Folia Psychiatrica et Neurologica Japonica Vol. 7, No. 4, 1954.

ANALYTICAL STUDIES ON THE FLEXION REFLEX CURVE AND ITS SIGNIFICANCE IN THE

PRE- AND POSTCONVULSIVE STATE

BY Naosaburo Y oshii and Kazuya Hiraiwa

2 nd Department of Physiology, &aka University Medical School

Introduction

Many studies have been carried out on the flexion reflexl) j), in 1931 there appeared Shewington's detailed report 6). But most of these studies were made in decerebrated animals or spinal animals. In such cases, the flexion reflex tends to be very simple when recorded on the smoked drum"). On the contrary, the flexion reflex in uninjured animal shows a very complicated pattern because the entire central nervous system including the cerebral cortex come to be related into the reflex circuit.

If the flexion reflex curve be analyzed as, for instance, in the pre- and post-seizure animals, the physiological significance of it and the functional state of the central nervous system might be cleared up. In this paper, experiments were made in regard to this point of view.

Experimental methods Rats were used throughout the experiment. The neck and loins were

fixed by a metal frame to a wooden plank leaving both hind legs free for movement. In order to record the flexion reflex, the myographic method was used, time recording was made by electromagnetic tuning-fork. Two small silver electrodes were bound to the right paw which was connected to a isometric tension lever, while a single super-maximal break shock was given by inductorium.

Experimental results

The flexion reflex of normal rat recorded the latent period as 12-15msec., the peaks of contraction appearing at 30 (sometimes this was hardly differentiated from 60), 60-80, 100, 150, 200 msec. and more (fig. 1).

I. T h e effect o f narcotics The changes in the flexion reflex curve after drug application

can be divided into three groups according to the drug used. In the first group of narcotics (Chloralose, Evipan-Na, Dial) the latent

~~ ~~ ~~ -~~~ ~~ ~~

Received for publication, June 30, 1953.

'294 K. I'oshii and K. Hiniwa:

Flexion r e f l e x curve of normal rat

L- ucer . iy I

12-15 m s r c

C h l o r a l o s e

,f -2_ 1 bbou t 1 8 mSeC

Br ov ar in

6 -c- , 12 -15 m s r c

Pent obar b l t a1 -Na

- I:! I5 msec

Urethan (1) I

25-50 mSec

Fig. 1.

period gets observable in prolonged peaks of less than 10msec.. the flexion reflex curve become remarkably flat after 100msec. (fig. 1 and 2). In the second group of narcotics 4 Brovarin, Pentobarbital- Na, Adalin, Luminal, Chloralhydrate, Chlorethylr , the latent period reads the same, but the peaks expected to appear up to 250403 msec. fail to appear while other series of peaks do appear 400 mser. or later. In the third group !,Urethane, Alcohol, Ether), it is noted that, when the latent period is prolonged more than 25-50 msec., the peaks do appear at 60msec., then at 400msec. or later, rather resembling to narcotic function on the 2nd group. But with the narcosis working much deeper, the preceeding peaks start now to appear, while the latent period gets suddenly prolonged to 300 msec. and over (fig. 1 and 2). I t is worthy of reminding here that the central conduction is affected much more rapidly through certain drugs, especially through narcotics and anesthetics

IT. Development of thc floxiori ruflex in the infant rat The latent period of the flexion reflex on the first day after

Analytical Studies on the Flexion Reflex Curve 295

2nd group pentobwbita) -Na

'296 N. Yoshii and K. Hiraiwa:

3 rd g roup U ve tnan - - 1

-+

E t h e r

h n __f

Fig. 2. (b)

birth measures very long (about 145-326 msec.) and the flexion curve shows only one single peak at ZKO-'iOOnisec- The latent period becomes now abruptly shorter measuring 24-95msec. and a number of peaks start to appear one week after the birth (fig. 3). Yoshii et al. has reported that on the 4 t h or 5 t h day of birth convulsive EEG pattern was noticed after the electroshock, but i t was about after 7 days that an actual convulsion of limbs was associated with the EEG changes'). The record of the 25th day would show a latent period about the same, and the same formof reflex curve as in the adult ra t (fig. 3 ) . It is suggested that a much longer latent period of flexion reflex observed shortly after birth must be due to incomplete development of the nerve axons in transmitting path ways.

Day after birth 1 Peak 2 Peak 3 I'eak

18-20 22-23

3

Adul t rat

23-110

25- "5 Z5-1 CO 25- 07

145-255 21 C-405

110-220 20-500 153-530 235-477 90-375 125-508 78-5SO 105-470 60-210 I I O - ~ O O

05-210 105-469

6 2 - 2 3 I30--3?0 55-143 S3-2 5

4 Peak 1 5 Peak

SO--530 300-575 330-695 167-ji-6 130-570

9CO--400

IFO--579 135--485 110-230

570-650 c73-7v3

2-70 - 670 190-520 270-500 200-343

102-500 145-273

Analytical Studies on the Flexion Reflex Curve %J7

msec.

Latent period

111. Analysis o f the flexion ref lex curve Analysis of the curve with some physiological methods such as

with the conditioned reflex methods, with decorticate and decere- brate preparations, and with injection of Curare, Myanesin and Sodium cyanide was performed in turns.

The flexion reflex curve can duly be separated into the pre- ceeding (30, 60-80 msec.) , the intermediate (100-200 msec.) and the delayed (200msec. and later) peak responses, as was written in the experiment I. Only the pesks of the delayed response did not appear in decorticated rats, where the motor area shown by Lashley was completely removed 1’) on both sides (fig. 4). In some curves taken in record 20-30min. after decortication of both sides, there

N. Yoshii and K. Hiraiwa;

Region of decoptication

Decerebration

comm. post : commissura posterior n. ant. : nucleus anterior thalami comm. ant : commissura anterior s.: septum

comm. hip. : commissura hippocampi

h. sc. : hippocampus supracommis-

post. : rn. : nucleus rukr

suralis posterior nucleus of thalamus

Fig.

p*st

n. ant

hab. : habenula c. man.: corpus mamillare n. pop. : nucleus preopticus h. pc. : hippocampus precommis-

tub. f . dent : tuberculum fasciae dentatae

col. forn. : columna fornicis

i. : intestinal nucleus nig. : substantia nigra

suralis

4.

Analyt-ical Studies on the Flexion Reflex Curve 299

Decort i c a t ion

200 300 480 500 600 7CO msec StinuLLat i o IL

Fig. 5.

Inject ion of Curare

appeared the preceeding and intermediate responses of peaks and the flat curve of rigid contracture after 200msec. instead of the expected delayed one of peaks (fig. 5).

Thp same result was obtained through injection of Curare (1%. 0,lcc) which knowingly suppresses the excitability of the cerebral cortex 13) (fig. 6 ) .

The flexion curve produced by conditioned avoidance reflex could be seen with the latent period of about 150msec. and the peak of contraction nearby at 200 msec. in response to the conditioned

300 N. Yoshii and K. Hiraiwa:

I f 30 I

Distribution curve of L a t e n t period of conditioned re s p ons e

t I I 8 1

100 120 140 160 160 200

1 I0 130 150 1'10 190 210 I I I I I I msec

f 30

i Distribution c u r v e of

peak of c o n d i t l o n e d response

Analytical Studies on the Flexion Reflex Curve

145msPc. / i

300 &>O 500 Goo lioo m s e t 100 ZOO

301

n~ nv.tej 60 later

w

Cmdit ioned respcnae

Do cure bration C o n t r n L

s o o n after deccrc bration a.

15 ccc.

5 minuLte: Later b -4 15mcrc.

Injection of Myanesin

4o minurkj Later

A 1

15 ec.

pm- 700 200 300 400 500 600 TOO msec.

~ ; m L z f ; o 7 L . Fig. 10.

302 N. Yoshii and K. Hiraiwa:

Direct st1mu:ation of spinal cord

200 300 400 500 600 700 msec.

Fig. 11.

Direct atimulation of sciatic nerve con t re L -

\

too 500 600 700 met. 200 3m

Fig. 12.

Injaction of Ha-cyanlde

Analytical Studies on the Flexion Reflex Curve 303

stimulus, an electric one given to the ipailateral ear (fig. 7 and 8). With decerebrated rats, the expected peaks of the flexion reflex

curve after 150 msec. failed to appear, in a few cases, the flat curve of rigidity did appear at 150msec. or later (fig. 4 and 9).

When Myanesin was injected (5%, 0.2-0.5~~ every 10 minutes), the flexion reflex curve showed a valley at 150-200 msec. (fig. 10). I t is said that Myanesin has an inhibitory action on the multisy- napi.ic pathway and the brain stem structure gets affected here-

With the spinal cord transected at the 10 th thoracic segment and stimulated a t the distal cut end, the flexion of the hind limb took place within 100msec (fig. 11). And, with the sciatic nerve cut and stimulated at the distal cut end, the flexion of the limb occurred but was over within 80msec. (fig. 12).

Now, Sodium cyanide was injected (1% 0 . 1 ~ ~ ) purporting t3 accomplish functional decerebration g), the delayed response O E peaks, then the intermediate ones, only excepting the preceeding ones, appeared (fig. 13).

From these experimental results, the authors will conclude that the delayed group of peaks after 200msec. comes into display chiefly by merit of the reflex activity involving the cerebral cortex, the intermediate group OE peaks at about 150 msec. through activity of the centers in the brain stem, while the preceeding group of peaks at 30, 6&80msec must signify reflex function of the spinal center.

in 9) 10) 11) 12).

IV. Effect o f the audiogenic seizure At about 40 to 60seconds after auditory stimulation Galton

whistle attached about 15 cm. afront the subject and with air current of a pressure of 200 mmHg., thus producing a tone of 12 KC, there was induced tonic, tonic-clonic, or running seizure. The height of the flexion reflex curve was seen suppressed just before the audiogenic seizure. After the seizure, the height of the reflex curve became remarkably small, even disappeared entirely in a few cases (fig. 14). In most cases, the latent period was not changed after the seizure so long as the reflex persisted. But in a few cases, the latent period was prolonged a few milli seconds. Within 10 seconds after tonic or tonic-clonic seizure, the peaks of contraction usually appearing at 103msec. or later grew very small and the peaks refused to appear by far at 150msec. or later (fig. 14).

The peaks at 200 msec. or later began to appear 40- 60 seconds after the audiogenic convulsion, and then the reflex curve compo- nents and magnitude of contraction gradually recovered its normal form within about 40 minutes. Only after the running seizure was induced exclxsively, there was no remarkable change of the flexion reflex curve except a considerable suppression in the height. When convulsion did not occur by auditory stimulation, the magnitude of flexion reflex got rather exaggerated.

304 N. Yoshii and K. Hiraiwa:

PLHXION RElrLEX CWRm CHANGED BY AUDIOGDlJIC SKI-

12 -)t‘

J jE soon afrer the 5e;zure

From the experiments written in 111, it stands conclusive that just before the audiogenic seizure, the spinal part of the flexion reflex circuit got already suppressed, and soon after the convulsion the activity of cerebral cortex and also of the brain stem must stand under complete suppression. After convulsion, the functions of the cerebral cortex, brain stem, and spinal cord recover in about 40 minutes or so. By not so violent a convulsion, the inhibition in the refles center remains slight not requiring so much time to recover, whereas in rase of sustained convulsion, the reflex activity of the centers must be rather excited.

V. E f j c c t 0.f electroshock 60 cis alternating current was given for one second at an inten-

sity of 15 volts through ear holes of both sides with pincette-shaped brass electrodes. Tonic-rlonic convulsion appeared during 15 seconds after the electroshock. The flexion reflex curve of the rat on the process of recovery from the convulsion gave the latent period of the flexion reflex to be unchanged for 15 seconds after the convul- sion. But the magnitude of contraction grew small and the peaks appearing a t 100 msec. and later in the presejzure state failed to

Analytical Studies on the Flexiox Reflex Curve 305

ii convulsion . . . . . . . . . -

306 N. Yoshii and K . Hiraiwa:

appear. We call this pDriod “ 1st stage” ifig. 15, a and b, fig. 16, a and hi. Now, one minute later, the latent period was prolonged to about 20msec. and the peak; appeared a t 200msec. or later only scarcely. We might call this period “ 2 nd stage ” ifig. 15, c and d, fig. 16. c and d ) .

After 2 m i c u t e from the shock, the flexion reflex curve and the magnitude of the contraction recover now gradually to those of normal state, requiring 40 to 60 minutes before returning to the preseizure states.

At times, a curve seemingly showing the elevated tonus of the hind limb appeared at the 2nd stage cfig. 4, c and di. It is also olyservable here that the magnitude of contraction was suppressed gradually just after the convulsion (fig. 4, a and bl.

After the subcutaneous injection of adrenalin (0.1%. 2 cc) and acetylcholin 5%, 0.2-0.4 C C I the flexion reflex curve remained well unchanged, thus telling so far that sympathico-or parasympdthico- tonus have nothing to do with the flexion reflex curve, even induced through convulsion. .4nd, f ronr experiments described in this paper, it will be concluded safely that, in the first stage, the spinal part of the flexion reflex circuit remains unaffected while parts of the circuit including che cerebral cortex and the brain stem are rompletely blocked. Also, it is well seen that the function of the brain stem recovers in the 2nd stage. Two minutes later, the function of cerebral cortex, too, seirns to recover gradually; after 40MO minutes, the function of the cerebral cortex, the brain stem and the spinal rord all related to the flexion reflex bocom? entirely normal.

1 liscu ssion

In t h e e experiments about the flexion reflex, the nerve element was electrically stimulated through the skin without exposure of the former. In our preliminary experiments one will see that many muscles reacted reflexwise by a single shock which was given to the hind limb of rat. Creed reports that in flexor reflex many flexor muscles contracted concurrently. H J

The flexion reflex is the most primitive pattern of response in higher vertebrates, representing the mechanism for withdrawing an extremity from injury, as was named a “ ncciceptive ” response by Slzcriingion, a defense reaction against a noxious stimulus. 1;)

Really, even in case of such a simple spinal reflex, many muscles do co-operate synergetically.

Many studies have been made in spinal or decerebrate animals, but in this study the reflex movement of limb instead of one muscle was taken as the expression of function of the refiex centers, upwwdly involving the cerebral cortex. Because the flexion reflex can be observed a:+ an arranged movement pattern of many impulses through final common paths which are concentrated sp:icially and

Analytical Studies on the Flexion Reflex Curve 307

temporarily from extensive parts of the central nervous system downward to the ventral horn cells of the spinal cord so that this reflex represents a reflection of so many motor centers exsisting in cerebral cortex, brain stem and spinal cord. These considerations can well be ratified from the experiments on narcotics described in this paper. From the analytical experiment of the flexion reflex, the authors will suggest that the delayed group of peaks after 200msec. are originated chiefly from the reflex activity of the cerebral cortex, the intermediate group of peaks at about 150 msec. from that of the brain stem, while the preceding group of 30, 6@80msec, shall represent the function of the spinal center.

Then, the authors should like to conclude that the “ 1st stage ” subsequent to the electroshock represents hypofunction of motor centers of the brain stem and cerebral cortex, but in the “2nd stage ” only the function of the cerebral cortical centers stands inhibited, as 2 minptes later the function of the cerebral cortex begins to recover gradually.

In the typical audiogenic seizure, the function of the cerebral cortex goes suppressed together with that small part of the brain stem and spinal cord within 10 seconds following the seizure. And I minute later the function of cerebral cortex gets recovered. The shock of the central nervous system following the audiogenic seizure is always less competent than that following electro- convulsion.

Summary 1 . The flexion reflex curve was analyzed by a series of phy-

siological methods, and the effect of some narcotics, electroshock and audiogenic seizure upon this reflex and also the development of flexion reflex in infant rats were studied.

2. The flexion reflex curve consists of three components, the preceeding peaks (30, 60-80 msec.) which originate from the spinal center, the intermediate ones (100-200 msec.) from the brain stem, and the delyayed ones (200 msec. and later) from the cerebral cortex.

3. It might be considered that the 1 st group of narcotics (Dial, Chloralose, Evipan-Na.) exhibits effect upon the cortical function, the 2 nd group (Erovarin, Pentobarbital-Na, Adalin, LuminaI, Chlo- ralhydrate, Chlorethyl) take effect upon the thalamic function, and the 3rd group (Urethan, Alcohol, Ether) effect on the spinal cord.

4. The latent period of the flexion reflex reads very long on the first day after birth, to get abruptly shorter one weak later.

The record of the 25 th day proves about the same latent period and the same form of flexion reflex curve as in the adult rat,

5. Within 10 seconds after the audiogenic seizure, the activity of brain stem and cerebral cortey gets abolished, the activity of the cerebral cortex starting to recov6r from I minute on. The activity of the spinal center is facilitated in no-seizure state, but inhibited just before the seizure.

308 N. Yoshii and K. Hiraiwa:

6. Within 15 seconds after electroshock, the activity of cerebral cortex and brain stem gets wholly abolished, this activity of cerebral cortex tends to begin to recover only gradually from 2 minutes on.

References

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