Title the LOWER BRAIN STEM and CONSCIOUSNESS

Title THE LOWER BRAIN STEM AND CONSCIOUSNESS

Author(s) MORIYASU, HISASHI

Citation 日本外科宝函 (1959), 28(1): 25-55

Issue Date 1959-01-01

URL http://hdl.handle.net/2433/206754

Right

Type Departmental Bulletin Paper

Textversion publisher

Kyoto University 25 25

THE LOWER BRAIN STEM AND CONSCIOUSNESS

By HISASHI HISASHI l¥IoRI YASU

From the 1st Surgical DiY is ion, Kyoto Uni versity Medical School (Director (Director Prof. Dr. Cm~ATO ARAK I) Recei Recei ¥'Cd for Publication Oct . 13 . 1958

SECTION I NICOTINE-COJIA INDUCED FRO:.¥! THE LOWER BRAIN STEl¥I AND THE EFFECT OF THE RECTANGULAR PULSE STIMULATION OF THE LOWER BRAIN STEM* Concerning Concerning the relation between the lower brain stem and consciousness, it has been been found long since that unconsciousne~s occurs in the operation of the posterior fossa fossa more frequentl y than in that of any other locus of the brain, but compara- tively tively few studies have ever proved this fact by experiment (BRESLAUER). It is only only late ！）ァ that MAGOUN ’s theory of the ascending reticular activating system has elucidated elucidated the function in consciousness mechanism of the reticular system of the brain brain stem including the lower brain stem. Some yc a r8 ago, ＂’ e met ¥Yith a patient of probable pontine or “reticular ” epilepsy, epilepsy, which had some connection with this problem. A twent ；.可 ight-year-old man had commotio cerebri a year and a half ago, and at times s ince then he had epileptic epileptic fits, which caused first the loss of consciousness and next the convulsions of of the right half of the body. Neurologicallγ ，we noticed a crossed hemihypesthesia. Pain, Pain, thermal and tactile sensibilities were reduced in the right upper and lo w er extremities extremities and in the left half of the face, and there was motor paresis in the right right half of the body except the face . The findings led us to guess that there might be a traumatic disorder in the left half of the pons. The fit could be caused instantly・ instantly・ b~· pain stimuli given to an~· part of the body. First there came the loss loss of consciousness; about ten seconds later tonic convulsions of the right upper and lower limbs; then clonic convulsions or twitchings; and the fit died away. After an intravenous anaesthesia of Ravonal (thiopental sodium) the patient had stronger stronger convulsions. The electroenc epha logram during the fit showed low vo l tage fast fast waves both in the period of coma and in the period of convul sions, and never showed slow waves. After all, in this case, the epileptic focus was suppose d to be probably probably n ear the reticular formation of the caudal part of the pons, the abnormal excitement excitement of which caused a~ 1 arousal reaction in elec troencephalogram and coma in in behavior. Thus it seems that there can be a disturbance in co ns ciousness in case of a

場 Read at the 53rd General :¥Iccting of the Japan Neuropsychiatric Society in Niigata on April 26, 26, 1956. 26 26 日本外科宝函第28巻第1 号 disorder disorder of the lower brain stem. The aim of the present ぉtu 向・liE:s in proving it it in ananimal expe r iment. Now, what is most difficult in an experiment of this kind is how to jud ge objective ！~， the consciousness of animals. In animals that can not answer in words whatever, w’e ha¥'e no means of judging it except to use as a mark th eir behavioral behavioral reaction or their noci-rcflex:. Therefore , we classif~ · the stages of the disturbance disturbance of consciousness in animals as follm ＼丸 based on the 町・mptoms of a cat cat when it is anaesthetized b.¥・ ether or barbiturate . I) I) Unresponsiveness I (semi-coma I) In In this stage, spontaneous mo vements disappear . The postural re flex becomes rather rather sluggish; and the react ion to li g ht and sound as ¥ ¥・e ll as the escape -mo ve m ent caused caused lη ・ the tactile stimuli upon the surface of the bod ＞ァ are lost for the most part , but the reaction to pain and olfactory stimuli remains clearl y. (Girndt II ・・ IV) II) II) Unresponsiveness II (semi-coma II) In In thi ss ta ge, spontaneous m 川 ℃me nts and the postural reflex di sa ppear comp- let e ly. Th e o lfactor~ reflex is lost, too, to sa~ nothin g o f th e reflexes caused b ~ · optic, optic, acoustic, and tactile stimuli . The noci-1 ℃ flex from the surface of the bod y is is weakened, but remains a little . The sneezing reflex from the nasal septum, the noci-reflex noci-reflex to the nose, and the phar y ngeal reflex all re main. (Girndt IV ーベ’） III) III) Unresponsi vcness III (coma ) In In thi s stage, the noci- re fl ex to the nasal septum and the no se, and the ph ar - ~· ngeal reflex are all lost; but the corneal reflex, the pupillar y reaction to lig ht, and the re 自ex to the pain stimuli in the ears ma y remain. The patellar refl ex m 叫・remain or may not. (Girndt V ・－） The spontaneous movements that we have examined here are blinking, voca- tion, tion, lick of the chips, chewing, sw allo wing, and mo ＼℃ ments of the ear s, the head, the the limb s, and th e tail.

:.¥Ietho 〔l

A cat of 2 or 3 kg in weight is fixecl on a hammock and is allowed to let the the extremities hang down naturall:- ・. Then, und er et her anaesthesia, trephination is is performed a日 small 部 poss ibl e in the parietal or su IJο cci pit al r e広ion. When et her e仔ect is go ne completcl:-, th e cat is punctured with パ needle, 1/4 mm in size, size, 12 cm in leng th reachin ロ・ a certain lo cus in the low er brain ;; t ern from the trephination trephination openin g under the guidance of the HORSLEY －ぐ LAH1'E0 S st 仁1・eotaxic instru- ment, which is previously placed on the head of the cat. 人 nrl then the cat is given given an injection of pure nicotine or a solution of nicotine diluted twice as weak b~ · a m et hyl cellulo se so luti on . A nd accor din g to th e above sa id criteria, th e change of of i℃日pons i vene ；~s is examin e〔l twice , 0/lCC <1 ft 仁r the pun c ture of the ne ed le and once once again afte r th e inj ection of nic ot in e. When the injection is giv en twi ce in two places in th e same cat, the ccc oncl one is to be given w he n the cat has returned returned to normal after the inter¥'a l of o¥・er three hours. THE LO 羽TER BRAIN STEM AND CO N SCIOUSNESS 27

And in order to compare wi th this nicotine cx1 1c riment, the change of responsiveness nsiveness is examined, b;; stimulating the animal at nearl y the same area by rectangular rectangular pulses. To be precise, b ~ ， stimulating with 1 msec. rectangular pu l"cs , after after the insertion of a 12 ・cm-long bipolar electrode, which had a diameter of 0 .5 mm and is insulated except about 0.3 mm at the tip, the change of responsiveness and behavior is examined according to the above-said criteria. The condition of the the stimulation 3, is 30, 10, 60 and 100 c vcles, and 1, 2, 4 and 8 vol ts respectivel y. Ten volt direct current is applied for 7 seconds to mark the stimula te d locus for the the purpose of histological examina tion. The brain is 白xed with pure alcohol, embedded in celloidin and is cut into 30 ・； .i-serial s ections, and the stimulated loci were ascertained \J~ ， NrssL stain and m ≫ elin sheath stain in the case of nicotinization and 同 ironcarmine stain besides them in the case of the electrol y tic foci.

Results Results

A. Experiments with pure nicotine In 35 suryiyals we could observe the state of consciousness . Injection was performed in 48 loci. 1) 1) Mesencephalon Groups In In the cats which had a lesion in the central gre y matter at the level between the the oculomotor and trochlear nuclei and in the adjacent reticular formation, i. e. the the locations which had been IJOinted out bγYA BuN o before, tw o out of five (No s. 38, 38, 39, 42, 68, 69) f ell into unrespon siv e ness II and III, No. 38 (Fi.s. 1) for about 10 minutes, and No. 39 (Fig. 2) for about 4 minutes respectivel y.

Fig・. Fig・. 1 Transverse sections throu g・ h the mi dbrain (A ) and pons (B ) of N 0 ・38 cat. (coma ) Abbreviation s are as follows: C. Q ‘a., C. Q. p.; corpus qua

The Cat No. 38 （♀， 2.6 kg ): mew s a nd behav es viol entl y befor e the pun cture . The noci-

refl ex is norm al目 No cha nge du e to th e m t> r巴 punctu re with th e nee dl e is ob serv able. It me w s

and and 111 りves its forelimbs feebly e Ye11 after t he injection of nicotine. T¥v t> 11t y-fi vぜ seconds later, the the c at becomes completely quiet, and c1:>a ses to m ew . Onl y re spiration accel erates. The pupils dilate dilate moderately. The pupillary reaction to light is lost. Th e corneal refl ex is we akened . The 28 日本外科宝函第28 勲第l 号

Fig ・. 2 Transver se sect ions throu gh th 巴 midbrain at th e le¥"el of nu cleu s o culomotorius (A ) and nucleus trochlearis (B ) of No ・39 cat. ( coma)

noci-reflex noci-reflex and the tonus of the muscles are lost (coma). Th ree minutes and a half later, the ears ears begin to respond to painful stimuli . Four minutes la ter , the sneeze reflex due to the stimulation stimulation of the nasal 民 ptum and the pharyngeal reflex are recovered sligh t ly. The pupils dilate dilate mojeratel y and the corneal reflex is recovered, but the noci-refl ex is still lost . The tonus of of the muscle s somewhat recO¥ ・e: s. Six minut es lat er, the pharyngeal reflex and the tonus of the the muscles b氏、》.ne no rmal (se:ni c: ):JUl IT ). Te n minutes late r, cat the licks the chips if it is given given a pharyngeal stimulation (recovery ). Tw e lve minutes la ter, the cat begins to mew at intervals intervals and behave violentlJ ・ The pupillary reaction to li g ht, the corneal and the noci- reflexes reflexes become normal. In two cases (Nos. 35, 41 ), inj ect ion was given to the mesenceph ali c reticul ar formation, but unresponsiveness did no t occ ur at all. 2) 2) Pons Groups In In one case (No . 57) (Fig. 3), in which the center of the lesion m ’as in the floor floor grey matter of the fourth ve n tricle at the rostral leYel of the pons and in its its adjacent reticular formation, but the rostral end of the le s ion was close to the wall of the aqueduct, unre sponsi veness II was ob se rved for about 11 n:inutes.

Fig. Fig. 3 Transv ers: sectio ns through Lh c pons at the leve l of ros tral (A J and caudal (B) e nd of of No・57 cat. (s emicoma) Abb reYiat ions are a s follows; F. L p; fast:iculus longitudina lis pos t., L. L. coer.; locu s coer ul eus, L. 1.; lem nis c us late rali s, P. p. c.; pes ped ua culi ce rebri .

The Cat Nu 57 （♀， 2.8 kg ): mew 巧 and behav es violentl y before the pun cture. The noci - reflex reflex is no rmal. No change due to the mere puncture with the ne臥 Il e is ob serv able. Simul ・ taneously taneously with the injection, mewing and spontan 印 us mo vement cease . O ne minute later, THE LO 羽TER BRAIN STEM AND CONSCIOUSNESS 29

I rN1ECTION OF NICOTtNe •

川.r~川内~t叫Jへ川，liJ'''tif'Jハ'1,f\.-.v.仰附V内州h1W'' "'vy('ぺI～v内叶川ヘ~.Jl叫川·~削νlif州〆、Aw)0J~11-r.~ ＇·ぺ

'PI 'PI N"CH ＂＂＇~；－~~·片、‘＼v\Jへ~がもv内川ノ凡人＇＂＂＇〆い/"v.tr州ヘ....,..rvヘP吋川Aハ～イ~~~ l門川／ヘ／叫~;J川川~ヘ.~／＼f'N川川＼ F 乙’ Mo' ト小川～ヘ＼や～~J..f"~ 九~..，，. rt-小川~＇ A .’阿，‘ v 1. 帆刈れ刊Jト＼、．冒－コP、v I

Fig. Fig. 4 Serial electroencephalographic tra c ings in cat '¥/o. 57, in which the lesion involv ed the rostral rostral pontine grey matter. All r巴cords characterized by low-voltage fast activity and no change is is found by painfull stimuli. Upper beams are recorded from cortex and lower beams from adjacent adjacent portion of lesion . 1A l before and 1B l during- injection 1 C1 (D l ! E l semicoma (F ) waking 30 30 日本外科宝函第28 巻第1 号

gasping gasping begins and the pupils dilate modera tely. The tonu s of the muscles is lo st . One minute and twen もy seconds later, a slight reflex to the stimulati on of the nasal septum and the

pharynx is observable; but the other noci 『 reflexes and the corn eal reflex are all lost and the complete complete stilln,ess continues (semi-coma 0). Two minutes and a half lat er, th e pupils dilate slightly, slightly, and the reflex to the olfactory stimuli is slightly present; but the 11oci-reflex is

utterly utterly lost. Three minutes and a half later, the right corneal reflex is re l＇けY引札la little. Then t}ie cat vomits. Six minutes later, the tonus of the muscles somewh at recovers. Nine minutes minutes later, the reflex to the olfactory sti muli and the painful stimulation of the ears come back. back. Eleven 'minutes later, the twitching of the ears begins an d the no ci-re flex is r巴covered

almost almost completely 1re e＜》 w ry). Fifteen minutes later, the corneal reflex co mes back. Twenty minutes minutes later; the phar:-・nge <1 I reflex comes back. Thir tyfou r minutes la te r, spontan 回 us movement can be observed again.

In this case, the electroencephalogram during 叩 mi-coma (Fig. 4) shows fast waves (but of somewhat low yυltage) (30 to 50a V, 30 to 50 c/ s), much the same as before the injection; and slo w wave clement or spindle burst, etc. are not observable. observable. Besides, it sho¥v 日 no change C¥'Cll when the painful ぉti mu 日 are gi¥'cn. In those four cases 〔 ~OS. 1, 60, 64 (Fig. 5. A), 67 〕・， vhen the nicotine, which was inje cted in the floor /! l' C~ matt er on the borders of the 11ons an d medull a (locus (locus coeruleus), reached the tegmental reticular formation, and in another 河＼＇ E:ll cases 〔Xos. 37 (Fig. 5. B), 38・; 42, 44, 71, 73, 75 〕， wh en nicotine wa 日 injected in the J)ontine r℃ ticular formatio'n, m1rc s1m11 日iYc11cs:-; did not occur at all. Besides, in the ;;ix cases among them (N 川. 37, 64, 67, 72, 73, 75) ＼γe couldυ \J ~c r \'c running 8

Fig-. Fig-. 5 Transverse sections through the pons of No. 64 ,A 人 37 ( BJ, 72 IC ) Cat . (11 0 disturbances incon sciousness) and of No. 41 cat (D). (c oma 〕 THE LOWER BRAL¥I STEM A::-.ID CONSCIOUSNESS 31 movement, and in the two (Nos. 38, 60), exaggeration of excitabilit y. In In the three cases (Nos. 4, 69, 70 ), too, when injection was gi ven in one side of of the nuclei pontis, unresponsiveness did not occur. Only in one case (No. 41) (Fig. (Fig. 5. D) out of the two (Nos. 39, 41), wh en injec t ion was giveri in the caudal part of the nucleus interpeduncularis, urn ℃日 pon ぉivc ncss II (ll!Cl III lasted for about 7 minutes; but to cause coma after the injection about three minutes ¥¥・ere requir ed in in striking contrast to the short time such as 30 sec onds to 1 minute required in those those cases so far dea lt with. The Cat No. 41 （♀， 2. 7 kg) : mews loudly and keep s struggling before the puncture. The ncci-reflex ncci-reflex i s brisk. Wli en the needle is inserted, it mews and behaves vio lently ,a nd e ven after after injection keeps mewing and struggles a littl e. One minute and a half later, the c at 汀： ews feebly but sponta n eous movement ceas 四. Respira ti on accelerate~ ， and the light pupil dilates dilates moderately. but the noci-reflex is normal. Three mi nutes later, it stops mewing and keeps keeps still. Myosis occurs. The reaction to light, the phar yn geal and the nod- reflexes, and the the tonus of the muscles are all losf The corneal reflex becomes weakened (coma ). S ix πinutes later, the to nus of the mus cles in・ the rig ht forelimb returns . Ni ne 11 1inutes late r, the the pharyn gea l re flex and the noci -r efl ex to the ears , the nasa l septum , and t he tip of the nose nose are recovered slightly; and the tonus of the muscles becomes nearly normal ( semi-coma fi). fi). Ten minutes later, spontaneous rr:ovement in the lef t fo re limb appear s, but mewing d oes

not not come back yet. The noci 司 reflex is almost normal (recove ry). Fifteen minutes later, the cat cat begins to lick the ch ips. Twenty-seven minutes later, it begi ns to m ew loudl y and struggle. 3) 3) l¥I e dulla Groups For convenience ’ sake, the medulla is divided into thr ee parts. The rostral part is from th e leve l of dec ussatio le mnisci, nucleus nerv i trigeinini, and nucleus olivaris olivaris superior to the appearance of the root fib ers of nervus abducens and facialis lis (E to F in Fig . 12). The middle part denote s the area including nucl eus vestibularis vestibularis and facialis (G to I in Fig. 12.). The caudal part is from the level of nucleus nucleus vagus, nu cleus olivaris er inf ior and the root fib ers of nerv us hypog lo ss us to to decuss at io pyramidalis (K to ?. I in Fi g. 12 ). In In the rostral pa rt group, No. 46 (Fig. 6. A), which had in jec tion in the tegmental reticular formation, showed unresponsi Y encss II and JII for about two

Fig・. Fig・. 6 Transverse sections at the rostral bulbar leγel of No. 46 cat (A ) and No. 74 cat. (coma ) Abbreviations Abbreviations are as follows : F. R. 1. et m .; formatio reti culari s lat eralis et m edi alis , G. VIII; ge nu ner vi facialis, N. d.VIU; nenus dor sa lis ne n i octavi, N . p. o .m.; nucleus paroli, ・aris sup. med. , Ne. VI VI et 刊； ner vus abducens et Iacialis, P yr; tra ct us pyramidalis , 0. s.; nucl e us oli varis super ior. 32 日本外科宝函第28 巻第1 号 minutes, and No. 74 (Fig. 6. B) of the four ca 日C 日（N os. 21, 69, 73, 74), which had injection in the ventromedial part of the reticu la r formation (nucleus papillio ・ formis), showed unresponsivenc~ 只 II and III for about eight minutes and a half. The Cat No . 46 （♀， J.9 kg) : continues mewing before the puncture and spontaneous movement is very active. No change due to the mere punc t ure is visible . Immediately after

the the injection, no remarkable change 巴xcept the dilation of pupils is visible . O ne minute later, respiration respiration accelerate s and the c日， t stops mewing but struggles with its limbs . The corneal

reflex reflex and the pharyngeal reflex are weakened strikingly. One minute and fort y 司 five 蹴 ands later, later, it is still reactive to tactile stimuli. Two minutes la t er it l.Jecomes comple tely still, and the~reflexes to olfactory and tactil e stimuli the noci-reflex except in the ears, the pharyngeal reflex , and the ton us of the muse Je s all disappe:i.r (coma ). Thr ee mi n utes later, th e t on us of the muscles muscles in the right foreleg is recovered slightly. Four minutes a11d a half later respiration is is still accelerated, and the cat som 巴times begins to struggle with the foreg s. The tactile and the the pharyngeal reflexes are recovered, and the corneal reflex is provable though sluggish (awakening). (awakening). Sex minutes later respiration becomes calm, m yosis is observed, and the corneal and the noci-r eflexes and the tonus of the muscles are all normal. Eight minutes and forty seconds seconds later , the rat mew-; again and spontaneous mυγemen t becomes actiY 己・ The Cat No. 74 （企. 2 .2 kg) : mews and stru gg les 、io lently before the puncture, and the noci-reflex noci-reflex is normal, and licks the chips when pharyngeal stimuli are given. It becomes a little little calmer after the mere puncture . Immediately after injection the cat is in rage and continues continues to mew. Thirty seconds later respiration accelera tes, and the cat stops both mewing and struggling and bec omes quite still. Urinar:-・ inconti nency is obse1Yed, and the noci- and the the pharyngeal reflexes disappear and only the left corneal reflex remai ns (co ma ). One munute later the cat mews feebly . No re flex to the olfac t ory stimuli is obs erved, and onl y the the noci-refl ex in the nose is provable (semi -com a>. Two m i nutes lat er the ton us of th e muscles muscles disappears. Three minutes later the cat shows the twit 巴hing of the ears . Four miitutes later later the corneal and the pharyngeal reflexes are reco vere d, and the cat li cks the chips when

pharyngeal pharyngeal stimuli are given 目 Fom minu t es and a l1alf later, the tonus of the muscles is recovered recovered slightly. Six minutes bter the mt blinks spasmo dic ally. 目立ht m in ut es later the spasmodiC spasmodiC movement of the forelegs is observed once. N ine minutes later the olfactory and the the noci-reflexes are recm・ered (recovery ). Fourteen minutes I日ter it mews and struggles

violently, violently, and bit es and li cks the chips . Th 巴 noc 白i-and the postural reflexes are recovered . In In the middle part group, the Cat No. 45 (Fig. 7. A) of the two cases (Nos. 45, 45, 81), which were given injection in the floor gre y matter (nucleu s vc stibularis ), ceased to move instantly after inject ion and seemed un responsive; but spontaneous movements and the noci-refl cx became acti¥・e rapidl y 30 seconds after . The four ‘

Fig. Fig. 7 Transverse sections at the middle bul b ar level o.f No ・45 cat 1A 1 (momen ta ry coma) and l'¥o l'¥o 80 cat (no disturbances in consciousn ess ). Abbreviations are as follows: ¥/. V[ ; nucleus facialis, N. N. d. ]]J; nucleus dorsalis nervi odm・i. THE LOWER BRAIN STEM AND CONSCIOUSNESS 33 cases 〔Nos. 16, 48, 68, 80 (Fig. 7. B ）〕 which were given injection in the reticular formation did not show unresponsiveness. In In the caudal part group, No. 47 (Fig. 8. A), which had injection in the floor grey matter (nucleus vagus, h~＇ poglossus), did not show unresponsiveness; but No. 2 stopped moving simultaneously with the mere puncture, and unresponsivene ss lasted lasted for about three minutes. Out of the five cases (Nos. 12, 17, 59, 60, 61) w hich had the lesion in the unilateral unilateral medial and lateral reticular formation, one ca~e (No. 12, Fig. 8. B) showed unresponsiveness III for two minutes anct a half; and out of the three cases cases (Nos. 14, 2 0, 63) which had the lesion in the bilateral medial reticular formation, formation, two cases showed unresponsiveness II and III. In No . 14 (Fig. 8. C), the the lst puncture (L. 1) in which injection was given in the :μJedial reticular formation formation resulted in unresponsiveness II and III for about five minutes and a half, half, while the 2nd puncture (L. 2) in which injection was given in the lateral reticular reticular formation caused no unresponsiveness; and No. 63 (Fig . 8. D) showed unresponsiveness unresponsiveness II and III for about three minutes . It It is noteworthy that in all these bulbar cases showing coma respiratory movement became as much quick as in the mesencephalic or the pontine groups but any particular dyspnoea or apnoea was not accompanied, although bulbar nicotine injection injection was apt to cause respiratorγstop in other cas es.

Fig. Fig. 8 Transv ers e sec tions at the ca udal bulbar leve l of No. 47 cat (A). (no disturbances in consciousness) ciousness) and of No ・ 12 (B) , 14 1C1 ( L1 : lesion in the medial reticular formation; coma, L2:

lesion lesion in th e lateral reticul 且 r formation; no di st urbances in consc iousness. 〕and 63 (D ) cat. (coma ) Abbreviations Abbreviations are as follows: '.¥/. G.; nucleus Goll, N. Bu . ; nucleus Burdach, XX; nucleus γagus , N. N. Xll; nucleus hypogfossus , '.'le. XH; nerYUs hypoglossus, 0. i. : nucleus oliYaris inf ., P. 0. i. m.; nucleus nucleus parolivaris inf. med. 34 白木外科宝函第28 巻’第 1 号

r・ r・ INJECTION OF NICOTINE

c 2'2 げ

D 4 乏勿州州州~

1 sec .

Fig. Fig. 9 Elc 、じいり？nce p halo grap hi c recordi ngs from cat '¥o . 63,i n which the le s;on involved the m 巴dial bulbar reticular formation . :>Jot o pers i stent low ,・olta'.!: e fast act ivity in all tracings, absence of respon se to painful! stimuli. U pper beams are recorded from cortex and lo wer beams from adjacent portion of "lesion . (A 1 before and 1 B l during injection. (. C l tD l 〔E ) coma. (F ) waking. THE LOWER BRAIN STEM AND CONSCIOUSNESS 35

The Cat No. 63 （会. 2.8 kg) : mews and struggles violently and licks the chips before the the puncture. No change due 句 the mere puncture is obser ved . The noci-reflex is normal. The cat cat rages after injection , Twenty five seconds later respiration accelerates and the pharyngeal reflex reflex disappel!.rs. A minute later it still moves its forelimbs violently and the noci-reflex is normal. normal. Two minutes later spontan 田 us movement a nd mewing stp, and it be comes still . The reaction reaction to olfactory and tactile stimulat i on and the noci-reflex are all lost . The tonu~ of the muscles muscles is weakened and the corneal reflex is retained al it tle but is slug gi sh (coma). E ve n four four minutes later it is still commpletel y quiet. The pu pil s are dilated moderately. Fi ve minutes minutes -later the noci-reflex is nearly rec o vered, but the pharyngeal and t he co rneal refl exe s are are weakened (recovery ). Seven minutes and a half later t he c at begins to s truggle w ith its forelimbs. forelimbs. Eight minutes and a h alf later the ph a ryngeal reflex becomes normal a nd the cat begins begins to bite and lick the chips. As for the electroencephalographic tracings during the coma of N o. 63, bo th surface surface and deep E. E. G. s were lo w voltage fast w aves (10 to 50;1 V, 30 to 60 c/s) c/s) and showed no change by painful stimuli. In the more caudal level group , all the three ca s es (Nos . 1 7, 18, 58) which had injection in the medull ary central gre y m at ter and the re tic ular form atio n did did not show any ・unresponsiveness. B. B. Experiments with diluted nicotine When we first injected pure nicotine in the caudal bulbar part that contained the the respiratory center, the animal in s tantly fell into c lyspnoea and died soon afte r. As we had .a considerable number of such cases ,w e turned to us ing a1 /2 solution of of nicotin e dilut ed b y a 0. 8 }0 m eth yl ce llulo se s olution whi ch i s not stimul at ive ~nd has adequate viscosity. And the dose of injection was limited to 0.01 cc or less. less. 1) 1) Pons Groups Neither the on e case (No . 34) w hich was gi ven injection in the pontine tegm- e ntal reti cu la r fo rmation n or th e th r ee c ases (No s. 29, 33, 34) w hic h w ere give n injection injection in th e unil ate ral m ed ialr eti cul ar fo rm atio n at th e leve l betwee n th e pons and the rostral bulb arp a rt showed unr esponsi ve nes s or any sp ec ifi cm ovement. 2) Medulla Groups Of the three ca se s (Nos. 23,2 4,2 7), which we re given inje ction in the ventro ・medial part of the rostral bulb ar reticular formation (nucl e us papillioformi s), No. 24 (Fig . 11) and No .2 7 (Fi g. 10) fe ll in to unrespon sive n ess II and III, th e form er for th ree minut es and a halfa nd th e latte r fo r abo ut fo ur minut es . No . 22, 22, which was given injection in th e dorso-m e dial reti c ular form at ion at th e sam e level level showed no unresponsiveness. The Cat No. 24 （♀， 2. 5 kg ) ; mews and moves violentl y before the pun cture and the noci-reflex noci-reflex i s brisk. It m ews loudly and rages when the need le is inse rt 吋 . Th e pupils are dilated dilated m oderatelya fter injection. Tw en ty secods lat er res pir ati on acce lerates sli ghtl ya nd mewing an d str ugg lin g stop . T he pupils are contract ed, the pupill ary reacti on to li ght disappears, disappears, andt he cornea l re fl ex is wea kened . Th e ph ary ngea l r efl ex and t he tonus of the muscl 回 are lost and the noci-reflex is nearly lost, too (semi-coma ). One minute and fift y seconds seconds later the cat is completely still ; the light and the pharyngeal refle x es are eli citable only only very little , and the corneal reflex is sluggish . The noci-reflex is entirel y lost (coma ). 36 日本外科宝函第28 巻第1 号

Fig. Fig. IO Transverse sections at the rostral bulbar level (A-B ) of No・27 cat. (coma ) Abbreviations are as follows : N. d. VIII; nucleus dorsalis nervi octavi, Ne. VI . Vll ; nervus abducens and facialis, 0 . s.; s.; nucleus oli 、・aris superior.

Fig. Fig. 11 Transv erse sect i ons at the rostral bulbar level (A-B ) of No ・24 cat. (coma ) Abbreviations are are as follows : Br. p.; brachium posticum, F. l. p.; fasciculus longitudinalis posterior, N .p. o. m.; nucleus nucleus parolivaris superior rnedial is, N .m . V, N .s. V; nucleus motorius and sensibiliis ner vi trigemini. trigemini.

Two minutes and twenty 1'econds later urinary incontinerre and the Jess of the tonus of the muscles muscles are observed. Three minu_tes and forty seconds la t er the tonus of the muscles is recovered recovered and sp ontaneo us movement appears, but no reflex to olfactory stimuli is observable. The pupils are dilated m od eratel y and the light , corneal, and pharyngeal reflexes are all recovered recovered (recovery ). Four minutes late r the cat vomits and the noci-reflex is almrnt nonnal. Five minutes later it n淀川s, shakes its head and licks the chips .

TABLE 1.

Site Site of Lesion I Cat's 氏。 Lat 町 up to Corna I Du 叫 on of Coma

38 I 25 11 j（， ’ Midbrain central grey matter 39 I 3011 4’ ll， Grey m 出回 of the pontin!! tegrnentum J 57 1’20 11

Nucleus Nucleus interpeduncularis I 41 l 7’ Tegmental reticular formation at at rostral bulbar level 1 46 I 2’00 11 1・ 2 ’3011 Ventro-medial Ventro-medial reticularformation 24 20 " 313011 at at rostral bulbar leve l 27 3011 4' ( Nucleus papillioformis J 74 3011 8 ’3011 TIn，＆唱hdAτ 30 11 4130 11 Medial Medial reticular format ion ipo 2011 5 ’3011 at at caudal bulbar level 『 u 2’ 00 11 3’ THEILOWER BRAIN STEM AND CONSCIOUSNESS 37

Fig. Fig. 12 Diagram of cross sections showing electrically stimulated points. A-B : miclbrain, C-D : pons, E-F : rostral, G-1 : intermediate, J -l¥I : caudal bulbar lev els. 38 日本外科宝函第28 巻第1 号

But unresponsiveness was not evoked at all in the :four cases (N os. 22, 24, 2Q, 28) 28) which were given injection in the medial reticular formation at the middle part of of the medulla, in the two cases (Nos. 25, 26) which were given injection in the floor floor gr ey matt er, and iii the two 四時 s (Nos. 23, 2 7) which were given injection in in the caudal bulbar reticular formation. After all, it follows from this that if diluted diluted nicotine is used death 同 respirator~· paral ~ ·s i s seldom occur 日 and u.nrespon- siveness siveness also seldom occurs, that is to sa>, it is not suitable for our expetiment. C. C. Stimulation experiments with rectangular pulses In In contrast with the nicotine experiments, ＂ ’e examined the changes .of responsiveness onsiveness in 13 cats h ’ giving 1 msec rectangular pulses directl~· to about 32 places places of the lower brain stem. The stimulated loci are shown in Fig. 12. Stimu- latory latory conditions are 3, 10, 30, 60 and 120 c/s and 1, 2, 4 and 8 volt respectively for for each region. a) a) Mesencephalic central gre y matter: In 1, the noci-reflex ha s partly and the the corneal reflex has totall ＞’ disappeared with 60 c /s, 4V, but the tonus of muse- les les is normal. In 2 3, the midriasis and the increa s ed tonus of muscles have appe ・ ared ared with the same condition. b) b) Pon tine floor grey matter (locus coerul eus) : In 4 5, midriasis and the slight slight general activation are observed with 30 c /s, and over 2V. c) c) Pontine reticular formation : In 67 8, midriasis and rage w ith 60 c /s, and over V1 . In 6 8, in the dorsal part, the ton us of muscles has increased . In 8, 8, running movement in the forelegs. d) d) Nucleus int erped uncularis: In 9 10, the noci-reflex does not disappe ar, an d the the tonus of muscles is strengthened . e) e) Raphe nucleus: In 11, no remarkable chan ge occurs. f) f) Bulbar reticular formation: In 12・・・ 14, 17 ・・ 20, and 23 ・・31, ingeneral, as cy cle ancl voltage increa se, the tonu s of muscles increases from tremor to rigidit y or or tonic state, which spreads gradual ！~· oyer the face, the neck, the body, th e forelimbs, forelimbs, the hindlimbs till it becomes genera li zed and is accompanied lη ’ activation ation or rage. In 12 ・・・14, in the rostral part, the maximal dilatation of the pup ils and the clonic convulsion of the leg s occur. In 17 ・・ 19, in the medial part, midriasis , and in 18 19 running movem en t is observed. In 23 31, in the causal part , acce ler ated respiration and vomitin g occur in most cases. In the dorso-medial stimulation stimulation cases, the face becomes tonic, but the tonus of the legs is normal, while while in the ventro-medial stimu latio n cases, the tonus of the l egs is also increased. g) g) Nucleus vestibularis: In 15 16, and Nucleus vagus: In 21 22, only the face face becomes tonic . The cat opens its eyes and mouth, and rolls its tongue, and the the pupils are dilated. In 21 22, rage also i日 observed. h) h) In 32 w hic h has been given stim uli in the caudal bulbar central gre y matter show s only the acce leration of the tonus of the muscles. After all, in the bulbar leve l stimu lations the increase of tonus of the mu scles and activation or ra 江C occurred, and unresponsiveness did not occur in all the cases. cases. THE LOWER BRAIN STEM ANDCONS CIOUSNESS 39

Summarv To summarize the above results :・・・ I) I) The midsagittal reconstruction of the regions intimately concerned with the the nicotine-coma is shown in the Fig. 13, involving the mesencephalic central gre~’ matter, the rostral pontine floor grey matter and the rostral, and the caudal medial medial bulbar reticular formation.

Fig・. Fig・. 13 Midsagittal reconstruction of the lower bra in stem showing sites of lesions diagrammatically diagrammatically (shaded areas) in which coma was induced by injection of nicotine.

2) 2) The laten c ~ー of nicotine-coma and its duration are not characteristic of each each region of the brain stem, as in Table I. 3) 3) The changes of the spinal motor activit~ ’ due to the in jection of nicotin e in in the brain stem were various ; sometimes the tonus of the muscles , spontaneous movement and escape movement from the noci-stimuli were all nearly normal, while while at other times the limbs were flaccid with no motor activ ity. In the latter case case the ftaccidit~ · of the unilateral limbs or of the bilateral limb s w as seen and the the hindlimbs tended to become flaccid sooner than the forelimbs. All the cas es of of coma showed the ftaccidit~＇ of the limbs, the disappearance of spontaneous movement, and a remarkable weakening or disappearance of the patellar reflex. The running movement of the limbs was seen when injection was given in the medial medial reticular formation to the extent from the pons to the middle-third of the medulla, medulla, and also at the border bet wee n the medulla and cervical cord. The clonic and the tonic convulsions were induced al rn from much the same r egion, and also from the late ral bulbar reticular formation of the ca udal part of the medulla . And sometimes clonic convulsions changed into running movement. Hence the area area where such motor phenomena in the limbs are induced and the region where coma occurs are different in most parts except the rostral bulbar m edial reticular 40 日本外科宝函第28 巻第1 号 formation. formation. And convulsion and running movement may be assumed to be very closely closely related to each other.

4) 4) Respiraton ’ paral:-・sis due to the injection of nicotine occurred only in the caudal caudal bulbar reticular formation. This is in accord with the statements of PITTS and MAGOUN. It seems ve1γimportant that we have been able to separate coma from both respirator ：－ー paral:-・sis and convulsion in the present studγ ． Discussion Discussion From these results it is obvious that the disturbance of consciousness can be evoked by some kind of stimulation in the lower brain stem, i.e. that there is some part in the lower brain stem that has much relation to the maintenance of consciousness. consciousness. This is not a fact found bγus for the first time, but a considerable number of opinions to support it have been reported. Experimentally, Experimentally, FLOURENS, by puncturing the “LEBENS- KNOTEN ”（ respiratory center) center) in the caudal bulbar region, and BRE2LAUER (1917), b：－’ mechanical pressure on the trans-orall ＞可 xposed bulbar hれ c or b:- ・ arachinoideal haemorrhage of the bulbar bulbar base in operative manipulation b:: mistake, noticed that fulminant unconsciousness iousness occurred suddenly, accompanying respirator y paral ＞百 iぉ， and presumed that the the chief cause of unconsciousness in commotio cerebri might be in the medulla olilongata. olilongata. Similar experiments were made by TILANus , HEuBEL, DEGE, and others. This transient unconsciousness is rather similar to the transient unresponsiveness caused caused in this experiment by puncturing the floor grey matter of the fourth ventricle ventricle (No. 2), or by injecting of nicotine into it (No. 45), or at the sudden thurst thurst of an injection needle upon the skull base. In opposition to BRESLAUER,

KNAUER (1922) said that, if the experiment n郁 done taking much care to avoid excessive excessive narcosis, rough operative manipulation and respiratorj ア paralysis, the animal showed onlγexcitation, but never unconsciousnc ＇.－＇品切’ the pressure which was given either to dorsal or ventral side of the medulla oblongata . As for respiratory iratory paralysis, we succeeded in causing unresponsiveness without accompanying respirator:-- paralysis. :VIAGOUN :VIAGOUN proved the important relation between consciousness and the brain stem reticular formation, including the bulbar reticular formation. He ぉavs that the the brain stem reticular formation does ascenclinl! background activit y to maintain arousal. arousal. How should ¥¥ ・e explain the coma h> ・ the injection of nicotine according to to his theor:i ァ？The answer seems to be as follows : ・The difference between arousal and coma would be the di 百erence in the e町ects due to the i11te11 日it> ・ of stimulation. Stimulation Stimulation usually produces an influence conforming to the pattern of normal nervous nervous excitement inherent in the central nervous system, but an excessive, explosive explosive stimulation like nicotine drives the central nervous sy 日tern to abnormal excitement excitement or seizure discharge and brin g日 about a depressive paral y tic effect of normal function. This is like a general convulsion lJγan abnormal excitement of the the cerebral cortex: due to the nicotine locall? applied. Examining the nicotine- injected injected locus hi 日tυlog・icall.¥", we find a tissue defect in the central part, and the intercellular intercellular infiltration of nicotine in the marginal part. Therefore, it is considered THE LOWER BRAI)J STEM AND CONSCIOUSNESS 41 that that in such a case a forcible stimulation accompanying destruction was given. But coma in all such cases is short lasting only for about ten minutes. If it is caused caused b~· functional loss due to tissue destruction, it must last for a considerably Ion 広 time. After all, it seems most reasonable to consider that such a coma state originates originates from paralytic influence caused by a forcible stimulation. By electrolytic destruction of the central cephalic portion of the mesencephalic tegmentum, LINDSLEY and MAGOUN (1950) in cats, and FRENCH and MAGOUN (1952) in in monkeys, respectively, found remarkable behavioral and E. E. G. changes and named the state hypersomnolence or simulating coma. But compared with our unresponsiveness unresponsiveness it seems considerabl~ ’ slighter in the grade of the disturbance of consciousness. consciousness. BAILEY BAILEY and DAVIS (1942) succeeded in bringing about a state like CAIRNS' akinetic akinetic mutism in cats bv a circumscribed electrol ~· tic destruction of the mesencephalic ephalic periaqueductal grey matter, a state in which spontaneous activity was completelγabolished, completelγabolished, onl~ ， a slight responsiveness being left to a forcible stimulation; ion; and the y called that state “ arrest of consciousness ’＇. The ）’ also brought about an apathetical state in a monkey in which the animal showed responsiveness to stimulation stimulation but never spontaneous drive and called it “ lack of drive." These are also also much slighter or weaker in grade than our unresponsiveness. As important anatomical data in connection with our nicotine-coma is to be regarded regarded the report of BRonAL (1955). He made hemisection at various levels between the mesencephalon and the diencephalon in kittens and examined the retrograde retrograde degeneration of cells of the caudal brain stem reticular formation, and found found that cellular degeneration was abundant at the level of the rostral third of the the inferior olivery nucleus (the caudal bulbar portion) and at the level of the root root fiber of nervus abducens (the rostral bulbar portion) and was restricted to the the medial two-thirds of the reticular formation at these levels . He said that such such retrograde degeneration occurred because the cells had rostral projection be yond the the midbrain. It is very interesting that the sites of these degenerat ed cell groups are are equal to the bulbar portion concerned with nicotine-coma in our experiment. Again, Again, according to OLSzEwsKY ’s cytoarchitectonic atlas of the human brain stem reticular reticular formation (1954) (he says that there is no great di 百erence between man and animals), the remarkable cell aggregates in th e two nicoti ne-co ma regions in the the bulbar r eticular form at ion correspond to the nucl e us centralis pontis, the snucleu papillioformis papillioformis and nucleus centralis medullae oblongatae, and all the E:e nuclei have not not so many large cells, but consist chie 百y of small or medium-sized multipolar cells, cells, while in the midbrain, no such remarkable cell aggregate can be seen. From the the fact that a distinct di 百erence in the cellular ty pe does ex i:-; t between the midbrain and the medulla, it may be supposed that there ma y be som e di 百erence in in the details of the mech anism of occurr e nce between nicotin e-coma from the midbrain and that from th e medullae oblongat ae . The electroencephalogram during coma is genera llyγ believed to consist of slow waves, waves, but during our nicotine-coma it was found to consist of low voltage fast waves. waves. This seems appar ℃ntl ）アstrange, but not incomprehensible ¥¥'hen we consider 42 日本外科宝函第28 巻第l 号 that that a forcible stimulation of nicoti ne may cause coma in behavior and low voltage fast fast waves in electroencephalogram. So the initial co ma in head injur~· ma~ ’ be analogous. analogous. In our laborator> ' such coma accompan> ・ing fast waves was ~·ee n in a patient patient of coma immediat e ly aft er head injurj ’ or in a patient of reticular cp iler 何？ of of w hich ARAKI et al reported else where. WALKER, too, noticed this in experimental commotio cerebri. And LoEB, in a patient of coma owing to the haemorrhage of the the tegmentum of the pes peduncu li which perfora ted into the fourth ventricle, and GAsTAUT also, in a patient who had similar perforation into the third ventricle, or or in a patient of anoxia owing to an anaesthetic acci 【Ient, noticed deep coma with a rapid rh≫thm in E. E. G . and concluded that unconsciousn ess without acco ・ mpanγing slow wan~日 is sure to ex is t, though no much attention has been called to to it before. What is the area essential for the maintenan ce of consciou sne ss is the fina l end of our study. From the fact that the nicoti ne -coma from the lower brain stem is lighter in grade, more difficult to indu ce and shorter in duration than that that from the mesencephalic central gre>' matter, and also from the results of a serie so f experiments w ith nicotinization and with electrical stimulation in our laborat01≫ ・, we are led to believe that the portion w hich holds the most important control control for the maintenance of consciousness is the mesencephalic central grey matter. matter. Co nclu sion 1. 1. Th e regi ons in the brain stem where coma occ urs b> ・th e injection of pure nicotine nicotine are the mesencephalic central greγmatter , the rostral pontine floor grey matter, matter, the rostral and caudal parts of the bulbar medial reticular formation. 2. 2. The latency from the injec tion of nicotine till the occurrence of coma was from tw ent>・ second s to tmJ minutes. The duration of coma was from thr ee minutes to ele ve n. 3. 3. Both s urface E. E .c; . and deep E. E. G. durin g nicotine-co ma showed lo w ¥'Oltage ¥'Oltage fast wa ves, and neith er slo w waves nor spindle bursts w ere seen . And the

E. E. E. G. during this coma did not change 、 at all even h＞’ painful st imuli. 4. 4. When re c tangular pulse st imulation was given to the sam e areas, no disturbance disturbance in cons c iousness but acti, ・at ion in behavior occurred. 5. 5. Nic otine -com a did not occ ur from th e m ese ncephalic and th e rostra l pontine reticu l ar formatio n. 6. Nicotin e-coma from the lower brain stem was ligh ter in grade, more difficult difficult to induce and shorter in duration than that from the mesencephalic central central grey matter. 7. Judging from these facts, it ma y be said that it is th e mesencephalic central central grey matter ra th er than the medulla that is more important for the maintainanc e of consciousn ess. Thanks Thanks ar e expresse d to Dr. Kazuki Sak ata for hi s kind help throughout the expe riments. THE LOWER BRl¥IN STEM AND CONSCIOUSNESS 43

SECTION II AN INVESTIGATION ON THE BULBAR AND MESENCEPHALIC

INHIBITORY SYSTEM IN UNANAESTHETIZED ANIMALS 事 According According to MAGOUN, electrical stimulation of the ventromedial part of the caudal caudal bulbar reticular formation inhibits the cortical motor response, the blink reflexes, reflexes, the flexor reflex of the forelimb, and the patellar reflex of the hindlimb, etc, etc, whereas stimulation of the lateral part of the bulbar reticular , formation, the suprabulbar suprabulbar reticular formation, the mesencephalic central g陀 y matter, and the hypothalamus etc, facilitates the cortical motor responses and the patellar reflexes, ・・・ that is to say, the bulbar reticular formation exerts a descending inhibitory and facilitatory facilitatory influence on spinal motor activity, whether it is voluntary or reftectic. In In discussing coma (or unresponsiveness) from the medulla oblongata, we must, therefore, therefore, consider the following possibilities:・・・ (1) (1) :'.¥fay the activation of this inhibitory system cause unresponsiveness (the disappearance disappearance of the noci-refl.ex) which we have applied as the criteria of coma? (2) (2) According to MAGOUN ’s theor y of the ascending reticular activating system, electrical electrical stimulation of the brain stem reticular formation causes E. E .. G. desvn- chronization chronization and behavioral arousal. If it is supposed that there may be an ascending ascending inhibitory system as well as a descending one, though MAGOUN says nothing nothing about it, may it (the ascending inhibitory system) not be responsible for disturbance disturbance of consciousness ? (3) (3) And again, may there not be a descending or ascending inhibitory influence influence from the mesencephalic central grey matter, which we have regarded as being being important in relation to consciousness? The aim of the present experiment is to examine these three points. Methods In In cats 1.5 to 2 kg in weight, anaesthetized moderately so as to nearly lose their their spontaneous movement by intramuscular injections of divided doses of barbituate barbituate (Isomital), cortical motor responses were induced by s timulating the exposed exposed motor cortex regularly at two-second intervals by means of rectangular pulses pulses of 4.4 to 6 msec . duration at 20 to 24 volts, and the responses of the contralateral contralateral forelimb and hindlimb wer e recorded on a kymograph. For inducing the the patellar reflexes cats were placed in the dorsal position with fixation of the spinal spinal process and the femoral bone, and the patellar tendon was tapped with constant constant power regularly at 4 seconds intervals by JoHNsoN's apparatus and the resulting resulting reflexes were recorded on a k~ · mograph. The brain stem was stimulated on the same side as that of the motor responses to be recorded, by employing 60 cycle, cycle, sine wave current, at 0.5 加 8 volts, through the bipolar el e ctrode being oriented oriented with the HoRsLEY-CLARK E technique. And while the cortical motor responses and the patellar reflexes were being inhibited by the brain stem stimulation, the

事 Read at the Sixth General Meeting of the Japan E. E.G. Society in Sapporo on July 3, 1957. 44 日本外科宝函第28 巻第 1 号 noci-stimuli noci-stimuli were given and the responses were macroscopically ob s erved. And in addition we examined how spontaneous E. E. G. and the electromyogram of of various skelet muscles （臼 exor and extensor muscles of lim bs, neck muscles, masseter muscles and respiratory muscles) were influenced at the time of descending inhibition. inhibition. In order to keep away artifacts from the records, 150 to 200 cy cle rectangular rectangular pulses at 1 msec. duration were employed for the brain stem stimulation, tion, and under this experimentary condition, descending inhibition was likewise observed. observed. In each animal, the stimulated points of the brain stem w ere affirmed histologically histologically in serial sections 同・ NrssLE stain and iron-carmin stain. Results Results 1) 1) Bulbar inhibition of the cortical motor response and the patellar reflex, and the disappearance of responsiveness to noci-stimuli during the inhibition. The stimulation of the medial part of the bulbar reticular formation was found to inhibit the cortical motor response in the forelimb and the hindlimb and the the patellar reflex. As shown in Fig. 14 . B, cortical motor respon ses disappeared completel y during stimulation b~ · 60 cycle, sine w ave current at 4 yoJt (i. e. during ・ the period marked b~＇ the signal), and after the cessation of stimuli the responf'. ,e augmented on rebound, owing to the release from inhibition. The reduction of the tonus of the limbs b~· bulbar stimulation in this case is shown in C As soon as stimulation stimulation set in, the tremor of the limbs stopped and the tonus was gradually reduced, reduced, and after the cessation of stimuli the reduction of the tonus became mor 色 remarkable for a time and then rapidly recovered. ' Inhibition Inhibition of the patellar reflex is shown in E. Sixtyγcycle, sine waye current at 1 volt caused a complete inhibition of the patellar patellar reflex. 60 c~ · cle , rectangular pulses at 1 msec.' 1 volt cau sed an in complete inhibition, inhibition, the patellar reflex sometimes appearing during the inhibition. During such bulbar inhibition, the tonus of the limbs was reduced, and respiration stopped.

TABLE 2. Chan ges of Respons 』veness to Noci-Stimuli during Bulba r Inhibition of Cortical Cortical Motor Responses & Patellar Reflexes.

Case Case No. 1 I 2 I 3 i 4 ! 5 句、ーー、み回勺 Bulbar Bulbar Stimulation ~ i ~ ﹈「 ?? ~ － l? 同 h 角田叫二 C 『 T ’司。..： . 円 Items Items of "Igo H 』 If If 号＝｜号！話~ 勺コ円ー’~ ::l -・。 7。，.， 10 :i<;~a_minations of Re.>pons iven e8s "' )0 JC 巾 oq Spontaneous Spontaneous Mo vemen t Responsiveness Responsiveness to olfactory Stimui 一＋＋＋＋＋＋＋＋一一一 Resi: 抽出iveness to Painfull Stimuli to Ear ＋＋＋＋＋＋＋＋＋ Responsiveness Responsiveness to Painfull Stimuli to Nose ＋＋＋＋ Responsiveness Responsiveness to Painfull Stimuli to Nasal Septum Responsiveness Responsiveness to Painfull Stimuli to Ext remity ＋＋ Corneal Corneal Reflex 一＋＋＋一一一＋一 Pharyngeal Pharyngeal Refl ex

Tonus Tonus of '.¥Iuscl es 、ノ Respiratory Respiratory MO¥ ℃ ment THE LOWER BRAIN STEM AND CONSCIOUSNESS 45

And responsivenesses to the noci-stimuli were near ＼~· extinguished, but some of them were still remaining (Table 2). And bulbar inhibition is demonstrable even in deep anaesthesia, and persists so so long as cortical motor responses or reflex activities are demonstrable. A

Fig. Fig. 14 B: Kimograph record of the effect of b<1lbar stimulation (showed by arrow in fig. A) on on the cortical motor responses. C :Reduction in muscle tonus evoked by the same stimulus. E : Kimograph Kimograph _record of the effect of.bulbar stimulation (showed by arrow in fig. D) on the patellar r、eflexes.

2) 2) Mesencephalic (central grey matter) inhibition of the cortical motor re 刷 sponse sponse and the patellar reflex, and the disappearance of responsiveness to noci- stimuli stimuli during the inhibition. The cortical motor response of the hindlimb, caused in the same way as in 46 日本外科宝函第28 巻鍔1 号

Fig. Fig. 15 B: Kimo,;!:raph records of the effect ofm べIbrnin cen tral grey matter stimu lation (showed by arrow in fig. Ai on the cortical moto r respons~s・ D~ ： Kimo~raph ；~records of the same:sti ；；－司ふ＇ tion tion rarrow in fi g. C) on the patellar reflexes. the the pr evious expe rim ent, was remarkabl> ・ reduced w hen stimu lation was given to mesencephalic mesencephalic central grey with 60 c >・cle, sine wave current at 4 volts, as is shown in Fig. 15. B. What di 汀ered from the bulbar inhibition ＂’ a只 that inhibition was incomplete and accompanied no rebound augmentation of res11011ses after the cessation cessation of stimuli. Inhibition of the patellar respo nse under the same condition is is shown in D. 八日 soon as stimulation set in, the to nu s of the lim bs was reduced, and the patellar reflex was remarlrnbly diminished. This inhibitor v influence cont ” inued inued lo ng after the cessation of はimuli and w 加 gradual!γlost. Resp::msiveness Resp::msiveness to noci-stimuli wa s found to -di sap pear almost completely during inhibition inhibition from the mesencephalic central gre~・ matter (Table 3) . THE LOWER BRAIN STEM AND CONSCIOUSNESS 47

TABLE 3. Change s of Responsivenes s to Noci-Stimuli during Mesencephalic Inhibition of of Cortical Motor Response s & Patellar Reflexes

Case Case No ・ I 1 I 2 『ー、ー『』ー一一一～ l¥ 在問ncephalic Stimulation , I During During Before During Items Items of －一一一一一一 j Before j Examinations Examinations of Responsiveness 一一一一一九 l‘ ： Spontaneous, Spontaneous, Movement ＋＋一＋＋＋＋＋＋＋＋＋ Responsiveness Responsiveness to Olfactory Stimuli H Responsiveness Responsiveness to Painfull Stimuli to Ear 甘＋ Respo/lSiveness Respo/lSiveness to Painfull Stimuli to Nose 廿＋H Responsiveness Responsiveness to Painfull Stimuli to Nasal Septum Responsiveness Responsiveness to Painfull Stimuli to Extremity 廿H Corneal Corneal Reflex 廿H Pharyngeal Pharyngeal Reflex Tonus Tonus of Muscles ＋ Respiratory Respiratory Movem ent ＋ Qn the other hand, when stimulation was given under much the same condition to to the mesencephalic and pontine reticular formation, the cortical motor respon se or or the patellar reflex was rather facilitated. Such descending inhibition from the bulbar reticular formation and mesencephalic halic central grey matter and decrea se or disappearance of responsiveness to noci- stimuli stimuli during the inhibition were observed in anima ls under moderate -anaes~hesia. The unr esponsive ness (the loss of noci-stimuli) that we have so far adopted ’as , the criteria criteria of coma in our experiment was the one in unanaesthetized animals, so simular simular observation must be done in unanaesthetized animals. 3) 3) Changes of the influence of stimulation of the bulbar reticular formation on the cortical motor response at various stages of anaesthesia . In In case of elect rical stimulation of the bulbar inhibitory area in unanaesthetized animals, animals, as already mentioned in the experiment b y electrical stimulation in Sect- ion ion I, we could see no tendency to unresponsiveness or inhibition but the increased muscle muscle tonus and behavioral activation or rage. Now, the e仔ect of stimulation given given to a certain point in the bulbar inhibitior y area, on the cortical motor response response was observed at various stages of graduall y deepening anaesthesia . In unanaesthetized unanaesthetized state or in light stage of Isomital anaesthes ia in which some sp - ontaneous ontaneous movement still remained, we could ob~＇. erve, on stimul at ing this point, a generalized generalized tonic reaction of the whole body, the flexion of the limbs, struggling, and behavioral rage. In the stage in which spontaneous movement disappeared but but the tonus of the muscles was st ill kept practically nor mall y, the bulba r stimulation lation caused a tonic fiexion of the limbs and activated the an im al in behaviour, as as is show n in Fig. 16. A. And as in Fig. 16 . B , as anaesthesia a little more deepened ened an'.i the tonus of the muscles was somewhat reduced, the cortical motor responses responses augmented during the bulbar stimulation, though the tonus of the muscles was strengthened and became rigid temporarily the initial stadium of stimulation; and as stimulation continued the tonus of the muscles got further strengthened 48 目本外科宝函第28 挙第1 号

Tー’・ I

Fig. Fig. 16 Chan geso f the effe ct of th e sam e bulbar stimulation on the cortical motor responses in various various anaesth etic condi tion s. A: T on ic 珂ex ion ofl egs in li g ht ana esth esia .(

Fig . 17 Shows the EM G c hanges 1 lo＼＼ ’ er s ix beams) led fro m a ntago ni sti c muscles onb o th sides evok ed b y t heb ul ba r st imul ation 「dur in 宮 the per iod mar k ed by the si εna li n the lowes tb ea m ). and reponses ＼＼℃ l℃ w eakened; and in stant ！；，ア aft er the cessation of stimuli the tonus of the muscles was strengthened to an extreme d egree and~ then THE LOWER BRAIN STEM AND CONSCIOUSNESS 49

‘イホ｛ヘ付ず~ヘ

i 門ぃ“” 伸M 哨 i

‘ ”’ ~ . UI') ー輔、ー」 4 円いやおい仲

v 門 t’＇＂＇＇州州州部吋 4 汽ンァ仰、

、＂， B E 門 ~ I N A(A5[C ＞’ i ~HI Biτs ON ＂ ιl l("J f[O Fig・ Fig・ .. 18 A .: EMG changes (l ower six SY 51 i刊U 』 AT :ON ・o r M rSENtt 科•ALIC CG 仇，.u.,.· 1~ I同小・i・＂＇＂＇” 句眠、..，怖い＇＇＂ d，もう， be2,~S ) elicited by the electrical sti- .. c~.. n mulation mulation of mesencephalic ccentral ，，・ W 向＂＇＂正、 . ・..... J grey grey matter . B : Os ci llographical ' " " l 司＇＂＂＇ ’‘ • »At‘ー－ ~・P“‘’＇＂＂白9 ・，＇・＂＇・＇＇＂ recordings of the same eff ect. ~ .. f'~ ~1; ' 1 1－.凶

dd 、＂＂~川 . . ca’U U5i町 aea4 hHa ei唱h - －RJ‘4c 園圃－d h 軒 to to the prestimulator y state . At も、，＇＂＇、 ...・－ MVγ＂＂＇＂＂＂‘ぷ倉町 the next stage follo w ing this period ~＂，、．吟‘＇＂＇＂於 " －・＂円 of light anaesthesia facilitation i 極圏ち。。” (B), as anaesth e sia deepened, the tonus tonus of the muscles was weakened ~：：：·.：；：“ A as soon as stimulation began as in 田園ぃ (C), ウ作F while the response itself sho- 唱険、ヘ電 wed neither facilitation nor inhib- 予．とー，ω 二ダ ition, and then limbs became extr- －、‘に p em ely 、e L flaccid instant ly aft er the ，． ‘ ’， ι 、 e 司‘ ，畠祖 1．巳内 F ，色ら 4 、‘’t n ♂肘v‘ cessation of st imuli, and at the next next moment showed tonic flexion and then graduall y restored (C). Inhibitory Inhibitory effect did not appear till anaesthesia furth er deepened to a stage, when the the tonus of the muscles was more reduced, and the limbs had become flaccid (D) . At this stage, facilitation of cortical motor respon s es was obs e rved as a rebound phenomenon after the cessation of stimuli . In In short, descending inhibition did not occur by a mere stimulation of the inhibitory inhibitory area, without moderate anaesthesia. Thus -unresponsivene ss (coma) in 50 日本外科宝函第28巻第 1 号 unanaesthetized unanaesthetized animals, with which we have dea lt Lefore, should be di 百erent from unresponsivene ss due to such des cending inhibi tion. 4) 4) E. l¥I. G. under inhibitor y influences During such descending inhibition, E. M . G. s w ere recorded from various skelet muscles muscles (neck, chew, interc os tal and 自exor and defi e xor muscles, etc. ). Not onl y during during bulbar inhibition as in Fig . 17 , but also during mesencephalic inhibition as in in Fig. 18, waves in E. l¥I. G . di sappeared. The stoppage of w aves occurr ed bilaterally, bilaterally, and in both antagonistic m uscles simulta ne ously; that is to s ay, it w as non-reciprocal, a non-reciprocal, ard gc1 ~ eEeralized stonage covεri ng a11 the limb im 、1".cl es ard the intercostal intercostal mm:cles ar :d tl:e other s, ard often :: ho" ed a rel:;our.d phe no me no n aftu th e cess ati on of stimuli . 5) 5) E. E. G. under inhibitor y influences Changes of elect r ocorticogram recorded from the six points , na mely both an anterior anterior and a posterior pole on either side and each two points of the right and the the left side of the cerebral cortex , during obviou s desc ending inhi bitio n, sho w ed a complete complete stoppa ge of bur st acti v it~ · bγa naesthetic s and the reduc t ion of hi gh voltage tage w aves . Suc h ch ange s were particul arl y rem ark ab le in th e tfron al area . Fi g. 19 19 shows changes during the stimulation of the bulbar inhibitor ~・ area, and Fig. 20 shows those during the stimulation of the me se ncephalic centr al gr町アmatt er. Discussion Discussion

In In their inhibition theo ry, MAGOUN and RHIN ES (1946) sa ：－・；“ In cats under chlorolos ane anaes th es ia, th e fi exor re fl ex of th e fo releg , th e pate ll ar refex o f th e hindle g a nd th e blink re fl ex of th e e ＞℃ lids we re reduc ed or aboli shed b y bul ba r stimulation. stimulation. These reflexes, initiated respectivel y bγ nocicepti ve, p roprioceptive and tactile tactile stimuli, in ml ve muscles ・ft exor, exten s or, and postura ll >' incli 汀erent …

I－ヨ ,, . ,. 10~ 0.1 ，” t G .. M 寸’ ぷい叫~～吋ラト←一叶 l

人〕ー

＇，，－ーー一

一一寸~

Fig. Fig. 19 EE G cha nges elic ited by th 巴 bulb ar electr ical st im ulati on dur ing th e p eriod m ark edb y th es ig・ nal in th e low es t bea m . E EG trac in gsw 0rc le d from midlin e fr ont al ( I) and occi p ital ( 2) end so fc erebral con 、ex ity, left (3 ) and righ t r tl coronari us g yrus and lef t l5) and ri g ht (6) p os terius ectosylvius gy rus. THE LOWER BRAIN STEM AND CONSCIOUSNESS 51

《ぷ石〈〆ゾしんヘf「八へr， ~\J,~ －w.. rv 」－＂ t1へノ A A/ /¥J 「 λノνLム .f'v- J"/" Jしヘ f

介~~吋引('IV'lf"l1ij\o_,,,~叫ん4川r-"~Ji. , , .. t>Jvv"tvν\f'v'V~ムJV\J\J Jぷ礼入向、f、刊rJ~＼内川刊J人、「V門ノ（＼，／＼／1ヘ~ナーハ～ル~ん

む一一色 •\r州ノ，州ザJへ、川

<-l ~ぺf、作／、 G-2 .r------~－－ーーーー，，、.－－、J、、－－－

川州州W州 W 附吋州市』、ィー－ゆ吋』，＊守 e 、ー、ーー自制トーー－『－司

＇＂岡＂・＂、 t.i.I ••‘ ＿，，＿＿＿＿，，；，…）一一 F」＿＿＿，.＿＿川一叶ー＿＿，＿＿＿，

I へ〆

j 刊日ザJJ'v ＼川〆〆

...... ，...ゾ.／＇，

/'Ji/ '[

J ルザy ～ハノん

。。”u L－

一一一一一一〕同州川州州州ψや V

J 一一一一 Fig~＇ 20 EEG changes elicited by the electrical stimulation of the mesencephalic central grey matter. matter. distributed distributed over the length of the IJocly. The bulbar inhibitor y influence thus appears ars to be a general one, not limited in its action to functionally specific or topogr 」 aphically aphically circum sc ribed reflex acts .” And they go on to say that such inhibitor y e百ect of the bulbar reticular formation upon re 日ex activity and cortically induced movement is bilateral but more remarkably ipsilateral ; that after inhi!Jition the augmenting of responses is often observed as a rebound phenomenon as a result of rele ase from inhibition; and that the site of inhibition here is evidentl~’ spinal rather rather than corti ca l. If such generalized inhibition of reflex activit y and corticall y induced induced movement should occur, the resulting state may be suppo se d to be similar to to the unresponsiveness which we ha ve been considering. But according to our experience experience unresponsiveness due to such an inhibition is not rn complete as that which we have been using as criteria of coma. Be sides , we must not forget that 52 52 日本外科宝函第28 巻第1 号 the the above-said experiments on inhibition were all in anaestheized animals. The coma at the time of head injur~’ and also our experimental coma were all under unanaesthetizecl unanaesthetizecl state, so ＇ γe must again examine whether inhibition can really occur occur or not in unanaesthetized animals. And as alrcad~ ’ said in the rectangular pulse pulse stimulation experiment in Section I of this stucly, the 8timulation of the bulbar bulbar inhibitor~· area in unanaesthetized animals resulted in onl:- ・ generalized activation activation or rage, which was di 仔erent far from inhibition. We canno t find any such such experiment of inhibition in references. So, in order to make the matter clear clear to understand, we made an cx11e riment to examine the changes of the effect of of stimulation of the lrnlhir inhibit on・ area in ¥'arious .sta 昨日 of anaesthesia, and found that on ）~－ generalized activation and exaggeration of motor activity or tonic flexion flexion of the limbs occurr ℃d in unanaesthetized animals. And inhibition occurred only only in the fairly deep anaesthetized state, while in the light stage of anaesthesia temporan ' facilitation was olisen'Crl. Accordingly, ge neralized inhibition is a phenomenon occurring- onl>・ under specific condition of anaestl1csi~. It is not right to consider consider that the bulbar reticular fo1 ・rnation lrn 日 a faci litator> ・and inhibitor~ · inftu- ence ence on spinal motor activit> ・ uncler ususal physiological condition. Ge1;eralized inhibition inhibition under anesthesia is di 町ere nt from the coma (unresponsivcnc~s) which we ha ,-e obsenccl urnlc1 ・unanaestheti ze d condition. To regard our unresponsiYcne~s as as a state influenced lハcentral inhibition in the sense of ::'IIAGOl 'N. 日 is not assuring. SPRAGUE et （’HAMBERS (1954), too, say that inhibi to ry influe1 1e c does not occur under unanesthetized condition. When the>・ gave electrical stimulation to the medial medial or lat era l bulbar reticular fυrmation in unana es th et ize d animals the y could observe observe only speci 白c movement; and under light Nembutal anaestl 1c sia, in most cases, cases, reciprocal inhibition or facilitation of the postural tonus wa 日 observed; and a change from rec iprocal inhibition to generalized in hib ition was vcr> ・ rarely found; and a generalized inhibition, if occurred, was found to originate from both medi al and lateral bulbar reticular formation. The y s 幻 ’in conclusion ，“The concept of generaliz ed, diffuse, non-1 ・cc ipr 田 al 'inhibitory ’ and ‘facilitatory ・functions of the reticular reticular formation is valid onl ≫ w ithin rather limited e:qierimental condition s.” In our opinion ‘limited experimental conditions ’m 川・ m n 111 ' adequate anaesthetic depth', depth', for according to our finding s, generalized inhibition is pr etty easy to occur under fairly deep anaesthesia. And the inhibitor y area is not limited to the

ventro-meclial ventro-meclial part of the bulbar reticular formation but is also near the dor ・so 縄 medial medial part, i. e. fasciculus longitudin als posterior . And the inhibition we got under dee1) anaes thesia wa 同 a generalized one, as is obv ious from the electromyog- raphical raphical tracings. And the descending facilit ato ry area refenccl to b> ・RHINES and MAGOUN (1946) include s the ascending reticular activating s~·stem except the medial bulbar reticular ular formation ・・・ namel y, the lat era l bulbar reticular formation, the pontine and mesenceph alic reticular formation, the sub-and hypothalamus an d so me thalarnic nuclei, nuclei, etc. ・ and ・・ even the mesencephalic central grey m atter, believe it or not. We have so far reganled the mesencephalic central gre~’ matter as the part in THE LOWER BRAIN STEM ANQ CONSCIOUS .¥J ι：ss 53 the the brain stem most likely to bring about disturbances of consciousness lη F various stimulatory stimulatory methods. Does similar inhibition not occur from the mesencephalic central central grey matter as well as from the bulbar reticular formation? We have examined about it, and found that much the same inhibition occurs, though not so so remarkable as the one from the medulla. And further, we ha¥ 'e found that inhibition inhibition from the mesencephalic central grey matter is bilateral, and does not accompany any facilitatory rebound phenomenon after inhibition, and all the responsiveness responsiveness to noci-stimuli disappears just as the unresponsiveness of our former nicotine nicotine study. But even in this case it must be remembered that the inhibitory phenomenon is still the one under deep anaesthesia. As for descending facilitatory influences, by the way, aside from light anaesthesia thesia facilitation from the medial bulbar reticular formation, de 白nite facilitation occurs occurs from the lateral bulbar reticular formation and the mesencephalic and the pontine pontine reticular formation. Also in the latter case, under light anaesthesia, stimulation stimulation causes the tonic flexion of the limbs and only under deep anaesthesia it it causes typical facilitation, which never changes into inhibition, however deep anaesthesia anaesthesia may be. To summarize, we will show the results in the following table. table.

depth depth of anaesthesia nonanaesthesia nonanaesthesia ＿ー争一一歩 light light anaesthesia .or modera te anaesthesia deep anaesthesia stimulation stimulation area stimulation stimulation of inhibitory inhibitory area ｜山 l…→凶…批ili

sti~1;1lation of facilitatory facilitatory area ｜… exio 創 ili

And it seems that the inhibitory and the facilitatorγarea cannot be so clearl~’ separated separated in certain regions as MAGOUN and other say, but ev en the rem ove of the stimulation stimulation point for 1 mm dorsal, or ventral, or medial, or lateral may cause the the disappearance of inhibitory effect . The changes that the stimulation causing descending inhibitor y influence brings on E . G. E. was found to be considerabl y remarkable at the s timulation of both the the mesencephalic central gr 町・ matter and the bu l bar reticular formation, but we dare dare not say that this is an ascen ding inhibitor y influence to cerebral function. Conclusion Conclusion 1) 1) In Isomital anaesthetized cats, the noci-stimu li , given during the inhibition of of the cortical motor response and the patellar reflex by the stimulation of the bulbar bulbar inhibitor y area, fail to induce most of the various noci-refl exes. 2) 2) In unan acst hetiz ed animals, the electrical stimulation of the inhibitor y bulbar bulbar reticular formation ac ti vates the animals, an d all the motor acti¥・ities are exaggerated. exaggerated. Under anaesthesia, as it deepen 日， a change through temporary facilitation tation of the motor response into inhibition i只 seen.

3) 3) The same inhibitor~ ー influence under anaesth es ia is gained al川 from the 54 54 日本外科宝函第28 巻第 1 号 mesencephalic central gre~γmatter, but it is not so complete as from the medulla oblongata. But in this ca 叫 the noci-reflex disappear s comple 旬ly during inhibition. 4) During descending inhibition, the E. lVI. G. pattern of the skelet muscle s (involving the respirator ~ ・ muscles) in various parts of the body disappear. 5) 5) The changes of E. E. G. during descending inhibition are a complete disappearance of burst activity and a remarkable change of spontaneous E. E. G. in the frontal region . 6) 6) Consequentl y we cannot regard in the same light the state under descending inhibition as the unresponsivene ss (coma) tha t have so far been seen in our previous expe riments, the former being the state under anaesthesia, and the latter a phenomenon under nonanaesthesia. Thanks are expressed to Dr. :¥Iorio Matsunga for his kind he lp throughout the experiments.

References Patholo g isc he Physiologie der Hirnderschi.it-

1) 1) Alf. Brodal, l¥I. D. , : Ascending Fiber s in terung・ nebst Bemerkung 、en iiber verwandte Brain Stem Reticular Formation of Cat. A rch. Zustiinde. Journ. f. Ps ycho !. u. Neurol., 29 , Neurol. Neurol. & Psy chi at ., 74 , 68, 1953 . 2) Araki, !, 19 22 . I'.'i ) Lindsl ey, D. B., Schreiner, L. H. , C., C., : Diencephalon an

和文抄録下部脳幹と意識障碍

京都大学医学部外科学教室第 l 講座（指導：荒木千里教授）守安久

下部脳幹と意識障害との関係、を追究する目的で次の i) MA GOUN bこ倣つで麻酔猫でP 脊髄運動性が延実験を行った．髄内側網様織刺激によって下行性に抑制されている間 i) 下部脳幹の一定の部分をねらってニコチンの微に，侵害刺激を加えるとそれに対する諸反応は一部を量注射をすると，中脳では中心灰白質，橋脳：では吻端除き大部分が消失する．

部第四脳室底灰白質，延鎚では吻端部被蓋網儀織と尾 ii ）無麻酔猫で同擦の実験を行うと p 抑制は起らず端部の内網様織から昏睡（無反応）が起った．従って逆に activate され運動現象はすべて克進する．麻酔これらの部分は意織の維持に深く関与している部分とを加えると，麻酔が深くなるにつれて一過性の運動反

思われる．応の促進期を経て抑制期えと移行する．従ってMA- ii) ii) ニコチン昏睡中の脳波は表函，深部脳波とも低 <:OUN の generalized inhibition と吾々の無反応と電位速波で覚醒時と殆ど変りがない．即ちニコチン昏は麻酔という条件の異いがあるために同一に論ずるわ睡は behavior 上では昏陸を脳波上ではarousal pa- けにゆかない． ttern を示す． iii ）同僚の麻酔下抑制は中脳中心灰白賓の刺激によ

iii ）対照実験として略同じ部分を直接矩形波電流でっても起るがp 延髄性ほど完全ではない．然し中脳性刺俄すると，意識障害は起らず behavior 上の act- 抑制中は侵害反応は全く消失する． ivation を示す． iv ）下行性抑制中は諸種の筋電図波形は停止し p 脳次で延髄抑制系（延髄尾端部内網様織）の刺激によ波では burst activity の完全な停止と，前頭部に著って起る generalized inhibition (MAGOUN ）と吾々明な自発脳波の変化がみられる．の無反応とを対比吟味する意味で次の実験を行った．