**2.2.2 Methods**

2 Neuroimaging – Cognitive and Clinical Neuroscience

year 2010 has marked the 125th birthday anniversary of Koskinas (1 December 1885) and the

As soon as the Atlas and Textbook of Cytoarchitectonics were published in 1925, Koskinas briefly returned to Greece and donated a set to the Athens Medical Society. On that occasion, he delivered a keynote address, which summarises the main points of his research with von Economo. That address (Koskinas, 1926) forms the main focus of this paper. There are only two other presentations known to have been made by Koskinas: one with von Economo at the Society for Psychiatry and Neurology in Vienna in February 1923 (von Economo & Koskinas, 1923), presenting an initial summary of cytoarchitectonic findings on the granularity of sensory cortical areas especially in layers II and IV; and the other with Sträussler at the 88th Meeting of the German Natural Scientists and Physicians in Innsbruck in September 1924 (Sträussler & Koskinas, 1925), reporting histopathological findings on the experimental malaria treatment of patients with general paralysis from

The following is an exact English translation of the *Proceedings* of the Athens Medical Society, Session of Saturday, 23 January 1926, rendered from the original Greek text

"I am in the gratifying position of announcing an exceptional donation, made to the Society by the colleague Dr. G. Koskinas, sojourning in Athens; having temporarily come from Vienna, he brought with him a copy, as voluminous as you see, but also as valuable, of the truly monumental compilation, produced by the two Hellenic scientists in Vienna, C. Economo and G. Koskinas, who is among us today. It involves the book—text volume and atlas—*Cytoarchitektonik der Hirnrinde des erwachsenen Menschen*, about the value of which we had learnt from reviews published in foreign journals, but also convinced directly. Dr. Koskinas deserves our warm thanks, as well as our gratitude, for being willing to deliver a

"Thanks to the ardour of the honourable President of the Society, Professor Dr. Mermingas, who is meritoriously making every attempt to highlight the Society as a centre of noble emulation in scientific research and the promotion of science and at the encouragement of whom I have the honour of being a guest at the Society today. Enchanted by that, I owe acknowledgments because you are offering me the opportunity to briefly occupy you in person about the work published by Professor von Economo and myself in German, and deposited to the chair of the Society, "The Cytoarchitectonics of the Human Cerebral Cortex" *(Die Cytoarchitektonik der Hirnrinde des erwachsenen Menschen)*. An attempt on my behalf to analyse that work requires much time and many auxiliary media which, simply hither passing through, I lack. That is why I wish to confine myself, such that I very briefly cover the following simply and to the extent

centennial of his graduation from the University of Athens (M.D., 1910).

neurosyphilis.

possible.

**2. The 1926 presentation by Koskinas** 

(Koskinas, 1926) by the author of the present chapter.

**2.1 Introductory comment by Constantin Mermingas, presiding** 

synopsis of that original scientific research and achievement."

**2.2 Main lecture by Georg N. Koskinas, keynote speaker** 

At the outset of our studies we came across various obstacles and difficulties deriving on one hand from the very structure of the brain and on the other from the deficiency of the hitherto available research means. That is why we were obliged to modify numerous of the known means, to incise absolutely new paths, taking advantage of any possible means towards a precise, reliable and indelible rendition of nature. We modelled an entire system of new methods of brain research from the autopsy to the definitive photographic documentation of the preparations. Thus, we were able to not only solve many of the problems, but also, and above all, to provide to anyone interested various topics for investigation, as well as the manner for exploring them.

Allow me to mention some of the employed research means.

*Sectioning method.* Instead of the hitherto used method of sectioning the whole brain serially perpendicular to its fronto-occipital axis (Fig. 5), whereby gyri are rarely sectioned perpendicularly, we effected the sections always perpendicular to the surface of each gyrus and in directions corresponding to their convoluted pattern (Fig. 6). We arrived at that act

Cytoarchitectonics of the Human Cerebral Cortex:

The 1926 Presentation by Georg N. Koskinas (1885–1975) to the Athens Medical Society 5

Fig. 4. Constantin Mermingas (1874–1942), Professor of Surgery at the University of Athens and President of the Athens Medical Society (left), Georg N. Koskinas (1885–1975) in the centre, and Spyridon Dontas (1878–1958), Professor of Physiology and Pharmacology at the

Through our work an extremely precise and detailed description was achieved of the normal histological structure of the cerebral cortex as it is depicted in the photographic plates and explained in the text. Our photographic plates in the atlas, as such, constitute an ageless, imprescriptible opus, the basis and the control of any future research on the cerebral cortex. Whatever in such research is in agreement with the plates, must be considered as normal, and whatever diverges constitutes a pathological condition. From that precise knowledge of the architectonic structure of the cerebral cortex, which we achieved, it is allowable to anticipate the solution of numerous and different questions and issues of utmost importance; from their endless number I suffice in mentioning e.g. the following. a. *The problem of problems, i.e. the problem of the psyche.* When, as anatomists and physiologists, we speak of the psyche, we do not refer to it as a metaphysical being that finds itself a priori outside any anatomical and physiological weight, but as a moral, mental, active and

University of Athens and President of the Academy of Athens (right). © 1957 *Helios* 

historical personality which interacts with others and influences ourselves.

b. *The problem of individual mental attributes, i.e. intellectual talents,* such as rhetoric, music, mathematics, delinquency and the variations in the mental development of human phyla on the earth. By comparing e.g. the centres of music in individuals who genetically present a total lack of music perception to individuals who possess an evolved musical talent we may exactly pinpoint differences in such music centres.

*Encyclopaedical Lexicon* (signatures from the author's archive)

**2.2.3 Accomplished and anticipated results** 

by the idea that, in order to compare various parts of the brain cytoarchitectonically, sections must be oriented perpendicularly to the surface of the gyri, insofar as only then is provided precisely the breadth of both the overall cerebral cortex and of each cortical layer.

Fig. 3. The *Proceedings* of the Athens Medical Society for the Session of 23 January 1926

*Staining method.* The staining of the preparations was perfected by us such that a uniform tone was achieved not only of a single section, but of all the countless series of sections into which each brain was cut for study. And that was absolutely mandatory, on one hand in order to define the gradual differences of the histological elements of the neighbouring areas of the cerebral cortex, and on the other hand to achieve a consistent photographic representation.

*Specimen depiction method.* The hitherto occasional histological investigations of the brain depicted things schematically and therefore subjectively. Instead of such a schematic depiction, aiming at a precise representation of the preparations with all the relationships of the countless and polymorphous cells, we used photography. Photographic documentation constitutes the most truthful testimony of the exact depiction of nature, providing truly objective images of things as they bear in natural form, size and arrangement (Fig. 7). But to succeed in the photographic method it became necessary to turn to the study of branches foreign to medicine, such as advanced optics and photochemistry. We took advantage of both of these as much as we could. Lenses, light beams, filters, photographic plates and finally the photographic paper itself were all adopted towards the accomplishment of the intended goal of the most perfect, i.e. the photographic, depiction.

by the idea that, in order to compare various parts of the brain cytoarchitectonically, sections must be oriented perpendicularly to the surface of the gyri, insofar as only then is provided precisely the breadth of both the overall cerebral cortex and of each cortical layer.

Fig. 3. The *Proceedings* of the Athens Medical Society for the Session of 23 January 1926

representation.

*Staining method.* The staining of the preparations was perfected by us such that a uniform tone was achieved not only of a single section, but of all the countless series of sections into which each brain was cut for study. And that was absolutely mandatory, on one hand in order to define the gradual differences of the histological elements of the neighbouring areas of the cerebral cortex, and on the other hand to achieve a consistent photographic

*Specimen depiction method.* The hitherto occasional histological investigations of the brain depicted things schematically and therefore subjectively. Instead of such a schematic depiction, aiming at a precise representation of the preparations with all the relationships of the countless and polymorphous cells, we used photography. Photographic documentation constitutes the most truthful testimony of the exact depiction of nature, providing truly objective images of things as they bear in natural form, size and arrangement (Fig. 7). But to succeed in the photographic method it became necessary to turn to the study of branches foreign to medicine, such as advanced optics and photochemistry. We took advantage of both of these as much as we could. Lenses, light beams, filters, photographic plates and finally the photographic paper itself were all adopted towards the accomplishment of the

intended goal of the most perfect, i.e. the photographic, depiction.

Fig. 4. Constantin Mermingas (1874–1942), Professor of Surgery at the University of Athens and President of the Athens Medical Society (left), Georg N. Koskinas (1885–1975) in the centre, and Spyridon Dontas (1878–1958), Professor of Physiology and Pharmacology at the University of Athens and President of the Academy of Athens (right). © 1957 *Helios Encyclopaedical Lexicon* (signatures from the author's archive)

#### **2.2.3 Accomplished and anticipated results**

Through our work an extremely precise and detailed description was achieved of the normal histological structure of the cerebral cortex as it is depicted in the photographic plates and explained in the text. Our photographic plates in the atlas, as such, constitute an ageless, imprescriptible opus, the basis and the control of any future research on the cerebral cortex. Whatever in such research is in agreement with the plates, must be considered as normal, and whatever diverges constitutes a pathological condition. From that precise knowledge of the architectonic structure of the cerebral cortex, which we achieved, it is allowable to anticipate the solution of numerous and different questions and issues of utmost importance; from their endless number I suffice in mentioning e.g. the following.


Cytoarchitectonics of the Human Cerebral Cortex:

hatched areas indicate the "cancelled" tissue

**2.3 Response by Spyridon Dontas, annotator** 

as well, to the great benefit of science."

tamed, has to fall."

The 1926 Presentation by Georg N. Koskinas (1885–1975) to the Athens Medical Society 7

effected, foci can be defined with precision and brain surgery can be enhanced.

Fig. 6. Indication on the convex cerebral facies around the lateral (Sylvian) fissure of the von Economo & Koskinas (1925, 2008) method for dissecting each hemisphere into an average of 280 4mm-thick blocks perpendicular to the course of each gyrus for cytoarchitectonic study;

Sirs, in the phylogenetic line of living beings, nature, at times acting slowly and at times saltatorily, but always continually, produces new complex and viable animal forms. The same resourceful force that has given over the eons wings to the eagle to fly, has indirectly bestowed humans, by understanding their mind, with the capacity to construct wings themselves in order to defeat the law of gravity and to conquer the air. Nonetheless, the mind has its organic locus, its seat, its altar in the cerebral cortex. That is why one would be justified in saying that the anatomical and the physiological exploration of that noblest of organs deserves the utmost attention of science. The mind which explores and tends to subjugate everything, which tames everything and cannot be

"The work of Drs. Economo and Koskinas is monumental and constitutes a milestone of science, opening up new pathways towards the understanding of the brain from an anatomical, physiological and pathological viewpoint. It further forms the first comprehensive reference on the architecture of the adult human brain. And because the most precise of known methods was used, the optical, and through it a reproduction of the structure of the brain was achieved, in the natural, I reckon that this work will persevere as an everlasting possession of science. I further wish that Drs. Economo and Koskinas continue and complement their work, studying the remaining parts of the nervous system

problem also possesses utmost sense, insofar as in that way diagnosis can be readily

Fig. 5. Horizontal section through the left human cerebral hemisphere, depicting the sizeable regional differences in cortical thickness and the random orientation of the gyri (Koskinas, 2009). Weigert method. *F*1 and *F*2, superior and middle frontal gyrus; *Ca*, precentral gyrus; *R*, central sulcus; *Cp*, postcentral gyrus, *P*, parietal lobe; *O*, occipital lobe; *L*, limbic gyrus


Fig. 5. Horizontal section through the left human cerebral hemisphere, depicting the sizeable regional differences in cortical thickness and the random orientation of the gyri (Koskinas, 2009). Weigert method. *F*1 and *F*2, superior and middle frontal gyrus; *Ca*, precentral gyrus; *R*, central sulcus; *Cp*, postcentral gyrus, *P*, parietal lobe; *O*, occipital lobe; *L*, limbic gyrus

c. *The problem of pathological lesions in numerous mental disorders* both primarily and

d. *The problem of the localisation of various centres.* The various localisations of sensation, movement, stereognosis, speech, etc., which thus far were mostly defined without an exact histological control, from now on, admittedly, can be readily and precisely defined on the basis of the cerebral cortical areas that we have designated, which from a total number of 52 known thus far we brought to 107 (Fig. 8–10). The solution of this

secondarily encountered in the brain.

problem also possesses utmost sense, insofar as in that way diagnosis can be readily effected, foci can be defined with precision and brain surgery can be enhanced.

Fig. 6. Indication on the convex cerebral facies around the lateral (Sylvian) fissure of the von Economo & Koskinas (1925, 2008) method for dissecting each hemisphere into an average of 280 4mm-thick blocks perpendicular to the course of each gyrus for cytoarchitectonic study; hatched areas indicate the "cancelled" tissue

Sirs, in the phylogenetic line of living beings, nature, at times acting slowly and at times saltatorily, but always continually, produces new complex and viable animal forms. The same resourceful force that has given over the eons wings to the eagle to fly, has indirectly bestowed humans, by understanding their mind, with the capacity to construct wings themselves in order to defeat the law of gravity and to conquer the air. Nonetheless, the mind has its organic locus, its seat, its altar in the cerebral cortex. That is why one would be justified in saying that the anatomical and the physiological exploration of that noblest of organs deserves the utmost attention of science. The mind which explores and tends to subjugate everything, which tames everything and cannot be tamed, has to fall."

#### **2.3 Response by Spyridon Dontas, annotator**

"The work of Drs. Economo and Koskinas is monumental and constitutes a milestone of science, opening up new pathways towards the understanding of the brain from an anatomical, physiological and pathological viewpoint. It further forms the first comprehensive reference on the architecture of the adult human brain. And because the most precise of known methods was used, the optical, and through it a reproduction of the structure of the brain was achieved, in the natural, I reckon that this work will persevere as an everlasting possession of science. I further wish that Drs. Economo and Koskinas continue and complement their work, studying the remaining parts of the nervous system as well, to the great benefit of science."

Cytoarchitectonics of the Human Cerebral Cortex:

The 1926 Presentation by Georg N. Koskinas (1885–1975) to the Athens Medical Society 9

Fig. 8. The cytoarchitectonic map of von Economo and Koskinas, depicting their 107 cortical modification areas on the convex and median hemispheric facies of the human cerebrum

Fig. 7. Section of the dome of a gyrus from the frontal lobe of a human cerebral hemisphere, showing the normal six-layered (hexalaminar) cortex. The white matter (*Mark* in German), which is devoid of nerve cells, is seen on the lower-right hand corner. The six superimposed cortical cell layers are denoted in Latin numbers (I–VI). Photographed with a Carl Zeiss 2.0 cm Planar, a special objective lens with a considerably larger field than could be obtained with common microscopy objectives, especially valuable for large area objects under comparatively large magnifications and an evenly illuminated image free from marginal distortion. Planar micro-lenses are used without an eyepiece. ×50 (von Economo, 2009)

Fig. 7. Section of the dome of a gyrus from the frontal lobe of a human cerebral hemisphere, showing the normal six-layered (hexalaminar) cortex. The white matter (*Mark* in German), which is devoid of nerve cells, is seen on the lower-right hand corner. The six superimposed cortical cell layers are denoted in Latin numbers (I–VI). Photographed with a Carl Zeiss 2.0 cm Planar, a special objective lens with a considerably larger field than could be obtained with common microscopy objectives, especially valuable for large area objects under comparatively large magnifications and an evenly illuminated image free from marginal distortion. Planar micro-lenses are used without an eyepiece. ×50 (von Economo, 2009)

Fig. 8. The cytoarchitectonic map of von Economo and Koskinas, depicting their 107 cortical modification areas on the convex and median hemispheric facies of the human cerebrum

Cytoarchitectonics of the Human Cerebral Cortex:

**3. Conclusion** 

The 1926 Presentation by Georg N. Koskinas (1885–1975) to the Athens Medical Society 11

Fig. 10. The cytoarchitectonic map of von Economo and Koskinas, depicting their 107 cortical modification areas on the ventral hemispheric surface of the human cerebrum

Besides a histological mapping criterion, variations in cellular structure (cytoarchitecture) of the mammalian cerebral cortex reflect regional functional specificities linked to individual cell properties and intercellular connections. With the current interest in functional brain imaging, maps of the human cerebral cortex based on the classical cytoarchitectonic studies of Korbinian Brodmann (1868–1918) in Berlin are still in wide use (Brodmann, 1909; Garey, 2006; Olry, 2010; Olry & Haines, 2010; Zilles & Amunts, 2010). The Brodmann number system comprises 44 human cortical areas subdivided into 4 postcentral, 2 precentral, 8 frontal, 4 parietal, 3 occipital, 10 temporal, 6 cingulate, 3 retrosplenial, and 4 hippocampal. Following in the footsteps of the Viennese psychiatrist and neuroanatomist Theodor Meynert (1833–1892), who is considered to be the founder of the cytoarchitectonics of the cerebral cortex (Meynert, 1872), von Economo and Koskinas, also working at the University

Fig. 9. The cytoarchitectonic map of von Economo and Koskinas, depicting their 107 cortical modification areas on the dorsal hemispheric surface of the human cerebrum

Fig. 10. The cytoarchitectonic map of von Economo and Koskinas, depicting their 107 cortical modification areas on the ventral hemispheric surface of the human cerebrum
