Neurophysiol., 1969, 27:412--421
i
I
RECRUITING RESPONSES DURING SLEEP
tained waves were seen in the same record (e.g., Fig. 4). There was no considerable difference between the latencies of sustained and recruiting waves. In different animals these latencies varied from 12 to 20 msec, and the difference between their thresholds from 0.05 to 0.15 mA. Fig. 1 shows the threshold values corresponding to the first appearance of sustained waves (small circles) and of recruiting responses (large circles). Measurements were made during low voltage fast sleep (shaded columns in Fig. 1) and, for comparison, also during slow wave sleep and wakefulness. All the data shown in Fig. 1 were sampled from one animal in the course of one recording day, but the same general type of relationship between threshold levels was found in every animal. The thresholds in Fig. 1 are roughly grouped into two zones, upper and lower. In this figure all thresholds show a gradual rise as a function of time, and this change is about equivalent in the two zones. This kind of gradual rise of threshold was not a consistent finding in all animals and on all recording days and was not further investigated in this study. It can be seen in Fig. 1 that within the lower zone the threshold values for sustained waves during low voltage fast sleep and wakefulness and, on the other hand, for recruiting responses during slow wave sleep are about the same. These facts with respect to low voltage fast sleep and slow wave sleep can also be found in Fig. 2, A, but from another point of view. The figure shows a gradual transition from the latter to the former during the course of the same thalamic stimulation. The stimulus strength was chosen to be liminal for the appearance of recruiting responses. In the beginning of this recording the ongoing cortical activity is interrupted by recruiting response groups. Later the recruiting tendency decreases while the sustained waves start to appear. Eye movements typical of low voltage fast sleep emerge with these events. The threshold values composing the upper zone in Fig. 1 show more dispersion than in the lower one. It has to be remembered that in the present study we are dealing with quiet wakefulness; if the animal was restless the threshold for recruiting responses was much higher, or these phenomena could not be elicited at all. Measurements made during slow wave sleep
415
have been indicated in Fig. 1 with the same symbols as for other stages, although the meaning of the symbols is somewhat different: the large circles in Fig. 1 within S columns represent thresholds for eliciting recruiting responses without concomitant sustained waves and, on the other hand, the small circles in S columns indicate the first appearance of sustained waves in the intervening periods of successive recruiting response groups. Thus slow wave sleep with respect to the background of recruiting responses is clearly different from both low voltage fast sleep and wakefulness, which in this respect are quite similar. During the latter the recruiting responses never develop from a background of mere spontaneous cortical activity, as is the case when the animal is drowsy, in slow wave sleep or under barbiturate anaesthesia, but they are always connected with sustained waves coming up during the periods between successive recruiting responses. In addition, during the course of continuous repetitive stimulation the frequency of int~mittent recruiting response groups during slow wave sleep is higher and their temporal distribution more regular than in low voltage fast sleep and wakefulness.
The relationship between recruiting responses and rapid eye movements The investigation of the relationship between recruiting responses and REMs was always started by choosing the lowest intensity of repetitive thalamic stimulation which provoked intermittent recruiting responses, i. e., the level which within the shaded columns in Fig. 1 is indicated by large circles. For example, in Fig. 2, A the stimulus intensity was below the threshold level and was therefore raised until recruiting responses started (Fig. 2, B-D). This type of thalamic stimulation did not cause any clear temporary cessation of ongoing motor activity in awake animals and never produced any kind of repetitive twitching or obvious autonomic reactions. It has to be emphasized that, when long lasting, it did not prevent shifts from low voltage fast to slow wave sleep or vice versa, nor did it clearly activate such transitions. Fig. 2, B-D give examples of cases in which the stimulation periods were varied and attempts were made to start the stimulus either during Electroenceph. clin. Neurophysiol., 1969, 27:412-421
416
I. LEHTINEN AND P. VALLEALA REM
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.
.
.
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Fig. 3 Temporal distribution of recruiting responses (RR) and rapid eye movements (REM) during one low voltage fast sleep period lasting about 3 min. The continuous recording should be read from left to right and from top to bottom. Stimulation periods of 10 sec alternated with pauses of the same duration. In only one case did recruiting responses and REMs overlap in this recording.
strong REMs or absence of REMs. Fig. 3 shows results from one low voltage fast sleep period during which a systematic stimulation schedule was used (see Methods). The data of Fig. 2 and 3 are from the same animal (Cat 1). In these figures, which are representative of all experiments of this kind, it can be seen that recruiting responses and REMs did not usually occur simultaneously. This was most consistent during the period corresponding to the culmination of recruiting
spindling. As shown in Table I the simultaneous occurrence of recruiting responses and REMs in a group of three animals was only of the order of 1%, whereas "Only R R " and "Only R E M " classes combined varied from 32.7% to 42.4% of the total stimulation time. On the other hand, the cortical evoked potentials not contributing to intermittent recruiting phenomena, i.e., sustained waves, could occur regularly with REMs. One low voltage fast sleep period lasting about 3 min is schematically shown in Fig. 3. In the final phase of this period the EEG is actually changing to that of slow wave sleep. This change is indicated by the paucity of REMs and the tendency for recruiting responses to occur with the start of stimulation, while their number during a 10 sec stimulation period tends to increase. In fact, the first spindles characteristic of slow wave sleep started immediately after the last recruiting response group depicted in the lowermost line of Fig. 3. In those exceptional cases in which recruiting response and REMs occurred simultaneously the waxing of the former was slower and their culmination in spindling was of smaller amplitude as compared with recruiting responses occurring without concurrent REMs. On the other hand, it was also very uncommon that EOG bursts of large amplitude occurred during such overlapping periods. Fig. 2, E and F represent experiments from the same recording session as that illustrated in Fig. 2, A-D, but in this case the animal was awake. The cat sat still and looked through the window of the cage, which was now partly illuminated. One can observe the same type of
TABLE I Occurrence of recruiting responses (RR) and rapid eye movements (RE M) during low voltage fast sleep in three animals. For analysis see Methods.
Cat (No.)
1 2 3
Number of 200 msec periods
7639 3050 2600
Stimulation
No stimulation
Only REM
Only RR.
R E M and R R simultaneously
Total REM
Total REM
%
%
%
%
%
25.5 27.5 20.0
12.8 14.9 12.7
0.93 1.15 0.62
26.5 28.7 20.6
32.8 30.2 28.3
Electroenceph. clin. Neurophysiol., 1969, 27:412~-21
RECRUITING RESPONSES DURING SLEEP
417
Fig. 4 Relation of recruiting responses to the electrical activity of left levator palpebrae superioris muscle during low voltage fast sleep (4 samples). Upper traces: ECoG of left anterior sigmoid gyrus. Lower traces: E M G of levator muscle. Stimulation is continuous in the second and fourth samples and its start in the first and third samples is indicated by an arrow. Calibrations: 50/zV (ECoG), 1 sec.
relationship between recruiting responses and the eye movements of visual inspection as that encountered in the same animal during low voltage fast sleep. Finally, the relation of recruiting responses to the electrical activity of levator palpebrae superioris was similar to that to REMs. Thus they did not usually occur concurrently during low voltage fast sleep (Fig. 4). It was sometimes found that the tonic component of the E M G burst which just preceded the recruiting response decreased in parallel with the waxing phase of recruitment (Fig. 4, A). DISCUSSION
in the present study recruiting responses during slow wave sleep and sustained waves
during low voltage fast sleep represented the first reactions in records from the anterior sigmoid gyrus when the strength of repetitive stimuli to "non-specific" thalamus was gradually raised. With further increase of stimulus strength during low voltage fast sleep, recruiting responses started as intermittent groups; in this situation the recruiting and sustained waves thus occurred in the same recording and were apparently quite closely related. Among the similarities between recruiting and sustained waves in this stage of sleep are the relatively long equal latencies, the similar type of minimal or absent initial positivity and the same general wave forms. On the other hand, such characteristics of sustained waves as the increase of the surface-negative component following the second thalamic stimulus as compared to Electroenceph. clin. Neurophysiol. , 1969, 27:412~-21
418
I. LEHTINEN AND P. VALLEALA
that following the first stimulus (e.g., Fig. 4,C), and the lack of the typical spindling to continuous repetitive stimulation are reminiscent of the augmenting response (Dempsey and Morison 1942b; Brookhart and Zanchetti 1956). In the present study the intermingling of sustained waves, i.e., the "augmenting-like" component and the recruiting response varies essentially according to the state of the animal. It has to be remembered that in this study the thresholds for recruiting responses during slow wave sleep and for sustained waves during low voltage fast sleep were about the same, so that the appearance of sustained waves cannot be explained by the spread of stimulating current but rather by a change in transmission circumstances. It seems obvious that repetitive stimulation of "non-specific" thalamus will uncover one kind of periodic tendency which essentially would determine the frequency of recruiting response groups both during slow wave sleep and low voltage fast sleep. During slow wave sleep these groups often appear with rather regular intervals and at relatively high frequency. During low voltage fast sleep, on the other hand, their occurrence is lower and the intervening intervals between successive groups are irregular. It seems probable that during low voltage fast sleep there are some factors which can modulate and also totally inhibit the periodic tendency. A later discussion will indicate that the factors which are effective during low voltage fast sleep, and possibly strongly modify the influence of this kind of periodic tendency, are the phasic events concurrent with REMs. A tendency to sustained waves during slow wave sleep (Fig. 2, A) and that to recruiting responses during low voltage fast sleep would be a sensitive indication of an alteration in the actual sleep stage. Sensitivity of recruiting responses to reveal slight changes in arousal level has been emphasized by Weinberger et al. (1968). When stimulating "non-specific" thalamus during low voltage fast sleep at threshold intensity for recruiting responses, it was highly uncommon for the latter and REMs to occur concurrently. This finding, which confirms and extends the results obtained by Allison (1965), may be explained in two ways. First, the low voltage fast sleep mechanism itself and its phasic accentuations, being temporarily related to REMs, may
depress the so-called synchronizing thalamocortical system and thus prevent the appearance of recruiting responses during thalamic stimulation (Rossi et al. 1961; Yamaguchi et aL 1964; Allison 1965). Supporting this possibility is the higher threshold for recruiting responses during low voltage fast sleep than during slow wave sleep. Moreover, during low voltage fast sleep there is a varying delay to the first recruiting response from the start of stimulation, as can be seen in Fig. 3. During slow wave sleep, on the contrary, the first recruiting response tends to build up soon after the start of stimulation (See transition to slow wave sleep in lower part of Fig. 3). it is possible that REMs which sometimes filled up such a delay were also a causal factor for it, by preventing the appearance of recruiting responses. Secondly, the repetitive stimulation of "nonspecific" thalamus itself, and especially the events relating to recruiting responses during this kind of stimulation, might inhibit the mechanism responsible for REMs. A background to this assumption are the findings concerning the induction of recruiting responses in the mesencephalic and bulbar reticular formation (Schlag and Faidherbe 1961), as well as the changes in motor behaviour, e.g., in the form of an "arrest reaction" (Hunter and Jasper 1949) and the cessation of conditioned movement (Rougeul et al. 1967). The finding that recruiting responses and REMs usually did not occur concurrently could be stated in another way: it was highly uncommon for REMs to start during recruiting responses. This point of view indicates that the events caused by thalamic stimulation, being concurrent with recruiting responses, could inhibit the mechanism producing REMs. It is unlikely, however, that this kind of thalamic stimulation, in the present study, exerted any marked effect on the causal mechanism of REMs because of the small difference to be found in cats 1 and 2 in Table I between Total REM (Stimulation) and Total REM (No stimulation). It has to be remembered that the intensity of thalamic stimulation was no higher than was necessary to elicit recruiting responses. Naturally one can not exclude the possibility that such a stimulus could influence some other qualities of REMs than merely the temporal occurrence which was analysed in this study. Electroenceph. clin. Neurophysiol., 1969, 27:412~-21
419
RECRUITING RESPONSES DURING SLEEP
When dealing with the relationship between recruiting responses and REMs it thus seems probable that both factors, low voltage fast sleep with REMs and thalamic stimulation with recruiting responses, must be taken into account, although the influence of the former factor is assumed to be the more important and will be further discussed below. During low voltage fast sleep the generalized thalamo-cortical system can be inhibited by the descending influence mediated by the somatosensory and motor cortex (Krauthamer et al. 1968). This influence could explain findings made in the present study providing that its timing corresponds to that of REMs. Some studies could point to such a possibility, because during low voltage fast sleep phasic enhancements in the pyramidal discharge are often related in time with the bursts of REMs and originate from motor (Marchiafava and Pompeiano 1964) as well as from somato-sensory cortex (Morrison and Pompeiano 1965). Recent evidence suggests that the mechanism causing the spontaneous spindle burst probably is a necessary prerequisite for the presence of the recruiting response (Lehtinen and Valleala 1968). The so-called "spindle-tripping" (Jasper and Droogleever-Fortuyn 1947) can sometimes be demonstrated during the intervals of the REM bursts, thus indicating an increased susceptibility to spindle activity during these periods (Lehtinen and Valleala, in preparation). In the light of the present study and the findings mentioned above it seems that during low voltage fast sleep in the course of continual repetitive thalamic stimulation the occurrence of the recruiting response indicates a tendency to slow wave sleep. By stimulating the "non-specific" thalamus during this stage of sleep, and thus creating the possibility of the presence of recruiting responses, we are actually measuring the intensity of the mechanism maintaining the state of electrocortical desynchronization. Occasional decrease in this intensity, i.e., a tendency to spindle activity, will then afford the necessary prerequisite for the appearance of the recruiting response. SUMMARY
1. During sleep characterized by a low voltage
fast EEG, recruiting responses could be elicited in cats in the course of repetitive stimulation of "non-specific" thalamus by using a stimulus strength slightly supraliminal for recruiting responses during sleep characterized by EEG slow waves. 2. The occurrence of recruiting responses and "sustained waves" depended on the stimulus strength and the actual state of the animal. 3. In the same animal the thresholds for eliciting recruiting responses during slow wave sleep and "sustained waves" during low voltage fast sleep and quiet wakefulness were about the same. There was no remarkable difference between the latencies of the "sustained" and recruiting waves during low voltage fast sleep. 4. During low voltage fast sleep, recruiting responses and rapid eye movements (REMs) usually did not appear simultaneously; i.e., if stimulation was started during REMs the first recruiting response was often delayed. From another point of view, REMs did not usually start during recruiting responses. A similar relationship was found between recruiting responses and the electrical activity of the levator palpebrae superioris muscles. The decrease of the tonic component of the levator EMG was often parallel with the waxing phase of the recruiting response. In the waking state also the searching eye movements and recruiting responses did not usually occur concurrently. 5. It can be assumed that during low voltage fast sleep in the course of continual repetitive stimulation, the temporal distribution of recruiting response groups corresponds to fluctuations of the low voltage fast sleep level. These fluctuations might indicate an occasional tendency to slow wave sleep. R~SUM~ REPONSES
PAR
CALES PENDANT
RECRUTEMENT LE SOMMEIL
THALAMO-CORTICARACTERIfiE PAR
UN EEG RAPIDE DE BAS VOLTAGE
1. Pendant le sommeil caractCris¢ par un EEG rapide de bas voltage, des r~ponses par recrutement ont 6t6 obtenues chez des chats au cours de stimulations r6p6titives du thalamus "non sp6cifique",enutilisantune intensit6 de stimulation 16g~rement supraliminaire ~t l'intensit6 n6cessaire Electroenceph. clin. Neurophysiol., 1969, 27:412-421
420
I. LEHTINEN AND P. VALLEALA
p o u r o b t e n i r des r6ponses p a r r e c r u t e m e n t p e n d a n t le s o m m e i l caract6ris6 p a r des ondes E E G lentes. 2. L a survenue de r6ponses p a r r e c r u t e m e n t et d ' " o n d e s e n t r e t e n u e s " d6pend de l'intensit6 d u stimulus et de l'6tat actuel de l ' a n i m a l . 3. Chez le m~me animal, le seuil n6cessaire ~t l ' a p p a r i t i o n de r6ponses p a r r e c r u t e m e n t pend a n t le sommeil lent et d ' o n d e s entretenues p e n d a n t le sommeil r a p i d e et p e n d a n t l'6tat de veille tranquille, est sensiblement le m~me. I1 n ' y a p a s de diff6rence n o t a b l e entre les latences des ondes entretenues et des ondes p a r recrutem e n t p e n d a n t le s o m m e i l rapide. 4. P e n d a n t le s o m m e i l rapide, les r6ponses p a r r e c r u t e m e n t et les m o u v e m e n t s oculaires r a p i d e s n ' a p p a r a i s s e n t p a s h a b i t u e l l e m e n t de fa~on simultan6e, c'est-~t-dire que si la stimul a t i o n d6bute p e n d a n t les m o u v e m e n t s oculaires rapides, les premieres r6ponses p a r r e c r u t e m e n t sont souvent retard6es. D ' a u t r e part, les m o u v e m e n t s oculaires r a p i d e s ne d 6 b u t e n t p a s h a b i t u e l l e m e n t p e n d a n t les r6ponses p a r recrutement. U n e relation similaire s ' o b s e r v e entre r6ponses p a r r e c r u t e m e n t et activit6 61ectrique des muscles p a l p 6 b r a u x 616vateurs sup6rieurs. L a d i m i n u t i o n de la c o m p o s a n t e tonique de I ' E M G d u muscle 616vateur est souvent parall~le la p h a s e a s c e n d a n t e de la r6ponse p a r recrutement. A l'6tat de veille 6galement, les mouvements oculaires d ' e x p l o r a t i o n et les r6ponses p a r r e c r u t e m e n t ne surviennent h a b i t u e l l e m e n t p a s de faqon c o n c o m i t a n t e . 5. O n p e u t d o n c p o s t u l e r que p e n d a n t le sommeil rapide, a u cours d ' u n e s t i m u l a t i o n r6p6titive continue, la d i s t r i b m i o n t e m p o r e l l e des groupes de r6ponses p a r r e c r u t e m e n t corr e s p o n d aux fluctuations d u niveau de s o m m e i l rapide. Ces fluctuations p o u r r a i e n t i n d i q u e r une t e n d a n c e occasionnelle a u s o m m e i l lent.
REFERENCES ALLISON,T. Cortical and subcortical evoked responses to central stimuli during wakefulness and sleep. Electroenceph, clin. Neurophysio l., 1965, 18: 131-139. BROOKHART, J. M. AND ZANCI-IETTI, A. The relation be-
tween electrocortical waves and responsiveness of the cortico-spinal system. Electroenceph. clin. Neurophysiol., 1956, 8: 427--444. DEMPSEY, E. W. AND MORISON,R. S. The production of
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ANNOUNCEMENTS THE
SOCIETY
OF BIOLOGICAL
The Society of Biological Psychiatry announces two awards to be given in May, 1970. The first is the Gold Medal Award to a distinguished senior scientist in the field of Biological Psychiatry. The second are two $750 awards: one for clinical research and one for basic research in the fields related to Biological Psychiatry.
PSYCHIATRY
These latter two awards are to be given to young men under 35 years of age. The deadlines for entries are February 1, 1970. For details please contact Williamina A. Himwich, Ph.D., Chairman, Committee on Research Awards, Society of Biological Psychiatry, Galesburg State Research Hospital, Galesburg, Illinois 61401, U.S.A.
Electroenceph. clin. Neurophysiol., 1969, 27:421
THE
SOCIETY
FOR
Following discussions and assessment of the response by interested scientists throughout the United States, a new society has been formed to promote better undecstanding of the functioning of nervous systems including the part they play in determining behavior. A steering group was organized by the Committee on Brain Sciences of the National Research Council, culminating in the formation of the Society for Neuroscience. The new group will foster interdisciplinary communication and investigation among scientists from the many fields involved and at all levels of biologic organization. It will also seek to attract potential investigators, to advance their education, and to inform the general public of
NEUROSCIENCE current research in this area and its implications. Specific activities envisioned for the society, in addition to national meetings, include sponsorship of local chapters to arrange meetings of scientists of differing backgrounds interested in nervous systems, and establishment of a central source of information on interdisciplinary curricula and training programs in neuroscience. The society will also produce nontechnical reports on new information in this broad area, underlining its relevance to the h u m a n condition. Inquiries should be addressed to the Society for Neuroscience, c/o Dr. Louise H. Marshall, 2101 Constitution Avenue, N.W., Washington, D.C. 20418, U.S.A.
Electroenceph. clin. Neurophysiol., 1969, 27:421