Talk:Paper - Morphophysiology of the cerebral cortex
Sarkisov S. Morphophysiology of the cerebral cortex. (1945) Br Med J. 2(4410): 37–40.
Sarkisov S. Morphophysiology of the cerebral cortex. (1945) Br Med J. 2(4410): 37–40.
BRITISH MEDICAL JOURNAL
LONDON SATURDAY JULY 14 1945
Some New Developments In The Morphophysiology Of The Cerebral Cortex
Prof. S. Sarkisov, M.D.
The study of the mechanism of the physiological and pathophysiological processes of the brain has for a long time occupied the attention of investigators. The work of I. P. Pavlov on conditioned reflexes has opened new ways to the understanding of the activities of the brain up to the most complicated ones—i.e., the highest nervous activities. There is no need to stress the importance of these experimental investigations, which furnish us with new ideas and methods for the better understanding of the cerebral processes, both normal and pathological, of man. A few examples of the work done will illustrate the position.
M. K. Petrova, one of the oldest pupils of Pavlov, succeeded in establishing in different dogs different types of nervous system with the precise characteristics of the various breeds. Petrova has furthermore ascertained that by inducing conditioned reflexes it is possible to produce experimentally in dogs nervous conditions which are characteristic of typica!l forms of neurosis. It is important to note, too. that she has ascertained that by the administration of a special dosage of bromine this experimentally produced neurosis can be completely cured.
Very interesting from the point of view of the influence of the cerebral cortex on the pathology of the organism are the experiments on conditioned reflexes in combination with the application of camphor. In the laboratories of Pavlov one of his pupils, Dolin, combined the use of the conditioning stimulant with the introduction into the organism of the dog of camphor, which, as is well known, causes convulsive epileptic fit. Having established the conditioned reflex through the introduction of camphor, Dolin succeeded, solely by means of the conditioning stimulant, without the introduction of camphor, in causing epileptic fits in the dog.
The investigations into the problem of the influence of the cerebral cortex upon the inner organs are, for medicine, in the broadest sense of the word, of particular importance. While up till now we have been able to speak only a priori of the influence of the ‘“ psyche ” on somatic processes, the experimental investigations of K. M. Bukow and his pupils, using the methods of conditioned reflexes, have revealed definite physiological laws and the interdependence of the cerebral cortex and the inner organs—the heart, stomach, spleen, liver, urogenital organs, etc. These investigations show how, by causing certain conditioned reflexes in dogs, one can influence and alter the action of such organs as the liver, the kidneys, and the stomach. On the other hand, by a series of experiments, changes in the highest nervous activities of an animal, dependent on the condition of the inner organs, have been established. These experiments have shown the influence on the cerebral cortex of the impulses originating from the inner organs—in other words, the place which the most complex inner world of an animal has in its physiological behaviour has been established.
In these experiments it was found that, in causing conditioned reflexes or conditioned reflexive activity in an animal, new “temporary connexions ” between the various sections of the central nervous system and the various organs and tissues of the organism are apparently created.
These investigations, in further developing the teaching of Pavlov on conditioned reflexes, have made it necessary to deal
with the question of the morphophysiological nature of these “temporary connexions ” formed in the complicated processes of the brain. Knowledge of the mechanism of these processes and their morphophysiological relations would offer new possibilities for the identification of pathological symptoms in the brain.
Recent Electro-physiological Investigations
Of great importance for this research work are the recent electro-physiological investigations, particularly of the bioelectrical phenomena of the brain, and also the new data on the finest structural features of the cerebral cortex. Bioelectrical investigations (electro-encephalograms)—carried out in various laboratories of the Soviet Union by Sarkisov, Livanov, Russinov, and Steinberg; in England by Adrian, Matthews, Walter, Ultridge, and others ; and in America by Lenox, Gibbs, Davis, and others—have opened up fresh possibilities of a dynamic conception of the delicate mechanism involved in brain activity.
The numerous investigations of the last 10 to 15 years have considerably enriched our knowledge of the electro-physiological mechanism of the various sections of the central and peripheral nervous system in both the normal and the pathological state. We have now definite conceptions of the chief characteristic peculiarities of the bio-electrical current curves of the cerebral cortex, of its various sections, of the finest laminae of the cortex, of the post-cortical formations, of the peripheral nervous system, and so on. A series of investigations have also been made on bio-currents in the state of waking, sleeping. hypnosis, and so on.
Very interesting are the investigations into the bio-electrical manifestations of the brain under different influences. We were able to establish, for instance, the laws governing the variations in these manifestations under the influence of various narcotic substances—e.g., strychnine, morphine, and others (Sarkisov). It is important to note, for instance, the following fact. As we know, morphine has a depressing effect on the central nervous system. Yet our electro-encephalograms have shown that it acts differently on each region of the cerebral cortex, and that in the different stages of narcosis the potentials of the various sections of the cortex and the post-cortex are dissimilar.
Our investigations, and those of others, have shown numerous changes of the normal brain potentials in cases of mental disease—e.g., epilepsy, schizophrenia, manic-depressive conditions, and so on—and also as a result of various changes in metabolism. Of great importance also is the study of the bioelectrical manifestations in the case of organic diseases of the brain. Characteristic alterations of the ordinary encephalogram occur, for instance, in cases of tumours of the brain. Of considerable and practical interest, in this respect, are the investigations of Grey Walter, who has suggested a novel method of using bio-currents for ascertaining the seat of disease in a case of brain tumour. Our investigations of the bio-electrical phenomena in the presence of artificially caused tumours of the brain in animals have produced curious results. It was found that the bio-electrical phenomena are directly dependent on the seat and also on the character or nature of the tumour. We have produced tumours in the brain of rabbits experimentally, and have carried out series of investigations on these animals by
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ADVANCES IN MORPHOPHYSIOLOGY OF THE BRAIN
BRITISH MEDICAL JOURNAL
means of electro-encephalograms. “ paraffinous,” and “ cancerous.”
These investigations (Sarkisov and Penzik—published in 1940) revealed characteristic slow vibrations of the bio-electric potentials near the tumour. We noticed alterations of a somewhat different character at a considerable distance from the tumour, and it is particularly necessary to emphasize that the bio-currents of the brain vary according to the kind of tumour.
The tumours were muscular,
Fig. 1 shows an electro-encephalogram of a tumorous human brain with characteristically slow vibrations of 4 to 5 per second, instead of 10 to 12 vibrations in the normal state.
F1G. 1.—An a clectro-encephalogram of a tumorous human brain, 13/10/43. A, left temporal; B, right temporal.
Fic. 2.—Same brain as Fig. 1. À, left occipital; occipital. Recording, 30/10/43; operation, 22/11/43. Follicular abscess in right parietal area. Restricted injury of the cortex and of the white substance of the upper temporal area. Time recording, 0.2 sec.
FiG. 3.—Same brain as s Figs. 1 and 2. A, left central; B, , right central. Time recording, 0.2 sec.
FIG. 4.—A, left occipital; B, right occipital. Deep injury of the left premotor region reaching the subcortical ganglia, with a metal fragment in the left frontal zone. Cicatrization not complicated by the purulent process. Time recording, 0.2 sec.
In our laboratories, Russinov, Livanov, Preobrashenskaya, and Lurya have during the wär done a considerable number of electroencephalograms (more than 1,300) in cases of various forms of cranium-brain wounds, and particularly of abscesses of the brain. The curves in Fig. 2 characterize the bio-electrical currents of the occipital regions of the brain in cases of various diseases of the parietal area. In Fig. 3 the curves depict the variations in the bioelectrical currents of the central region (right and -left) of the same brain. Fig. 4 shows the curves of the right and left occipital regions of the injured cranium. The deep wound is in the left premotor region (reaching to the subcortical ganglia, with a metallic fragment), and in the left frontal region with a cicatrix (without abscess).
These examples should suffice to prove that the electroencephalograms represent the separate nervous processes of the tissue of the brain in both normal and pathological states. However, it is necessary to emphasize that in each single case much in the electro-encephalogram is as yet obscure—that is, not accessible to analysis in the light of our physiological knowledge. Still, the data of the electro-encephalograms undoubtedly aid the examination of the various aspects of the complex brain processes. By means of the encephalogram we are now able, in a considerable percentage of cases, to pronounce on the character and periods of epilepsy, on tumours and abscesses, on, the seat of a disease ; and we can speak of a disease in the sense of its being local, and so on.
I have no space here to deal with another aspect of the electroencephalographic investigation—the functions of the nervous tissue, central and peripheral, the laws governing the processes of excitation and inhibition, and other questions. Much has been done in this field in the Cambridge laboratories (Adrian) and in the Moscow Brain Institute (Livanov), and by others.
Physiology of the Brain
In connexion with our new ideas on the physiology of the most differentiated nervous activity and on the physiology and pathology of the cerebral cortex, our knowledge of the minute morphological organizations and connexions of the cortex is also broadening. We have now considerable knowledge of the brain, and especially of the cortical formations and the various architectonic cellular structures of the most highly organized matter of that organ. At the Moscow Brain Institute during the last 15 to 20 years specialized investigations in the phylogenesis (pertaining to a species) and ontogenesis (individua)] development) of the brain, and particularly of the cerebral cortex, have considerably extended our knowledge of its complex organization. Specific laws have been established governing the formation of the minute architectonic structures of the cortex and the cerebrum as a whole, in the various stages of their phylogenetic and ontogenetic development. The results of these investigations have been publishd in the form of separate works and monographs byÿ the research workers at the Moscow Brain Institute—Philimonoff, Sarkisov, Kolonova, Blinkov, Preobrashenskaya, and others.
In emphasizing these achievements of modern neurology it may be said that our conceptions of the architectonic features of the cerebral cortex do not suffice to reveal the fundamental morphophysiological mechanism of the cortical function. In order to extend further our knowledge of the morphophysiological mechanism of the functions of the brain it is necessary to study the multiformity of the cellular architecture together with the picture of the elaborate and complex intercellular connexions and their dynamics.
Structure of the Cerebral Cortex
The methods of architectonic investigation have been of great use in establishing the general features of the structure of the cerebral cortex, its division into separate areas and regions according to the character of the various cellular and fibroid laminae, and so on. These investigations play a particular part in solving one of the fundamental problems of modern neurology—i. e., the problem of localization. The data obtained in this way are the basis for further advancement in the study of the brain. It will be necessary, however, to ascertain how the formation of the neurons of the cortex in their entirety proceeds—i.e., to trace the development of the different types of neural cells of the cortex with all their appendices ; that is, the dendrites and their axons. Furthermore, it is necessary to discover how in the process of development the connexions between the various groups of neurons establish themselves inside the individual cortical formations, as well as between the various cortical regions. What I have in mind is the significance of the most delicate connexions—i.e., the synapses in the cerebral cortex. The treatment of this question is indispensable to the understanding of the intimate physiological and pathological processes of the brain.
It is well known that the method of Golgi provides the possibility for this study. It is particularly necessary to emphasize that up till now the finest connexions between the neurons in the cortex, as distinct from the synapses of the peripheral JuLy 14, 1945
nervous system and, to a certain degree, of the lower section of the central (cerebrospinal) system, have been studied quite inadequately, if one leaves out of account the well-known work of Ramôn y Cajal and others. This is due, in the first place, to the enormous difficulties arising in the study of the synaptic mechanism, especially in the cortex—as the most complicated part of the cerebral nervous system. These diffculties arise particularly in the study of the cerebral cortex of an adult. Therefore it should be expedient to study, by the method of Golgi, the cerebral cortex in ontogenesis, when the interçellular connexions and their structural features are comparatively simple and more easily accessible.
So far as we know, the study of the ontogenetic development of the cerebral cortex by Golgis method has not yet been fully carried out. (Cajal investigated chiefly the brain of the newborn and in the first months after birth.) The first to start these researches was Dr. G. I. Polyakov, in the Moscow Brain Institute. It is not:my aim to give a full account of his investigations into the study of the functioning of the cerebral cortex. Polyakov is about to publish his results in a monograph. Still, I would like to give at least a few illustrations from his studies, so as to convey some idea of the importance of the data obtained.
F1G. 5.—Four-lunar-months foetus. Above, formation of the precentral cortex (area 4). Below, formation of the optical cortex (area 17)
Fic. 6.—Five- and-a-half-months foetus. Left, precentral area
4; right, postcentral area
Fig. 5 shows the picture of the cellular structure in an embryo of 4 lunar months, where the upper lamina of the cells has been taken from the precentral region, and the lower lamina from the optical .cortex—i.e., from the occipital pole of the brain. We notice here, in the earliest stage of the organization of the cortical cellular elements of neuroblasts, an apparently similar picture of the cells and their appendix in the precentral and optical regions. Still, it is not difficult, even to the naked eye. to notice, already in this stage, the differences in the shape of the cells and the characteristics of their appendices.
Fig. 6 represents the organization of the cortical structure in an embryo of 5k months. To the left is the cortex from the precentra]l region ; to the right, from the postcentral region. Here the difference in the shape of the cells, and particularly in the shape of the appendices, seems even more distinct.
The next differentiation of these connexions in an embryo of 8 months is of great interest with regard to .those of the cortical structure. In Figs. 7 and 8 are shown the formation of the intercellular connexions of the frontal, lower-sinciput, and postcentral regions. One notices very fine cellular appendices of extraordinary multiformity and peculiarity in the three regions of the cortex in the embryo of 8 months; in the frontal region (precentral and motorial), strongly developed cells with significant vertical appendices. Contrary to this, the cells in the postcentral, and especially in the lower-sinciput (associatory), region of the cortex are considerably smaller and at the same time their appendices are distinguished by greater delicacy and multiformity. And, what is most important, they are distinguished by significant appendices extending laterally—i.e., in a horizontal direction—which obviously is largely
F1G. 7.—Eight-lunar-months foetus. Precentral agranular cortex
FIG. 8.—Eight-lunar-months foetus. Middle part of the cross-section of the cortex. Above, lower parietal area 39: below. nostcentral area 1
characteristic of the receptive type of cortex. These fine neuron formations are obviously best distinguishable in the last month of uterine gestation.
1 shall not dwell here on a full description of all the details of this amazingly diverse picture of the cellular structures and their appendices. They will be dealt with separately by Dr. Polyakov. Particularly important are the examination and the establishment of these structures in the adult. The examples given above convey some idea of the new data concerning the finest and most complicated structural features of the cerebral cortex. There is no need to prove that on these data the processes of the cerebral cortex in the normal and pathological state are based. Can one doubt the intimate physiological part
which these minute intercellular formations play ? Can one doubt that in various pathological affections of the brain as a whole, and of the cerebral cortex in particular, these delicate intercellular structures are the first to be exposed to disease, being the most vulnerable? Of special interest are these data from the point of view of pathological changes of the brain in the so-called “ functional diseases ” of the nervous system. Obviously, in various “ functional diseases,” and also in many cases of psychosis, where we are not in a position to identify definite changes in cellular structure, one must assume first ot all an affection of these intercellular connexions. The examination of these amazingly fine and diverse structural formations of the cortex presents us with more problems, the resolving of which is one of the chief tasks of modern neurology and neurophysiology. The work of the research staff of the Moscow Brain Institute is dedicated to the study of these questions.
The classical method of Pavlov in conditioned reflexes enriches considerably our knowledge and understanding of the part which the cortex plays in the most diffrentiated nervous activity and of the connexion of the cortex with the functions of the inner organs. The novel method of bio-electrical currents, and the exploration of the finest morphological structures of the cortex and its intercellular connexions, open new ways and opportunities for establishing the laws governing the fundamental morphophysiological mechanism of the complicated activity of the cerebral cortex.