il 5T182 1 B^9 Pil / ^.s-o I ANATOMICAL, PHYLOGENETICAL AND CLINICAL STUDIES ON THE CENTRAL NERVOUS SYSTEM THE JOHNS HOPKINS UNIVERSITY, SCHOOL OF MEDICINE, LECTURES ON THE HERTER FOUNDATION, SEVENTEENTH COURSE, 1926 Anatomical, Phylogenetical AND Clinical Studies on the Central Nervous System BY B. BROUWER Professor of Clinical Neurology University of Amsterdam ^^ Iu.j|lig)^ary'' PUBLISHED FOR THE JOHNS HOPKINS UNIVERSITY BY THE WILLIAMS & WILKINS COMPANY BALTIMORE 1927 Copyright 1927 The Williams & Wilkins Company Made in United States of America Published June, 1927 Composed and Printed at the WAVERLY PRESS FOR The Williams & Wilkins Company Baltimore, Md., U. S. A. THE HERTER LECTURES ^^<^ In November, 1902, Dr. and Mrs. Christian A. Herter, of New York, gave to the Medical School of The Johns Hop- kins University the sum of $25,000 '^for the formation of a memorial lectureship designed to promote a more intimate knowledge of the researches of foreign investigators in the realm of medical science. ^^ According to the terms of the gift, some eminent worker in Physiology or Pathology is to be asked each year to deliver a lecture at the Johns Hopkins University upon a subject with which he has been identified. The selection of the lecturer is made by a committee representing the department of pathology, physiological chemistry, and clinical medicine of The Johns Hopkins University, and if ^'in the judgment of the committee it should ultimately appear desirable to open the proposed lectureship to leaders in medical research in this country there should be no bar in so doing. ^^ PUBLISHER'S ANNOUNCEMENT The earher Herter Lectures, 1904 to 1923 inclusive, have appeared in The Bulletin of the Johns Hopkins Hospital. The pubUshers plan to issue the lectures in book form. Announcement of titles will be made as each book is issued from the press. PREFACE It was to me a great honour to be invited to deliver the Herter Lectures. I am very grateful for the splendid re- ception, given me by the Medical Faculty at Baltimore, April 1926. It is not necessary to thank each of my col- leagues individually, because Johns Hopkins University is a real unit. As a representative of Dutch neurology I have given my lectures, based on the anatomy and the physiology of the nervous system. Many of us in Holland work along this line. I know that not a few of my explanations in my lectures were hypothetical and that many facts might be differently interpreted. But in preparing these Herter lectures I felt that it was not wise to limit myself to bring facts, found b}^ my research work. My American colleagues did not ask me to come to Baltimore to hear only some objective facts. They desired also to get an impression of my per- sonality. A personality is always dualistic, good and bad. This psychological fact is not always clear, but is always true. My ideas may be right or wrong, in any case they are part of my personality, for I beheve in them. B. Brouwer. University of Amsterdam 1926. CONTENTS LECTURE I The Projection of the Retina in the Brain 3 LECTURE II Pathology of Sensibility 27 LECTURE III The Significance of Phylogenetic Studies for the Neu- rologist 45 ^0^J^f THE PROJECTION OF THE RETINA IN THE BRAIN FIRST HERTER LECTURE THE PROJECTION OF THE RETINA IN THE BRAIN The subject of my first Herter lecture is the projection of the retina in the brain. Several of your scientific workers in America have given much thought to this problem. I refer, for example, to the studies of Adolf Meyer, Gushing and G. E. de Schweinitz. I like very much to speak on this subject, because this problem has attracted me very much for several years. There is however one difficulty. I must give my lecture in a language, which is not mine and which, I fear, is also not yours. I have therefore brought a number of plates and lanternshdes with me. They speak an inter- national language and hence I hope you can understand me. To introduce you to the problem I have to remind you that the experiences of the Great War have renewed our interest in the cerebral organization of the optic pathways. We have only to recall the careful investigations of Gordon Holmes and Lister in England, of Pierre Marie and Chatelin in France and of Axenfeld and others in Germany. The optic stimuli are caught by the retina, thus reaching the layer of the ganglion cells. These cells send their fibres into the brain, forming in the beginning the optic nerves. These nerves, in lower animals, wholly cross. This is so in fishes, amphibians, reptiles and in birds. It is also the case in some groups of mammals. In these classes of vertebrates, however, it is usually different. In rabbits, for instance, some of the optic fibres do not cross, but remain on the same side of the brain. In monkeys and also in men, as you know, the number of non-crossing fibres is much larger. Centuries ago Newton emphasised the fact that the optic nerves in men only partially cross in the chiasma. This was a theory he had deduced in his studyroom. His 3 4 STUDIES ON THE CENTRAL NERVOUS SYSTEM opinion was contested by several anatomists and much work had to be done before the correctness of Newton^s theory was proved. This once more demonstrates that a good theory often anticipates the facts. It depends only on the nature of the theory or, perhaps more correctly, on the quality of the brain, from which the theory issues. What is the reason why the optic nerves in higher animals, and in men, only partly cross? This depends on the posi- tion of the eyes in the head. The more frontal they are the more non-crossing fibres are present. Cats and dogs, for example, belong to the same class in the scale of evolution. In dogs the eyes stand more laterally than in cats. Experi- mental-anatomical study has proved that the number of non-crossing fibres in cats is larger than in dogs. There is still another difference in the ascending scale. I mean the development of the macula. We all know that man has a very finely organized macula. It is by this spot in the retina we can see very distinctly. A similar spot is also present in monkeys but not in rabbits and is absent in by far the largest number of vertebrates. It is also found in some animals whose sight is highly developed, for example, in many birds. The optic fibres terminate in two primary optic stations in the brain, the external geniculate body and the corpus quadrigeminum anticum. It is often asserted that there is still a third primary station, the pulvinar. Later on I shall return to this point. Fibres proceeding to the geniculate body conduct the stimuli by which conscious sight is made possible. They are spread throughout the geniculate body, where the second optic neuron begins. Its cells send their fibres by a long tract to the cortical optic centre, lying in the occipital lobe. The other optic fibres, proceeding to the midbrain, conduct stimuli, which may cause reflex movements of the eye muscles and of the pupils. For many years there have been two lines of thought as PROJECTION OF THE RETINA IN THE BRAIN 5 to how the optic fibres are spread throughout the central nervous system. The chief representatives in this field are two celebrated workers, S. E. Henschen and C. von Monakow. Henschen holds the localizations theory. In his opinion every spot of the retina has a sharp localization in the geniculate body, in the central optic radiation, as well as in the cortex. Also in his review of 1924 he holds a mathe- matical projection of the retina in the calcarine cortex. The upper half of the retina always lies dorsal in the optic path- ways, the lower half ventral. The significance of this con- ception for clinical purposes is evident. When a tumour destroys the whole cortical centre on the right side, we get a left-side hemianopsia. When a tumour only destroys the dorsal half, we get the symptom of hemianopsia inferior. Inferior because the light stimuli, which are caught by the dorsal half of the retina, come from the inferior half of the field of vision. Pathological processes in the ventral part of the calcarine cortex must cause hemianopsia in the dorsal half of the field of vision. In Henschen's opinion the macula forms no exception. It must be locahzed like an isle in the different pathways and also in the cortex. Views on the representation of the macula in the calcarine cortex have varied in his papers. Lately Henschen accepts the opinion, that the macula must be projected near the occipital pole. von Monakow and his school do not believe, that the different parts of the retina can be definitely localized in the brain. The idea of a sharp localization does not appeal to them. Above all von Monakow denies that the macula has a circumscribed localization in the brain. In his opinion an isolated representation of the macula in the central parts of the brain is anatomically impossible. The high physio- logical significance of the macula led von Monakow to put forward the theory that the impulses from this part of the retina are spread over the whole external geniculate body, 6 STUDIES ON THE CENTRAL NERVOUS SYSTEM where they may be associated with impulses from other parts of the retina. In von Monakow's view the fibres carrying macular impressions must also be scattered over a large part of the optic radiations and of the occipital lobe. This hypothesis may explain why in lesions of the optic radiations and of the occipital cortex the hemianopsia fre- quently spares the central part of the field of vision, and why in cases of hemianopsia duplex central vision often remains intact. Experiences in the Great War have led many occulists and neurologists to adopt Henschen's theory. His idea of an exact localization has come more and more to the front. Gunshots through the occipital part of the brain caused in many soldiers small circumscribed defects in their field of vision, just as might be expected according to Henschen's conception. These war cases certainly point to a certain localization, but a post-mortem examination, however, has been rarely made by these investigators. Holmes and Lister published an anatomically confirmed case of a circumscribed defect in the field of vision. A complete microscopical examination, however, has not yet appeared. To solve the problem of the cerebral organization of vision, an exact analysis has to be made of the conditions in the external geniculate body, in the occipital lobe and in the tracts between them. Even the best clinical observations without post-mortem examination cannot give sufiicient data. When older investigators of such a high level as Henschen and von Monakow could not come together, the younger generation will have to follow other lines of research. Pick and Herrenheiser, many years ago already, pointed out another way. They made small lesions in the retina of rabbits and cats and studied the secondary degenerations in the optic nerve, in the chiasma and in the optic tracts, with the help of the Marchi method. PROJECTION OF THE RETINA IN THE BRAIN 7 These investigators, however, did not examine the pro- jection of the retina in the primary optic stations themselves. Recently Lubsen published a careful research on the tectum opticum of a fish (Leuciscus rutilus) . In this animal Zeeman made small lesions in the retina and Lubsen studied the secondary degeneration in the primary optic neuron. Stimulated by their work, I have made a study in rabbits and in higher mammals. All the investigations in this sub- ject have been made along with Dr. W. P. C. Zeeman, pro- fessor of Ophthalmology at the University at Amsterdam. We have examined about sixty brains of animals and studied them with the help of the Marchi method microscopically in a complete series. Prof. Zeeman made different kinds of lesions in the retina of rabbits, cats and monkeys. To dilate the pupil atropine was dropped into the animal's eye a day and again an hour before the operation. Ether was used during the operations on the monkeys and cats, in rabbits only cocaine was administered in the eye. The eyehds were kept open by retractors and by means of an electric lamp placed on the forehead of the operator light was thrown on and into the eye of the animal. With his right hand the surgeon inserted a cataract needle with a sickle-shaped edge, through the bulbar conjunctiva about 4 mm. behind the temporal border of the cornea and then through the sclera into the vitreous. With his left hand he now placed an ophthalmo- scope lens of 20 dioptries before the eye. In this way he could distinctly see the fundus and also the point of the cataract needle in the vitreous. With his right hand he brought this needle to the part of the fundus where the lesion was to be made. In operations on the macula the blunt side of the instrument was always turned towards the centre of the macula, and after injuring the quadrant desired, the incision was if necessary enlarged centrifugally. In a very few cases the instrument had to be quickly extracted owing 8 STUDIES ON THE CENTRAL NERVOUS SYSTEM to the animal making an unexpected movement. This necessitated a second prick. These operations are easily made, provided, of course, one has not to do it oneself. After eighteen days the animal was killed. The size and exact position of the lesion was controlled by post-mortem examination. In all lesions of the macula in monkeys and in several of the peripheral retina, a microscopical examina- tion in serial sections was made. In this way we got a good oversight of the conditions in the periphery. The nervous system was treated by the Marchi method. A complete series was cut through the chiasma, the optic tracts and the primary optic stations. In several cases the peripheral nerve was also examined by this method. Our investigations were started in the Central Institute for Brain Research (Director Dr. C. U. Ariens Kappers) and have been continued in the neurological and ophthal- mological laboratories of the University of Amsterdam. In rabbits a localization of the various parts of the retina up to a certain degree is already seen in the optic nerve. The fibres coming from the ganglion cells of the dorsal half of the retina are situated more dorsally in the optic nerve than those of the ventral part. The fibres issuing in the nasal part of the retina proceed medially from those of the temporal part. This locaHzation is, how- ever, not an absolute one in the optic nerve. One can find fibres of various quadrants mixed together. It is very difficult to show a special localization in the chiasma of the rabbits. This is easier in the optic tract. We have found that the upper quadrants of the retina send their fibres through the ventro-medial part of the optic tract and the lower quadrants through the dorso-lateral part. The turning of these quadrants takes place chiefly in the chiasma. Hence we may deduce that in the chiasma of the rabbit there is not only a partial crossing from the left side to the right and the reverse but also a crossing from dorsal to ventral and vice versa. PROJECTION OF THE RETINA IN THE BRAIN 9 Thus far this locahzation was not an absolute one, but a very distinct localization of the different parts of the retina in the primary optic centres was found. The cells of the upper quadrants of the retina send their fibres to the ventral part of the external geniculate body, while those of the lower quadrants terminate dorsally. Further, the nasal part of the retina is always projected laterally to the temporal half. CROSSED ORAAL UNCROSSED CAUDAAL ORAAL CAUDAAL i=Temporal Lower lv1j= Nasal Lower =Temporal Upper = Nasal UPPER FiG.'l. Projection of the Various Quadrants of the Retina on the Crossed and Uncrossed External Geniculate Body in Rabbits (After Overbosch) The uncrossed tract in rabbits is very small as I have already mentioned, because the eyes are situated so far sidewise in the head. These uncrossed fibres terminate in a pretty large, but circumscribed portion in the medial part of the geniculate body. They there mix with fibres of the crossed retina. Again the lower half lies above the upper half of the retina. In .this medial portion of the external geniculate body the part of the retina by which the animal 10 STUDIES ON THE CENTRAL NERVOUS SYSTEM can look with both its eyes together, may be seen pro- jected. Here binocular vision is made possible. The figure 1 shows this projection of the crossed and uncrossed fibres through the whole external geniculate body. They are made by Dr. Overbosch, who will shortly give a full description of the material. Regarding the uncrossed part, one point must still be mentioned. This part does not occupy the whole external geniculate body but leaves the oral part free. In rabbits there is also a very fine projection of the retina on the corpus quadrigeminum anticum. The lower quadrants are lying oral and medial, the upper quadrants caudal and lateral. This ganglion is in rabbits of much higher significance for sight than in higher mammals and does not merely serve for lower reflex movements. Recapitulating we conclude that the principle of localiza- tion in rabbits distinctly comes to the foreground. The position of the different quadrants of the retina is, however, unexpected. In cats an exact localization in the external geniculate body is also found. Cats differ from rabbits. This is not surprising, seeing that the eyes in the former stand more frontal in the head, and that the form of the external geniculate body is not the same. Hence the number of non-crossing fibres is much greater than in rabbits and the binocular part of the external geniculate body has become bigger. Here also it is situated medially, as Minkowski was the first to show. We have further found that the upper quadrants of the retina lie a little more frontal than the lower. It has not been possible to determine the localization of various parts of the retina in the midbrain of cats. The secondary degenerations to this part of the brain after partial lesions of the retina were not sufficiently in- tense to enable us to come to a definite conclusion. Fig- ure 2 shows Dr. Overbosch's and our results about the pro- jection of the retina in cats. PROJECTION OP THE RETINA IN THE BRAIN 11 We shall now turn to monkeys. This animal is of the highest interest for clinical purposes, because in this respect the relations in monkeys and in men are about the same. The eyes stand quite frontal in the head, just as in man. There is a real macula, just as in man. The form of the geniculate body is about the same and this ganglion is shifted to the outside of the brain. It lies at its base, just as m man. CROSSED CAUDAAL UNCROSSED CAUDAAL ORAAL X^= NASAL LOWER, =NASAL UPPER. ^=Temporal lower. [W]=Temporal Upper Fig. 2. Projection op the Various Quadrants of the Retina on the Crossed and Uncrossed External Geniculate Body in Cats (After Overboseh) The operations were always made on the left eye. In one case the left eye was totally extirpated, while in fifteen other animals partial lesions were made. These may be divided into three groups. In the first, different parts of the retina were injured without damaging the macula; in the second group the macula was involved, the remaining part of the retina being spared; while in the third, lesions were made in the macula as well as in the periphery. 12 STUDIES ON THE CENTRAL NERVOUS SYSTEM On looking over our observations of secondary degenera- tions in the optic nerve we find there is, to a certain degree, a locahzation of the peripheral quadrants of the retina. The fibres from the upper half of the retina are situated above those from the lower; further, the temporal fibres lie lateral and the nasal medial. The difficult point is the localization of the macular fibres. It is certain that the number of those fibres is large. Near the eye they are situated laterally in the optic nerve, but towards the chiasma the degenerated area has a tendency to pass more centrally into the nerve. We believe that the macular fibres separate those from the temporal upper and lower quadrants of the peripheral retina from one another. There is not a very exact localization of the macular fibres in the optic nerve, for it is certain that several of them are found between fibres from the various quadrants of the retina. We shall now pass to the relations in the chiasma. Our experiments have shown that the fibres from the upper part of the retina generally cross dorsally in the chiasm.a and those from the lower half ventrally. The macular fibres cross chiefly in the middle of the chiasma. In the middle and in the most proximal sections of the chiasma it is per- fectly evident that the macular fibres have a tendency to move towards its dorso-lateral part. In this way the posi- tion occupied by the macular fibres in the optic tracts, as we shall presently see, has already been determined in the chiasma. Our observations in regarding to the position of the various parts of the retina in the chiasma of the monkey correspond to what Henschen and Wilbrand found in man. From their and our own observations we can understand why it is that tumours of the hypophysis so often cause an early defect in the superior temporal quadrants of the field of vision, since the tumour presses first on the ventral border of the chiasma and consequently damages the function of the ventral quadrants of the retina. From our investiga^ PROJECTION OF THE RETINA IN THE BRAIN 13 tions on the structure of the chiasma in monkeys the con- clusion may be deduced that pressure on its dorsal surface may first cause defects in the inferior quadrants of the field of vision; some of our clinical observations point in this direction. If this is correct we should here have a means of distinguishing between tumours of the hypophysis on the one hand and suprasellar tumours or dilatation of the third ventricle on the other hand. In this line we can also use our results on localization in the optic tracts. We have found that there is certainly a locaHzation of the fibres from the upper and lower parts of the periphery of the retina. The projection is approximately the same in both the crossed and uncrossed tracts. The fibres from the upper quadrants of the periphery lie dorsally, those from the lower ventrally; there is no overlap between these. The macular fibres are situated in the centre and gradually become larger in a lateral direction. The medio ventral position of the macular fibres overlap the fibres from the dorsal and ventral parts of the peripheral retina. This localization remains the same throughout the whole length of the optic tract. We shall now discuss the primary optic centres, but first, however, I must say something about the pulvinar. This forms a part of the optic thalamus and lies in the immediate neighbourhood of the geniculate body. It is often regarded as a third primary optic station. In rabbits it has been up to now very difficult to decide which part of the optic thalamus corresponds to the pulvinar of higher animals. After operations on the eye of rabbits, many fibres are seen to turn round the external geniculate body and then pass along the dorsal border and through the most dorsal part of the optic thalamus. We must not infer, however, that these terminate here, as there is reason to beheve that they all only pass through this region of the brain in order to reach the midbrain. In cats a pulvinar can be easily recognized, and after retinal operations a secondary degeneration can be seen in its dorsal border, smaller and less intense than 14 STUDIES ON THE CENTRAL NERVOUS SYSTEM in rabbits. We can definitely say that these fibres do not terminate there, but proceed to the anterior colHculus. We have checked this conclusion by cutting a series of sections horizontally after extirpating the left eye. In monkeys these degenerated fibres go along the medial border of the pulvinar but do not terminate there. They avoid the external geniculate body, bend caudally through the bracchium anterius and terminate in the corpus quadrige- minum anticimi. Furthermore, the arguments that the pulvinar in man takes up primary optic fibres, are weak. Hence we believe it is better not to regard the pulvinar as a primary optic centre. This does not mean, however, that this region of the brain has nothing to do with vision. The connection of the pulvinar with the gyrus angularis makes it possible that it has something to do with the movements of the eye muscles and with the higher visual functions (stereoscopic vision, the recognition of the relative and absolute distance). When the left eye of the monkey is totally extirpated, we see an extensive degeneration in both external genicu- late bodies. But this is not the same on both sides. In the crossed ganglion the degeneration is more intensive than in the non-crossed. It is very clearly seen, that in a part of the periphery of the crossed geniculate body the degenera- tion is more intensive than at the other side. At the ventral border of the uncrossed corpus geniculatum externum a small layer is seen which is lighter and less degenerated in our sections than on the other side. What is the significance of this fact? The idea was forced upon us that it is in this layer that the monocular part of the field of vision is to be localized. When we compare the relations between the monocular field of vision and the binocular in rabbits, cats and monkeys, we are led to con- clude as follows. In rabbits the binocular field of vision is small because the eyes stand so far lateral in the head. Hence the part of the external geniculate body reserved for FIELDofVISIOM. FlQ. MONOCULAR VISION. BINOCULAR VISION_ IN THE FXTERNAL GENICULATE BODY 3. Relation Between the Monocular and Binocular Fields of Vision and Their Projection on the External Geniculate Bodies in Rabbits 15 16 STUDIES ON THE CENTRAL NERVOUS SYSTEM binocular vision is relatively small, the fibres of the monocu- lar vision occupying the greatest portion. We have seen that the field of binocular vision must be localized medially in this ganglion (fig. 3). In cats the part for binocular vision becomes greater, and finally in monkeys it occupies by far the larger portion of the external geniculate body (fig. 4). Yet in monkeys, and also in man, there always remains a part of the field of vision where only one eye sees. This lies very laterally. Hence the division of the field of vision into monocular and binocular parts is of great im- portance. As assumed above, the former in monkeys is probably situated in the ventral layer of the crossed ex- ternal geniculate body. Further investigations proved, that this view is correct. When Professor Zeeman extir- pated the most nasal part of the retina, which belongs to this monocular part, in two cases, I saw degeneration only in this peripheral border of the crossed geniculate body. The largest part of this ganglion serves for binocular vision, a much smaller one for monocular vision. The significance of the pathology of the monocular field of vision in man has been especially shown by Behr. Lutz has recently reviewed cases from the literature in which defects in the monocular field of vision were present. The anatomical aspect of this problem is, however, still unsolved. But localization of the monocular field of vision in the exter- nal geniculate body in apes may stimulate further studies in this direction. We should not be surprised if a special area is found to be reserved in the calcarine cortex also for this part of the retina. All the secondary degenerations seen in our sections end in the corpus geniculatum externum and in the corpus quadrigeminum anticum. Our references to the anterior colliculus may be brief. In monkeys these bundles are very small, especially on the uncrossed side. The course and ending of the degenerated fibres after partial lesions in the retina differed from one another, suggesting that also in 4 tf' FIELD OF VISION. BINOCULAR VISION MONOCULAR VISION IN THE EXTERNAL GENICULATE BODY. Fig. 4^ Relation Between the Monoc0lar and Binoculab Fields o'f Vision and Their Projection on the External Geniculate Bodies in Monkeys 17 18 STUDIES ON THE CENTRAL NERVOUS SYSTEM monkeys there is a localization of the different parts of the retina in the cortex of the corpus quadrigeminum anticum. Our material is, however, too limited to give a detailed scheme, as has been done in rabbits. A distinction should be made between lesions in the macula and lesions in other parts of the retina. Hence we speak of macula lesions and of peripheral lesions. Our experiments show that the upper quadrants of the retina lie medial in the external geniculate body and the lower quadrants lateral. In the medial part the crossing and non- crossing fibres lie close to one another. Hence the upper nasal part of the left retina and the upper temporal quadrant of the right retina are here localized. The same is the case with the lateral parts of this ganglion, where the right lower quadrants of both retinae meet one another. The fibres from these two parts do not overlap. The difference between the specimens with lesions in the upper and in the lower halves of the retina is already apparent in the optic tracts in the neighbourhood of the ganglion; after an operation on the upper quadrants the degenerated fibres are situated medially and remain there, while after a lesion in the lower half of the retina the fibres tend to pass to the lateral side. It has not been possible to give a more detailed localiza- tion of various parts of the different quadrants. On the contrary, we were struck by the fact that the secondary degenerations due to differently situated lesions in the same quadrants resemble each other very much. This is also the case in rabbits and in cats. From a study of our sections of the external geniculate body it is easy to determine whether the operation has been made in the upper temporal or upper nasal, in the lower temporal or lower nasal quadrant, but with the exception of the part of the retina belonging to the monocular field of vision one cannot, in this way, decide whether the lesion was made in the neighbourhood of the macula or more peripherally. PROJECTION OF THE RETINA IN THE BRAIN 19 The secondary degenerations after macula lesions were very distinct. Two points struck us here. First, that the degeneration after lesion in the macula is very large. The macular fibres are widely spread throughout the corpus geniculatum externum. They are chiefly found in those parts of the gangKon where degenerated fibres were not present after lesions of the upper and lower halves of the peripheral retina, that is, in the centre. Secondly, that in the oral part there is an overlap between the degenerated spots after injury of the macula and outside of the macula. The question now arises whether this is a real or only an apparent overlap. This matter cannot be decided with ab- solute certainty as we have here reached the limits of Marchi's method, but we have the feeling that there is not a real overlap. During our investigations in rabbits and cats the probability of a sharp localization always forced itself on us. This is also the case in monkeys and especially also in macula-lesions. When Professor Zeeman extirpates only the upper part of the macula, a large degeneration is seen in the geniculate body, but it shows a clear tendency to remain medially. But when he operates on the lower half of the macula the degeneration always tends to go laterally. Hence the upper part of the macula lies in the immediate neighbourhood of the upper part of the periphery. It is only in the more oral sections of the external geniculate body that this sharp locaUzation is not found. We must not forget, however, that a large part of the optic tract passes through the oral part of the ganglion, and we believe that many of these fibres only penetrate this portion of the ganghon on their way to more central parts. Hence we arrive at the conception, given in figure 5. In each geniculate body there is a small part for monocular vision. This is represented at the ventral border of the periphery. The greatest portion serves for binocular vision. There is a sharp locaUzation, the upper half of the retina lying medial, the lower half lateral. The macula has a 20 STUDIES ON THE CENTRAL NERVOUS SYSTEM PROJECTION OF THE RETINA IN THE BRAIN 21 pretty large projection between them, but it is a localised one. The upper quadrant of the macula borders on the up- per part of the peripheral retina and the lower part of the macula on the lower periphery. Further we believe that the horizontal meridian of the retina remains vertical, but somewhat oblique, in the corpus geniculatum externum. You may now ask me, what is your opinion about the more central localization in the brain? I am at present engaged in my laboratory with this side of the problem and hence cannot give sufficient data. I am convinced, how- ever, that the various opinions, generally held at this moment, cannot be correct. Because the results of our investigations enable us to conclude, that in monkeys — and also in men- — two parts have to be distinguished in the optic cortical centres, one for monocular and one for bin- ocular vision. As regards the projection of the retina for binocular vision the idea of an exact locahzation must give the lead. But we are sure that the macula cannot be pro- jected on a small isle of the calcarine. This projection must be a locaHsed one, but it must be a large one. We have seen that the macular fibres are very widely distributed in the external geniculate body, but that a localization exists cannot be denied. On more careful examination we find a difference between macula and non-macula lesions. In the former the distance between the degenerated fibres is greater than in the latter. Hence they may touch more cells there than the fibres of the periphery. In many respects our results resemble those of Ronne in man. He studied the atrophy of the cells of the external geniculate body in cases where the macular bundle was degenerated as a result of chronic intoxication; he found that in man the macula is projected on the dorsal part of the ganglion. Ronne con- cludes that his findings prove the connectness of Henschen^s hypothesis. His diagrams, however, show that the distribu- tion of fibres in the external geniculate body is wide. As mentioned already above, views on the representation 22 STUDIES ON THE CENTRAL NERVOUS SYSTEM of the macula in the calcarine cortex have varied; lately it has been generally assumed that its position is in the occipital pole. In 1917 I advanced arguments showing that it was impossible to accept the idea that the macula is locaUsed exclusively here; in a case of hemianopia duplex caused by a lesion in both occipital lobes central vision was possible notwithstanding the fact that the occipital pole was severed from the central optic radiations. This case does not prove that the macular fibres do not terminate in the cortex of the occipital pole, but it proves that not all of them end here. In 1918 Gordon Holmes advanced the possibility- — after having studied many war cases- — that macular vision, being very highly specialised, has a relatively much more extensive cortical distribution than peripheral vision has. Holmes's suggestion approximates to von Monakow's theory. It may be also in agreement with our observations in monkeys. I made several lesions in the cortical optic centres of rabbits. Dr. Putnam of Boston studied in my laboratory the retrograde degenerations in the external geniculate body and has discovered several interesting results regarding the projection of the various quadrants of the retina on the occipital lobe, which he will publish soon. Such lesions have also been recently made in my laboratory in the calcarine cortex of several monkeys. In this way we shall be able to determine the projection of the different parts of the retina and also of the macula in the second optic neuron, because we now know the relations in the primary optic neuron. Both types of degenerations will here meet one another in the external geniculate body. One point, however, needs to be emphasized. In our investigations we also took account of the third dimension, as you have seen in my drawings. Up to now workers have always spoken of a localization dorsal and ventral, lateral and medial. It will also be necessary to determine a localization oral-caudal. Our feeling is, that this localiza- PROJECTION OF THE RETINA IN THE BRAIN 23 tion in the third dimension will explain several clinical facts better than was formerly possible. It was not, how- ever, my intention to tell you about my feelings on this subject, but to bring you the facts obtained through the research work of Professor Zeeman and myself. BIBLIOGRAPHY: LECTURE I ARifiNS Kappers, C, U. : Vergleichende Anatomie des Nerve nsystems der Wirbeltiere und des Menschen. Bohn, Haarlem, 1921. Brouwer, B.: tlber die Sehstrahlung des Menschen. Monatschrift fiir Psychiatrie und Neurologie, Band 41, 1917. Brouwer, B.: Experimentell-anatomische Untersuchungen iiber die Projektion der Retina auf die primaren Opticuszentren. Schweizer Archiv fur Neurologie und Psychiatrie, Band XIII, 1923. Brouwer, B., and Zeeman, W. P. C. : Experimental anatomical investiga- tions concerning the projection of the retina on the primary optic centres in apes. Journal of Neurology and Psychopathology, 1925. Brouwer, B., and Zeeman, W. P. C: The projection of the retina in the primary optic neuron in monkeys. Brain, Vol. 49, 1926. Gushing, H. : Distortions of the visual fields in cases of brain tumor. Transactions of the American Neurological Society, 1921. Holmes, Gordon, and Lister, W. T. : Disturbances of vision from cerebral lesions, with special reference to the cortical representation of the macula. Brain, Vol. XXXIX, 1916. Holmes, Gordon: Disturbances of vision by cerebral lesions. British Journal of Ophthalmology, 1918. Henschen, S. E.: Revue critique de la doctrine sur le centre cortical de la vision. XIII« Congres international de Medecine, Paris, 1900. Henschen, S. E.: On the value of the discovery of the visual centre. Scandinavian Scientific Review, Vol. Ill, 1924. Meyer, A.: The connections of the occipital lobes and the present status of the cerebral visual affections. Transactions Association American Physicians, 1907. Minkowski, M. : Etude sur les connexions anatomiques des circonvolu- tions rolandiques, parietales et frontales. Archives Suisses de Neurologie et de Psychiatrie, 1924. Minkowski, M. : Sur les conditions anatomiques de la vision binoculaire dans les voies optiques centrales. I'Encephale, 1922. von Monakow, C: Die Lokalisation im Grosshirn und der Abbau der Funktion durch kortikale Herde, Bergmann, Wiesbaden, 1914. Pfeiffer, R. a.: Myelogenetisch-anatomische Untersuchungen iiber den zentralen Abschnitt der Sehleitung. M onographieen aus dem Gesamt- gehiete der Neurologic und Psychiatrie, Heft, 43, 1925. 24 STUDIES ON THE CENTRAL NERVOUS SYSTEM RoNNE H : Die anatomische Projektion der Macula im Corpus genicu- lltum externum. Zeitschrift jilr die gesamte Neurologic und Psy- chiatric, Band XXII, 1914. • . .i. DE ScHWEiNiTZ, G. E. : The Bowman Lecture, 1923. Transactions of the Ovhthalmological Society, Yol.XLlU. WiLBRAND, H., AND Saengbr, H.t Die Neurologie des Auges. Wiesbaden, Bergmann, 1915. . , , i . i Winkler, C.:Lokalised atrophy in the corpus geniculatum laterale. Proceedings Royal Academy for Sciences, Amsterdam, 1912. PATHOLOGY OF SENSIBILITY SECOND HERTER LECTURE PATHOLOGY OF SENSIBILITY Pathology of sensibility is one of the chief means used in diagnosing and localising diseases of the nervous system. Important work on this field of study has been done by Henry Head and his co-workers in England. He examined many cases of lesions of the peripheral and central nervous system, where disturbance of sensibility was the most prominent symptom. Topping his investigations was an experiment, done on himself. One of the nerves on his left arm was cut and then sewn by a surgeon. The dis- turbances of sensibility, caused by the operation, and their recovery were for some years carefully studied by him and his friends. I take for granted that you know Head^s work, hence I shall only refer to the principal points. In the opinion of Head, Rivers, Sherren and others there are three chief means by which stimuli for sensibility are caught up in the periphery. The first is deep sensibility, which originates chiefly in the muscles and in the joints. By this, impulses produced by pressure and by movements are conducted to the central nervous system. The other two systems conduct stimuli, caught in the skin and in the subcutaneous tissue. These systems are the protopathic and the epicritic. The former responds to painful cutaneous stimuli and to the extremes of heat and cold. The latter, the epicritic sensibility, serves for light touch, for discrimination of two points and for appreciation of the finer degrees of temperature. This conception of Head and his co-workers was very revolutionary and hence this theory has been much criticised. In cooperation with one of my pupils — Dr. Schoondermark — I examined at Amsterdam many lesions of the peripheral 27 28 STUDIES ON THE CENTRAL NERVOUS SYSTEM nerves in man and studied their recovery. We have seen many of the facts described by Head. Om- investigations however, did not convince us, that the theory of the existence of two distinct pathways for protopathic and epicritic sensibility has yet been proved. But we felt that this work is a great advance in science, especially because phylogeneti- cal ideas have been introduced into the doctrine of clinical sensibility and that autonomic sensibility has been brought to the foreground. Protopathic sensibility namely, is the primitive form of peripheral sensibility and must be very old in phylogenesis. Epicritic sensibility is a higher and more complex form and develops later. In Head's opinion protopathic sensibility is closely connected with centripetal sympathetic fibres. In discussing the autonomic nervous system many physiologists and neurologists consider only the centrifugal side, that is, they speak about the sympathetic nervous system in so far as it has been analysed by Langley. But in my opinion, this is too narrow. We know there are also many sympathetic fibres, for instance, in the intestines, which send impulses in the direction of the central nervous system. This is also the case in the vagus, which belongs to the parasympathetic system of Langley. We are aware that many stimuli from the lungs, the larynx etc. are sent to the brain along this nerve. It is true, that this centripetal side of the autonomic nervous system has not been so clearly analysed as was the centrifugal by Gaskell, Langley and others. But still we know sufficient facts to work with in physiology and in clinical examination. Huber has proved that in the walls of the blood vessels there are many unmedullated sensory fibres. When stimulated by pinching the blood vessels during an operation under local anaesthesia, severe pain is often felt by the patients. Recently Leriche and Tournay in France have shown that sensory impulses may indeed be conducted by sympathetic fibres. PATHOLOGY OF SENSIBILITY 29 All the sensory stimuli, caught in the periphery of the body, are sent to the spinal cord and to the brain. For a better understanding of the matter we shall limit ourselves to the spinal cord. The same line of thought may be fol- lowed concerning sensibility of the head, which is conveyed to the oblongata by the trigeminal nerve. Thus the stimuli for touch, pain, temperature and the proprioceptive sensibility reach the intervertebral ganglions and then proceed through the posterior roots. Here in America Ranson found after careful investigations that there are many unmedullated fibres in the posterior roots. He believes that these conduct the protopathic sensibility of Head. What happens when all these stimuli are brought by the posterior roots into the spinal cord? In the conception of Head and others a new grouping of the sensory impulses arises as soon as they reach the central nervous system. One group reaches the gray substance on the same side and here the first sensory neuron ends. A new neuron issues in the cells of the posterior horns. It mostly crosses and pro- ceeds upwards in the antero-lateral part of the spinal cord. The other group avoids the gray substance and ascends in the posterior column on the same side. It ends in the nuclei of Goll and Burdach, which lie at the upper border of the spinal cord. Here it is that the second sensory neuron begins, crosses in the oblongata and ascends to the optic thalamus. The investigations of Petren, Fabritius, Head, van Valken^ burg and others have made us pretty well acquainted with the physiological significance of these two systems. The sensory pathways in the posterior columns of the spinal cord conduct stimuli of deep sensibility and a part of the tactile impulses. The other system comprises the stimuli for pain, heat and cold and the remaining part of tactile sensibility. Many investigators consider the sensibility of the posterior columns as a higher form. It enables us to 30 STUDIES ON THE CENTRAL NERVOUS SYSTEM recognise the shape and size of the objects and to distin- guish two points apphed simultaneously (discrimination). Amongst other things the function of stereognosis is ren- dered possible by the impulses conducted in this part of the spinal cord. The other form serves more for feeling and is more vital, while the former is more intellectual in character. Hence they are opposed to one another and are called the ^ Agnostic" and the ^ Vital" sensibility. All these sensory stimuli are sent upwards to the optic thalamus, which is a centre where sensory functions are associated. From the optic thalamus they are sent to the cortex of the brain and meet there with many other stimuli of different qualities. The way, however, in which these two systems are spread throughout the central nervous system differs greatly. The construction of the socalled gnostic sensibility is simple as compared with the other. It is composed of three well- known neurons. The first is the tract in the posterior column, the second is the mesial fillet, the third the radiation between the optic thalamus and the cortex. This tract ends in the gyrus centralis posterior. The pathway for vital sensibility is more complex. As above mentioned, the second neuron begins immediately after the first neuron has entered the spinal cord. Several of these stimuli are con- ducted through the socalled spino-thalamic tract, but many of them are also led by short pathways, connecting the gray substance of different levels of the spinal cord, the oblongata and the midbrain. There is not much known about the termination of vital sensibility in the cortex, but we are sure, that these fibres have a large and diffuse projection in the cortex of the brain. A great part of the cortex cerebri may be destroyed in men and in animals without causing any defect to vital sensibility. In opposition to this, a circum- scribed destruction of the sensory cortex, by gunshot wounds for example or by a tumour, may cause clear disorders of the PATHOLOGY OF SENSIBILITY 31 functions of gnostic sensibility. Astereognosis especially is frequently seen in such cases. Clinical and anatomical studies have given me the con- viction that the same division into two pathways is present in the sensibility of the head, conducted by the trigeminal nerve. The so-called spinal root of the fifth nerve is the homologon of the gray substance of the posterior horn. Here stimuli are conducted for pain, heat and cold and a part of those for touch. The other sensory functions are led by the frontal trigeminal nucleus, which is the homologon of the nuclei of GoU and Burdach. From these centres also two different pathways proceed in the direction of the optic thalamus and of the cortex. The fact that several investigators regarded the sensory functions of the posterior columns as a higher form of sen- sibility, has led me to make a study of the development of these sensory systems in the scale of evolution. In the Central Institute for Brain Research I studied sections of the spinal cord, stained after Weigert-Pal, van Gieson and with Carmine, of the following animals. Fishes: Chimaera, Amia calva, Acipenser sturio, Rhombus maximus, Silurus glanis, Lophius boudegassa. Amphibians: Rana, Siren lacertina. Reptiles: Python, Lacerta, Varanus, Chamaeleon, Chelone mydas. Birds: Ciconia alba, Spheniscus demersus, Colymbus septentrionalis, Casuaris. Mammals: Homo, Cebus, Leontopithecus rosalia, Callitrix, Simla Satyrus, Hylobates, Cedipomidas, Felis, Canis familiaris, Heli- arctos malayanus, Putorius putori. Bos taurus, Hippotragus niger, Elephas, Tragulus javanicus, Lepus, Dasyprocta, Phocaena, Sorex, Talpa, Macropus, Tamandua, Didelphys marsupialis. The first cervical segment of these animals was measured and the relation between the size of the posterior columns and of the remaining part of the white substance was deter- mined. For details I refer to my article formerly published. The principal results w^ere the following. LIBRARY ^Asi>