Epilepsy & Behavior 15 (2009) 123–130

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Epilepsy & Behavior

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International Classics in Epilepsy and Behavior: 1870

Electric excitability of the cerebrum (Über die elektrische Erregbarkeit desGrosshirns) q

G. Fritsch *, E. Hitzig

Physiology lays claim to all nerves as a necessary condition ofthe concept of the property of excitability, i.e., the capacity to re-spond to all influences with their specific energy, through whichtheir state is changed at a certain velocity. Other views, whichadmittedly are only generally accepted in a few points, predomi-nate only for the central parts of the nervous system. It would takethe discussion too far, and not serve the special purpose of thepresent study, if from the enormous literature we only wished topresent the results that appear reliable to us and which were ob-tained by excitation experiments on all individual parts of theCNS. While, however, a great difference of opinion exists aboutthe excitability of the organs comprising the brain stem by otherthan organic stimuli. While very recently a vigorous argumenthas erupted about the excitability of the spinal cord, since thebeginning of the century the conviction has very generally spreadthat the cerebral hemispheres are absolutely unexcitable by allthe common physiologic stimuli.

Haller and Zinn1 admittedly maintained that they had seen con-vulsive movements after injury to the medullary substance of thecerebrum. However, at that time we were too little accustomed toa strict limitation of the excitation employed, which admittedlyencountered almost insurmountable hindrances on the brain, forthese statements to be believed at a later point. As even Longetnotes, it is rather probable that those experimenters had penetratedforward to the medulla oblongata with their instruments.

Longet2 himself, however, has the following to say about this:‘‘In dogs, rabbits, and goat kids we irritated the white substance

of the cerebral lobe with a scalpel, we cauterized it with potash, ni-tric acid, etc., here we passed galvanic current through it in all direc-tions without managing to set in motion involuntary muscularcontraction or developing convulsive twitches: the same negativeresult in directing the same agents at the gray or cortical substance”.

The vivisections of Magendie3 led to the same results.In the following we will discuss in detail the rather similar

sounding conclusions of Flourens, which are based on results ofdissections and resections.

1525-5050/$ - see front matter � 2009 Published by Elsevier Inc.doi:10.1016/j.yebeh.2009.03.001

q This article has been reprinted with permission from NIH-92-85, Arch AnatPhysiol Wissen 1870;37:300–332. Translations provided by Ted Crump and ShariLama of the NIH Library Translations Office.

* Corresponding author.1 Reports on the sensory and irritable nature of the animal body. Lausanne,

1756;l:201ff[Fr.].2 Anatomy and physiology of the nervous system of humans and vertebrate

animals. Paris, 1842;1:644 and elsewhere[Fr.].3 Lectures on the functions and diseases of the nervous system. Paris, 1839; 1:175

and elsewhere[Fr.].

Matteucci4 also found the cerebrum and cerebellum of the rabbitcompletely unresponsive to electric excitation.

Van Deen,5 whose name has recently been linked to the doc-trine of the unexcitability of the cerebrospinal center, went stillconsiderably farther in his conclusions than all experimenters be-fore him and most after him. While earlier the property of irritabil-ity was attributed to at least some basal parts of the brain, inaddition to the spinal cord, he completely disputed it for the entireCNS on the basis of his at best inadequately described experimentson the rabbit.

Likewise, Eduard Weber6 in experiments with the rotation appa-ratus on the cerebrum of frogs saw no appearance of muscle twitches.

Budge,7 who also sacrificed an extremely large number of mam-mals, apart from many other similarly sounding passages, expresseshimself thusly:

‘‘If in accord with the current viewpoints of science one couldconclude that in a nerve section in which after a excitation notwitches occur the motor fibers are absent, then with the greatestcertainty one could maintain that not a single fiber of such nerveswhich goes to the voluntary muscles courses through the hemi-spheres of the cerebrum. Not one single observer saw movementof such muscles after excitation of the named central parts”.

Finally we present the opinion of Schiff,8 one of the most expe-rienced vivisectionists: ‘‘According to the statements of many inves-tigators, I can confirm that excitation of the brain lobes, the corpusstriatum, and the cerebellum produces no trace of twitching in allfree muscles of the body. Also the intestinal viscera remain quietduring excitation of these parts when I maintained the circulation,as is indispensable in such experiments”.

One can see that there can hardly be any question, even in an-other science besides physiology, about which the views sound soin accord, and which appears so completely resolved, as the ques-tion of the excitability of the cerebral hemispheres. Moreover, itwould be an easy matter to pile up more citations which readsimilarly, if this would serve any purpose.

As far as we know, only one author in addition to Haller and Zinnhas seen anything different, and his statement evoked so little beliefin Eckhard,9 who cites the fact, that he does not give the name andsource. The passage in question reads as follows: ‘‘It has been claimed

4 Treatise on the electrophysiologic phenomena in animals. Paris, 1843:242[Fr.].5 MoIeschott’s studies, etc. vols. 7, 2, 4:381[Ger.].6 R. Wagner’s concise dictionary of physiology. 3(2):16[Ger.].7 Studies of the nervous system. Frankfurt/M, 1842;2:84[Ger.].8 Textbook on human physiology. 1858-59; 1:362[Ger.].9 Experimental physiology of the nervous system. Giessen, 1867:157[Ger.].

124 Classics in Epilepsy and Behavior / Epilepsy & Behavior 15 (2009) 123–130

that lively movements of the forelegs have been seen during layer-by-layer resection of the frontal lobes of the brain”. In and of itselfthis is admittedly not much; for one cannot see from this how theexperiment was set up. If, however, it is presented with the necessaryreservations, then it would prove an important principle, the princi-ple that with one kind of excitation or another, be it that of thescalpel, or that of oxygen, or that of blood, from the frontal lobesmovement of the voluntary muscles can be induced. In any event, thissingle observation does not seem to have been followed any fartherby anyone; for this passage in Eckhard is the only trace left of it.

Before we turn to our own experiments it is necessary to pres-ent the view of the motor processes in the central organs whichgrew up following the above-mentioned experiments and thefamous brain resections of Fleurens.10

This ingenious and lucky researcher was able, with the use ofthe purest methods possible, to arrive at results that deserve tobe regarded as the basis for almost all knowledge in this area thatwas acquired later.

After numerous resections of the cerebrum, which were mostlyundertaken on birds, but also on mammals, Flourens saw all signs ofthe will and consciousness of sensations extinguished; neverthe-less, by excitations penetrating from outside only very mechanicalmovements in all muscles of the body could be induced. Such ani-mals stand well on their feet, run when one prods them, birds flywhen they are tossed into the air, they defend themselves whenthey are teased, they swallow objects placed in their mouth, andalso contract the iris when light is directed into their eyes.However, such movements never appear without the effect of anexternal excitation. Animals robbed of the cerebrum always sit asif sunken in themselves, as if sleeping, and nothing can be changedin this status even if after starving they are placed on a heap of food.

Flourens concluded from this that the cerebral hemispheres arenot the site of the direct principle (principe immédiat) of the musclemovements, but must be the only site of the will and sensations.11

As satisfactory as this series of experiments and the conclusionsdrawn from them may seem, just as little can the further resultsand conclusions now to be presented be harmonized with findingsobtained in other ways.

If Flourens’ animals only bore one hemisphere, they were in factblind in the eye of the opposite side, but they retained theircomplete will power over all voluntary muscles, and after over-coming a weakness of the opposite half of the body, they in noway differed from animals that were not mutilated. Moreover, ifhe resected the cerebrum of other animals layer-by-layer, whetherfrom front to back or from back to front, rather from top to bottomor from outside to inside, under all these conditions he noted aneven general decline of sensory perceptions and will. However, ifwe went past a certain boundary, suddenly all these propertiesattributed to the mind were extinguished all at once, and theanimal sank into the described dream-like state.

Moreover, if he held within a certain boundary with the resec-tion, then the animal within a few days recovered the lost capacitiesand then could continue to exist for a long time with the same men-tal properties as if it had never lost anything from its brain sub-stance. Flourens concluded from this,12 that the lobes of the brainstep in with their entire mass for the unconstricted exercise of theirfunctions, and that there is no separate site either for the variouscapacities of the various perceptions. He further concluded, in contra-diction to the first conclusion, that a portion of the hemispheres leftbehind can recover the complete use of all functions.

Most striking of all experiments carried out, however, is that de-scribed in the place cited, p. 101 under II. Here Flourens clearly had

10 Experimental research on the properties and functions of the nervous system invertebrate animals. 2nd ed., Paris, 1842[Fr.].

11 loc cit.:35[Ger.].12 loc cit.:99, 101[Ger.].

resected the entire accessible cerebral cortex of a pigeon, that is,the ganglionic part, the part which is customarily regarded asessential and harboring the primary tools of the mind. This pigeonbegan to exercise all its mental functions again starting on the 3rdday, and on the 6th day it had recovered everything that hadappeared taken away by the operation. Nevertheless, these exper-iments or their applicability have been little used on higheranimals, and Schiff13 refers to this in the same sense; even if thisresearcher points out the differences in structure and functionbetween human and animal brains.

Therefore, according to these and later only reinforcing investi-gations, approximately the following viewpoint can be formedabout the central elements of muscle movement:

In most parts of the brain stem, then also downward into thespinal cord, there are a number of preformed mechanisms, whichare capable of a normal excitation throughout their entirety alongtwo pathways. One runs from the periphery outward-the pathwayof the reflex; the other radiates from the center – the pathway ofthe will, of the mental impulses. This center conceivably lies inthe ganglionic substance of the cerebral hemispheres, withoutthe individual parts of the mental being localized on the individualparts of the organic center. However, its research, the research ofthe most likely site, or even of the primary tools of the mindremains closed to us for the moment, since the substrate doesnot respond to the stimuli coming to us with any apparent reac-tion.14 Whatever might be brought against these views from the sideof clinical observation was soon dismissed with the often not unjus-tified reference to the sparseness and ambiguity of the sections andto the simplicity and transparency of the vivisections. Finally cases ofcongenital or acquired defect of individual parts of the brain withoutcorresponding disorder of cerebral functions were used asevidence of how insignificant the brain is to life.

These views were only gradually modified in limited areas evenby a number of well-ascertained facts that were predetermined byother circumstances. For a long time (1825) it has been knownfrom Bouillaud that the symptom complex now called aphasiacan be determined by destruction of a small eccentric part of thecerebrum. Recently numerous authors have contributed to a moreprecise definition of this thesis. Moreover, there exists a notinsignificant number of cases in the literature which intra vitamexhibited paralysis of an arm, even of a leg, and on section smalldisorganizations of the cerebrum. Unfortunately one cannot seefrom Andral’s15 sums drawn from his well-known compilationhow many of these cases pertain to the cerebrum itself and howmany to its large ganglia. Nevertheless, one must completely concurwith what he says at the end of this discussion:

‘‘How can we not conclude that in the present state of scienceone still cannot assign a distinct site in the brain to the movementsof the upper and lower extremities? Without a doubt such a siteexists, since each of these limbs can be paralyzed singly, but westill do not know the point”.

One could add to this that one would have to exclude fromconsideration cases involving the corpus striatum and the opticthalamus as soon as one wished to apply these statistics for deter-mination of the first origin site of the lost movement, since in thesetwo large ganglia conduction pathways from the hemispheres tothe periphery are already laid down. Such facts neverthelessindicate that the origin of at least individual mental functions islinked to circumscribed parts of the brain. Goltz came to the sameconclusion in that in a frog whose cerebrum he had extirpated hecould still demonstrate a remainder of intelligence harbored in thecorpora quadrigemina.

13 loc cit.:336[Ger.].14 In this respect see the latest textbooks of physiology by Ranke, Grundziige, etc., p.

750ff; – L. Hermann. Outline, 3rd ed., 1870:426 and 436, etc.[Ger.].15 Clin Med Paris 1834;5:357ff.

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The only person to take a viewpoint thoroughly different fromthe dominant view was Meynert, who based it on anatomic studieswhose possibility was doubted by many. According to him, in anyevent the cerebral cortex considered as the focus of ideas disinte-grates in many less circumscribed areas, whose importance forthe individual types of ideas is determined by the nerve fibers ofthe so-called projection system which run into its ganglion cells.

In the meantime, the premises for many of the conclusions to bedrawn from the basic properties of the cerebrum are not inconse-quentially changed by the results of our own studies.

The point of departure for these studies consisted of observa-tions which one of us had many occasions to make on humansubjects,16 and which involved the first observed movements of vol-untary muscles induced by direct excitation of the central organs inman. The investigator found that by passing a constant galvanic cur-rent through the posterior part of the head, one could easily obtainmovements of the eyes, which, judging by their nature, could onlyhave been triggered by direct excitation of cerebral centers. Inas-much as these movements only appear with galvanization of thatarea of the head, one could regard them as caused by excitation ofthe corpora quadrigemina, which many things indicate, or of adja-cent parts. Since, however, in the use of certain manipulations whichincrease excitability, such eye movements are also seen in galvaniza-tion through the temporal region, the question arose whether in thelatter method current loops reaching to the base could be the causeof the eye movements, or whether the cerebrum in contradiction tothe general view actually possesses electrical excitability.

After a preliminary experiment by one of us involving a rabbityielded generally positive results, we chose the following directionfor a definitive resolution of the latter question.

In the dogs, which were not anesthetized in the first experi-ments, but were later anesthetized, the skull was opened on themost level possible place by means of a trephine crown. Then witha bone-cutting forceps rounded in front either an entire half of theskull cap or only the part covering the frontal lobe was removed. Inmost cases after the use of one hemisphere the same procedurewas carried out with the other half of the skull cap in exactly thesame way. In all these cases, however, after a dog had once bledto death from a slight injury of the longitudinal sinus, we left themedian bone bridge protecting one of these blood vessels com-pletely intact. Now the dura, which up till then had been intact,was slightly incised, grasped with the tweezers, and completelyresected as far as the bone margins. Here the dogs would expresssharp pain by crying out and characteristic reflex movements. La-ter, however, when the air irritation had exerted its effect for a longtime, the remnants of the dura mater became far more sensitive, acircumstance that must be given careful consideration in arrange-ment of excitation experiments. However, we could not irritate thepia by mechanical or any other excitation to the same degree with-out the animal showing a sign of sensitivity.

The electric excitation apparatus was arranged in the followingmanner: The pole of one chain of 10 Daniel cells ran via a commu-tator toward two terminal screws of a Pohl commutator, fromwhich the crosspiece was removed. On the two terminal screws,which faced each other, current from a secondary induction spiralflowed in on incoming conducting wires. Two wires led from themiddle pair of terminal screws to a rheostat of 0–2100 X resis-tance. The series connection continued via a Du Bois [key? (‘‘DuBoissche Schlussel”) – Tr.] to two small, isolated, roller-shaped ter-minal screws, which on the other side bore the electrodes in theform of very fine platinum wires, which in front were equippedwith a very small head. These platinum wires ran through two cork

16 Hitzig. Galvanic dizziness sensations and a new method of galvanic excitation ofthe eye muscles. Proceedings of the Berlin Medical Society, January 19, 1870 in Berlin.In: Berl Klin Wochenschr 1870;(11). An extensive treatment will follow shortly.

pieces whose front portions they bored through, not parallel toeach other, but rather at a small angle, so that the distance be-tween the heads could be rapidly changed with a light push. As arule, this distance was approximately 2–3 mm. It was necessaryto give the platinum wires only very little mechanical resistanceand the heads, since otherwise every uncertainty of the hand, eventhe respiration movements of the brain, could immediately lead toinjuries of the white mass of the central organ.

The chain that was used consisted of Siemens-Halske cardboardelements which, according to an earlier experiment, did not havethe full electromotor strength of a Daniel cell, and each had a resis-tance of approximately 5 X. As a rule, the resistance of the bypasswas low, namely measured at 30–40 X. The current strength there-by was so low that metallic closure only caused a tactile sensationon the tongue, which was touched by the heads. Considerably high-er current strengths, as well as the exclusion of the bypass, wereused only for control experiments. In the much more rarely under-taken excitation experiments with the induction current, the resis-tance of the bypass naturally depended on the spiral position ineach case. For most of the experiments we likewise used a currentwhich just barely produced a tactile sensation on the tongue.

With the use of this method we arrived at the following results,which we present as the outcome of a very large number of exper-iments on dogs’ brains that for the most part coincided down tominute details, without having to describe all these experimentsthemselves. Given the precise description of the method and takinginto account the elements to be mentioned in the following, thereproduction of our experiments is in any event so easy that con-firmations will not be long in coming.

Part of the convexity of the dog cerebrum is motor (this expres-sion is used in Schiff’s sense), another part is not motor.

Generally expressed, the motor part lies more forward, the non-motor part toward the back. By electric excitation of the motor partone obtains combined muscle contractions of the opposite half ofthe body.

These muscle contractions can be localized in certain narrowlylimited muscle groups with the use of very weak currents. Withstronger currents and excitation of the same or very adjoiningareas, muscles of the corresponding side of the body also immedi-ately become involved. The possibility of isolated excitation of acircumscribed muscle group when very weak currents are used istherefore limited to very small places, which for the purposes ofbrevity we shall call centers. Very slight displacement of the elec-trodes as a rule sets the same extremity in motion; if, however,first stretching comes about, for example, then the displacementresults in flexion or rotation. We found the parts lying betweenwhat we have called centers of the brain surface to be unexcitablewith the described excitation method and with the use of the min-imal current strength. However, if we increased the distance be-tween the two electrodes or increased the current strength, thentwitches could be induced; but these muscle contractions involvethe entire body in such a manner that not once could it be decidedwhether they were unilateral or bilateral.

In the dog the locality of the centers, which will soon be desig-nated more precisely, was very constant. At first there were somedifficulties in precise determination of this fact. However, we elim-inated them by first seeking those which produced the strongesttwitching of the affected group at the lowest current strengthwhich was still exciting. Then we sank a pin between the two elec-trodes in the brain of the still living animal, and, after removal ofthe brain, compared the individual points so marked with thoseof the alcohol preparations of earlier experiments. However con-stantly the same centers are similar can be best seen from the factthat we repeatedly were able to find the desired center withoutfurther opening of the skull in the midpoint of a single applied tre-phine crown. After resection of the dura, the muscles dependent on

19 We intentionally avoid the designation by lobes, since in the dog neither does a

126 Classics in Epilepsy and Behavior / Epilep

it twitched with the same certainty as if the entire hemisphere hadbeen exposed. In the beginning admittedly we had great difficultieseven with an entirely free operation field. For even if, as is known,the individual gyri of the brain are very constant, still their devel-opment in its individual parts and its stratification exhibits verysignificant differences. Therefore, rather as a rule than an excep-tion, it is found that the corresponding gyri of the two hemispheresof the same animal are formed differently in individual parts.Moreover, on the one hand sometimes the more medial parts ofthe convexity are more developed, and another time it is the partswhich lie farther forward or to the rear.17 If one adds to this thenecessity to leave the brain in its coverings for a not inconsiderabledistance, as well as the darkening of the picture by the vessel distri-bution, which each time makes an area unclear, but mostly the gyri,then even if it is easy now, one does not wonder at the difficulty thatwe first encountered.

Moreover, in order to facilitate reproduction of our experiments,we give the following more precise data on the locality of the individ-ual motor centers, wherein we follow the nomenclature of Owen.18

The center for the neck muscles (see D of the illustration) lies inthe middle of the prefrontal gyrus, there where the surface of thisgyrus assumes the steep downward decline of this gyrus. The out-ermost end of the postfrontal gyrus harbors the center for theextensors and adductors of the forepaw in the end region of thefrontal fissure (see + of the illustration). Somewhat toward theback from there and nearer the coronary fissure, (see + of the illus-tration) lie the central areas that are responsible for flexion androtation of the limb. The site for the hind leg (see # of illustration)is likewise to be found in the postfrontal gyrus, but mediad fromthe site for the front leg and somewhat more toward the rear.The facial nerve (see �o of the illustration) is innervated from themiddle part of the supersylvian gyrus. The affected area frequentlyexceeds 0.5 cm in extent, and extends forward and backward fromthe main flexure above the sylvian gyrus

17 On this point see also Reichert. The structure of the human brain. Leipzig,1861;2:77.

18 On the anatomy of vertebrates. London, 1868;3:118.

We must add that in not all cases was it possible to put the neckmuscles in motion from the first-named site. We did in fact often

.

enough cause muscles of the back, tail, and abdomen to contractfrom points lying between those illustrated, however a circum-script site from which the contraction could be induced in isolationcould not be determined with certainty. We also found the entirepart of the convexity19 lying to the rear of the facial nerve centerto be absolutely unresponsive to quite disproportionate currentintensities. Even when the bypass was excluded, that is in the effectof a current from 10 Daniel cells, no muscle twitches resulted.

The nature of the twitches brought about by excitation of thesemotor centers varies, depending on the type of excitation. Excita-tion by means of a simple metallic closure of the iterative currentproduces only a simple, rather rapidly passing twitch. If, instead ofclosing the chain in its metal part, this was done by placing theelectrodes, then one would only need greater current strengthsto achieve the same effect. Therefore, the law of Bois-Raymondholds true here as well. The metallic inflection always produces agreater excitation effect than simple closure, without, however,two twitches occurring (the second for the opening). Not infre-quently, however, in this type of excitation tetany of the affectedmuscle groups also occurs, namely if the toe flexors are involved,although other excitatory elements do not enter in. If one electrodehas first exerted its effect, even if for only a short time, then imme-diately afterward the other electrode on the same spot brings agreater excitatory effect than it previously could have or will beable to do shortly thereafter.

While this entirely coincides with that which we know of theproperties of the peripheral nerves, for reasons that will soon be gi-ven, we must not fail to briefly call attention to an excitation ele-ment deviating from this and of the highest physiologic interest.This has to do with a constant predominance [? – text obscured,Tr.] of the anode. It even seems as if within the minimal currentstrength only the anode triggers the twitches. To establish thispoint, first of all because its knowledge is very necessary for facil-itating the study, we performed and often repeated the followingexperiments.

(1) With the usual distance of the electrodes from each other,the place was sought from which one could induce twitches withthe minimal current strength, and in order to proceed with utmostcertainty, first the circuit was metallically closed. Thereupon withopen chain the current was applied without the electrodes chang-ing their place and closing anew. Now the twitch did not occur. Ifnow the circuit was opened again, used, and closed, then the excit-atory effect was somewhat greater than in the first closures. Thiscan be repeated as many times as desired. If now one or the otherof the electrodes loses its place during repeat closures of the chain,then this could be the cathode, without interrupting the excitatoryeffect. The anode, however, may not be far removed from the exci-tation point without quiet or twitches appearing in other musclegroups.

(2) The anode lies on the extensor center, the cathode on theflexure center, for the frontal extremities. Closure producedstretching, turning – (with a closed chain) flexure, turning–stretch-ing, turning – flexure, and so forth. Therefore, each time the centercorresponding to the anode was excited.

In view of recent physiologic studies, we are quite tempted tolink observations of chemical processes during nerve activity tothese facts. However, we prefer to let this go for now. The new factsthat revealed themselves to us in this study are so multifaceted,and their consequences extend in so many directions, that for

sy & Behavior 15 (2009) 123–130

clear lobe formation exist, nor does anything which one could regard as such, whichcorresponds to the human brain lobes in location, finally also because thus far wepractically have no idea which parts of the dog are adequate to regard as certain partsof the human.

21 Moreover, it must not be superfluous for this or that reader to note that amongthe many physicians to whom we have demonstrated our experiments, there wereseveral who were very competent specialists in this very field, e.g., Prof. Nasse(Marburg) and Munk (Berlin).

Classics in Epilepsy and Behavior / Epilepsy & Behavior 15 (2009) 123–130 127

the matter at hand it would certainly be of little advantage to wan-der down all these pathways, which require detailed research, inone attempt.

Here we must also add that with a somewhat longer [chaincircuit? (‘‘Kettenschliessung”) – Tr.] the more strongly exciting ef-fect of the change of electrodes also is expressed in the followingmanner. If we produced a twitch because the anode was locatedon a center and the cathode on one of the indifferent sites withthe current strength applied, and we left the chain closed some-what longer, then sometimes after a previous opening the closureof the current applied induces a single twitch, very rarely a twitchwith one repetition. This means that after somewhat longer effectof the anode the central nerve substance reacts for a short timeeven with minimal currents to the cathode as well. For severalreasons one must use only very weak currents for this experiment,namely also because stronger currents immediately destroy thesubstance by electrolysis.

In excitation with tetanizing induction currents the excitatoryeffects by their nature are not quite so constant. Frequently toniccontractions of the muscle masses involved appear, which onlysubside in their intensity after a long time. Frequently an initialcontraction maximum is present, which after a second-long dura-tion of the current is followed by such a substantial diminishmentthat one could regard the contraction as entirely extinguished, if atthe moment of the opening a slight movement in the sense ofdiminished contraction did not take place. The individuality ofthe experimental animal – its greater or lesser excitability – seemsto be in a causal relationship to these variances as well as to somephenomena that will be mentioned shortly.

With continued use of stronger currents, symptoms of exhaus-tion appear – the requirement for stronger currents to achieve thesame effect, even complete absence of twitches. Very often bloodysuffusions of the cortical substance come about. More frequently,however, one namely observes a number of phenomena even afterweak currents, which must be explained in the opposite sense.

Eduard Weber20 has already stated that after the opening of acurrent that had tetanized the spinal cord of a frog, subsequentmovements appeared in all muscles of the body. This fact seems tohave fallen into total obscurity. At least we might believe that other-wise it could have been used as an argument by the defenders of theexcitability of the spinal cord.

One can find something quite similar after tetanization of thebrain substance. Even after an excitation of a few seconds induration, follow-up movements appear in the dependent muscula-ture, which in the area of the facial nerve take on a tremorous char-acter. The extremities show more the picture of clonic convulsions– differences which in any event are dependent on the differenttype of muscle attachment. These local seizures can have multiplerepetitions, even if the brain is left undisturbed. In individual casesthey also appear after mishandling of the brain substance with clo-sures of the chain circuit. As a rule, however, they are not observedafter excitation with these currents. In two of our experimentalanimals completely characteristic epileptic seizures formed fromthese follow-up movements. The seizure began unilaterally withtwitches in the previously excited musculature, then spread to allmuscles of the body, so that a complete extension tetany cameabout. The pupils thereby were dilated to the maximum. One ofthe animals had two such attacks, the other three. One could objectthat the dogs had been epileptic even earlier. One of the dogs, how-ever, had been with the same master for 6 years, and had neversuffered from seizures. The antecedents of the other remainunknown.

We now turn to refutation of the objections that have beenraised against our experiments.

20 R. Wagner’s Concise dictionary of physiology. 3(2):15.

The first objection, that in electric excitation experiments isalways raised by experts21 and non-experts, is based on the currentloops, which could have been included in the removed parts. Thisobjection, if we dispense with the question of whether the corticesor medullary substance of the cerebrum are excitable, is easier thanany other to eliminate. For one thing, the currents that we used forthe conclusive experiments were entirely too weak. Since, however,the substance of the brain has very great resistance, and moreover,other conductive parts were not nearby, and finally because the dis-tance of the electrodes one from the other was very small, accordingto the laws of current distribution in non-prismatic conductors, thecurrent density at a very small distance from the influx site could beonly very minimal. This would already a priori sufficiently refute thequestionable objection. However, we also have a whole series of di-rect proofs. If the current loops should first make their way to theperipheral nerves, then the nerves of the side with the same namewould always lie nearer, and they would not have the remotest rea-son to exclusively betake themselves to the other side. Moreover, themotor ocular nerves of the same side would lie much nearer to themthan any other nerves that might come under consideration. Theeyeball, which is so movable, so balanced in a labile equilibrium,without requiring any preparation makes up the most preferablephysiologic rheoscope, it would move much more readily, even withminimal current loops, than a forelimb, to say nothing of a hindlimb.However, on the entire convexity, insofar as one can expose it, thereis not a single place from which one can induce a movement of theeyeball, even with current stronger than we are accustomed to using.Herewith a part of the question which prompted one of us to do thisstudy is taken care of.

Finally we present a fact of high physiologic and pathologicinterest. It is the fact that with exsanguination the excitability ofthe brain sinks with enormous rapidity, and is almost extinguishedeven before death.

Directly after death it is also immediately and totally lostagainst the strongest currents, while muscles and nerves still reactsuperbly. This seems to require us to undertake experiments on theexcitability of the central organs in undisturbed circulation.

Secondly, one could infer that brain provinces other than thelarge hemispheres would be affected by the current loops, if notthe peripheral nerves or the spinal cord, of which exactly the samecould be said [as of the central organs]. If this is so, then thedemonstration of electric excitability of other brain provinceswould be an important finding. For even for most of them it is to-day generally asserted that they are inaccessible to direct excita-tion. However, this is not so, as can be demonstrated for theelectric excitation itself. Those parts whose excitability could besubstantiated at all, even if by few investigators, are the posteriorpart (cauda) of the corpus striatum, optic thalamus, crus cerebri,corpora quadrigemina, and pons. If for the moment we leave thecorpus striatum out of consideration, then all other mentionedmorphologic components of the brain lie so far posteriorally thatin frontal sections they must all be first encountered if one worksbackwards through the no longer reacting parts of the cerebrum.The only exception is the corpus striatum, whose cauda likewiselies in the region of the unexcitable22 zone. It would also be possiblethat specifically the anterior or middle portion of this ganglion, thepart which is supposed to be unexcitable, is excitable, and wouldbe the site of origin of our excitation effects. From the very beginningthe latter would already be improbable because with the same cur-rent strength the twitches already ceased as soon as the electrodes

22 Here without prejudice we call unexcitable all those areas from which twitchescan no longer be induced

24 One of us (Hitzig) has observed such a case during his service as medical directorof the general military hospital in Berlin in 1866. A grenade shard had buried itselfdirectly in the glabella of a soldier (Angelmeier), and there had made a triangularhole. Out of this hole there was a constant flow of brain substance for at least 14 days.Finally the wound healed by itself. This patient was not very brilliant, on the contrary,he appeared to be slow-witted. Inasmuch as no one had known him before the

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changed their location by a few millimeters. For if one draws straightlines through the two suspected influx sites and a point lying per-pendicular beneath their connecting line in the corpus striatum,one obtains an equilateral triangle whose equal sides would yieldto circuits of the slightest resistance. Since the resistance of bothmust be approximately the same, all else being equal, the excitatoryeffect must also be the same, which is not the case.

Not satisfied with this a priori proof, even if it is convincing,we set upon the path of direct demonstration. For this purposewe gave Carlsbad insect pins a dense isolating sheath by repeat-edly immersing them in a solution of gutta percha in chloroform.Only the tip and the head were left conductive. Then if we sankthese pins into the posterior part of the cerebrum, even with infi-nitely stronger currents we obtained no trace of a twitch until the[rheophores? (Rheophoren) – Tr.] that were embedded several cmdeep touched the crus cerebri. Then, however, the animal made aviolent leap and its muscles shook overall. There was a differenteffect if in the same manner the frontal half of the brain was ex-cited. If one were to assume that current loops reaching as far asthe corpus striatum brought about the twitches that appear withsuperficial excitation, then the latter would have had to graduallyintensify as the electrodes were stuck in. However, this was notthe case, rather the twitches extended to other muscles and gen-erally exhibited a different behavior, about which we will notnow go into detail. Accordingly, one can assume with certaintythat neither the named ganglion nor the structures comprisingthe brain stem were involved in the twitches originating fromthe convexity.

Another objection that could be raised and which has beenraised against all earlier successful excitation experiments on thecentral organs (spinal cord, brain stem), would base itself on thereflex origin of the contractions. This objection as well can be de-fused by convincing proofs.

Reflexes could be triggered by the nerves of the dura and piamater, for we were protected from excitations of the adjoiningnerves of the skull cap by extensive exposure of the brain surface.Moreover, the partially detached temporal muscle mass lay on oneof the wound margins. This structure, which certainly retained itsexcitability, would have let us know immediately of even weakcurrent loops. However, no sensory fibers in the cerebrum itselfhave yet been demonstrated or even assumed. Also the wholeinsensitivity of its substance does not provide the slightest reasonfor such an assumption.

As regards the dura, we have already stated above23 that it has acertain sensitivity even in the physiologic state, but that this veryrapidly increases after opening of the skull cap. Therefore, it is alsorecommended that the operation be performed quickly, becauseotherwise the experimental animal, even if it is securely tied, withits violent jumping enormously complicates sparing of the brain sub-stance as this membrane is removed. However, once it has been re-moved as far as the bone margins, one is sufficiently protected fromthe reflexes of its nerves. We made sure of this in different ways. Wedid indeed first induce crossed twitches in our excitation experi-ments, while reflexes always first appeared on the same side (Pflue-ger). Second, the twitches ceased with slight change of site but withthe same distance from the remnants of the dura. Third, they evenceased when we came closer to the dura, assuming that we didnot directly encounter motor centers. Indeed, always under thelast-mentioned precondition, not once did we induce twitches ifthe electrodes stood right against the dura but still on the brain sub-stance. Fourth, if we touched the dura itself, then in many cases,even if no current was running through it, the most violent reflexmovements would occur in a highly characteristic form. These hadan entirely different appearance, however, from our other excitation

23 In accord with Longet and others.

effects. At first they always had the appearance of suitability; throw-ing back the head, contractions of the back muscles, screaming andwhimpering even under morphine anesthesia, infrequently movingthe legs. The picture of our excitation experiments was totally differ-ent. Here often even non-anesthetized animals lay unmoving andindifferent, while sometimes we induced movement of a forelimb,sometimes of a hindlimb, with electric excitation.

Admittedly the pia cannot be exposed rearward in the samemanner; on the contrary, one must deal with it as sparingly as pos-sible. For an injury to a single one of its countless, abundant vesselsfloods the operation field with blood and can defeat the entireoperation, so that the animal has been sacrificed for no purpose.However, this does not hinder the demonstration of its unimpor-tance for the coming about of our excitation effect. Apart from allthe reasons which we already presented in the discussion of thedura, the following is more than sufficient. We found the pia (asLonget and others also did) to be insensitive. We cut around itvia a motor center with sparing of the larger vessels, without theexcitation effect changing. We resectioned it on such a place –the twitches did not disappear. We stuck isolated pins into thebrain substance; even then the muscles still twitched. If this oc-curred in the area of the motor sphere, they twitched under noneof these conditions if we passed over the posterior margin of thesesphere. Moreover, it could be of interest here to include the factthat neither the morphine nor the ether anesthesia had any sub-stantial influence on the success of the experiment.

Finally one would ask how it then came about that so many ear-lier investigators, including the most brilliant names, arrived at theopposite results. Here we have only one answer: ‘‘The method cre-ates the result”. It is impossible that our predecessors could haveexposed the entire convexity, for otherwise they would have hadto obtain twitches. The posterolateral wall of the skull cap of thedog, under which in any event no motor parts lie, recommends it-self by its formation for the placement of the first trephine crown.Here the operation was probably begun and neglected to break outtoward the front, under the erroneous view that the individualfields of the surface are of the same importance. One rested onthe assumption, developed at the beginning and still widespreadtoday, of the ubiquitousness of all mental functions in all parts ofthe cerebral cortex. If one had only thought of a localization ofthe mental functions, then one would have observed the apparentunexcitability of individual parts of the substrate as somethingself-understood and not left any of its parts unexamined. For cer-tainly no previous investigator would have presupposed that wewith our excitations would awaken images or would be able tocause awakened images in a vivisectioned animal to evidencethemselves.

This leads us to a discussion of one question which, howeverunjustifiably, has been directed toward us. We could be calledupon to explain the observations that in a sufficient number ofcases some kind of function is present above surgical injuries tothe brain.24 First of all, it is not even our problem to explain thisapparent contradiction. For before this obligation falls to us, onemust demonstrate to us that specifically the parts about which weare talking were injured or lost – possibly a difficult undertaking.However, neither we nor anyone else knows anything more preciseabout other parts of the convexity; perhaps apart from that which isknown about the third frontal gyrus, and that speaks directly for us.

wounding, it could not be decided whether he was mentally deficient by nature. Inany event, he presented with no gross motor or sensory disturbances.

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As we have said, the contradiction is only apparent, the parts of thecerebrum are not of the same importance.

Furthermore, it seems to us very appropriate to recall the fol-lowing observation of Griesinger, which is completely fitting onthis point.25 ‘‘Many objections can be raised against most of theseobservations. In almost all cases only the intelligence is consideredin the narrower sense, the emotional makeup and state of the willare left totally out of consideration, and also usually only the slight-est demands are made of the intelligence, e.g., the answering of sim-ple questions from the doctor, in order to declare it unimpaired. Innone of these observations has the intelligence been examined inits full extent, and in many of them, namely in all hospital observa-tions, a comparison of the mental state after the disease or the loss ofsubstance with the earlier state was absolutely impossible, etc.”.

Here Griesinger, as his material demands, has only the mentalstate in mind. Exactly that which he demands of research on thecondition of the mind we can promote with even greater justifica-tion with respect to somatic functions. Where are the studies ofmuscle properties or the qualities of the sense of taste, whichwould specifically be more appropriate here, than in many otherplaces, where they, a scientific humbug, only serve to throw sandin the eyes of the harmless reader! How well-founded our require-ment is can be shown by a few experiments, of which we willspeak in the following.

If we now look at the results thus far of our experiments and askourselves what has been achieved with them by way of knowledgeof the properties of the central organ, then we have the duty to dif-ferentiate between what can be concluded to be certain and whathas only been shown to be probable.

We can term a definite gain the unquestionably proven fact,reproducible at any time, that central nervous structures also ini-tially respond to our excitations with a reaction that is evident.This alone would have had a significant importance for physiology,insofar as therewith the contradiction in the definition is elimi-nated, which Fick recently pointed out with justification, and towhich the beginning of this paper is linked.

The fact is equally established that a considerable portion of thenerve masses permeating the cerebral hemispheres, one can say al-most one-half, are directly linked to muscle movement, while an-other portion clearly has nothing to do with it, at least directly.As simple and self-evident as this may appear to be, it was justas little evident before. For this purpose we refer to what was saidon the occasion of the historical overview. If one spoke of such cen-ters in the brain, in more recent times only the basal parts, pons,thalami, and so on have been referred to,26 and the explanation ofthose section findings kept carefully to the most general terms pos-sible. Only a few brain anatomists, among whom Meynert should benamed, have thus far expressed themselves in a different mannerfrom Gall, for a strict localization of the individual mental faculties.

However, if we raise the question of whether the excitation ef-fects which we induced are brought about by direct action on thosecenters in the gray cortex in which the motor will impulse comesabout, or whether one must consider excitation of the medullaryfibers, or whether there is a third possibility, our answer must re-main far more reserved.

Even if we assume that the proof for triggering of the question-able movements is provided by the ganglionic substance – and it isnot – then therewith it still would not be proven that now in thosemovements which are released by an internal event, specificallythis part of the cortex provides the substrate for the first link inthe chain directed outwardly, which begins with the first coming

25 The pathology and therapy of mental diseases. 2nd ed. Stuttgart, 1861:4.26 Cf., for example, Griesinger. loc cit.:4 and many other authors, as well as

Griesinger, p. 23.

about of a sensory impression, and finds its temporary end withthe expression of the will appearing as a muscle movement.

It is rather not unthinkable, and cannot be ruled out specificallyby what we know anatomically about the anastomosing structureof these parts, that the part of the brain which includes the place ofbirth of the will for movement is still different or perhaps evensimpler, that the areas which we call centers only provide media-tors, assembly points, in which similar or more expedient arrange-ments of the muscle movements take place than in the graysubstance of the spinal cord and base of the brain. We will soonsee to what extent we have even uncovered a certain physiologicjustification to make room for this view.

Now that in this restraint we have granted the widest possiblelatitude for the purely psychologic possibilities, and we emphati-cally emphasize this, we will turn to discussion of the questionabout the importance of the gray and white substance for the com-ing about of the excitation effects that we have described. If thequestion is posed in this form, then in part it may now alreadybe possible to answer it satisfactorily. If, however, instead of themore general concept of gray and white substance, one contraststhe words fibers and cells, then the possibility of a solution has alsoshown itself. For inasmuch as fibers and cells mix inseparably inthe gray substance, an isolated study of the individual morphologiccomponents cannot be carried out. Therefore, even if the directproof of the excitability for the gray substance could also have beencarried out, one would still always have been able to object that itis not the ganglion cells, rather the nerve fibers running betweenthem, which would provide this substance with the actual excitedpart. For the moment the question is whether by means of theexperiments presented above with insertion of isolated pins wehave sufficiently proven the excitability of the medullary sub-stance. Since the essential nervous components of the medullarysubstance – the nerve fibers-continue with the same anatomicproperties into the cortical substance, there is no reason to assumea substantial change of their physiologic properties rather thanthat their anatomic continuity is interrupted by new structures.For this reason the excitability of part of the fibers, as well as ofthe cortex, is correctly assumed. Whether only these alone, orwhether the cells are also excitable, as we have said, cannot bedecided with sufficient certainty with the means available thus far.

Nevertheless, in an indirect way a somewhat probable con-clusion can be drawn about the function, even if not aboutthe excitability, of the cellular part of the cortex. We saw indescription of our experiments that muscle contractions onlyappear in response to the minimal current strengths if the elec-trodes are found in very definite places, and that they cease orappear in other muscles if the electrodes are moved from theintended places even by a little. This behavior allows for twopossibilities. Either the excitation is taken up by the ganglioncells lying in the immediate vicinity of the electrodes and con-verted into muscle movement, or excitable medullary fibers ap-pear on the surface specifically at these sites, so that they areparticularly favorably placed for the excitation. Since no otherreason can be recognized why the questionable medullary fibersshould approach nearest to the ganglion cells specifically here,other than it is their fate to strive toward them, one can nev-ertheless assume that specifically those ganglionic masses aremeant for production of organic excitations for specificallythose nerve fibers.

Whether now a certain usually collaborating sum of these or-ganic excitations brings forth exactly the same expression ofmovement as our electrical excitation, cannot be conclusivelydecided with the methods that have been used thus far. Forthe simple doctrine of the specific energies does not suffice here,we must rather develop a new viewpoint for the new facts thathave been discovered. Here we do not have nerve fibers which

27 The second dog is not referred to here, inasmuch as for experimental reasons it

130 Classics in Epilepsy and Behavior / Epilepsy & Behavior 15 (2009) 123–130

run a direct route to the end organ, but rather that fibers origi-nating from the most central part of the cerebrum can get there,after first passing through a number of more and more peripheralstations in which their released resilience is transformed in a cer-tain way that is not more precisely known to form what we callpurposive movement. It is self-explanatory that by means of anexcitation applied at some point along this pathway at the mostwe can only demonstrate what tends to happen in the moreperipheral stretches and the more peripheral stations, while thefunctions of the more central stations avoid observation. Eventhis can only be expressed with a certain reservation, insofar asexcitation of a greater sum of fibers is required to bring abouta certain movement modality, which nevertheless do not lie socomfortably together in the central organs as in the stem of aperipheral nerve. However, there is another way to solve thequestion of the importance of the individual parts of the cortexexperimentally; this is the extirpation of circumscript and exactlyknown parts of it. We have also begun to take this tiresome pathin the following manner.

In two dogs, after the soft tissue was pulled back, the skullwas opened with a trephine crown at the site where believedthe center for the right foreleg to be. We chose the center foran extremity because at such a center any motor phenomenamust appear most clearly, and we did not choose the centerfor the hindleg, because its position possibly would have inter-rupted our opening of the longitudinal sinus. Thereupon thedura was removed from the exposed site, it was establishedby electric excitation that we had struck the desired spot, thepia was cut around as far as necessary, and then with a finescalpel handle it was slightly lifted up from the cortical sub-stance. In one case the removed piece was approximately thesize of a small lens, in the other case somewhat larger. Thenthe cutaneous wound was closed with button sutures. In thefirst case the animal lost only a few drops of blood in the entireoperation, in the other case the bleeding was not inconsiderable.The first case healed by first intention, the other case did not.Both experimental animals, however, presented with differentsymptoms only by degree. With respect to type their clinicalpicture with respect to motor disorders conformed as much aspossible. This complete correspondence of the results of bothexperiments and its importance for all viewpoints originatingfrom our other experiments prompted us to refer to it here,although we would have gladly collected still more similar re-sults for some kind of publication. The necessity to give thiswork a temporary conclusion has thus far hindered us in this,and moreover, we will see that for the conclusions that we havedrawn ad hoc even a single successful experiment is adequate.

Both experimental animals immediately after the operationundertaken with morphine anesthesia exhibited a certain generalweakness, which quickly passed. Then, however, the followingwas observed:

(I) When walking the animals placed the right forefoot inap-propriately, sometimes more toward the inside, sometimesmore toward the outside than the other, and slid slightly out-ward with this foot, which never happened with the other, sothat the animal fell to the ground. No movement was com-pletely absent, however the right leg was moved somewhatmore weakly.(II) When standing there were very similar phenomena. More-over, it occurred that the forepaw was always set down withthe back rather than the sole, without the dog noticing it.(III) When sitting on the hindquarters, if both forepaws wereplaced on the ground, the right foreleg slipped gradually out-ward until the dog lay completely on its right side.

Under all circumstances, however, it can immediately correct it-self. The skin sensitivity and the sensitivity to deep pressure exhib-ited no demonstrable deviations on the right forepaw.

The outcome of the following experiment, carried out with thefirst dog27 at a time when the wound had long been healed and allreactions had ceased, on the 15th and even on the 28th day afterthe operation, was most striking

While the dog was standing, we placed the front, upper edge ofits right forefoot inward and back, so that it lay between the other3 legs. Now if we hindered the dog from changing positions by pet-ting it, it would leave its paw in this uncomfortable position for anylength of time. However, if a movement impulse came over thedog, it would run away, moving its ailing leg with almost as muchliveliness as the other three. The same experiment could not beperformed at all with the left leg, inasmuch as the animal wouldalways pull the limb back and bring it in its earlier comfortableposition before one could place it in the desired position.

Here we will spare ourselves all further conclusions and obser-vations, namely certain comparisons to human pathology, foranother occasion, and we will only ascertain the following asessential for the present paper. The two experimental animals, asa result of extirpation of a part of what we have termed the centerfor the frontal extremity, only incompletely lost the capacity tomove the latter, and the sensitivity probably was not impaired atall. But they clearly had only a deficient consciousness of theconditions of this limb. The ability to form complete ideas aboutit had been lost; they therefore suffered from a symptom whichin a very similar manner occur in a form of the tabes disease group,only that the injury to a sensory conduction pathway certainly wasnot present here. In order to describe this condition in more detailone could perhaps express himself in the following way: There wassome kind of motor conduction from mind to muscle, while in theconduction from muscle to mind somehow an interruption waspresent. Possibly this interruption concerned the terminus of thehypothetical pathway for the muscular sense, in any event it hadits site at the location of the center which we injured.

However this may be, it is certain that an injury to this centeronly alters, but does not abolish, the voluntary movement of a limbthat is definitely dependent on it, that is, some kind of motor im-pulse still has other sites and pathways open to it in order to beborn and to race to the muscles of the leg, and that our reservation(see above) was completely appropriate. Further, it is also certainthat such an injury, although its importance disappears againstthe resections of Flourens, Hertwig, and others, brings forth veryclearly perceptible symptoms, if only the right location is involved;and in fact the symptoms are perceptible specifically on the samelimb whose muscles previously contracted in response to electricexcitation of the now destroyed masses.

This evidences that in the earlier colossal mutilations of thebrain either other parts were selected or that the finer perfor-mances of the motor mechanisms were not given the requiredattention. Moreover, from the sum of all our experiments, itemerges that by no means, as Flourens and most authors afterhim believed, is the mind a type of overall function of the totalityof the cerebrum, whose expression one would on the whole not beable to abolish in its individual parts by mechanical means, ratherthat certainly individual mental functions, probably all, are re-ferred to circumscript centers of the cerebral cortex for their en-trance into matter or for the coming about of matter.

Berlin, April 28, 1870.

only had three legs.