Brain Struct Funct DOI 10.1007/s00429-014-0806-9

ORIGINAL ARTICLE

A new myeloarchitectonic map of the human neocortex based on data from the Vogt–Vogt school Rudolf Nieuwenhuys • Cees A. J. Broere Leonardo Cerliani

•

Received: 27 February 2014 / Accepted: 19 May 2014 Ó Springer-Verlag Berlin Heidelberg 2014

Abstract The human cerebral cortex contains numerous myelinated fibres, the arrangement and density of which is by no means homogeneous throughout the cortex. Local differences in the spatial organization of these fibres render it possible to recognize areas with a different myeloarchitecture. The neuroanatomical subdiscipline aimed at the identification and delineation of such areas is known as myeloarchitectonics. During the period extending from 1910 to 1970, Oscar and Ce´cile Vogt and their numerous collaborators (The Vogt–Vogt school) published a large number of myeloarchitectonic studies on the cortex of the various lobes of the human cerebrum. Recently, one of us (Nieuwenhuys in Brain Struct Funct 218: 303–352, 2013) extensively reviewed these studies. It was concluded that the data available are adequate and sufficient for the composition of a myeloarchitectonic map of the entire human neocortex. The present paper is devoted to the creation of this map. Because the data provided by the Vogt–Vogt school are derived from many different brains, a standard brain had to be introduced to which all data available could be transferred. As such, the colin27 structural scan, aligned to the MNI305 template was selected. The procedure employed in this transfer involved computer-aided transformations of the lobar maps available in the literature, to the corresponding regions of the standard brain, as well as local adjustments in the border zones of the various lobes. The resultant map includes 180 myeloarchitectonic areas, 64 frontal, 30 parietal, 6 insular, 17 occipital and 63 temporal. The designation of the various

R. Nieuwenhuys (&)
C. A. J. Broere
L. Cerliani The Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, Meibergdreef 47, 1105 BA Amsterdam, The Netherlands e-mail: [email protected]

areas with simple Arabic numbers, introduced by Oscar Vogt for the frontal and parietal cortices, has been extended over the entire neocortex. It may be expected that combination of the myeloarchitectonic data of the Vogt– Vogt school, as expressed in our map, with the results of the detailed cytoarchitectonic and receptor architectonic studies of Karl Zilles and Katrin Amunts and their numerous associates, will yield a comprehensive ‘supermap’ of the structural organization of the human neocortex. For the time being, i. e., as long as this ‘supermap’ is not yet available, our map may provide a tentative frame of reference for (a) the morphological interpretation of the results of functional neuroimaging studies; (b) the selection of starting points (seed voxels, regions-of-interest) in diffusion tractography studies and (c) the interpretation of putative myeloarchitectonic features, visualized by in vivo and ex vivo mappings of the cerebral cortex with high-field magnetic resonance imaging. Keywords Architectonics
Cerebral cortex
Cytoarchitectonics
Myeloarchitectonics
Neuroimaging
Nissl technique
Weigert technique Abbreviations acg Anterior cingulate gyrus ambg Ambient gyrus ang Angular gyrus aog Anterior orbital gyrus aos Arcuate orbital sulcus asg Accessory short gyrus of insula attg Anterior transverse temporal gyrus atts Anterior transverse temporal sulcus calcs Calcarine sulcus ces Central sulcus cesins Central sulcus of insula

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cisins cols cs csab cun fg icg ifg ifgor ifgop ifgt ifs ipl ips itg its lg1, 2 log los lotg ls lsab lsan lsp mfg mog mos motg mtg mtps mtts og olfs ots pcg pcl pcun phg pocg pocs pog pos prcg prcs pron pttg ptts rhs ris rss sfg sfs sg1, 2, 3

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Circular sulcus of insula Collateral sulcus Cingulate sulcus Cingulate sulcus, ascending branch Cuneus Fasciolar gyrus Isthmus of cingular gyrus Inferior frontal gyrus Inferior frontal gyrus, orbital part Inferior frontal gyrus, opercular part Inferior frontal gyrus, triangular part Inferior frontal sulcus Inferior parietal lobule Intraparietal sulcus Inferior temporal gyrus Inferior temporal sulcus First and second long gyrus of insula Lateral orbital gyrus Lateral orbital sulcus Lateral occipitotemporal (fusiform) gyrus Lateral sulcus Lateral sulcus, ascending branch Lateral sulcus, anterior branch Lateral sulcus, posterior branch Middle frontal gyrus Medial orbital gyrus Medial orbital sulcus Medial occipitotemporal (lingual) gyrus Middle temporal gyrus Medial temporopolar sulcus Middle transverse temporal sulcus Occipital gyri Olfactory sulcus Occipitotemporal sulcus Posterior cingulate gyrus Paracentral lobule Precuneus Parahippocampal gyrus Postcentral gyrus Postcentral sulcus Posterior orbital gyrus Parieto-occipital sulcus Precentral gyrus Precentral sulcus Preoccipital notch Posterior transverse temporal gyrus Posterior transverse temporal sulcus Rhinal sulcus Rostral inferior sulcus Rostral superior sulcus Superior frontal gyrus Superior frontal sulcus First, second and third short gyrus of insula

smg spl stg strg sts stsp tp unc

Supramarginal gyrus Superior parietal lobule Superior temporal gyrus Straight gyrus Superior temporal sulcus Superior temporal sulcus, posterior part Temporal plane Uncus of hippocampus

Introduction The human cerebral cortex contains numerous myelinated fibres, many of which are concentrated in tangentially organized layers and radially oriented bundles. The spatial organization of these fibres is by no means uniform throughout the cortex. Local differences in the width and compactness of the fibre layers, and the length and strength of the radial bundles render it possible to recognize areas with a different myeloarchitecture. The neuroanatomical subdiscipline aimed at the identification of such areas is named myeloarchitectonics. A related subdiscipline is known as cytoarchitectonics whose aims and scope are similar to those of myeloarchitectonics, viz. parcellation but focus on the size, shape and arrangement of the neuronal cell bodies in the cortex, rather than on the myelinated fibres. The terms cytoarchitectonics and myeloarchitectonics were both introduced by Vogt (1903). In 1905 Campbell published a monograph entitled ‘‘Histological studies on the localization of cerebral functions’’. This study is based on an analysis of serial sections through the human brain, stained with the Nissl-technique for neuronal cell bodies, and with the Weigert-technique for myelinated fibres. Campbell distinguished 16 cortical areas, the cytoarchitecture and myeloarchitecture of all of which were extensively described and recorded in beautiful drawings. It is of note that the resultant map (see Nieuwenhuys 2013, Fig. 6) represents the only combined cytoand myeloarchitectonic map of the entire human cerebral cortex produced thus far. A few years later, Elliot Smith (1907) published a map of the human cerebral cortex which was exclusively based on a macroscopic study of sections through fresh or freshly fixed brains. The most conspicuous fibre zones of the cortex, which are known as the outer and inner stripes of Baillarger (1840), are macroscopically visible in unstained preparations, manifesting themselves as whitish bands contrasting with the darker hue of the cortical grey matter. Using local differences in the width and distinctness of the stripes of Baillarger as the principal criteria for his parcellation, Elliot Smith was able to distinguish some 50

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sharply delineated areas in the human cortex. Remarkably, the resultant map (see Nieuwenhuys 2013, Fig. 7) represents the most recent myeloarchitectonic map of the entire human cortex available at present. During the period extending from 1910 to 1970, Oskar and Ce´cile Vogt (from now onward the Vogts) and their numerous disciples published a large number of myeloarchitectonic studies on the human cortex. Almost all of these were based on one or several serially sectioned cerebral hemispheres, stained with the Weigert technique (Table 1). These myeloarchitectonic studies formed part of a comprehensive research program (see Vogt 1903), which also included a cytoarchitectonic analysis of the human cortex entrusted to Korbinian Brodmann. The central aim of this program was the parcellation of the cortex into areas or fields, designated as ‘Rindenfelder’ or ‘topistische Einheiten’. The Vogts believed that the human cortex was composed of some 200 of such fields, which in their view represent structural as well as functional units (Vogt 1903, 1906; Vogt and Vogt 1919). They were convinced that cytoarchitectonics and myeloarchitectonics represent complementary approaches, leading to similar parcellations and, hence ultimately to a single architectonic map. In retrospect, it must be said that the—in essence absolutely sound—scientific ideas of the Vogts have never Table 1 The myeloarchitectonic studies of the human neocortex on which the present meta-analysis is based, in chronological order Author(s)

Structure

Brain(s) analysed

Vogt (1910) Vogt (1911)

Frontal lobe Parietal lobe

A 18 R A 18 R, A 20

Vogt and Vogt (1911)

Insula

A 18 L

Lungwitz (1937)

Occipital lobe

A 37

Strasburger (1937)

Frontal lobe

A 39 R

Strasburger (1938)

Broca’s region

A 20, A 22, A 27, A 34, A 38, A 39

Brockhaus (1940)

Insula

A 18, A 39, A 40, A 61, A 65, A 66

Gerhardt (1940) Hopf (1954, 1955)

Parietal lobe Temporal lobe

A 61 L* MB 59 L

Batsch (1956)

Parietal lobe

A 37 L

Braitenberg (1956)

Frontal lobe

?

Hopf (1956)

Frontal lobe

A 18, A 39

Hopf and Vitzthum (1957)

Parietal lobe

A 37 L

Sanides (1962, 1964)

Frontal lobe

A 58*, Ri 61

Hopf (1968a)

Temporal lobe

MB 59 L

Hopf (1968b)

Frontal lobe

A 18, A 39

Hopf (1969, 1970)

Parietal lobe

A 37 L

L left hemisphere, R right hemisphere. The sections of the brains marked with an asterisk were stained according to Heidenhain; those of all other brains were stained with modifications of the Weigert technique

received the attention they deserved. The results of the cytoarchitectonic and myeloarchitectonic parts of their program have been separately judged and, as we shall see, highly differently appreciated by the neuroscience community. Brodmann published in 1909 a monograph entitled:‘‘Vergleichende Lokalisationslehre der Grosshirnrinde in ihren Prinzipien dargestellt auf Grund des Zellenbaues’’, containing cytoarchitectonic maps of the cortex of a variety of mammals, including man. The human map showed a parcellation of the cortex into about 40 areas, which were designated with Arabic numerals. These areas were only cursorily described and systematic pictorial documentation was entirely lacking. In spite of these shortcomings, Brodmann’s map became world famous and represents up to the present by far the most widely used reference system for the localization of cortical functions. The results of the detailed and well-documented myeloarchitectonic studies of the Vogt–Vogt school, on the other hand, were never integrated into a single map. It was generally felt that Brodmann’s subdivision into some 40 areas came somewhere near to what is ‘reasonable’ and that the much more detailed myeloarchitectonic parcellations reported by the Vogts represented the fruits of a strange, ‘esoteric’ subculture, rather than the results of sound scientific research. Hence, the Brodmann cytoarchitectonic map became an icon of neuroscience, whereas the results of the myeloarchitectonic analysis of the cortex sank into oblivion. Needless to say the ultimate goal of the Vogt–Vogt enterprise, i.e. the creation of a unified (cytoarchitectonic ? myeloarchitectonic) parcellation of the human cortex, was never achieved. Recently, one of us (Nieuwenhuys 2013) scrutinized the total body of myeloarchitectonic studies on the human cortex of the Vogt–Vogt school. It was concluded that (1) the data available are adequate and sufficient for the composition of a myeloarchitectonic map of the entire human neocortex and that (2) a combination of the data embodied in this map with those of Brodmann (and other cytoarchitectonists) could lead to the architectonic ‘supermap’ once envisioned by the Vogts. The results of the meta-analytic research program just outlined will be communicated in four publications. In the first, i.e., the present publication, an atlas is presented consisting of eight standard views of the human telencephalon, generated from the colin27 brain average, provided by the Montreal Neurological Institute (http:// www.bic.mni.mcgill.ca/ServicesAtlases/Colin27). Next, the myeloarchitectonic data available in the literature are integrated and transferred to the plates of our atlas, using computer-aided topological transformations. Finally in this presentation, the myeloarchitectonic map of the human neocortex, thus obtained, will be evaluated and discussed.

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Brain Struct Funct b Fig. 1 Samples of the pictorial material on which the present meta-

analysis is based. Myeloarchitectonic parcellations of: a lateral aspect of frontal lobe (Vogt 1910); b medial aspect of parietal lobe (Gerhardt 1940); c superior aspect of temporal lobe (Hopf 1954); d inferior aspect of occipital lobe (Lungwitz 1937); e transverse sections through temporal lobe (Hopf 1954)

In the second publication a 3D version of our myeloarchitectonic map will be provided to facilitate use in computer-assisted research. In the third publication, the overall degree of myelination in the various myeloarchitectonic areas distinguished and charted in our map will be semi-quantitatively characterized and pictorially recorded as very low, low, medium, high and very high. This study will be principally based on data from Hopf (1955, 1956, 1968a, b, 1969, 1970) and Hopf and Vitzthum (1957). In the fourth and final publication of this series, our new myeloarchitectonic map of the human neocortex will be compared with the classic cytoarchitectonic map of Brodmann and with the results of the detailed cytoarchitectonic and receptorarchitectonic studies of Karl Zilles and Katrin Amunts and their numerous collaborators. Conceivably, these comparisons will yield a ‘supermap’ of the architecture of the human neocortex.

Materials and methods

Some of the publications employed contain, apart from lobar aspect maps, diagrammatic drawings of sets of sections through particular cerebral lobes, in which the results of the pertinent myeloarchitectonic analysis are indicated (e.g. Fig. 1e). We have used these sets of sections for the preparation of graphical reconstructions of some lobar aspect maps, which were lacking in the literature. All in all, our meta-analysis of the myeloarchitecture of the human neocortex is based on 43 lobar aspect maps: 39 of these were directly derived from the literature and the remaining four were reconstructed from published sets of transverse sections (Table 2). It is important to note that the starting material available for our meta-analysis of myeloarchitecture of the various cerebral lobes is unequal. Reference to Table 2 shows that for the analysis of the various aspects of the frontal, parietal, and insular lobes, Table 2 Some data related to our meta-analysis of the myeloarchitecture of the human neocortex A

B

D

Frontal Lateral

1

5

Medial

2

5

Superior

3

4

Inferior

4

5

Lateral Medial

5 6

4 4

Superior

7

4

Inferior

8

2

Lateral

9

2

Lateral

10

1

Medial

11

1a

Superior

12

1b

Inferior

13

1b

Lateral

14

1

Medial

15

1b

Superior

16

1

Inferior

17

1 43

Parietal

Material The publications on which the present meta-analysis is based are listed in Table 1. All of these publications relate to the cortex of one of the cerebral lobes, and all contain maps showing various aspects of the lobe studied, as for instance the lateral, medial, superior, and inferior aspects of the frontal lobe. From now onward we will designate these partial maps as lobar aspect maps. These lobar aspect maps, some of which are shown in Fig. 1a–d, form the starting material of this study. They generally show/contain the following features: (1) the external contour of the lobar aspect; (2) the course of principal sulci; (3) boundaries of myeloarchitectonic entities, and (4) symbols (numbers; combinations of letters), indicating the identity of the myeloarchitectonic entities distinguished. The boundaries of the myeloarchitectonic entities delineated are the fruits of microscopic studies carried out on myelin-stained serial sections through the various lobes (Table 1). In general, the myeloarchitectonic entities delineated in the various lobar aspect maps are of three kinds: regions, areas, and subareas. In our meta-analysis, we focused on the myeloarchitectonic areas and neglected the regional and sub-areal parcellations.

C

Insular Occipital

Temporal

Total

E

F

64

1–66c

30

67–96

6

97–103

17

103–119

63

120–182

180

A, cerebral lobes involved; B, aspects or views of these lobes studied; C, sequential numbers of these aspects; D, numbers of maps of each lobar aspect, available in the literature; E, number of myeloarchitectonic areas in each lobe; F, numerical designation of the various areas a

Partially reconstructed from published sets of transverse sections

b

Reconstructed from published sets of transverse sections

c

Areas 7 and 29 are lacking; see text

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two or more lobar aspect maps were available, whereas the starting material for the analysis of the occipital and temporal lobes was confined to a single map for each aspect. Introduction of a standard reference brain Because the data to be employed and the resultant lobar aspect maps are derived from many different brains (see Table 1), we have to introduce a standard reference brain, to be used as a template to which all data are to be transferred. As such, we have selected one of the brain templates provided by the Montreal Neurological Institute, viz. colin27, which is usually referred to as the ‘single subject MNI template’. The colin27 image is the result of averaging 27 linearly registered high-resolution T1-weighted scans of the same individual (Collins 1994; Holmes et al. 1998). The resulting average was then matched to the MNI305 space (Mazziotta et al. 2001). The colin27 template, which bears a highly detailed level of macroanatomical contrast, has been adopted by several neuroimaging software systems as the standard reference for representing results such as the cytoarchitectonic maps produced by Zilles and Amunts and their associates (see below). Here we make the same choice, to provide an overview of the myeloarchitecture of the neocortex on a template which is familiar to the vast majority of researchers in neuroimaging. We prepared four standard views, lateral, superior, medial and basal, from this brain, and four additional views Fig. 2 Lateral aspect of the standard brain

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including the orbitofrontal surface, the parietal operculum, the insula and the superior surface of the temporal lobe. The tracings from these eight views, which are shown in Figs. 2, 3, 4, 5, 6, form the standard reference atlas to be used throughout this project. In these figures, the frontal, parietal, occipital and temporal lobes of the cerebrum are indicated by different colours. Sulci, which feature in our starting material as landmarks, are accentuated and shown in red. Although the selected colin27 template brain appears to be fully suitable for the purpose indicated, it shows a few peculiarities worth mentioning. The Broca region of the inferior frontal lobe is very large, whereas the middle frontal gyrus is relatively narrow (Fig. 2). The superior temporal sulcus could not be traced into continuity with the groove marking the centre of the angular gyrus (Fig. 2). The collateral and cingulate sulci are both interrupted, and the posterior part of the latter shows a peculiar zigzag course (Fig. 4). Finally, the upper surface of the splenium of the corpus callosum shows a remarkable bump (Fig. 4). Procedure The procedure followed in the preparation of the new myeloarchitectonic map of the human neocortex, shown in Figs. 12, 13, 14, 15, 16, involved the following four steps: (1) establishing a neuroanatomical sequence for the partial analyses. (2) Transfer of the myeloarchitectonic information, contained within the various lobar aspect maps available in the literature, to the corresponding views of the

Brain Struct Funct Fig. 3 Superior aspect of the standard brain

Fig. 4 Medial aspect of the standard brain

Fig. 5 Inferior aspect of the standard brain

standard brain. (3) Creation of the four standard views of the cerebral hemispheres and (4) labelling of the myeloarchitectonic areas distinguished.

Ad 1. Establishing a neuroanatomical sequence for the partial analyses. All of the myeloarchitectonic studies on which the present meta-analysis is based relate to the

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Brain Struct Funct Fig. 6 Details of certain parts of the standard brain: a orbital surface of frontal lobe; b parietal operculum; c insula; d superior aspect of temporal lobe

cortex of particular cerebral lobes. We decided to process these studies in the following sequence: frontal lobe, parietal lobe, insula, occipital lobe, temporal lobe. For the composition of the new map in total 17 aspects of the various cerebral lobes were required: (1) lateral aspect of frontal lobe (Fig. 12); (2) superior aspect of frontal lobe (Fig. 13); (3) medial aspect of frontal lobe (Fig. 14); (4) inferior or orbital aspect of frontal lobe (Figs. 15, 16a); (5) lateral aspect of parietal lobe (Fig. 12); (6) superior aspect of parietal lobe (Fig. 13); (7) medial aspect of parietal lobe (Fig. 14); (8) inferior or opercular aspect of parietal lobe (Fig. 16b); (9) lateral aspect of insula (Fig. 16c); (10) lateral aspect of occipital lobe (Fig. 12); (11) superior aspect of occipital lobe (Fig. 13); (12) medial aspect of occipital lobe (Fig. 14); (13) inferior aspect of occipital lobe (Fig. 15); (14) lateral aspect of temporal lobe (Fig. 12); (15) superior aspect of temporal lobe or planum temporale (Fig. 16d); (16) medial aspect of temporal lobe (Fig. 14) and (17) inferior aspect of temporal lobe (Fig. 15). Ad 2. Transfer of the myeloarchitectonic information contained within the various lobar aspect maps available in the literature, to the corresponding views of the standard brain. For this operation we developed two algorithms, one simple and the other complex.

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The simple algorithm This was used in cases in which only a single source, i.e. a single map of the myeloarchitectonic parcellation of the pertinent aspect, appeared to be available in the literature. This lobar aspect map was harmoniously transformed towards the corresponding aspect of the standard brain, using GIMP image analysis software [www. gimp. org., version 8.2.6; specifically: the Cage Transfer Tool, as described in Lacarme and Delvare 2013)]. In this transformation, not only the outer contour of the original map, but rather its entire ‘content’, including the course of sulci and the boundaries of myeloarchitectonic areas, were involved (Fig. 7). If it appeared that, after this transformation, important sulci conspicuously present in the original map as well as in the corresponding template brain map did not match, the pertinent sulci in the original map were brought into conjunction with those of the template brain map by means of additional adjustments, in which, as a matter of course, the local boundaries of the myeloarchitectonic areas were included. After these additional adjustments, the meta- analytical myeloarchitectonic map of the pertinent aspect is completed. The complex algorithm In cases in which two or more myeloarchitectonic maps of a particular aspect were present in the literature, all of these maps were individually

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Fig. 7 Computer-aided topological transformation of Vogts’ (1910) myeloarchitectonic parcellation of the medial frontal lobe (left) to the corresponding region of the standard brain (right)

transferred to the corresponding view of our template brain, according to the simple algorithm indicated above. Next, the maps resulting from these individual transfers were superimposed. The end product of our analysis of the pertinent aspect was produced by averaging of the boundaries of equivalent myeloarchitectonic areas. This algorithm is applicable for the following special reason. All of the aspects of which two or more local maps are available in the literature (i.e. the frontal, parietal and insular lobes, see Table 2) were first analysed by Oskar Vogt. This author designated the results of his parcellations, i.e., the myeloarchitectonic areas, with simple Arabic numerals (Figs. 1a, 8a). Remarkably, all later students of the same lobar aspect were able to detect and delineate equivalents of all (or almost all, see below) of the myeloarchitectonic areas previously distinguished by Oskar Vogt. The equivalences were determined on the basis of similarities in structure and overall position of the areas. Due to this unanimity, the boundaries of corresponding or equivalent myeloarchitectonic areas could be averaged. Ad 3. Composition of the standard views. The four standard views of our new map, lateral (Fig. 12), superior (Fig. 13), medial (Fig. 14) and inferior (Fig. 15), were

created from their respective lobar partial maps (see above). The authors who produced these maps accept certain prominent sulci, including the central sulcus (Figs. 2, 3) and the parieto-occipital sulcus (Fig. 4), as natural lobar boundaries. The remaining lobar boundaries in their maps all coincide with boundaries of myeloarchitectonic areas, but are otherwise arbitrary. This explains why most boundaries of lobar aspects, when they were joined together in a given standard view, showed several small gaps and/or overlaps. In the final versions of our four standard views (Figs. 12, 13, 14, 15), these discrepancies were cancelled out by local adjustments. In advance of the preparation of the 3D version of our map (Nieuwenhuys, Broere and Cerliani, in prep.), the four standard views were matched by means of additional adjustments. Ad 4. Labelling of the myeloarchitectonic areas. In his pioneering investigations on the myeloarchitecture of the frontal and parietal lobes, Vogt (1910, 1911) labelled the delineated myeloarchitectonic areas with simple Arabic numerals, as already mentioned. This numbering has been adopted in all later studies on the myeloarchitecture of these lobes. In the present study, we extended Vogts’ numbering of myeloarchitectonic areas over the entire neocortex

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Brain Struct Funct Fig. 8 Preparation of a metaanalytical myeloarchitectonic map of the medial parietal cortex; step one. Myloarchitectonic maps of the medial parietal cortex according to a Vogt (1911), b Gerhardt (1940) and c Hopf (1956), and of the posterior part of the medial frontal lobe c’ according to Hopf (1956). The three maps of the medial parietal cortex (a– c) are individually transformed to the corresponding part of our template brain (d–f)

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(Table 2). It should be emphasized that the numerals used in our map have nothing to do with those also Arabic, used by Brodmann (1909) for his cytoarchitectonic areas.

Preparation of the new myeloarchitectonic map The literature on which our new map is based has been extensively reviewed by one of us (Nieuwenhuys 2013). In this publication most of the lobar aspect maps on which the new map is based are included. The new map is composed of the results of eight simple and nine complex transformations (see above). It is unfeasible to present detailed descriptions of all of these transformations; hence, we decided to discuss one of these, viz. the complex transformation which has led to the medial view of the parietal lobe, in some detail and to confine ourselves with regard to the remaining transformations, to some notes. Preparation of the map, showing the myeloarchitectonic parcellation of the medial parietal cortex (a) Our meta-analysis of the of the myeloarchitecture of the medial parietal cortex is based on the studies of Vogt (1911), Gerhardt (1940), Batsch (1956), and Hopf (1956), all of which contain myeloarchitectonic maps of the pertinent region. The maps of the two authors first mentioned are reproduced in Fig. 8a, b. Because the map of Hopf and Vitztum represents a slightly modified version of that of Batsch, only the map of the former two authors is reproduced here (Fig. 8c). (b) In the maps of Vogt, Gerhardt and Batsch, the posterior boundary of the medial parietal cortex is marked by the parieto-occipital sulcus, whereas the basal boundary is formed by the anterior part of the calcarine sulcus and the corpus callosum. The medial end of the central sulcus marks the superior border of the medial parietal cortex, and slightly more posteriorly, the ascending branch of the cingulate sulcus characteristically traverses the anterior medial parietal region. All of the landmarks mentioned are clearly present in our standard reference brain (Fig. 4) and will be considered as invariants in our transformations. (c) Vogt (1911) divided the medial parietal cortex into 21 myeloarchitectonic areas, which he designated with the numbers 67, 69–71, 75–85, and 91–96 (Fig. 8a). Gerhardt (1940), Batsch (1956) and Hopf and Vitzthum (1957) recognized equivalents of all of these ‘Vogt-areas’ in their material and designated them with the same numerals (Fig. 8b, c). All of the authors mentioned divided some of the parietal areas into two or more subareas (Fig. 8a–c). We decided to leave these subareas out of consideration in our meta-analysis, the more so because there appeared to

be no clear one-to-one correspondences at this level among the various authors. (d) Following the complex algorithm described in the previous section, the three parcellations of the medial parietal cortex (Fig. 8a–c) were individually transformed to the corresponding part of our standard brain (Fig. 8d–f). (e) The three transformations (Fig. 8d–f) were superimposed (Fig. 9a) and the boundaries of the individual myeloarchitectonic areas were determined by averaging (Fig. 9b). The averaging procedure of two areas, 67 and 84, is detailed in Fig. 10. In cases in which the superimposed transformed maps (Fig. 9a) showed that the boundaries of a given area, as determined by two authors, closely match, whereas that of the third author(s) clearly deviate(s), the deviating boundary was left out of consideration in the final transformation (Fig. 9a, b). The anterior boundaries of areas 67, 77 and 78 are cases in point. The anterior boundaries of area 67, as determined by Vogt (Fig. 8a, d) and Gerhardt (Fig. 8b, e) correspond well (Fig. 9a), whereas the corresponding 67-69-70 boundary in the Batsch-Hopf-Vitztum map lies far posteriorly, close to the ascending branch of the cingulate sulcus (Fig. 8c, f). Hence, we neglected the ‘Batsch-Hopf-Vitztum’ boundary in our final transformation and averaged the ‘Vogt’ and ‘Gerhardt’ boundaries (Fig. 9). This neglect of the ‘Batsch-Hopf-Vitztum’ boundary is justified by the considerable mismatch which appears if we bring the anterior border of the medial parietal cortex, as determined by Batsch-Hopf-Vitztum (Fig. 8c), into apposition with the posterior border of the medial frontal cortex, as determined by (Hopf 1956; Fig. 8c’). As regards the anterior boundaries of areas 77 and 78, it appeared that these boundaries, as determined by Gerhardt (Fig. 8b, e), and Batsch-Hopf-Vitztum (Fig. 8c, f), match fairly well, whereas those determined by Vogt are situated more posteriorly (Fig. 8a, d). In this case, we also disregarded the aberrant ‘Vogt’ boundary and constructed the final anterior boundary of areas 77 and 78 by averaging the ‘Gerhardt’ and the ‘Batsch-Hopf- Vitztum’ boundaries (Fig. 9). (f) All students of the myeloarchitecture of the human neocortex implicitly agree that myeloarchitectonic areas do not extend beyond the boundaries of the lobe within which they are situated. At the posterior side of the parietal lobe, the boundary between the medial parietal areas and the medial occipital areas is consistently marked by the parieto-occipital sulcus (Figs. 4, 9). Anteriorly, such a natural border is lacking; hence, the medial frontoparietal border has to be constructed. If we compare the posterior border of our map of the medial frontal cortex, which is the product of our complex algorithm (Fig. 11a), with that of the anterior border of our map of the medial parietal cortex (Fig. 11c), it appears that superiorly there is an overlap of frontal area 42 with parietal areas 67 and 69, whereas inferiorly there is an overlap of frontal areas 20, 24, 32 and

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Fig. 9 Preparation of a meta-analytical myeloarchitectonic map of the medial parietal cortex; step two. The three maps resulting from the transformations shown in Fig. 8 are superimposed (a), and the

boundaries of the individual myeloarchitectonic areas are determined by averaging (b)

Fig. 10 Determination of the size and shape of two individual parietal areas by averaging: area 82 (a), and area 76 (b)

39 with parietal areas 67, 77 and 78 (Fig. 11b). The ultimate medial frontoparietal border shown in our map (Fig. 14) is the product of slight adjustments aimed at eliminating these overlaps. Preparation of the maps, showing the myeloarchitectonic parcellation of the remaining aspects of the various lobes (a) The frontal lobe. Our meta-analysis of the myeloarchitecture of the cortex of this lobe is based on the studies of Vogt (1910), Strasburger (1937, 1938), Braitenberg (1956), Hopf (1956) and Sanides (1962, 1964). The papers of Vogt (1910), Strasburger (1937) and Hopf (1956) deal

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with all parts of the frontal cortex. Sanides (1962, 1964) excluded the cingulate region from his analysis, whereas Braitenberg (1956) essentially confined himself to the Broca- and lateral orbitofrontal regions. Vogt (1910) delineated 66 myeloarchitectonic fields in the frontal lobe, which he designated with the Arabic numerals 1–66. All later students of the myeloarchitecture of the frontal lobe adopted the numbering system of Vogt for the various areas. They failed, however, to identify Vogts’ areas 7 and 29. For this reason these two areas have been deleted from our map. It is noteworthy that Strasburger (1937) and Hopf (1956) remained unable to delineate area 45 from 46 and that they considered area 40 of Vogt and Sanides (Fig. 12) as the inferior part of area 38.

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Fig. 11 Medial frontoparietal matching. The figure shows (a) the posterior part of our map of the medial frontal cortex, (c) the anterior part of our map of the medial parietal cortex, and (b) superposition of the posterior border of (a) and the anterior border of (c)

The extent of the areas 52 and 53, which occupy the anterior portion of the middle frontal gyrus, varies considerably among the different authors. Thus, according to Vogt (1910), area 52 is very large, and area 53 is only small, whereas Strasburger (1937) and Hopf (1956), on the other hand, found that area 53 is large and that area 52 is confined to the orbitofrontal cortex. Sanides (1962, 1964), finally, reported that areas 52 and 53 can both be delineated on the lateral surface of the frontal lobe and are of about equal size. The compromise concerning the extent of areas 52and 53, as shown in Fig. 12, was attained with difficulty. The posterolateral portion of the orbitofrontal cortex is another region in which the myeloarchitectonic parcellations of the various authors appear to show considerable differences. Strasburger (1938), who presented a detailed analysis of areas 56–66 in both hemispheres of six different brains, noticed that area 60 can be situated in front, within, as well as behind the arcuate orbital sulcus (Figs. 6a, 15, 16a). Finally, it should be mentioned that area 43, which is actually hidden in the central sulcus, is exposed as a narrow strip in Figs. 12 and 13. (b) The parietal lobe. Our meta-analysis of the myeloarchitecture of the parietal cortex is, as already mentioned, based on the studies of Vogt (1911), Gerhardt (1940), Batsch (1956), and Hopf (1956). Vogt (1911) subdivided the parietal cortex into 30 myeloarchitectonic areas, which he numbered 67–96. All of these areas were also recognized by Gerhardt, Batsch and Hopf and Vitztum, and numbered accordingly. In the complex transformations leading to the superior and lateral aspects of the parietal lobe in our map (Figs. 12, 13), the central, postcentral, intraparietal, lateral and superior temporal sulci were used as invariants. In these two aspects, the

anterior surface of the postcentral gyrus is folded anteriorly. By this transformation, areas 67 and 68, which are actually hidden in the central sulcus, are exposed. Our map of the myelarchitecture of the parietal operculum (Fig. 16b), which is based on corresponding maps of Vogt (1911) and Batsch (1956), is somewhat arbitrary. This is due to the fact that constant sulci, which can be used as invariants, are lacking in this region. Because of the relations found on the lateral surface of the parietal lobe (Fig. 12), the basal end of the postcentral sulcus was used to determine the medial beginning of the boundary between areas 72 and 84 on the opercular surface (Fig. 16b). (c) The insula. The myeloarchitecture of the insula has been studied by Vogt and Vogt (1911) and by Brockhaus (1940). Vogt and Vogt divided the insular cortex into an inferior allocortical zone and a superior neocortical zone. Within the latter, they distinguished six, anteroposteriorly arranged areas, which they designated as i1–i6. Most of the boundaries of these areas appeared to coincide with the sulci separating the various insular gyri (Fig. 6c). The results of the very detailed, combined cyto- and myeloarchitectonic study of Brockhaus (1940) tallied, so far as the neocortex is concerned, with that of the Vogts, with the reservation that the areas i4–i6 were subdivided into several subareas. Confining ourselves to the areal level and continuing the numbering system of Vogt (1910, 1911) and Vogt and Vogt (1919), we designated the insular areas i1– i6 as 97–102 (Fig. 16c). (d) The occipital lobe. As is well known, Brodmann (1909) divided the human occipital cortex into three concentrically arranged cytoarchitectonic areas, the area striata (17),—occipitalis (18) and—praeoccipitalis (19). The only detailed myeloarchitectonic study on the

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Fig. 12 Our new myeloarchitectonic map of the human neocortex; lateral aspect

Fig. 13 Our new myeloarchitectonic map of the human neocortex; superior aspect

occipital cortex is that of Lungwitz (1937). This author found that the boundaries between the three occipital cytoarchitectonic areas of Brodmann have distinct myeloarchitectonic counterparts, but he confined his analysis to the preoccipital area. In this area he delineated 17 myeloarchitectonic fields, which he designated with combinations of two-to-four letters, such as pc, del, elsc. We

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transferred these fields to our map and indicated them with the numbers 103–119. For the correspondence between Lungwitz’ designations and our numbering we refer to Table 3. For the occipital areas not analysed by Lungwitz we maintained Brodmanns’ numbers: (BA) 17 and 18. The publication of Lungwitz does not include maps of the superior surface of the occipital cortex and of

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Fig. 14 Our new myeloarchitectonic map of the human neocortex; medial aspect

Fig. 15 Our new myeloarchitectonic map of the human neocortex; inferior aspect

the inferior part of the medial occipital cortex. We constructed maps of these regions from the series of diagrammatic transverse sections through the occipital lobe, included in the paper (Lungwitz 1937: Figs. 23–43) and transferred these maps to the corresponding regions of our standard brain (Figs. 13, 14).

(e) The temporal lobe. Our meta-analysis of the cortex of the temporal lobe is based on the detailed studies of Hopf (1954, 1955, 1968a). Hopf distinguished 63 myeloarchitectonic areas in the temporal lobe, which he designated with extensive full Latin names and corresponding abbreviations. Continuing the numbering of Vogt (1910,

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Fig. 16 Details of certain parts of our new myeloarchitectonic map of the human neocortex: a orbitofrontal region; b parietal operculum; c insula; d supratemporal plane. Note that the latter is depicted twice as large as the remaining three parts

1911), we indicated these areas with the numbers 120–182. For the correspondence of these numbers with Hopfs’ abbreviations, we refer to Table 4. Hopfs’ publications do not contain a map of the medial aspect of the temporal lobe. Such a map could be constructed, however, from the diagrammatic transverse sections, included in Hopf (1954: Diagr. 1–18). In the transformation of Hopfs’ maps to the corresponding parts of the standard brain, not only the external contours, but also the superior temporaland occipitotemporal sulci were considered as invariants.

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The cortex covering the superior surface of the temporal lobe is myeloarchitectonically highly differentiated and contains, according to Hopf (1954) 37 distinct areas (Fig. 16d). The transverse temporal gyri of Heschl, which sculpture this surface, are extremely variable in width and distinctness. In our standard brain, the anterior transverse temporal gyrus (Figs. 6d, 16d) appeared to be much narrower than the corresponding structure in the brain on which Hopfs (1954) myeloarchitectonic parcellation of the temporal lobe was based (Fig. 1c).

Brain Struct Funct Table 3 Correlation between Lungwitz (1937) designations of myeloarchitectonic areas in the occipital cortex and the numbers used for these areas in the present study edl,

103

eld,

107

dpp,

111

sced,

115

eda,

104

pt,

108

del,

112

scd,

116

edt,

105

elsc,

109

pc,

113

sct,

117

elt,

106

edpc,

110

scet,

114

scel,

118

pp,

119

Discussion The map The aim of the present study was the creation of a myeloarchitectonic map of the human neocortex based on data provided by the Vogts and their numerous collaborators (Table 1). Because these data are derived from many different brains, a standard brain had to be introduced to which all data available could be transferred. As such, brain template colin27 of the Montreal Neurological Institute was selected. The procedure followed in this transfer involved computer-aided transformations of the lobar maps available in the literature to the corresponding regions of the standard brain, as well as local adjustments in the border zones of the various lobes. The resultant new myeloarchitectonic map of the human neocortex is shown in Figs. 12, 13, 14, 15, 16. It comprises 180 areas: 64 frontal, 30 parietal, 6 insular, 17 occipital and 63 temporal. The highest area number is 182 rather than 180, because the presence of two areas in the frontal cortex, delineated and numbered 7 and 29 by Vogt (1910), could not be confirmed by any of the later students of the myeloarchitecture of the frontal cortex and hence are lacking in our map. The number of areas in our map is much higher than

Table 4 Correlation between the abbreviations used by Hopf (1954) for the myeloarchitectonic areas in the temporal cortex and the numbers with which these areas are designated in the present study

that in the combined cyto- and myeloarchitectonic map of Campbell (1905), which amounted to 16, and that in the myeloarchitectonic map ‘avant la lettre’ of Elliot Smith (1907), which was about 50. It is also higher than that in any of the cytoarchitectonic maps produced so far: Brodmann 1909, 1914): 43, Von Economo and Koskinas (1925): 107, Bailey and von Bonin (1951): 8, and Sarkissov et al. (1955): 71. On the other hand, the number of myeloarchitectonic areas in our map corresponds, not surprisingly, very well to the repeated estimations of the Vogts, according to which the human cortex is composed of about 200 architectonic units (Vogt 1951; Vogt and Vogt 1919, 1928). If we take into consideration that the Vogts included, apart from neocortical areas also allocortical areas in their estimation, their number appears to be practically identical to ours. The myeloarchitectonics of the cerebral cortex as a neuroanatomical subdiscipline The minute parcellations of the human cortex, resulting from the myeloarchitectonic studies of the Vogt–Vogt school have met with great mistrust and skepticism. Thus, Bailey and von Bonin (1951) reported in their extensive cytoarchitectonic analysis of the human cortex that vast regions of the frontal, inferior parietal, parieto-occipital and temporal regions form a continuum, showing a homogeneous cellular structure throughout and that they rejected for this reason ‘‘the excessive parcellations of the Vogt, Economo and Filimonoff schools as misleading and insignificant’’. Le Gros Clark (1952, p. 104) concluded a laudatory review of the work of Bailey and von Bonin (1951) who, it should be recalled, distinguished only 8 areas in the human neocortex, as follows: ‘‘Finally,

tp.m.i

120

tsep.l.a

136

ttr.lcm.ep

152

tmag.v.pif

tp.m.e

121

tsep.l.md

137

ttr.lcm.ip

153

tmag.cd.if

168 169

tp.m.p

122

tsep.l.p

138

ttr.2.ae

154

tmag.cd.s

170

tp.m.pt

123

tsep.l.pf

139

ttr.2.ai

155

tmag.cd.p

171

tp.m.if

124

tsep.m.e

140

ttr.2.pe

156

tmag.cd.lim

172

tp/mti

125

tsep.m.i

141

ttr.2.pi

157

tmag.cv.a

173

tp/mtm

126

tpari.l

142

tpartr.pf

158

tmag.cv.p

174

tp.v.if tp.v.s

127 128

tpari.im tpari.m

143 144

tpartr.a tpartr.p

159 160

tlim.o.a tlim.o.md

175 176

tp.l

129

ttr.lol.i

145

tpartr.s

161

tlim.o.p

177

tp.d.e

130

ttr.lol.md

146

tmag.d.as

162

tlim.o.i

178

tp.d.i

131

ttr.lol.e

147

tmag.d.aif

163

tlim.c.e

179

tp.d.p

132

ttr.lcl

148

tmag.d.md

164

tlim.c.i

180

mtm

133

ttr.lom.a

149

tmag.d.s

165

tlim.m.e

181

mti

134

ttr.lom.p

150

tmag.d.p

166

tlim.m.i

182

mtl

135

ttr.lcm.a

151

tmag.v.as

167

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Brain Struct Funct

neurologists should continue to regard with the greatest suspicion the incredibly complicated ‘‘crazy pavement’’ maps of cortical areas which have from time to time been elaborated by the Vogt school since Campbell’s and Brodmann’s original studies were first published’’. Sholl (1956, p. 24), finally, pointed out that whereas most architectonists relied on Nissl staining techniques, C. and O. Vogt and their pupils preferred some modification of the Weigert method and depended on suspected differences in the numbers and arrangement of myelinated fibres in different parts of the cortex. He continues with stating ‘‘These workers, carried their process of subdivision to an extreme that can only be described as fantastic and, moreover, maintained that each of these subdivisions had a sharp boundary from its neighbour.’’ The reasons for this lack of confidence in myeloarchitectonics and the results obtained therewith include (1) lack of acquaintance with the quirks of the Weigert technique, (2) lack of experience with the myeloarchitectonic approach, and (3) the complexity of the myeloarchitectonic terminology. Ad 1. The preparation of Weigert-stained sections suited for the study of the intracortical myelinated fibres requires great skill and experience. This expertise was abundantly present in the laboratories of the Vogts. The name of their chief technician, Margarete Woelcke, should be especially mentioned in this context. Ad 2. Beyond the Vogt–Vogt school, serious attempts at practising myeloarchitectonics have hardly been made. von Bonin and Bailey (1947, p. 18) stated at the beginning of their extensive architectonic studies: ‘‘We have attempted to study sections stained for myelin fibres, but time and again it became obvious that slight, almost unavoidable, local variations in the degree of differentiation suggested areal differences which, on closer scrutiny, could not be upheld. We have thus learned to distrust myeloarchitecture, at least so far as our own preparations are concerned. The only method which gives reliable results within wide limits of techniques is the Nissl method or its various modifications’’. All of this stands in stark contrast to the following statement of Hopf (1964, p. 6), a very experienced myeloarchitectonist: ‘‘If one is well versed in myeloarchitecture, one can easily assess structural differences and distinguish them readily from artifacts’’. Ad 3. As detailed in a previous publication (Nieuwenhuys, 2013), Vogt (1910, 1911) focused in his pioneering studies on the myeloarchitecture of the frontal and parietal cortices on differences in (a) the distinctness of the stripes of Baillarger and (b) the length of the of the radial bundles. As regards the first feature, he distinguished bistriate, unistriate, unitostriate and astriate types; as regards the second feature, he noted the presence of infraradiate, mesoradiate and supraradiate types. However, it appeared

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that an adequate description of all of the areal differences detected, required time and again the introduction of additional terms, referring, inter alia, to the overall wealth of myelinated fibres in a given area, the distribution of fibres within the various cortical layers and the size and course of certain individual fibres within the various areas. So, the Vogts and their collaborators ended up with a myeloarchitectonic vocabulatory encompassing more than 80 terms (Wahren 1960). Careful comparison of the detailed descriptions of the various cortical areas in the literature reviewed (Table 1) with the accompanying pictorial documentations has convinced us of the correctness and adequacy of the, admittedly very complex, myeloarchitectonic terminology. It is concluded that the criticism, levelled in the literature against the study of the disposition of myelinated fibres in the cortex with the aid of the Weigert technique or its variations, is undeserved and that the myeloarchitectonics of the cortex, as practised by the Vogts and their associates, is an absolutely sound neuroanatomical subdiscipline. The reliability of the parcellation of the neocortex, as shown in our map (Figs. 12, 13, 14, 15, 16) (a) We have seen that Vogt (1910, 1911) delineated in his pioneering myeloarchitectonic studies of the frontal and parietal lobes 66 areas in the frontal cortex and 30 areas in the parietal cortex. It is remarkable that all later students of the myeloarchitecture of the frontal lobe (Strasburger 1937; Hopf 1956; Sanides 1962, 1964) were able to detect 64 of the 66 ‘Vogt areas’ and that all later students of the parietal lobe (Gerhardt 1940; Batsch 1956; Hopf and Vitzthum 1957) were even able to confirm the presence of all of the 30 ‘Vogt areas’. (b) Strasburger (1938) presented a detailed myeloarchitectonic analysis of frontal areas 56–66, as distinguished by Vogt (1910), in both hemispheres of six human brains (Table 1). With a single exception (area 63 in A 20L), all of the 12 areas could be readily identified in all of the 12 hemispheres investigated. (c) The myeloarchitectonic analyses of Sanides (1962, 1964: frontal lobe). Gerhardt (1940: parietal lobe) and Brockhaus (1940: insula) actually formed part of combined cyto- and myeloarchitectonic studies. In all of these studies a perfect match of the cytoarchitectonic and myeloarchitectonic parcellations was ascertained. (d) Ngowyang (1934) has carried out a detailed cytoarchitectonic analysis of the cortex of the human frontal lobe. His results show a striking resemblance to Vogt’s (1910) myeloarchitectonic parcellation of the cortex of the same lobe. (e) It is true that the myeloarchitecture of the cerebral cortex, as practised by the Vogt–Vogt school is, by and

Brain Struct Funct

large, a purely descriptive and qualitative subdiscipline. It is of note, however, that the presence of numerous myeloarchitectonic areas has been confirmed by objective registrations of myeloarchitectonic features with photometric techniques (Braitenberg 1962; Hopf 1966, 1968a, b, 1969, 1970). (f) During the past decades, the C. & O. Vogt Institute of Brain Research in Du¨sseldorf and the Institute of Brain Research and Medicine, INM-1 and INM-2, Research Centre Ju¨lich, have produced a large number of detailed studies on the architecture of the human cerebral cortex (Geyer et al. 1996: primary motor cortex; Zilles et al. 1996: premotor cortex; Palomero-Gallagher et al. 2008: anterior cingulate cortex; Amunts and Zilles 2012; Amunts et al. 2010: Broca’s region; Bludau et al. 2013: frontal pole; Geyer et al. 1997: primary somatosensory region; Zilles and Palomero-Gallagher 2001; Scheperjans et al. 2005, 2008a, b: superior parietal cortex; Caspers et al. 2006, 2008: inferior parietal cortex; Eickhoff et al. 2006a, b: parietal operculum; Kurth et al. 2010: posterior insular cortex; Morosan et al. 2005: superior temporal gyrus; Zilles et al. 2004, Eickhoff et al. 2008: visual cortex). These studies, in which the results of quantitative, observerindependent cytoarchitectonic analyses (cf. Schleicher et al. 2005, 2009) are usually combined with receptorarchitectonic data (cf. Zilles and Amunts 2009), have shown that most of the cytoarchitectonic areas, delineated by Brodmann (1909, 1914), are divisible into two or more smaller units. Jones (2008, p. 2231) aptly remarked about the studies of the C. & O. Vogt Institute, just reviewed, that their numbers, though not yet finished, ‘‘seem well on the way to approximating those of the Vogts’’. (g) Combining data derived from the results of the research of the C. & O. Vogt Institute (see above), with the results of a detailed multiarchitectonic study of the ¨ ngu¨r human orbital and medial prefrontal cortex by O et al. (2003), and with numerous retinotopic fMRI mappings, Van Essen et al. (2012) estimated the total number of human neocortical areas to be about 150–200 areas. Taken together, the data presented above strongly suggest that our map, with regard to both number and position of areas, presents a realistic picture of the architecture of the human neocortex. Limitations of our map Our map shows the following important limitations: (a) It is incomplete. Myeloarchitectonic data on the occipital cortex are confined to the equivalent of Brodmann’s area 19 (Lungwitz 1937). Hence, we maintained

for the remainder of this cortex, provisionally, Brodmann’s designations (BA) 17 and 18 (Figs. 12, 13, 14, 15). (b) The map only shows the exposed, and not the intrasulcal, parts of the various areas. This is a serious limitation because in the human almost two-thirds of the cortex are hidden away in the depths of the sulci. It is of note, however, that the studies of Strasburger (1937), Batsch (1956), Lungwitz (1937, see Fig. 1e) and Hopf (1954), contain diagrammatic drawings of sets of sections through the frontal, parietal, occipital and temporal lobes, respectively, showing the myeloarchitectonic parcellation of the hidden portions of the cortices of these various lobes. (c) The map does not yield any information on the interhemispheric and interindividual variability of the various myeloarchitectonic areas. This is another serious limitation because this variability is known to be considerable for numerous areas (see, e. g. Fig. 10). Fundamental significance of our map Vogt and Vogt (1919, 1954, 1956) were convinced that the cytoarchitecture and the myeloarchitecture of the neocortex represent two aspects of the same reality. They explained the discrepancy between the relatively low number of cytoarchitectonic areas in the human cortex, distinguished by Brodmann (1909), and the much higher number, resulting from their own myeloarchitectonic studies by claiming that Brodmann had missed numerous boundaries (Vogt 1918). Vogt and Vogt (1919) emphasized to have found cytoarchitectonic counterparts of all of their myeloarchitectonic cortical areas. This finding is confirmed by the studies of Brockhaus (1940), Gerhardt (1940) and Sanides (1962, 1964), who carried out detailed combined cytoarchitectonic and myeloarchitectonic analyses on different parts of the human neocortex and reported complete concordance of the results obtained with the two approaches. Moreover Hellwig (1993), building on earlier work of Braitenberg (1974, 1978), was able to demonstrate that the myeloarchitectonic pattern of a given area of the human cortex can be computed and graphically displayed from cytoarchitectonic data derived from that area. Karl Zilles, Katrin Amunts and their numerous collaboraters are currently working on a mega-project, aimed at producing a probabilistic map of the human neocortex, based on quantitative, observer-independent cytoarchitectonic and receptorarchitectonic analyses of the brains of ten different individuals (see above). In light of what has been said above about the relationship between cytoarchitecture and myeloarchiteture, it may be expected that combination of the results of the Zilles-Amunts school, with those of the Vogt–Vogt school, as expressed in our map, will yield a comprehensive ‘supermap’ of the structural organization of the human neocortex.

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Brain Struct Funct

Practical significance of our map (a) The T1 signal in MRI is increasingly being used to characterize cortical regions according to relative differences in their estimated myelin content (Geyer et al. 2011; Geyer 2013; Glasser and Van Essen 2011; Van Essen and Glasser 2013; Glasser et al. 2013). It may be expected that our map will be helpful in the interpretation of the results of these in vivo and ex vivo MRI-based mappings. Additionally, recent developments in ultra-high field imaging at 7T are providing unprecedented spatial resolution at the submillimeter scale, raising the challenge of quantifying layer- specific differences in myelination (Turner and Geyer 2014; Waehnert et al. 2013). While very exciting results have already been obtained (Bazin et al. 2013; Lutti et al. 2013), methods of image acquisition and post-processing are still under development. In this context, we believe that our map represents a valid point of departure for the generation of experimental hypotheses regarding the location of myeloarchitectonic borders and layer-specific features of different cortical regions. This holds in particular for a special map, showing the overall fibre density in the various myeloarchitectonic areas, now in progress. This special map is based on the myeloarchitectonic feature-mapping studies and the photometric fibre-density registrations of Hopf (1955, 1956, 1968a, b, 1969, 1970), and Hopf and Vitzthum (1957). (b) The fact that each of the cortical areas displays a specific architecture indicates, according to Vogt and Vogt (1954), that each of these areas subserves a specific func¨ ngu¨r et al. tion. Similar ideas have been expressed by O (2003) and Roland and Zilles (1998). If so, it may be expected that the architectonic parcellation of the cortex provides an adequate framework for the anatomical interpretation of the results of functional imaging studies on the human brain. In such studies it is common practice to estimate the microstructural features of the activation foci detected by transferring these loci to the 3-D version of Brodmann’s map, incorporated in the stereotaxic reference system of Talairach and Tournoux (1988). However, it has become increasingly clear that this modified ‘Brodmannmap’ does not provide the morphological precision and accuracy for an adequate microstructural characterization of the locations where fMRI-activations were detected (Toga and Thompson 2007; Zilles and Amunts 2010; Geyer et al. 2011). There can be no doubt that the probabilistic multiarchitectonic map mentioned above, once completed, will offer an optimal tool for relating activation loci derived from fMRI-experiments to microstructural features. For the time being, i.e. as long as this ‘supermap’ is not yet available, our detailed myeloarchitectonic map may provide a useful provisional guide to the neural correlates of activation foci detected with fMRI. By reporting

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our myeloarchitectonic map onto the colin27 template, we provide an estimate of the location of different myeloarchitectonic areas superimposed onto an anatomical template, widely familiar to the neuroimaging community. Since the colin27 was registered to the MNI305 template, the forthcoming 3D version of our map will be matched into the standard system of coordinates of the MNI space, enabling its use in many popular neuroimaging software packages. (c) The fibre-streams, which form the human subcortical white matter, can be reconstructed with in vivo diffusion MRI tractography. Gross anatomical features (e. g. Gong et al. 2009) or purely theoretical cortical parcels (e. g. Hagmann et al. 2007; Li et al. 2013) are commonly taken as starting points (‘seed voxels’, ‘regions-of-interest’) for these reconstructions. The network of cortical and subcortical centres (‘nodes’) and their interconnections (‘edges’) are collectively designated as the ‘connectome’ (Sporns et al. 2005; Sporns 2011). Because the cortical nodes are, at the systems level, represented by the architectonic units, our map may be useful in the critical selection of natural starting points for tractography studies on the human brain. It may be added that the intracortical radial bundles, which show considerable interareal differences in length, size and fibre-calibre, form the grey matter origins and terminations of the subcortical fibre bundles. Hence, in a detailed analysis of the connections of the individual cortical areas, these salient myeloarchitectonic features, which have been systematically analysed by Hopf (1955, 1956) and Hopf and Vitzthum (1957), should be brought into focus. Acknowledgments The authors thank Prof. Lawrence Bannister for critically reading the ‘Materials and methods’ section, Mr. Ton Put for help with the illustrations, Dr. Joris Coppens for carrying out some initial transformations, Dr. Jenneke Kruisbrink for help with the collection of literature, and Suzanne Bakker M. Sc. for moral support and reference management.

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