Biomedical subjects

A Schleicher

Publications and source records attributed to A Schleicher.

At least 19 recordsLinked to original sources

PubMed2005

Mapping auditory cortex in the La Plata dolphin (Pontoporia blainvillei).

This study deals with the mapping of the primary and secondary auditory cortex. Due to their important role in echolocation they were the first areas to be examined [P.J. Morgane, M.S. Jacobs, in: R.J. Harrison (Ed.), Functional Anatomy of Marine Mammals, Comparative Anatomy of the Cetacean Nervous System, vol. 1, Academic Press, London, 1972, pp. 117-144]. We analysed the brain of a La Plata dolphin (Pontoporia blainvillei), which had been fixed in formaldehyde, embedded in paraffin, cut in sections of 20mum thickness and stained with cresyl violet. The experimental approach being impossible, we used cytoarchitectonic variations in the neocortex. Former electrophysiological data [T.F. Ladygina, A.Y. Supin, Localization of the projectional sensory areas in the cortex of the porpoise Tursiops truncates, Zh. Evol. Biokhim. Fiziol. 13 (1978) 712-718] [Sokolov, T.F. Ladygina, A.Y. Supin, Location of sensory zones in cerebral cortex of dolphin, Dokl. Biol. Sci., Russian Original 202 (1-6) (1972)] provided the framework for the exact determination of borders between functional cortical areas. We used a stereological observer-independent procedure based on changes in volume density of cell bodies throughout the neocortex [A. Schleicher, et al., Stereological approach to human cortical architecture: Identification and delineation of cortical areas, J. Chem. Neuroanat. 20 (2000) 31-47]. Due to the computer program's high sensitivity to changes in volume density it was possible to analyse the poorly laminated dolphin cortex. The 3D-reconstruction of the auditory cortex was processed using the AMIRA 3.0 Graphics software package comparing the main primary gyri in the histological sections with those in coronal magnetic resonance imaging scans of another intact Pontoporia brain.

Animals↗

PubMed2005

Quantitative architectural analysis: a new approach to cortical mapping.

Recent progress in anatomical and functional MRI has revived the demand for a reliable, topographic map of the human cerebral cortex. Till date, interpretations of specific activations found in functional imaging studies and their topographical analysis in a spatial reference system are, often, still based on classical architectonic maps. The most commonly used reference atlas is that of Brodmann and his successors, despite its severe inherent drawbacks. One obvious weakness in traditional, architectural mapping is the subjective nature of localising borders between cortical areas, by means of a purely visual, microscopical examination of histological specimens. To overcome this limitation, more objective, quantitative mapping procedures have been established in the past years. The quantification of the neocortical, laminar pattern by defining intensity line profiles across the cortical layers, has a long tradition. During the last years, this method has been extended to enable a reliable, reproducible mapping of the cortex based on image analysis and multivariate statistics. Methodological approaches to such algorithm-based, cortical mapping were published for various architectural modalities. In our contribution, principles of algorithm-based mapping are described for cyto- and receptorarchitecture. In a cytoarchitectural parcellation of the human auditory cortex, using a sliding window procedure, the classical areal pattern of the human superior temporal gyrus was modified by a replacing of Brodmann's areas 41, 42, 22 and parts of area 21, with a novel, more detailed map. An extension and optimisation of the sliding window procedure to the specific requirements of receptorarchitectonic mapping, is also described using the macaque central sulcus and adjacent superior parietal lobule as a second, biologically independent example. Algorithm-based mapping procedures, however, are not limited to these two architectural modalities, but can be applied to all images in which a laminar cortical pattern can be detected and quantified, e.g. myeloarchitectonic and in vivo high resolution MR imaging. Defining cortical borders, based on changes in cortical lamination in high resolution, in vivo structural MR images will result in a rapid increase of our knowledge on the structural parcellation of the human cerebral cortex.

Algorithms↗

PubMed2005

Multimodal architectonic mapping of human superior temporal gyrus.

Although it is generally accepted that human superior temporal gyrus is activated by a huge variety of auditory and linguistic tasks, little is known about the exact positions and extents of cortical areas that are located on the lateral convexity of the gyrus (e.g., Brodmann's area 22). Such information, however, is relevant for a rigorous testing of structural-functional relationships in both normal volunteers and patients suffering from disorders of auditory and language perception. The present combined cytoarchitectonic and receptorarchitectonic study identifies a distinct area (Te3) in the lateral bulge of the superior temporal gyrus by using an algorithm-based approach for the detection of cortical borders. Our mapping data show that, in contrast to Brodmann's area (BA) 22, only small portions of Te3 reach the dorsal and ventral banks of the gyrus. Therefore, we labelled the newly defined area as "Te3" and not as "BA 22". The cytoarchitectonically defined borders of Te3 coincide with abrupt changes in the receptorarchitecture of several classical neurotransmitters, suggesting that Te3 represents a functionally relevant area of the human superior temporal gyrus. Since position and extent of area Te3 varied considerably between subjects, probability maps were created that show for each voxel of the standard references space, the frequency with which Te3 was present in it. These maps, in combination with previously published maps of the primary auditory cortex, can directly be compared with functional imaging data, and may open new perspectives for the analysis of structural-functional correlations in the human auditory and language systems.

Algorithms↗

PubMed2002

Excitatory and inhibitory neurons express c-Fos in barrel-related columns after exploration of a novel environment.

Recent work has shown that behaviorally meaningful sensory information processing is accompanied by the induction of several transcription factors in the barrel cortex of rodents. It is now generally accepted that stimulus-transcription coupling is an important step in the sequence of events leading to long-term plastic changes in neuronal structure and function. Nevertheless, so far few data are available as to what types of neurons are involved in such a genomic response. Here, we determined the morphological and neurochemical identity of neurons in rat barrel cortex showing a c-Fos-immunoreactive nucleus after exploration of an enriched environment. Double stainings of c-Fos and glial fibrillary acidic protein excluded astrocytes as a possible cell type expressing this transcription factor. By morphological phenotyping with intracellular Lucifer Yellow injections, it was found that a large majority were probably excitatory pyramidal cells, but inhibitory interneurons were also found to contain c-Fos-immunoreactive nuclei. By neurochemical phenotyping of GABAergic interneurons with specific antibodies, a significant induction was found, in a layer-dependent manner, for the populations of glutamic acid decarboxylase-, parvalbumin-, calbindin- and vasoactive intestinal polypeptide-immunoreactive neurons but not for calretinin-immunoreactive cells in experimental compared to control columns. From these data we conclude that thalamic afferents effectively drive cortical excitatory as well as inhibitory intracortical circuits. Thus, the adaptations of receptive field properties of cortical neurons after different manipulations of the sensory periphery are likely to be caused by plastic changes in excitatory and inhibitory networks.

Afferent Pathways↗

PubMed2002

Architectonics of the human cerebral cortex and transmitter receptor fingerprints: reconciling functional neuroanatomy and neurochemistry.

The density of transmitter receptors varies between different locations in the human cerebral cortex. We hypothesized that this variation may reflect the cyto- and myeloarchitectonical as well as the functional organisation of the cortex. We compared data from different imaging modalities (postmortem studies: cyto- and myeloarchitecture, quantitative in vitro receptor autoradiography; in vivo studies: PET receptor neuroimaging) in order to test our hypothesis. The regional and laminar distribution of the densities of numerous receptor types representing all classical transmitter systems as well as the adenosine system are visualized and measured in different cortical areas. The receptor distribution patterns segregate motor, primary sensory, unimodal sensory, multimodal association and other functionally identified cortical areas from each other. Areas of similar function show similar receptor fingerprints and differ from those with other properties. Thus, receptor distribution patterns reflect an organisational structure strictly correlated with the architectonics and functions of the human cerebral cortex.

Aged↗

PubMed2001

Human primary auditory cortex in women and men.

Specific patterns of anatomical symmetry or asymmetry have been associated with sex differences in human brain structure and function. An observer-independent cytoarchitectonic method for the quantification of cell volume densities and areal borders was used to investigate the size and microstructure of primary auditory cortex (Brodmann area 41) in female (n = 14) and male (n = 13) postmortem brains. The total brain volume-adjusted volume of the primary auditory cortex was significantly larger in women than in men bilaterally. Inverse asymmetry towards the right side, as opposed to well-known asymmetries towards the left side, was more frequent in women. Laminar cell volume densities of BA 41 showed no gender effect. The morphometric data confirm (in part) gender differences in the cerebral organization of primary auditory cortex.

Adult↗

PubMed2001

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.

Anatomy, Comparative↗

PubMed2001

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.

Adult↗

PubMed2001

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.

Adult↗

PubMed2001

Localisation of mRNA for h5-HT1B and h5-HT1D receptors in human dorsal raphe.

In the mammalian mesencephalon, virtually all serotoninergic neurons are located in the raphe nuclei and the adjacent reticular formation. Pharmacological evidence obtained in rodents suggests that terminal and somatodendritic autoreceptors controlling serotonin (5-hydroxytryptamine, 5-HT) release belong to the 5-HT1B/D subtype of receptors, whereas somatodendritic autoreceptors controlling neuronal cell firing are predominantly of the 5-HT1A subtype. This study investigated the presence of h5-HT1D and h5-HT1B receptor mRNA within the subdivisions of the dorsal raphe of post-mortem human brains by means of in situ hybridisation. Although differences in the labelling intensity, which may be caused by different pre- and/or post-mortem conditions, were obvious among the specimens, all brains expressed both the h5-HT1D and the h5-HT1B mRNA in dorsal raphe neurons. In comparison to h5-HT1D mRNA, expression of h5-HT1B mRNA was slightly more abundant. Information on the existence and localisation of h5-HT1D and h5-HT1B receptors in human dorsal raphe neurons confirms that both subtypes may serve an autoreceptor function in humans. This finding is of pharmacological relevance since these receptors are potential new targets for therapeutic interventions in psychiatric disorders such as depression and anxiety.

Aged↗

PubMed2001

Multimodal characterisation of cortical areas by multivariate analyses of receptor binding and connectivity data.

Cortical areas are regarded as fundamental structural and functional units within the information processing networks of the brain. Their properties have been described extensively by cyto-, myelo- and chemoarchitectonics, cortical and extracortical connectivity patterns, receptive field mapping, activation properties, lesion effects, and other structural and functional characteristics. Systematic integrative approaches aiming at multimodal characterisations of cortical areas or at the delineation of global features of the cortical network, however, are still scarce and usually limited to a single data modality, such as cytoarchitectonical or tract tracing data. Here we describe a methodological framework for the systematic evaluation, comparison and integration of different data modalities from the brain and demonstrate its practical application and significance in the analysis of receptor binding and connectivity data within the motor and visual cortices of macaque monkeys. The framework builds on algorithmic methods to convert data between different cortical parcellation schemes, as well as on statistical techniques for the exploration of multivariate data sets comprising data of different types and scales. Thereby, we establish a relationship between intrinsic area properties as expressed by quantitative receptor binding, and extrinsic inter-area communication, which relies on anatomical connectivity. Our analyses provide preliminary evidence for a good correspondence of these two data types in the motor cortex, and their partial discrepancy in the visual cortex, raising hypotheses about the different organisational aspects highlighted by receptors and connectivity. The methodological framework presented here is flexible enough to accommodate a wide range of further data modalities, and is specific enough to permit novel insights and predictions concerning brain organisation. Thus, this approach promises to be very useful in the endeavour to characterise multimodal structure-function relationships in the brain.

Animals↗

PubMed2001

Integration of microstructural and functional aspects of human somatosensory areas 3a, 3b, and 1 on the basis of a computerized brain atlas.

In this study we analyzed structural and functional aspects of the human primary somatosensory areas 3a, 3b, and 1 on the basis of a computerized brain atlas. The approach overcomes many of the problems associated with subjective architectonic parcellations of the cortex and with 'classical" brain maps published in a "rigid" print format. Magnetic resonance (MR) scans were obtained from ten postmortem brains. The brains were serially sectioned at 20 microm, and sections were stained for cell bodies. Areas 3a, 3b, and 1 were delineated statistically on the basis of differences in the laminar densities of neuronal cell bodies. The borders of the areas were topographically variable across different brains and did not match macroanatomical landmarks of the postcentral gyrus. After correction of the sections for deformations due to histological processing, each brain's 3-D reconstructed histological volume and the volume representations of areas 3a, 3b, and 1 were adapted to the reference brain of a computerized atlas and superimposed in 3-D space. For each area, a population map was generated that described, for each voxel, how many brains had a representation of that area. Despite considerable interindividual variability, representations of areas 3a, 3b, and 1 in > or = 50% of the brains were found in the fundus of the central sulcus, in the rostral bank, and on the crown of the postcentral gyrus, respectively. For each area, a volume of interest (VOI) was defined that encompassed that area's representation in > or = 50% of the brains. Despite close spatial relationship in the postcentral gyrus, the three VOIs overlapped by < 1% of their volumes. Changes in regional cerebral blood flow (rCBF) were measured with positron emission tomography when six right-handed subjects discriminated differences in the speed of a rotating brush stimulating the palmar surface of the right hand. With co-registered MR images, the rCBF data were adapted to the same reference brain and superimposed with the microstructural VOIs. Discrimination of moving stimuli, contrasted to rest, increased the rCBF in the VOIs of areas 3b and 1, but not in area 3a. This approach opens up the possibility of (1) defining VOIs of cortical areas which are not based on macroanatomical landmarks but instead on observer-independent cytoarchitectonic mapping of postmortem brains and of (2) determining in these VOIs changes in rCBF data obtained from functional imaging experiments.

Adult↗

PubMed2001

Serotonergic polymorphisms in patients suffering from alcoholism, anxiety disorders and narcolepsy.

1. Alterations in the serotonergic neurotransmission have been frequently described for patients suffering from alcoholism, anxiety disorders and narcolepsy. 2. The authors tested for association of the 5-HT2A receptor polymorphism (T102C) and the intron 7 tryptophan hydroxylase (TPH) polymorphism (A218C) among 176 alcohol dependent patients, 35 patients with panic disorder, 50 patients with generalized anxiety disorder, 55 patients with narcolepsy and 87 healthy controls. 3. Allele and genotype frequencies of the 5-HT2A receptor polymorphism (T102C), the intron 7 TPH polymorphism (A218C) were almost similar between the patients suffering from alcohol dependence, panic disorder, generalized anxiety disorder and narcolepsy. 4. There was no association between the 5-HT2A receptor polymorphism (T102C), the intron 7 TPH (A218C) polymorphisms and alcohol dependence, panic disorder, generalized anxiety disorder and narcolepsy in our subsets of German patients.

Adult↗

PubMed2001

Variability and asymmetry in the human precentral motor system. A cytoarchitectonic and myeloarchitectonic brain mapping study.

The morphology of the region of the primary motor cortex in the human brain is variable, and putative asymmetries between the hemispheres have been noted since the beginning of last century. Such variability may confound the results of clinical lesion or functional activation studies. We measured Brodmann area (BA) 4 and the identifiable precentral component of the pyramidal tract (PRPT) in 11 human post-mortem brains using techniques of quantitative cytoarchitectonic and myeloarchitectonic image analysis. Topography and variability in the localization of architectonic borders were analysed and mapped to a computerized spatial reference system, which consists of an individual in vivoMRI brain. All maps were superimposed to produce probabilistic maps of BA 4 and PRPT which can be co-registered with any image of brain structure or function that has also been transformed to Talairach coordinates. These maps can be readily applied to future brain mapping studies. We observed a considerable degree of variability between hemispheres (intra-individual) and between brains (inter-individual). The variation zones of BA 4 and PRPT differ from the templates of the Talairach atlas. Voxel-based morphometry shows significant side differences with larger volumes of PRPT in the left hemisphere than in the right hemisphere. This larger volume of the descending cortical motor fibres may be related to the known left-hemisphere dominance for handedness in >90% of the population. In contrast, BA 4 was symmetrically organized. The lack of a significant correlation between the size of BA 4 and the size of PRPT may relate to the fact that additional non-primary motor and sensory cortices contribute to the origins and size of the pyramidal tract proper.

Adult↗

PubMed2000

Automated image analysis of disturbed cytoarchitecture in Brodmann area 10 in schizophrenia: a post-mortem study.

1. Among different etiological concepts in schizophrenia research is the disconnect on hypothesis involving distributed brain regions. Adequate empirical research requires correlational studies of multiple brain regions. In this pilot study, the authors therefore tested the applicability of an automated image analysis device as a scanning tool to detect cytoarchitectural abnormalities in Brodmann area (BA) 10. 2. The authors applied the gray level index (GLI) method as automated image analysis on 10 schizophrenic brains compared to 10 controls. The GLI as perikarya-neuropil-ratio is obtained as the ratio between the area covered by cellular cross sections and the area of the total measuring field in 101 continous measuring fields from pial surface to the cortical depth. Resulting data provide a specific cytoarchitectonic profile curve. An analysis was performed separately for mean GLI and GLI values in six compartments covering approximately the different cortical laminae. 3. A statistically significant reduction of the mean GLI was demonstrated in the schizophrenic group covering laminae III to VI, as detected by multivariate analysis and corroborated by univariate analyses and t-tests. 4. This result clearly underlines a cytoarchitectonic disturbance with a perikarya neuropil-ratio reduction in BA 10, that is associated with schizophrenia. This is suggestive either of an increased neuropil fraction or a decreased neuronal perikarya fraction. The latter could either be due to a volume or a total number reduction of neuronal perikarya. These data are compatible with previously published data on cell loss in schizophrenics in BA 10.

Autopsy↗

PubMed2000

Exploration of a novel environment leads to the expression of inducible transcription factors in barrel-related columns.

Tactile information acquired through the vibrissae is of high behavioral relevance for rodents. Numerous physiological studies have shown adaptive plasticity of cortical receptive field properties due to stimulation and/or manipulation of the whiskers. However, the cellular mechanisms leading to these plastic processes remain largely unknown. Although genomic responses are anticipated to take place in this sequel, virtually no data so far exist for freely behaving animals concerning this issue. Thus, adult rats were placed overnight in an enriched environment and most of them were also subjected to clipping of different sets of whiskers. This type of stimulation led to a specific and statistically significant increase in the expression of the protein products of the inducible transcription factors c-Fos, JunB, inducible cyclic-AMP early repressor and Krox-24 (also frequently named Zif268 or Egr-1), but not c-Jun. The response was found in columns of the barrel cortex corresponding to the stimulated vibrissae; it displayed a layer-specific pattern. However, no induction of transcription factors was observed in the subcortical relay stations of the whisker-to-barrel pathway, i.e. the trigeminal nuclei and the ventrobasal complex. These results strongly suggest that a coordinated transcriptional response is initiated in the barrel cortex as a consequence of processing of novel environmental stimuli.

Animals↗

PubMed2000

A stereological approach to human cortical architecture: identification and delineation of cortical areas.

Stereology offers a variety of procedures to analyze quantitatively the regional and laminar organization in cytoarchitectonically defined areas of the human cerebral cortex. Conventional anatomical atlases are of little help in localizing specific cortical areas, since most of them are based on a single brain and use highly observer-dependent criteria for the delineation of cortical areas. In consequence, numerous cortical maps exist which greatly differ with respect to number, position, size and extent of cortical areas. We describe a novel algorithm-based procedure for the delineation of cortical areas, which exploits the automated estimation of volume densities of cortical cell bodies. Spatial sampling of the laminar pattern is performed with density profiles, followed by multivariate analysis of the profiles' shape, which locates the cytoarchitectonic borders between neighboring cortical areas at sites where the laminar pattern changes significantly. The borders are then mapped to a human brain atlas system comprising tools for three dimensional reconstruction, visualization and morphometric analysis. A sample of brains with labeled cortical areas is warped into the reference brain of the atlas system in order to generate a population map of the cortical areas, which describes the intersubject variability in spatial conformation of cortical areas. These population maps provide a novel tool for the interpretation of images obtained with functional imaging techniques.

Brain Mapping↗

PubMed1999

Broca's region revisited: cytoarchitecture and intersubject variability.

The sizes of Brodmann's areas 44 and 45 (Broca's 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.

Adult↗