Rudolf Nieuwenhuys

The first, introductory part of this paper presents an overview of the long quest for a universal map of the human cortex, useful as a standard reference for all remaining studies on this brain part. It is pointed out that such a map does still not exist, but that systematic comparison of some recently produced 3D maps may well be conducive toward this important goal. Hence, the second part of this article is devoted to a detailed comparison of two of such maps, the multimodal MRI-based parcellation of Glasser et al. (Nature 536:171–178, 2016) and the myeloarchitectonic parcellation presented by Nieuwenhuys and Broere (Brain Struct Funct 228:1549–1559, 2023), with the specific aim to detect areal concordances between these two maps. In the search for these concordances, the following three criteria were used: (1) the relative or topological position of the various areas, (2) the relation of the areas to particular invariant sulci, and (3) the overall myelin content of the areas. In total 61 concordances were detected, most of which were located in the frontal and parietal lobes. These concordances were recorded in standard views of the two maps compared (Figs. 5, 6, 7, 8), as well as in Table 1. We consider these findings as a first step towards the creation of a unified, consensus (canonical) parcellation of the human neocortex.

At the end of 2023, the Whole Mouse Brain Atlas was announced, revealing that there are about 5300 molecularly defined neuronal types in the mouse brain. We ask whether brain models exist that contemplate how this is possible. The conventional columnar model, implicitly used by the authors of the Atlas, is incapable of doing so with only 20 brain columns (5 brain vesicles with 4 columns each). We argue that the definition of some 1250 distinct progenitor microzones, each producing at least 4–5 neuronal types over time, may be sufficient. Presently, this is nearly achieved by the prosomeric model amplified by the secondary dorsoventral and anteroposterior microzonation of progenitor areas, plus the clonal variation in cell types produced, on average, by each of them.

At the end of 2023 the Whole Mouse Brain Atlas was announced, revealing that there are about 5,300 molecularly defined neuronal types in the mouse brain. We ask whether brain models exist that contemplate how this is possible. The conventional columnar model, implicitly used by the authors of the Atlas, is incapable of doing so with only 20 brain columns (5 brain vesicles with 4 columns each). We argue that definition of some 1,250 distinct progenitor microzones, each producing over time minimally 4-5 neuronal types, may be sufficient. This is nearly achieved presently by the prosomeric model amplified by secondary dorsoventral and anteroposterior microzonation of progenitor areas, plus clonal variation of cell types produced on average by each of them.

During the period extending from 1900 to 1970, Oskar and Cécile Vogt and their numerous collaborators (‘the Vogt–Vogt school’) published a large number of studies on the myeloarchitecture of the human cerebral cortex. During the last decade, we have concerned ourselves with a detailed meta-analysis of these now almost totally forgotten studies, with the aim to bringing them into the modern era of science. This scrutiny yielded inter alia a myeloarchitectonic map of the human neocortex, showing a parcellation into 182 areas (Nieuwenhuys et al. in Brain Struct Funct 220:2551–2573, 2015; Erratum in Brain Struct Funct 220: 3753–3755, 2015). This map, termed 2D’15, which is based on data derived from all of the 20 publications constituting the myeloarchitectonic legacy of the Vogt–Vogt school, has the limitation that it is two-dimensional i.e. it shows only the parts of the cortex exposed at the free surface of the cerebral hemispheres and not the extensive stretches of cortex hidden in the cortical sulci. However, a limited set of data, derived from four of the 20 publications available, has enabled us to create a 3D map, showing the myeloarchitectonic parcellation of the entire human neocortex. This map, designated as 3D′23, contains 182 areas: 64 frontal, 30 parietal, 6 insular, 19 occipital and 63 temporal. We have also prepared a 2D version (2D′23), of this 3D′23 map to serve as a link between the latter and our original 2D′15 map. Detailed comparison of the parcellations visualized in our three maps (2D′15, 2D′23 and 3D′23) warrants the conclusion that our new 3D′23 map may be considered as representative for the entire myeloarchitectural legacy of the Vogt–Vogt School. Hence it is now possible to compare the rich amount of myeloarchitectonic data assembled by that school directly with the results of current 3D analyses of the architecture of the human cortex, such as the meticulous quantitative cyto- and receptor architectonic studies of Zilles, Amunts and their numerous associates (Amunts et al. in Science 369:988–992, 2020), and the multimodal parcellation of the human cortex based on magnetic resonance images from the Human Connectome Project, performed by Glasser et al. in Nature 536:171–178, 2016).

This paper presents a survey of the cell masses in the brainstem of the Australian lungfish Neoceratodus forsteri, based ontransversely cut Bodian-stained serial sections, supplemented by immunohistochemical data from the recent literature. This study is intended to serve a double purpose. First it concludes and completes a series of publications on the structure of the brainstem in representative species of all groups of anamniote vertebrates. Within the framework of this comparative program the cell masses in the brainstem and their positional relations are analyzed in the light of the Herrick-Johnston concept, according to which the brainstem nuclei are arranged in four longitudinal, functional zones or columns, the boundaries of which are marked by ventricular sulci. The procedure employed in this analysis essentially involves two steps: first, the cell masses and large individual cells are projected upon the ventricular surface, and next, the ventricular surface is flattened out, that is, subjected to a one-to-one continuous topological transformation [J Comp Neurol. 1974;156:255–267]. The second purpose of the present paper is to complement our mapping of the longitudinal zonal arrangement of the cell masses in the brainstem of Neoceratoduswith a subdivision in transversely oriented neural segments. Five longitudinal rhombencephalic sulci – the sulcus medianus inferior, the sulcus intermedius ventralis, the sulcus limitans, the sulcus intermedius dorsalis and the sulcus medianus superior – and four longitudinal mesencephalic sulci – the sulcus tegmentalis medialis, the sulcus tegmentalis lateralis, the sulcus subtectalis and the sulcus lateralis mesencephali – could be distinguished. Two obliquely oriented grooves, present in the isthmic region – the sulcus isthmi dorsalis and ventralis – deviate from the overall longitudinal pattern of the other sulci. Although in Neoceratodus most neuronal perikarya are situated within a diffuse periventricular gray, 45 cell masses could be delineated. Ten of these are primary efferent or motor nuclei, eight are primary afferent or sensory centers, six are considered to be components of the reticular formation and the remaining 21 may be interpreted as “relay” nuclei. The topological analysis showed that in most of the rhombencephalon the gray matter is arranged in four longitudinal zones or areas, termed area ventralis, area intermedioventralis, area intermediodorsalis and area dorsalis. The sulcus intermedius ventralis, the sulcus limitans, and the sulcus intermedius dorsalis mark the boundaries between these morphological entities. These longitudinal zones coincide largely, but not entirely, with the functional columns of Herrick and Johnston. The most obvious incongruity is that the area intermediodorsalis contains, in addition to the viscerosensory nucleus of the solitary tract, several general somatosensory and special somatosensory centers. The isthmus region does not exhibit a clear morphological zonal pattern. The mesencephalon is divisible into a ventral, primarily motor zone and a dorsal somatosensory zone. The boundary between these zones is marked by the sulcus tegmentalis lateralis, which may be considered as an isolated rostral extremity of the sulcus limitans. The results of this study are summarized in a “classical” topological map, as well as in a “modernized” version of this map, in which neuromere borders are indicated.

The comprehensive research programme of the Vogt–Vogt (V–V) school, which was active during the period 1900–1970, included detailed cytoarchitectonic and myeloarchitectonic analyses of the human cerebral cortex, with the aim to integrate the data obtained into a map, showing a parcellation of the human cerebral cortex into fundamental structural and potentially functional units. The cytoarchitectonic V–V analyses yielded two maps of the human cerebral cortex, the famous map of Brodmann (Vergleichende Lokalisationslehre der Grosshirnrinde in ihren Prinzipien dargestellt auf Grund des Zellenbaues. Barth, Leipzig, 1909), Brodmann (in: Bruns P (ed) Neue deutsche Chirurgie, Enke, Stuttgart, 1914), and the less known, but more detailed map of Sarkisov et al. (Cytoarchitecture of the human cortex cerebri. Medgiz, Moscow, 1949). Sarkisov et al. used in their cytoarchitectonic parcellation of the cortex the same numbering scheme as Brodmann. They confirmed the presence of most of the areas delineated by the latter, but they subdivided several of these areas into two or more separate areas or subareas. Within the realm of the myeloarchitectonic V–V analyses, numerous meticulous studies of the cortex of individual cerebral lobes were carried out, but these were not united into a single map. Consequently, the envisioned integration of cytoarchitectonic and myeloarchitectonic data mentioned above was never realized. Some years ago, we (Nieuwenhuys et al. in Brain Struct Funct 220:2551–2573, 2015a, Nieuwenhuys et al. in Brain Struct Funct 220:3753–3755, 2015b) reanalyzed the V–V myeloarchitectonic data, and succeeded in constructing a complete myeloarchitectonic map of the human neocortex from these data. Because the data provided by the V–V school were derived from many different brains, a standard brain had to be introduced as a template to which all data available could be transferred. As such the MNI305 template was selected. Having made available now the cytoarchitectonic maps of Brodmann and Sarkisov et al. and the recently prepared myeloarchitectonic map, an attempt is made here to realize at last the original aim of the V–V school, viz. the preparation of a single, combined (cyto + myelo) architectonic map of the human cortex. To this end, the following three steps have been made. First, Brodmann’s (BR) map, and the map of Sarkisov et al. (SA) were harmoniously transferred to the same template brain as the one used during the construction of our myeloarchitectonic map. Second, the standardized BR and our myeloarchitectonic (NI) map were compared, and the data contained within these maps were integrated into a single standardized combined BR–NI map (Fig. 11). The standardized SA and NI maps were subjected to the same procedure (Fig. 12). Finally, the standardized combined BR–NI and SA–NI maps were united into a single combined BR–SA–NI map (Fig. 13). This map renders it possible to make direct comparisons between the results of the architectonic studies of the V–V school and current parcellations of the human neocortex.

During the period extending from 1910 to 1970, Oscar and Cécile Vogt and their numerous collaborators published a large number of myeloarchitectonic studies on the cortex of the various lobes of the human cerebrum. In a previous publication [Nieuwenhuys et al (Brain Struct Funct 220:2551–2573, 2015; Erratum in Brain Struct Funct 220: 3753–3755, 2015)], we used the data provided by the Vogt–Vogt school for the composition of a myeloarchitectonic map of the entire human neocortex. Because these data were derived from many different brains, a standard brain had to be introduced to which all data available could be transferred. As such the Colin 27 structural scan, aligned to the MNI305 template was selected. The resultant map includes 180 myeloarchitectonic areas, 64 frontal, 30 parietal, 6 insular, 17 occipital and 63 temporal. Here we present a supplementary map in which the overall density of the myelinated fibers in the individual architectonic areas is indicated, based on a meta-analysis of data provided by Adolf Hopf, a prominent collaborator of the Vogts. This map shows that the primary sensory and motor regions are densely myelinated and that, in general, myelination decreases stepwise with the distance from these primary regions. The map also reveals the presence of a number of heavily myelinated formations, situated beyond the primary sensory and motor domains, each consisting of two or more myeloarchitectonic areas. These formations were provisionally designated as the orbitofrontal, intraparietal, posterolateral temporal, and basal temporal dark clusters. Recently published MRI-based in vivo myelin content mappings show, with regard to the primary sensory and motor regions, a striking concordance with our map. As regards the heavily myelinated clusters shown by our map, scrutiny of the current literature revealed that correlates of all of these clusters have been identified in in vivo structural MRI studies and appear to correspond either entirely or largely to known cytoarchitectonic entities. Moreover, functional neuroimaging studies indicate that all of these clusters are involved in vision-related cognitive functions.