Biomedical subjects

Hartmut Mohlberg

Publications and source records attributed to Hartmut Mohlberg.

12 recordsLinked to original sources

PubMed2006

A new toolbox for combining magnetoencephalographic source analysis and cytoarchitectonic probabilistic data for anatomical classification of dynamic brain activity.

Size and location of activated cortical areas are often identified in relation to their surrounding macro-anatomical landmarks such as gyri and sulci. The sulcal pattern, however, is highly variable. In addition, many cortical areas are not linked to well defined landmarks, which in turn do not have a fixed relationship to functional and cytoarchitectonic boundaries. Therefore, it is difficult to unambiguously attribute localized neuronal activity to the corresponding cortical areas in the living human brain. Here we present new methods that are implemented in a toolbox for the objective anatomical identification of neuromagnetic activity with respect to cortical areas. The toolbox enables the platform independent integration of many types of source analysis obtained from magnetoencephalography (MEG) together with probabilistic cytoarchitectonic maps obtained in postmortem brains. The probability maps provide information about the relative frequency of a given cortical area being located at a given position in the brain. In the new software, the neuromagnetic data are analyzed with respect to cytoarchitectonic maps that have been transformed to the individual subject brain space. A number of measures define the degree of overlap between and distance from the activated areas and the corresponding cytoarchitectonic maps. The implemented algorithms enable the investigator to quantify how much of the reconstructed current density can be attributed to distinct cortical areas. Dynamic correspondence patterns between the millisecond-resolved MEG data and the static cytoarchitectonic maps are obtained. We show examples for auditory and visual activation patterns. However, size and location of the postmortem brain areas as well as the inverse method applied to the neuromagnetic data bias the anatomical classification. Therefore, the adaptation to the respective application and a combination of the objective quantities are discussed.

Acoustic Stimulation↗

PubMed2006

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 area's 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.

Adult↗

PubMed2006

Cerebellar localization of the NO-receptive soluble guanylyl cyclase subunits-alpha(2)/beta (1) in non-human primates.

Nitric-oxide-sensitive guanylyl cyclase (NO-sGC) plays a pivotal role in many second messenger cascades. Neurotransmission- and neuropathology-related changes in NO-sGC have been suggested. However, the cellular localization of NO-sGC in primate brains, including humans, remains unknown. Biochemical evidence has linked the alpha(2)-subunit of NO-sGC directly to neurotransmission in rodents. Here, we have used a recently characterized subunit-specific antibody for the localization of the alpha(2)-subunit on sections from the cerebelli of the common marmoset (Callithrix jacchus; New World monkey) and macaque monkeys (Macaca mulatta, M. fascicularis; Old World monkeys). In contrast to the more ubiquitous cytoplasmic presence of subunit-beta(1), the alpha(2)-subunit is mainly confined to the somato-dendritic membrane including the spines of the Purkinje cells. Only limited colocalization with presynaptically localized synaptophysin has been seen under our staining conditions, indicating a higher abundance of subunit-alpha(2) at the postsynaptic site. This localization indicates that subunit-alpha(2) links NO-sGC to neurotransmission, whereas subunit-beta(1) may act as a cytoplasmic regulator/activator by contributing to active heterodimer formation via translocation from the cytoplasm to the cell membrane. The last-mentioned action may be a prerequisite for generating nitric-oxide-dependent, subcellular, and postsynaptically localized cGMP signals along neuronal processes.

Animals↗

PubMed2006

Head motion during overt language production in functional magnetic resonance imaging.

Head motion parameters (translation, rotation) during an event-related functional magnetic resonance imaging experiment of overt picture naming were investigated for two fixation conditions. We compared normal fixation with cushions and belts with the additional use of a bite-bar. Neither mean nor maximum values differed between the two conditions for any of the parameters. By applying the head motion parameters to the cytoarchitectonically defined volume of the left Brodmann area 44, we demonstrated volume overlap of 95% (normal fixation) to 100% (bite-bar) that did not differ significantly between fixation conditions. The data encourage further use of overt language production in functional magnetic resonance imaging with careful head fixation but no bite-bar.

Adult↗

PubMed2006

Cytoarchitectonic analysis of the human extrastriate cortex in the region of V5/MT+: a probabilistic, stereotaxic map of area hOc5.

Functional imaging studies identified a motion-sensitive area (V5/MT+) in the vicinity of the posterior branch of the inferior temporal sulcus that has no correlate in any classical cytoarchitectonic map. The aim of the present study was to identify a cytoarchitectonic correlate of this region in 10 human postmortem brains and to provide a probability map of this area. Observer-independent mapping revealed an area, hOc5 (h for human, Oc for occipital lobe), that has a broad layer III, a high cell density in layer II/III, and a low one in layer V. Most of area hOc5 is found in the depths of the anterior occipital sulcus and the anterior parts of either the inferior lateral occipital or the inferior occipital sulcus. After 3-dimensional reconstruction and registration to a standard reference space, a probability map of the area measured the individual variability of its size and location. The mean spatial locations of area hOc5 are -43, -73, 10 (left) and 49, -70, 11 (right). The locations and their relationships to sulci strongly suggest that hOc5 is the cytoarchitectonic correlate of human V5/MT+. This hypothesis was supported by comparing the cytoarchitectonic probabilistic map with results from a functional imaging study.

Adult↗

PubMed2006

Cytoarchitectonic identification and probabilistic mapping of two distinct areas within the anterior ventral bank of the human intraparietal sulcus.

Anatomical studies in the macaque cortex and functional imaging studies in humans have demonstrated the existence of different cortical areas within the intraparietal sulcus (IPS). Such functional segregation, however, does not correlate with presently available architectonic maps of the human brain. This is particularly true for the classical Brodmann map, which is still widely used as an anatomical reference in functional imaging studies. The aim of this cytoarchitectonic mapping study was to use previously defined algorithms to determine whether consistent regions and borders can be found within the cortex of the anterior IPS in a population of 10 post-mortem human brains. Two areas, the human intraparietal area 1 (hIP1) and the human intraparietal area 2 (hIP2), were delineated in serial histological sections of the anterior, lateral bank of the human IPS. The region hIP1 is located posterior and medial to hIP2, and the former is always within the depths of the IPS. The latter, on the other hand, sometimes reaches the free surface of the superior parietal lobule. The delineations were registered to standard reference space, and probabilistic maps were calculated, thereby quantifying the intersubject variability in location and extent of both areas. In the future, they can be a tool for analyzing structure-function relationships and a basis for determining degrees of homology in the IPS among anthropoid primates. We conclude that the human IPS has a more finely grained parcellation than shown in Brodmann's map.

Adult↗

PubMed2006

Pattern reversal visual evoked responses of V1/V2 and V5/MT as revealed by MEG combined with probabilistic cytoarchitectonic maps.

Pattern reversal stimulation provides an established tool for assessing the integrity of the visual pathway and for studying early visual processing. Numerous magnetoencephalographic (MEG) and electroencephalographic (EEG) studies have revealed a three-phasic waveform of the averaged pattern reversal visual evoked potential/magnetic field, with components N75(m), P100(m), and N145(m). However, the anatomical assignment of these components to distinct cortical generators is still a matter of debate, which has inter alia connected with considerable interindividual variations of the human striate and extrastriate cortex. The anatomical variability can be compensated for by means of probabilistic cytoarchitectonic maps, which are three-dimensional maps obtained by an observer-independent statistical mapping in a sample of ten postmortem brains. Transformed onto a subject's brain under consideration, these maps provide the probability with which a given voxel of the subject's brain belongs to a particular cytoarchitectonic area. We optimize the spatial selectivity of the probability maps for V1 and V2 with a probability threshold which optimizes the self- vs. cross-overlap in the population of postmortem brains used for deriving the probabilistic cytoarchitectonic maps. For the first time, we use probabilistic cytoarchitectonic maps of visual cortical areas in order to anatomically identify active cortical generators underlying pattern reversal visual evoked magnetic fields as revealed by MEG. The generators are determined with magnetic field tomography (MFT), which reconstructs the current source density in each voxel. In all seven subjects, our approach reveals generators in V1/V2 (with a greater overlap with V1) and in V5 unilaterally (right V5 in three subjects, left V5 in four subjects) and consistent time courses of their stimulus-locked activations, with three peak activations in V1/V2 (contributing to C1m/N75m, P100m, and N145m) and two peak activations in V5 (contributing to P100m and N145m). The reverberating V1/V2 and V5 activations demonstrate the effect of recurrent activation mechanisms including V1 and extrastriate areas and/or corticofugal feedback loops. Our results demonstrate that the combined investigation of MEG signals with MFT and probabilistic cytoarchitectonic maps significantly improves the anatomical identification of active brain areas.

Adult↗

PubMed2005

The role of the left Brodmann's areas 44 and 45 in reading words and pseudowords.

In this functional magnetic resonance imaging (fMRI) study, we investigated the influence of two task (lexical decision, LDT; phonological decision, PDT) on activation in Broca's region (left Brodmann's areas [BA] 44 and 45) during the processing of visually presented words and pseudowords. Reaction times were longer for pseudowords than words in LDT but did not differ in PDT. By combining the fMRI data with cytoarchitectonic anatomical probability maps, we demonstrated that the left BA 44 and BA 45 were stronger activated for pseudowords than for words. Separate analyses for LDT and PDT revealed that the left BA 44 was activated in both tasks, whereas left BA 45 was only involved in LDT. The results are interpreted within a dual-route model of reading with the left BA 44 supporting grapheme-to-phoneme conversion and the left BA 45 being related to explicit lexical search.

Adult↗

PubMed2005

White matter fiber tracts of the human brain: three-dimensional mapping at microscopic resolution, topography and intersubject variability.

The position and extent of individual fiber tracts within the white matter of human brains can be identified in vivo using diffusion tensor imaging (DTI) and fiber tracking methods. Previous to this study, however, the lack of three-dimensional (3-D) probability maps precluded comparing the anatomical precision of MRI studies with microscopically defined fiber tracts in human postmortem brains. The present study provides 3-D registered maps of the topography, course and intersubject variability of major fiber tracts, which were identified at microscopic resolution. The analyzed tracts include the corticospinal tract, optic and acoustic radiations, fornix, cingulum, corpus callosum, superior longitudinal, superior and inferior occipito-frontal and uncinate fascicles; sources and targets of fiber tracts include the lateral and medial geniculate nuclei and mamillary bodies. Tracts and nuclei were identified in serial myelin-stained histological sections of ten postmortem brains. The sections were 3-D reconstructed and registered to a standardized stereotaxic space of an in vivo MR reference brain by means of linear and non-linear, elastic transformations. The individual fiber tracts and nuclei were superimposed in the reference space, and probability maps were generated as a quantitative measure of intersubject variability for each voxel of the stereotaxic space. This study presents the first stereotaxic atlas of the course, location and extent of fiber tracts and related nuclei based on microscopically defined localization and topographic data taken at multiple levels on each of the three orthogonal planes. The maps are useful for evaluating and identifying fiber bundles in DTI, for localizing subcortical lesions visible in anatomical MR images and for studying neuronal connectivity.

Adult↗

PubMed2005

The human parietal operculum. II. Stereotaxic maps and correlation with functional imaging results.

In this study we describe the localization of the cytoarchitectonic subdivisions of the human parietal operculum in stereotaxic space and relate these anatomically defined cortical areas to the location of the functionally defined secondary somatosensory cortex (SII cortex) using a meta-analysis of functional imaging results. The human parietal operculum consists of four distinct cytoarchitectonic areas (OP 1-4) as shown in the preceding publication. The 10 cytoarchitectonically examined brains were 3-D-reconstructed and spatially normalized to the T1-weighted single-subject template of the Montreal Neurological Institute (MNI). A probabilistic map was calculated for each area in this standard stereotaxic space. A cytoarchitectonic summary map of the four cortical areas on the human parietal operculum which combines these probabilistic maps was subsequently computed for the comparison with a meta-analysis of functional locations of SII. The meta-analysis used the results from 57 fMRI and PET studies and allowed the comparison of the functionally defined SII region to the cytoarchitectonic map of the parietal operculum. The functional localization of SII showed a good match to the cytoarchitectonically defined region. Therefore the cytoarchitectonic maps of OP 1-4 of the human parietal operculum can be interpreted as an anatomical correlate of the (functionally defined) human SII region. Our results also suggest that the SII foci reported in functional imaging studies may actually reflect activations in either of its architectonic subregions.

Brain Mapping↗

PubMed2005

A new SPM toolbox for combining probabilistic cytoarchitectonic maps and functional imaging data.

Correlating the activation foci identified in functional imaging studies of the human brain with structural (e.g., cytoarchitectonic) information on the activated areas is a major methodological challenge for neuroscience research. We here present a new approach to make use of three-dimensional probabilistic cytoarchitectonic maps, as obtained from the analysis of human post-mortem brains, for correlating microscopical, anatomical and functional imaging data of the cerebral cortex. We introduce a new, MATLAB based toolbox for the SPM2 software package which enables the integration of probabilistic cytoarchitectonic maps and results of functional imaging studies. The toolbox includes the functionality for the construction of summary maps combining probability of several cortical areas by finding the most probable assignment of each voxel to one of these areas. Its main feature is to provide several measures defining the degree of correspondence between architectonic areas and functional foci. The software, together with the presently available probability maps, is available as open source software to the neuroimaging community. This new toolbox provides an easy-to-use tool for the integrated analysis of functional and anatomical data in a common reference space.

Brain↗

PubMed2004

Analysis of neural mechanisms underlying verbal fluency in cytoarchitectonically defined stereotaxic space--the roles of Brodmann areas 44 and 45.

We investigated neural activations underlying a verbal fluency task and cytoarchitectonic probabilistic maps of Broca's speech region (Brodmann's areas 44 and 45). To do so, we reanalyzed data from a previous functional magnetic resonance imaging (fMRI) [Brain 125 (2002) 1024] and from a cytoarchitectonic study [J. Comp. Neurol. 412 (1999) 319] and developed a method to combine both data sets. In the fMRI experiment, verbal fluency was investigated in 11 healthy volunteers, who covertly produced words from predefined categories. A factorial design was used with factors verbal class (semantic vs. overlearned fluency) and switching between categories (no vs. yes). fMRI data analysis employed SPM99 (Statistical Parametric Mapping). Cytoarchitectonic maps of areas 44 and 45 were derived from histologic sections of 10 postmortem brains. Both the in vivo fMRI and postmortem MR data were warped to a common reference brain using a new elastic warping tool. Cytoarchitectonic probability maps with stereotaxic information about intersubject variability were calculated for both areas and superimposed on the functional data, which showed the involvement of left hemisphere areas with verbal fluency relative to the baseline. Semantic relative to overlearned fluency showed greater involvement of left area 45 than of 44. Thus, although both areas participate in verbal fluency, they do so differentially. Left area 45 is more involved in semantic aspects of language processing, while area 44 is probably involved in high-level aspects of programming speech production per se. The combination of functional data analysis with a new elastic warping tool and cytoarchitectonic maps opens new perspectives for analyzing the cortical networks involved in language.

Adult↗