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The EEG in anaesthetized juvenile baboons
81
Eleetroencephalography and Clinical Neurophysiology Elsevier Publishing Company, Amsterdam - Printed in The Netherlands
LABORATORY
NOTE
THE EEG IN ANAESTHETIZED JUVENILE BABOONS RUTH HARRIS 1
The British Biological Research Association, Woodmansterne Road, Carshalton, Surrey (Great Britain) (Accepted for publication: July 9, 1971)
The EEG is often used to monitor the cerebral effects of procedures during experimental work involving baboons and other primates. If the animals are anaesthetized, the fluctuations of the on-going EEG activity due to the anaesthesia alone may be relevant in the evaluation of the effects of the experiment. The description of the anaesthetized baboon's EEG by Ellington et al. (1967) arose out of their work on the cerebral effects of oxygen toxicity but only one particular EEG pattern was discussed. In the work to be described there has been the opportunity to record the EEG from anaesthetized baboons and to study the time relationships of the changes in the EEG to the administration of the anaesthetic, METHOD AND MATERIAL Thirty-nine juvenile baboons from Kenya had EEGs recorded aspart ofawiderseriesofelectrophysiologicalinvestigations during a long-term dietary experiment to study the effects of vitamin B12 deficiency and chronic cyanide toxicity (Crampton et al. 1971). Thirty-six males were the subjects of the main part of the experiment; two males and one female were involved in various pilot studies. Their weights ranged from 3.0 to 6.0 kg at the start of the experiment so that their ages were probably between 1 and 3 years (Snow 1967). During the time covered by the EEGs examined, the weight increases were up to 10 kg. A total of 124 EEGs were obtained, 50 before the actual dietary experiment began and the remainder during the early stages of the experiment when eighteen of the thirty-six experimental animals were on a vitamin B12 free diet. Although the blood levels of vitamin B12 were falling steadily in the deprived animals, none had reached deficiency levels and there were no other relevant biochemical abnormalities or unusual clinical.findings. A technique of marking the electrode positions was used, measuring from various anatomical landmarks, and their locations over the different regions of the brain were confirmed by dissection in one of the pilot study animals. It was hoped that comparable electrode positions would be achieved in repeated recordings from the baboons over a period of fairly rapid growth and increase in head size. All the records were taken on an Offner Type T 8-channel
i Present address: Maudsley Hospital, Denmark Hill, London S.E. 5.
machine, using subdermal needle electrodes in bipolar connections of either antero-posterior or transverse chains. The HF response was 15~o down at 75 c/see and the time constant was 0.3 sec. The gain varied from 10 to 32/~V/mm pen deflection and the paper speed was 1.5 or 3 cm/sec. The animals were all in the fasting state and anaesthetized with pentobarbitone (Nembutal), using a standard dosage of 10 mg/kg body weight. This was preceded 15-20 min earlier by an intramuscular injection of phencyclidine hydrochloride (Sernyl or Sernylan), 1.5 mg/kg. At this dosage phencyclidine hydrochloride induced a state in which the animals became immobile and analgesic with loss of aggression. Muscular relaxation was poor. This drug was given to facilitate the handling of the animals during transfer from their cages to the laboratory and the necessary preparation for the various neurophysiological tests. These began immediately after the induction of anaesthesia and were followed by the EEG. Recording was often begun just as the animal was beginning to arouse, about 1 h after the injection of pentobarbitone, but the time intervals were variable and there were a number of occasions when it was possible to record during arousal and fresh induction of anaesthesia. In two of the pilot study animals recordings were continued for up to 6 h during prolonged cyfmide tolerance tests. The types of EEG pattern were then examined in relation to the time interval from the pentobarbitone injection to recording. RESULTS Table I gives information about time intervals between
TABLE I One hundred and twenty-four EEGs from thirty-nine baboons. Time interval (min) from pentobarbitone injection to start of recording
Number of records
< 5 rain 5-15 16-45 > 46 Recording during arousal
29 25 31 64 9
Electroenceph. clin. Neurophysiol., 1972, 32:81-83
82
R. HARRIS
EEGs and the anaesthetic injections. Experience with these recordings showed that different EEG patterns were found roughly within the time groups given in the Table. EEGs taken during an anaesthetic injection or within 5 min usually showed very large amplitude delta activity and faster rhythms. In nine animals the EEG changes were more dramatic. Periods of apparent equipotentiality were seen over all regions of the head, lasting several seconds, with delta waves appearing in the intervals (Fig. 1). These changes
J'~'~5-~~ ~ ' J ~ - ~
/\ ~j"
~ ~ ' / w ~ ~ . ~. / ~
/...__..L3 _.~/-.,~
~
~x.~. , 5
~
t~l' ,] y ~ . ~ 6 /~ ~ _ . ~ ,......_.L___M..~
~ - ~ - ~
I'~ ~ ~ Fig. 1. Episodes of apparent equipotentiality (5 min after the pentobarbitone injection). Calibrations: 100 #V, 1/sec time marker, ~2.
~,
t
,,~'~.,,~ ' ~ v , ' ~ " ~ 4 ~ . , ~ a , % ' t ~ ' ~ e C ~ v ' ~ ~ 4 ~ 5 .,~'~,~....~,~,~/'~/~-/~...~r 6 ~ . ~ , 7 • ' ~ / " ~
~ ~
. ~ ~
l,' ~ ~ ~ ' ~ Fig. 2. Fast activity, prominent about the vertex, alternating with large amplitude delta waves (40 f i n after the pentobarbitone injection). Calibrations : 180/IV, 1/sec time marker.
were seen very soon after an injection, within 3 min in all animals, and persisted for a variable period, as long as 10 f i n in one animal and for 25 f i n in another. The delta activity gradually became more continuous and faster activities appeared. Records taken from 5 to 15 min after an injection showed large amplitude delta waves and fast rhythms occurring more or less continuously over all regions of the head. Round about 15 min after starting the anaesthetic there was a gradual change in the EEG, which then showed a more fluctuating appearance. Episodes of large amplitude delta activity lasting several seconds alternated with periods when fast activity became more prominent (Fig. 2). This fast activity was often up to 40 c/sec in frequency and was particularly marked about the vertex and central regions• The delta waves also showed phase reversal about these regions. Fairly frequent large amplitude vertex and central sharp waves were seen spontaneously and could also easily be evoked by a sudden noise. Similar activity, but smaller in amplitude, was seen from bipolar temporal connections of electrodes. This EEG pattern continued until arousal. Six recordings made more than three-quarters of an hour after anaesthesia showed episodes of 6 8 c/sec or 14~15 c/sec activity over the vertex or central regions, in addition to the fluctuating pattern of fast and slow rhythms. About an hour or more after a dose of pentobarbitone the baboons began to arouse. Most animals began to move about so quickly that recording could not continue but on nine occasions the baboons lay sufficiently still. In this state the EEG showed generalized theta and delta rhythms, of smaller amplitude than was seen in the anaesthetized state. The fast rhythms disappeared but there were usually frequent action potentials from the scalp muscles (Fig. 3). In the animals whose EEG recordings were continued for several hours during the cyanide tolerance tests, fluctuations in the EEG features were seen, appropriately related to the repeated pentobarbitone injections. Three EEGs from one animal taken at intervals over a period of 10 months showed a consistent abnormality, with focal spikes in addition to more generalized paroxysmal activity. DISCUSSION
~ ~
.
.-
~
~ /~,L~,~..~\~C,~,~~~,.~ve%,,k ~
'
~ w ~ ~ " - ' , ~ . ~ ~ ~ , ~ N ~ , , ~ ~%.~"~,'-~e~,~~#"~..J~,,.~~
--
~..6--~,,-,,,.,~-q,~,~,~c~¢M.~ ~-~..,P~,C,t~k~ je~~ " - - ~ " " ' ~ ' * ' ~ ~ ~ Fig. 3. Generalized theta and delta activities seen on arousal together with muscle action potentials (65 f i n after the pentobarbitone injection). Calibrations : 100 #V, 1/sec time marker,
It is common experience that the EEG pattern will alter in relation to the depth of anaesthesia and the type of anaesthetic used and the varymg patterns seen in the recordings from these juvenile baboons are to be expected. The clinical observations of the effect of phencyclidine hydrochloride on monkeys (Chen and Weston 1960) and of the EEG changes which might be seen in human subjects given this drug (Meyer et al. 1959 ; Rodin et al. 1959), make it reasonable to assume that some of the EEG features found in the anaesthetized baboons in the present study were due to phencyclidine, in addition to the slow and fast wave activity induced by pentobarbitone. Paroxysmal activity was described as the characteristic EEG appearance in baboons during a similar form of anaesthesia (Ellington et al. 1967). Sharp components were found, alternating with runs of delta and theta activity. This description was based upon a monopolar recording technique Electroenceph. clin. Neurophysiol., 19'72, 32:81 83
83
EEG IN YOUNG 3ABOONS using the vertex position for the common reference electrode, Many of the wave forms described in the present work showed phase reversal about the vertex or were particularly marked in this region and, using similar monopolar connections, identical recordings could be obtained with similar paroxysmal activity derived from the active vertex electrode, Bipolar recordings showed fluctuations in the appearance of delta and fast rhythms with a particular distribution over various regions of the scalp and it is suggested that the reference electrode should not be placed over the vertex if monopolar recording is used. The rhythmic activities which were seen over the vertex and central regions nearly an hour after anaesthesia are similar to those described in telemetered recordings from baboons during stages 2 and 3 of natural sleep (Bert and Collomb 1966). No attempt was made to record other types ofspontaneouscerebralrhythmsand, ifsubtlealterationsoccurredduring the cyanide tolerance tests, it is unlikely that these would have been detected in the ongoing activity of the anaesthetized animal. Monitoring of the EEG during anaesthesia is most likely to be required during acute animal experiments and in these situations the pattern of the ongoing electrical activity at any particular time may be relevant, especially if transient alterations of cerebral circulation or metabolism are being tested. This study has shown the considerable variations that may be seen in the EEG recorded from baboons in relation to the administration of the anaesthetic drug alone. It is probable that there is stability of the EEG pattern for only 15--45 rain after a pentobarbitone injection, with individual animals showing some variation about these time limits, SUMMARY One hundred and twenty-four EEGs were obtained from thirty-nine juvenile baboons during anaesthesia with phencyclidine hydrochloride (Sernyl) and pentobarbitone (Nembutal). Changing EEG patterns were found which could be related to the time interval from the onset of anaesthesia. It was found, with some variations in individual animals, that a relatively stable EEG was seen from 15 to 45 min after starting anaesthesia. It is suggested that evaluation of these variations are important in experiments where the EEG is being used to monitor changes in cerebral function, RESUME L'EEG DE JEUNES BABOUINS ANESTHESIES Cent vingt-quatre EEGs ont 6t6 effectu6s chez trenteneuf jeunes babouins au tours d'anesth6sie par hydro-
chloride de ph6nicyclidine (Sernyl) ~t pentobarbitone (Nembutal). L'auteur a trouv6 des modifications des patterns EEG qui pouvaient 6tre mises en relation avec l'intervalle de temps A partir du d6but de l'anesth6sie. Ellea observ6, avec quelques variations individuelles entre les divers animaux, qu'un EEG relativement stable s'observait entre 15 et 45 rain apr6s le d6but de l'anesth6sie. Elle pense que l'6valuation de ces variations est importante dans toute exp6rimentation o/1 I'EEG est utilis6 pour contr61er les modifications de la fonction c6r6brale.
I am most grateful to the Welcome Trust for a grant of equipment for this work and for the help I have received from a committee under the Chairmanship of Professor R. H. S. Thompson. I would also like to acknowledge the facilities and technical assistance extended to me at the British Industrial Biological Research Association.
REFERENCES BERT, J. et COLLOMB,H. L'61ectroenc6phalogramme du sommeil nocturne chez le babouin. Etude par t616m6trie. J. Physiol. (Paris), 1966, 58: 285-301. CI4LN,G. M. and WESTON,J. K. The analgesic and anaesthetic effec, of 1-(1-Phenylcyclohexyl) piperidine HCI on the monkey. Anesth. Analg. Curr. Res., 1960, 3 9 : 1 3 2 137. CRAMPTON,R. F., GAUNT, I. F., HARRIS, R., LANGMAN, M . J . S . , LINNELL, J. C., MATTrmWS, D. M., SHARRATT, M., WATES, A. H. and WILSON, J. B12 deficiency and chronic cyanide toxicity in baboons: experimental plan. Proc. 1969 Welcome Symposium on Cassava, Cyanide and Nutritional Neuropathy. London, 1971, (in press). ELLINGTON, A., ETTINGER, M., BAKER, D. and ARNAR, O. The electroencephalogram in the anaesthetized baboon. In H. VgGvaog6 (Ed.), The baboon in medical research and its uses as an experimentalanimal. Point Texas, 1967: 775 782. MEYER,J. S., GREIEENSTEIN, F. and DEVAULT, M. A new drug causing symptoms of sensory deprivation. Neurological, electroencephalographic and pharmacological effects of Sernyl. J. nerv. ment. Dis., 1959, 129: 54~1. RODIN,E. A., LUBY, E~ D. and MEYER,J. S. Electroencephalographic findings associated with Sernyl infusion. Electroenceph. clin. Neurophysiol., 1959, 11: 796-798. SNOW, C. C. Some observations on the growth and development of the baboon. In H. VAGTBORG(Ed.), The baboon in medical research and its uses as an experimental animal. Point Texas, 1967: 187-199.
Reference: HARRIS, R. The EEG in anaesthetized juvenile baboons. Electroenceph. clin. Neurophysiol., 1972, 32:81 83.
Eleetroencephalography and Clinical Neurophysiology Elsevier Publishing Company, Amsterdam - Printed in The Netherlands
LABORATORY
NOTE
THE EEG IN ANAESTHETIZED JUVENILE BABOONS RUTH HARRIS 1
The British Biological Research Association, Woodmansterne Road, Carshalton, Surrey (Great Britain) (Accepted for publication: July 9, 1971)
The EEG is often used to monitor the cerebral effects of procedures during experimental work involving baboons and other primates. If the animals are anaesthetized, the fluctuations of the on-going EEG activity due to the anaesthesia alone may be relevant in the evaluation of the effects of the experiment. The description of the anaesthetized baboon's EEG by Ellington et al. (1967) arose out of their work on the cerebral effects of oxygen toxicity but only one particular EEG pattern was discussed. In the work to be described there has been the opportunity to record the EEG from anaesthetized baboons and to study the time relationships of the changes in the EEG to the administration of the anaesthetic, METHOD AND MATERIAL Thirty-nine juvenile baboons from Kenya had EEGs recorded aspart ofawiderseriesofelectrophysiologicalinvestigations during a long-term dietary experiment to study the effects of vitamin B12 deficiency and chronic cyanide toxicity (Crampton et al. 1971). Thirty-six males were the subjects of the main part of the experiment; two males and one female were involved in various pilot studies. Their weights ranged from 3.0 to 6.0 kg at the start of the experiment so that their ages were probably between 1 and 3 years (Snow 1967). During the time covered by the EEGs examined, the weight increases were up to 10 kg. A total of 124 EEGs were obtained, 50 before the actual dietary experiment began and the remainder during the early stages of the experiment when eighteen of the thirty-six experimental animals were on a vitamin B12 free diet. Although the blood levels of vitamin B12 were falling steadily in the deprived animals, none had reached deficiency levels and there were no other relevant biochemical abnormalities or unusual clinical.findings. A technique of marking the electrode positions was used, measuring from various anatomical landmarks, and their locations over the different regions of the brain were confirmed by dissection in one of the pilot study animals. It was hoped that comparable electrode positions would be achieved in repeated recordings from the baboons over a period of fairly rapid growth and increase in head size. All the records were taken on an Offner Type T 8-channel
i Present address: Maudsley Hospital, Denmark Hill, London S.E. 5.
machine, using subdermal needle electrodes in bipolar connections of either antero-posterior or transverse chains. The HF response was 15~o down at 75 c/see and the time constant was 0.3 sec. The gain varied from 10 to 32/~V/mm pen deflection and the paper speed was 1.5 or 3 cm/sec. The animals were all in the fasting state and anaesthetized with pentobarbitone (Nembutal), using a standard dosage of 10 mg/kg body weight. This was preceded 15-20 min earlier by an intramuscular injection of phencyclidine hydrochloride (Sernyl or Sernylan), 1.5 mg/kg. At this dosage phencyclidine hydrochloride induced a state in which the animals became immobile and analgesic with loss of aggression. Muscular relaxation was poor. This drug was given to facilitate the handling of the animals during transfer from their cages to the laboratory and the necessary preparation for the various neurophysiological tests. These began immediately after the induction of anaesthesia and were followed by the EEG. Recording was often begun just as the animal was beginning to arouse, about 1 h after the injection of pentobarbitone, but the time intervals were variable and there were a number of occasions when it was possible to record during arousal and fresh induction of anaesthesia. In two of the pilot study animals recordings were continued for up to 6 h during prolonged cyfmide tolerance tests. The types of EEG pattern were then examined in relation to the time interval from the pentobarbitone injection to recording. RESULTS Table I gives information about time intervals between
TABLE I One hundred and twenty-four EEGs from thirty-nine baboons. Time interval (min) from pentobarbitone injection to start of recording
Number of records
< 5 rain 5-15 16-45 > 46 Recording during arousal
29 25 31 64 9
Electroenceph. clin. Neurophysiol., 1972, 32:81-83
82
R. HARRIS
EEGs and the anaesthetic injections. Experience with these recordings showed that different EEG patterns were found roughly within the time groups given in the Table. EEGs taken during an anaesthetic injection or within 5 min usually showed very large amplitude delta activity and faster rhythms. In nine animals the EEG changes were more dramatic. Periods of apparent equipotentiality were seen over all regions of the head, lasting several seconds, with delta waves appearing in the intervals (Fig. 1). These changes
J'~'~5-~~ ~ ' J ~ - ~
/\ ~j"
~ ~ ' / w ~ ~ . ~. / ~
/...__..L3 _.~/-.,~
~
~x.~. , 5
~
t~l' ,] y ~ . ~ 6 /~ ~ _ . ~ ,......_.L___M..~
~ - ~ - ~
I'~ ~ ~ Fig. 1. Episodes of apparent equipotentiality (5 min after the pentobarbitone injection). Calibrations: 100 #V, 1/sec time marker, ~2.
~,
t
,,~'~.,,~ ' ~ v , ' ~ " ~ 4 ~ . , ~ a , % ' t ~ ' ~ e C ~ v ' ~ ~ 4 ~ 5 .,~'~,~....~,~,~/'~/~-/~...~r 6 ~ . ~ , 7 • ' ~ / " ~
~ ~
. ~ ~
l,' ~ ~ ~ ' ~ Fig. 2. Fast activity, prominent about the vertex, alternating with large amplitude delta waves (40 f i n after the pentobarbitone injection). Calibrations : 180/IV, 1/sec time marker.
were seen very soon after an injection, within 3 min in all animals, and persisted for a variable period, as long as 10 f i n in one animal and for 25 f i n in another. The delta activity gradually became more continuous and faster activities appeared. Records taken from 5 to 15 min after an injection showed large amplitude delta waves and fast rhythms occurring more or less continuously over all regions of the head. Round about 15 min after starting the anaesthetic there was a gradual change in the EEG, which then showed a more fluctuating appearance. Episodes of large amplitude delta activity lasting several seconds alternated with periods when fast activity became more prominent (Fig. 2). This fast activity was often up to 40 c/sec in frequency and was particularly marked about the vertex and central regions• The delta waves also showed phase reversal about these regions. Fairly frequent large amplitude vertex and central sharp waves were seen spontaneously and could also easily be evoked by a sudden noise. Similar activity, but smaller in amplitude, was seen from bipolar temporal connections of electrodes. This EEG pattern continued until arousal. Six recordings made more than three-quarters of an hour after anaesthesia showed episodes of 6 8 c/sec or 14~15 c/sec activity over the vertex or central regions, in addition to the fluctuating pattern of fast and slow rhythms. About an hour or more after a dose of pentobarbitone the baboons began to arouse. Most animals began to move about so quickly that recording could not continue but on nine occasions the baboons lay sufficiently still. In this state the EEG showed generalized theta and delta rhythms, of smaller amplitude than was seen in the anaesthetized state. The fast rhythms disappeared but there were usually frequent action potentials from the scalp muscles (Fig. 3). In the animals whose EEG recordings were continued for several hours during the cyanide tolerance tests, fluctuations in the EEG features were seen, appropriately related to the repeated pentobarbitone injections. Three EEGs from one animal taken at intervals over a period of 10 months showed a consistent abnormality, with focal spikes in addition to more generalized paroxysmal activity. DISCUSSION
~ ~
.
.-
~
~ /~,L~,~..~\~C,~,~~~,.~ve%,,k ~
'
~ w ~ ~ " - ' , ~ . ~ ~ ~ , ~ N ~ , , ~ ~%.~"~,'-~e~,~~#"~..J~,,.~~
--
~..6--~,,-,,,.,~-q,~,~,~c~¢M.~ ~-~..,P~,C,t~k~ je~~ " - - ~ " " ' ~ ' * ' ~ ~ ~ Fig. 3. Generalized theta and delta activities seen on arousal together with muscle action potentials (65 f i n after the pentobarbitone injection). Calibrations : 100 #V, 1/sec time marker,
It is common experience that the EEG pattern will alter in relation to the depth of anaesthesia and the type of anaesthetic used and the varymg patterns seen in the recordings from these juvenile baboons are to be expected. The clinical observations of the effect of phencyclidine hydrochloride on monkeys (Chen and Weston 1960) and of the EEG changes which might be seen in human subjects given this drug (Meyer et al. 1959 ; Rodin et al. 1959), make it reasonable to assume that some of the EEG features found in the anaesthetized baboons in the present study were due to phencyclidine, in addition to the slow and fast wave activity induced by pentobarbitone. Paroxysmal activity was described as the characteristic EEG appearance in baboons during a similar form of anaesthesia (Ellington et al. 1967). Sharp components were found, alternating with runs of delta and theta activity. This description was based upon a monopolar recording technique Electroenceph. clin. Neurophysiol., 19'72, 32:81 83
83
EEG IN YOUNG 3ABOONS using the vertex position for the common reference electrode, Many of the wave forms described in the present work showed phase reversal about the vertex or were particularly marked in this region and, using similar monopolar connections, identical recordings could be obtained with similar paroxysmal activity derived from the active vertex electrode, Bipolar recordings showed fluctuations in the appearance of delta and fast rhythms with a particular distribution over various regions of the scalp and it is suggested that the reference electrode should not be placed over the vertex if monopolar recording is used. The rhythmic activities which were seen over the vertex and central regions nearly an hour after anaesthesia are similar to those described in telemetered recordings from baboons during stages 2 and 3 of natural sleep (Bert and Collomb 1966). No attempt was made to record other types ofspontaneouscerebralrhythmsand, ifsubtlealterationsoccurredduring the cyanide tolerance tests, it is unlikely that these would have been detected in the ongoing activity of the anaesthetized animal. Monitoring of the EEG during anaesthesia is most likely to be required during acute animal experiments and in these situations the pattern of the ongoing electrical activity at any particular time may be relevant, especially if transient alterations of cerebral circulation or metabolism are being tested. This study has shown the considerable variations that may be seen in the EEG recorded from baboons in relation to the administration of the anaesthetic drug alone. It is probable that there is stability of the EEG pattern for only 15--45 rain after a pentobarbitone injection, with individual animals showing some variation about these time limits, SUMMARY One hundred and twenty-four EEGs were obtained from thirty-nine juvenile baboons during anaesthesia with phencyclidine hydrochloride (Sernyl) and pentobarbitone (Nembutal). Changing EEG patterns were found which could be related to the time interval from the onset of anaesthesia. It was found, with some variations in individual animals, that a relatively stable EEG was seen from 15 to 45 min after starting anaesthesia. It is suggested that evaluation of these variations are important in experiments where the EEG is being used to monitor changes in cerebral function, RESUME L'EEG DE JEUNES BABOUINS ANESTHESIES Cent vingt-quatre EEGs ont 6t6 effectu6s chez trenteneuf jeunes babouins au tours d'anesth6sie par hydro-
chloride de ph6nicyclidine (Sernyl) ~t pentobarbitone (Nembutal). L'auteur a trouv6 des modifications des patterns EEG qui pouvaient 6tre mises en relation avec l'intervalle de temps A partir du d6but de l'anesth6sie. Ellea observ6, avec quelques variations individuelles entre les divers animaux, qu'un EEG relativement stable s'observait entre 15 et 45 rain apr6s le d6but de l'anesth6sie. Elle pense que l'6valuation de ces variations est importante dans toute exp6rimentation o/1 I'EEG est utilis6 pour contr61er les modifications de la fonction c6r6brale.
I am most grateful to the Welcome Trust for a grant of equipment for this work and for the help I have received from a committee under the Chairmanship of Professor R. H. S. Thompson. I would also like to acknowledge the facilities and technical assistance extended to me at the British Industrial Biological Research Association.
REFERENCES BERT, J. et COLLOMB,H. L'61ectroenc6phalogramme du sommeil nocturne chez le babouin. Etude par t616m6trie. J. Physiol. (Paris), 1966, 58: 285-301. CI4LN,G. M. and WESTON,J. K. The analgesic and anaesthetic effec, of 1-(1-Phenylcyclohexyl) piperidine HCI on the monkey. Anesth. Analg. Curr. Res., 1960, 3 9 : 1 3 2 137. CRAMPTON,R. F., GAUNT, I. F., HARRIS, R., LANGMAN, M . J . S . , LINNELL, J. C., MATTrmWS, D. M., SHARRATT, M., WATES, A. H. and WILSON, J. B12 deficiency and chronic cyanide toxicity in baboons: experimental plan. Proc. 1969 Welcome Symposium on Cassava, Cyanide and Nutritional Neuropathy. London, 1971, (in press). ELLINGTON, A., ETTINGER, M., BAKER, D. and ARNAR, O. The electroencephalogram in the anaesthetized baboon. In H. VgGvaog6 (Ed.), The baboon in medical research and its uses as an experimentalanimal. Point Texas, 1967: 775 782. MEYER,J. S., GREIEENSTEIN, F. and DEVAULT, M. A new drug causing symptoms of sensory deprivation. Neurological, electroencephalographic and pharmacological effects of Sernyl. J. nerv. ment. Dis., 1959, 129: 54~1. RODIN,E. A., LUBY, E~ D. and MEYER,J. S. Electroencephalographic findings associated with Sernyl infusion. Electroenceph. clin. Neurophysiol., 1959, 11: 796-798. SNOW, C. C. Some observations on the growth and development of the baboon. In H. VAGTBORG(Ed.), The baboon in medical research and its uses as an experimental animal. Point Texas, 1967: 187-199.
Reference: HARRIS, R. The EEG in anaesthetized juvenile baboons. Electroenceph. clin. Neurophysiol., 1972, 32:81 83.