Axel Schleicher

Broca's region revisited: cytoarchitecture and intersubject variability.

The sizes of Brodmanns areas 44 and 45 (Brocas speech region) and their extent in relation to macroscopic landmarks and surrounding areas differ considerably among the available cytoarchitectonic maps. Such variability may be due to intersubject differences in anatomy, observer‐dependent discrepancies in cytoarchitectonic mapping, or both. Because a reliable definition of cytoarchitectonic borders is important for interpreting functional imaging data, we mapped areas 44 and 45 by means of an observer‐independent technique. In 10 human brains, the laminar distributions of cell densities were measured vertical to the cortical surface in serial coronal sections stained for perikarya. Thousands of density profiles were obtained. Cytoarchitectonic borders were defined as statistically significant changes in laminar patterns. The analysis of the three‐dimensional reconstructed brains and the two areas showed that cytoarchitectonic borders did not consistently coincide with sulcal contours. Therefore, macroscopic features are not reliable landmarks of cytoarchitectonic borders. Intersubject variability in the cytoarchitecture of areas 44 and 45 was significantly greater than cytoarchitectonic differences between these areas in individual brains. Although the volumes of area 44 differed across subjects by up to a factor of 10, area 44 but not area 45 was left‐over‐right asymmetrical in all brains. All five male but only three of five female brains had significantly higher cell densities on the left than on the right side. Such hemispheric and gender differences were not detected in area 45. These morphologic asymmetries of area 44 provide a putative correlate of the functional lateralization of speech production. J. Comp. Neurol. 412:319–341, 1999.

Human Primary Auditory Cortex: Cytoarchitectonic Subdivisions and Mapping into a Spatial Reference System

The transverse temporal gyrus of Heschl contains the human auditory cortex. Several schematic maps of the cytoarchitectonic correlate of this functional entity are available, but they present partly conflicting data (number and position of borders of the primary auditory areas) and they do not enable reliable comparisons with functional imaging data in a common spatial reference system. In order to provide a 3-D data set of the precise position and extent of the human primary auditory cortex, its putative subdivisions, and its topographical intersubject variability, we performed a quantitative cytoarchitectonic analysis of 10 brains using a recently established technique for observer-independent definition of areal borders. Three areas, Te1.1, Te1.0, and Te1.2, with a well-developed layer IV, which represent the primary auditory cortex (Brodmann area 41), can be identified along the mediolateral axis of the Heschl gyrus. The cell density was significantly higher in Te1.1 compared to Te1.2 in the left but not in the right hemisphere. The cytoarchitectonically defined areal borders of the primary auditory cortex do not consistently match macroanatomic landmarks like gyral and sulcal borders. The three primary auditory areas of each postmortem brain were mapped to a spatial reference system which is based on a brain registered by in vivo magnetic resonance imaging. The integration of a sample of postmortem brains in a spatial reference system allows one to estimate the spatial variability of each cytoarchitectonically defined region with respect to this reference system. In future, the transfer of in vivo structural and functional data into the same spatial reference system will enable accurate comparisons of cytoarchitectonic maps of the primary auditory cortex with activation centers as established with functional imaging procedures.

The human pattern of gyrification in the cerebral cortex.

SummaryThe degree of cortical folding found in adult human brains has been analyzed using a gyrification index (GI). This parameter permits the description of a mean value for the whole brain, but also a local specific analysis of different brain regions. Correlation analyses of the GI with age, body weight, body length, brain weight and volume of the prosencephalon and the cortex show no significant results. GI values do not differ significantly between male and female brains, right and left hemispheres or right and left sides of the superior temporal plane. The GI shows maximal values over the prefrontal and the parieto-temporo-occipital association cortex. A comparison between the rostro-caudal GI patterns of human brains and those of prosimians and Old World monkeys shows the largest difference over the prefrontal cortex. The mean GI increases from prosimians to human brains with the highest values for non-human primates being in the pongid group.

Prefrontal cortex in humans and apes: A comparative study of area 10

Area 10 is one of the cortical areas of the frontal lobe involved in higher cognitive functions such as the undertaking of initiatives and the planning of future actions. It is known to form the frontal pole of the macaque and human brain, but its presence and organization in the great and lesser apes remain unclear. It is here documented that area 10 also forms the frontal pole of chimpanzee, bonobo, orangutan, and gibbon brains. Imaging techniques and stereological tools are used to characterize this area across species and provide preliminary estimates of its absolute and relative size. Area 10 has similar cytoarchitectonic features in the hominoid brain, but aspects of its organization vary slightly across species, including the relative width of its cortical layers and the space available for connections. The cortex forming the frontal pole of the gorilla appears highly specialized, while area 10 in the gibbon occupies only the orbital sector of the frontal pole. Area 10 in the human brain is larger relative to the rest of the brain than it is in the apes, and its supragranular layers have more space available for connections with other higher-order association areas. This suggests that the neural substrates supporting cognitive functions associated with this part of the cortex enlarged and became specialized during hominid evolution.

Probabilistic Mapping and Volume Measurement of Human Primary Auditory Cortex

Despite their potential utility in clinical and research settings, the range of intra- and interindividual variations in size and location of cytoarchitectonically defined human primary auditory cortex (PAC) is largely unknown. This study demonstrates that gyral patterns and the size and location of PAC vary independently to a considerable degree. Thus, the cytoarchitectonic borders of PAC cannot be reliably inferred from macroscopic-MR visible-anatomy. Given the remarkable topographical variability of architectonic areal borders, standard brain mapping which is made solely on the basis of macroanatomic landmarks may lead to structural-functional mismatch. Consequently, interpretations of individual auditory activity patterns might often be inaccurate. In view of the anatomic discrepancies, we generated probability maps of PAC in which the degree of intersubject overlap in each stereotaxic position was quantified. These maps show that the location of PAC in Talairach space differs considerably between hemispheres and individuals. In contrast to earlier cytoarchitectonic work which is based in most cases on studies of single brains, our systematic approach provides extensive microanatomic data as a reference system for studies of human auditory function.

The human inferior parietal cortex: Cytoarchitectonic parcellation and interindividual variability

The inferior parietal cortex (IPC) integrates information from different sensory modalities and plays an important role in a variety of higher cognitive functions. Brodmann (Brodmann, K., 1909. Vergleichende Lokalisationslehre der Grosshirnrinde. Barth, Leipzig) proposed a cytoarchitectonic subdivision of the IPC into only two cortical areas, a rostral (BA 40) and a caudal (BA 39) area. Although his scheme was repeatedly challenged by other observers, it is still used for the anatomical localization of functional imaging data. The apparent differences between all these cyto- and myeloarchitectonic maps may be caused partly by the observer-dependent procedure of defining cytoarchitectonic borders by pure visual inspection of histological sections and partly by the interindividual variability of cytoarchitecture. The present observations and the resulting cortical map of the IPC are based on quantitative, observer-independent definitions of cytoarchitectonic borders and take into account each areas topographical variability across brains. Ten human postmortem brains were scanned using an MRI 3-D FLASH sequence prior to histological processing. After embedding in paraffin, serial sections through whole brains were prepared, and the sections were stained for cell bodies. Following high-resolution digitization of sections containing the IPC, we defined the cytoarchitecture and borders of each cortical area of this brain region using a multivariate statistical analysis of laminar cell density profiles. In contrast to previous observations, we found seven cytoarchitectonic areas in the IPC: five in the rostral (covering the region of BA 40) and two in the caudal part (covering the region of BA 39). We observed considerable interindividual variability in the topography of each area. A consistent correspondence between macroanatomical landmarks and cytoarchitectonic borders was not found. This new cytoarchitectonic map of the human IPC demonstrates regional differences in the cortical microstructure that is suggestive of functional differentiation. Furthermore, the map is registered in three dimensions and thereby provides a robust anatomical base for interpreting functional imaging studies.

Areas 3a, 3b, and 1 of human primary somatosensory cortex: 1. Microstructural organization and interindividual variability

This study defines cytoarchitectonic areas 3a, 3b, and 1 of the human primary somatosensory cortex by objective delineation of cytoarchitectonic borders and ensuing cytoarchitectonic classification. This avoids subjective evaluation of microstructural differences which has so far been the only way to structurally define cortical areas. Ten brains were fixed in formalin or Bodians fixative, embedded in paraffin, sectioned as a whole in the coronal plane at 20 microm, and cell stained. Cell bodies were segmented from the background by adaptive thresholding. Equidistant density profiles (125 microm wide, spacing 300 or 150 microm) were extracted perpendicularly to the pial surface across cortical layers II-VI and processed with multivariate statistical procedures. Positions of significant differences in shape between adjacent groups of profiles were correlated with the cytoarchitectonic pattern. Statistically significant borders can be reproduced at corresponding positions across a series of nearby sections. They match visible changes in cytoarchitecture in the cell-stained sections. Area 3a lies in the fundus of the central sulcus, and area 3b in the rostral bank of the postcentral gyrus. Area 1 lies on its crown and reaches down into the postcentral sulcus. Interareal borders, however, do not match macrostructural landmarks of the postcentral gyrus, and they considerably vary in their positions relative to these landmarks across different brains. Hence, only genuine microstructural analysis can define the borders between these cortical areas. Additional significant borders which do not correlate with visible changes in cytoarchitecture can be found within areas 3b and 1. They may represent somatotopy and/or cortical representations of different somatosensory receptors.

Asymmetry in the human motor cortex and handedness.

Handedness is one of the most obvious functional asymmetries, but its relation to an anatomical asymmetry of the hand representation area in the motor cortex has not been demonstrated. This would be a crucial test for the hypothesis of structure-function correlation in cortical motor organization. Using magnetic resonance morphometry, we show for the first time that the depth of the central sulcus is related to handedness. In right-handers, the left central sulcus is deeper than the right, and vice versa in left-handers. Macrostructural asymmetry is complemented by a microstructural left-larger-than-right asymmetry in neuropil volume (i.e., tissue compartment containing dendrites, axons, and synapses) in Brodmanns area 4. These asymmetries suggest that hand preference is associated with increased connectivity (demonstrated by an increased neuropil compartment in left area 4) and an increased intrasulcal surface of the precentral gyrus in the dominant hemisphere.

Motor cortex and hand motor skills: Structural compliance in the human brain

Recent studies in humans and nonhuman primates have shown that the functional organization of the human sensorimotor cortex changes following sensory stimulation or following the acquisition of motor skills. It is unknown whether functional plasticity in response to the acquisition of new motor skills and the continued performance of complicated bimanual movements for years is associated with structural changes in the organization of the motor cortex. Professional musicians, especially keyboard and string players, are a prototypical group for investigating these changes in the human brain. Using magnetic resonance images, we measured the length of the posterior wall of the precentral gyrus bordering the central sulcus (intrasulcal length of the precentral gyrus, ILPG) in horizontal sections through both hemispheres of right‐handed keyboard players and of an age‐ and handedness‐matched control group. Lacking a direct in vivo measurement of the primary motor cortex in humans, we assumed that the ILPG is a measure of the size of the primary motor cortex. Left‐right asymmetry in the ILPG was analyzed and compared between both groups. Whereas controls exhibited a pronounced left‐larger‐than‐right asymmetry, keyboard players had more symmetrical ILPG. The most pronounced differences in ILPG between keyboard players and controls were seen in the most dorsal part of the presumed cortical hand representation of both hemispheres. This was especially true in the nondominant right hemispheres. The size of the ILPG was negatively correlated with age of commencement of musical training in keyboard players, supporting our hypothesis that the human motor cortex can exhibit functionally induced and long‐lasting structural adaptations. Hum. Brain Mapping 5:206–215, 1997.

Observer-independent method for microstructural parcellation of cerebral cortex: A quantitative approach to cytoarchitectonics

We describe a new, observer-independent procedure for identifying boundaries between cortical areas. The method is useful for images obtained from sections which provide microstructural information on the cortical laminar pattern, e.g., Nissl-, myelin-, or immunohistochemically stained sections or receptor autoradiographs. The laminar pattern is represented by profile curves extending from the cortical surface to the white matter boundary. These profiles are constructed from digitized images. Digitization is based on the grey level index (Nissl) or densitometry (myelin, immunohistochemistry, receptor autoradiography). The shapes of neighboring profiles are compared by calculating their distances according to feature vectors extracted from the profiles. Profiles derived from a homogeneous area can be expected to be similar in shape and hence show low distance values between each other. Maximum distances can be found between profiles which lie on opposite sides of a structural boundary. The Mahalanobis distance was found to be more sensitive and to yield greater spatial resolution than other distance measures such as the Euclidean distance. Cell-stained sections of the human neocortex were analyzed. The method not only verified boundaries which had been defined by visual inspection, it also revealed new ones which had not been detected visually. The procedure offers an important supplement to the traditional methods based on visual inspection which, for the first time, is based on quantitative data and therefore offers a new level of reproducibility and observer independence. Anatomical atlases based on this procedure thus provide a new tool for the interpretation of structural data obtained from functional imaging techniques.