Biomedical subjects

Karl Zilles

Publications and source records attributed to Karl Zilles.

At least 37 records · Page 2Linked to original sources

PubMed2006

Left-right asymmetry in volume and number of neurons in adult Broca's area.

Total neuron number in, and volume of, Brodmann areas (BA) 44 and 45 (Broca's area) were studied in Nissl-stained sections from the left and right hemispheres of five adult men and five adult women. The volume of BA 44 was greater in the left hemisphere than in the right in all ten cases, although asymmetry was only significant for the subgroup of male subjects. For six of the ten subjects (including all females), the volume of BA 45 was greater in the left hemisphere than the right. This asymmetry was significant only for the women. A significant left-over-right asymmetry has been found in total neuron number in male BA 44. Although the total number of neurons in left BA 45 was larger in all five female subjects, this asymmetry did not reach significant difference. In the male subjects no significant asymmetry difference in total neuron number was found in BA 45 either. There was no significant hemispheric asymmetry or gender interaction for neuronal number density, either in BA 44 or 45. This study is the first quantitative study of total number of neurons in BA 44 and 45 in adult subjects, and demonstrates that both the volume and the total neuron number of BA 44 and 45 on the left are generally greater than that of the right hemisphere, with the possible exception of the male BA 45. In addition, it shows that the inter-individual variability was also very large (more than twofold) in the numerical values of all variables.

Adult↗

PubMed2006

Towards multimodal atlases of the human brain.

Atlases of the human brain have an important impact on neuroscience. The emergence of ever more sophisticated imaging techniques, brain mapping methods and analytical strategies has the potential to revolutionize the concept of the brain atlas. Atlases can now combine data describing multiple aspects of brain structure or function at different scales from different subjects, yielding a truly integrative and comprehensive description of this organ. These integrative approaches have provided significant impetus for the human brain mapping initiatives, and have important applications in health and disease.

Anatomy, Artistic↗

PubMed2006

18F-CPFPX PET: on the generation of parametric images and the effect of scan duration.

UNLABELLED: 8-cyclopentyl-3-(3-18F-fluoropropyl)-1-propylxanthine (18F-CPFPX) is a novel PET ligand for in vivo quantification of cerebral A1 adenosine receptors. The present study investigated the applicability of voxelwise graphical analysis to the generation of parametric images of the total volume of distribution (DVt) of 18F-CPFPX as a prerequisite for voxel-by-voxel statistical analysis. The benefit of spatial smoothing for reduction of noise-dependent negative bias in graphical analysis was examined. Additionally, the effect of scan duration on the accuracy of analyses based on volumes of interest (VOIs) and individual voxels was explored. METHODS: Ten healthy male volunteers underwent bolus-injection 18F-CPFPX PET (90 min). The data were analyzed using a 2-tissue-compartment model and graphical analysis. Voxelwise graphical analysis was performed with and without preceding spatial gaussian smoothing. RESULTS: Voxelwise graphical analysis yielded high-quality parametric images. However, voxelwise graphical analysis suffered from a negative bias (mean bias in cortical regions, -9.6% to -7.5%), which could be attenuated considerably by spatial smoothing (using a kernel of 5 mm in full width at half maximum, bias of -4.0% to -1.9%). Shortening the total scan duration to 60 min had minor effects on the accuracy of VOI-based analysis (15 VOIs x 10 subjects); the resulting error only occasionally exceeded +/-5% in individual regions (n = 6 for 2-tissue-compartment model, n = 10 for VOI-based graphical analysis, always within +/-7.5%). Quantification accuracy was acceptable with scan durations of 60 and 75 min in voxelwise graphical analysis with spatial smoothing (mean bias in cortical regions, -8.4% to -5.9%) and without spatial smoothing (bias, -9.2% to -11.6%), respectively. CONCLUSION: High-quality DVt parametric images of 18F-CPFPX can be generated by voxelwise graphical analysis. The noise-dependent negative bias of voxelwise graphical analysis is greatly reduced by spatial smoothing. A shortened scan of 60 min will enhance the clinical applicability of 18F-CPFPX PET.

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

Differential brain activation according to chronic social reward frustration.

Neural correlates of reward frustration are increasingly studied in humans. In line with prediction error theory, omission of an expected reward is associated with relative decreases of cerebral activation in dopaminergic brain areas. We investigated whether a history of chronic work-related reward frustration influences this reward-dependent activation pattern by means of functional magnetic resonance imaging. Solving arithmetic tasks was followed by either monetary reward or omission of reward. Hyperactivations in the medial prefrontal, anterior cingulate and dorsolateral prefrontal cortex were observed in a group of healthy adults with high susceptibility to reward frustration as compared with a group with low susceptibility. Findings indicate a compromised ability of adapting brain activation among those suffering form chronic social reward frustration.

Adult↗

PubMed2005

Fully-automated detection of cerebral water content changes: study of age- and gender-related H2O patterns with quantitative MRI.

We present a simple and robust method for the automated image analysis of quantitative cerebral water content maps acquired with MRI. The method is based on a new approach for the absolute and quantitative mapping of water content in vivo. Water content maps were automatically segmented into grey and white matter by employing the quantitative T1 information acquired as part of the water content mapping procedure. Based on the segmented maps, twenty-two parameters sensitive to both absolute water content and its spatial organisation are automatically extracted without user interaction. The parameters include, amongst others, absolute water content in grey and white matter and spatial asymmetries of the cerebral water content distribution. Significant age- and gender-related changes in the parameters determined were observed in a study of forty-four healthy subjects. Most notably, the grey matter water content decreases at a rate of 0.034%/year for females between the 3rd and 8th decade of life, whilst a much stronger decrease is observed in males which sets in after the 5th decade of life. In addition, female grey matter water content is, on average, 1.2% higher than the respective male grey matter water content. In contrast to the heterogeneity observed in grey matter, no significant physiological variation was observed for white matter water content. In addition to absolute grey matter water content, characteristic age- and gender-specific variations were also observed in most of the other variables. To check the potential loss of information associated with the large reduction of the dimensionality of the dataset to 22 parameters only, the age and gender of each individual subject were predicted by employing robust linear discriminant analysis based on only the determined twenty-two variables. The median deviation between predicted and real age was 6.3 years resulting in a high correlation coefficient between both values (r = 0.69). Gender is correctly predicted in 68.2% of all cases which improves to 87.5% when age-dependent effects are first corrected, demonstrating the high information content present in the variables even though the dimension of the dataset was significantly reduced. These results form the baseline for future studies of cerebral pathology. The method presented is fully automated, robust and flexible, making it an ideal tool for routine application in both neuroscientific studies and clinical diagnosis based on the quantitative measurement of cerebral water content.

Adult↗

PubMed2005

Dependence of amygdala activation on echo time: results from olfactory fMRI experiments.

Echo time dependence of the BOLD sensitivity is an important topic in fMRI whenever brain regions are considered where the EPI data quality suffers from susceptibility gradients. Here, an fMRI study is presented showing that a reduced echo time EPI sequence significantly enhances the statistical inference in subcortical (limbic) brain regions, with special focus on the amygdala. As a consequence, to facilitate whole-brain fMRI with optimal echo times, a sequence with slice-dependent echo time is demonstrated with a focus on structures suffering from susceptibility changes. The applicability of this method is shown in a second fMRI study aimed at both, cortical, and limbic brain regions. The results are in good agreement with theoretical descriptions of the BOLD sensitivity under the influence of susceptibility gradients.

Adult↗

PubMed2005

1Alpha,25-dihydroxyvitamin D3 treatment does not alter neuronal cyclooxygenase-2 expression in the cerebral cortex after stroke.

The inducible prostaglandin synthase, cyclooxygenase-2, is upregulated in response to cerebral ischemia and contributes to potentiation of oxidative injury. Cyclooxygenase-2 expression is regulated by retinoic acid receptors, which form heterodimers with vitamin D receptors and vitamin D. In addition, vitamin D has been reported to have neuroprotective qualities. The aim of this study was to examine whether the biologically active vitamin D3-metabolite 1alpha,25-dihydroxyvitamin D3 (1,25-D3), influences the expression of inducible cyclooxygenase-2 in photothrombotically lesioned brain or is part of an independent neuroprotective mechanism. We compared groups of nonlesioned control rats and infarcted animals, which were treated with either 1,25-D3 or solvent at different times postlesion. In control animals, cyclooxygenase-2 immunoreactivity was readily evident in almost all cortical neurons of layers II/III as well as in a few pyramidal cells in layer V. Following photothrombotic infarction of the right cortical hindlimb area, there was a significant, but transient, increase in cyclooxygenase-2 labeling which was restricted to neurons of the injured hemisphere in both 1,25- D3-treated and solvent-treated rats. Highest levels of cyclooxygenase-2 immunoreactivity were seen at 12 and 24 h postlesion, followed by a gradual decrease at later time points. However, no significant differences were detected between 1,25-D3-treated and solvent-treated lesioned rats, indicating that postischemic neuronal cyclooxygenase-2 upregulation is not influenced by 1,25-D3. It is concluded that the neuroprotective effect of 1,25-D3 does not depend on modulations of neuronal COX-2 expression caused by postlesional hyperexcitation.

Animals↗

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

When visual perception causes feeling: enhanced cross-modal processing in grapheme-color synesthesia.

In synesthesia, stimulation of one sensory modality (e.g., hearing) triggers a percept in another, non-stimulated sensory modality (e.g., vision). Likewise, perception of a form (e.g., a letter) may induce a color percept (i.e., grapheme-color synesthesia). To date, the neural mechanisms underlying synesthesia remain to be elucidated. We disclosed by fMRI, while controlling for surface color processing, enhanced activity in the left intraparietal cortex during the experience of grapheme-color synesthesia (n = 9). In contrast, the perception of surface color per se activated the color centers in the fusiform gyrus bilaterally. The data support theoretical accounts that grapheme-color synesthesia may originate from enhanced cross-modal binding of form and color. A mismatch of surface color and grapheme induced synesthetically felt color additionally activated the left dorsolateral prefrontal cortex (DLPFC). This suggests that cognitive control processes become active to resolve the perceptual conflict resulting from synesthesia.

Acoustic Stimulation↗

PubMed2005

Transmitter receptors reveal segregation of cortical areas in the human superior parietal cortex: relations to visual and somatosensory regions.

Regional distributions of ligand binding sites of 12 different neurotransmitter receptors (glutamatergic: AMPA, kainate, NMDA; GABAergic: GABA(A), GABA(B); cholinergic: muscarinic M2, nicotinic; adrenergic: alpha1, alpha2; serotonergic: 5-HT1A, 5-HT2; dopaminergic: D1) were studied in human postmortem brains by means of quantitative receptor autoradiography. Binding site densities were measured in the superior parietal lobule (SPL) (areas 5L, 5M, 5Ci, and different locations within Brodmann's area (BA) 7), somatosensory (BA 2), and visual cortical areas (BA 17, and different locations within BAs 18 and 19). Similarities of receptor distribution between cortical areas were analyzed by cluster analysis, uni- and multivariate statistics of mean receptor densities (averaged over all cortical layers), and profiles representing the laminar distribution patterns of receptors. A considerable heterogeneity of regional receptor densities and laminar patterns between the sites was found in the SPL and the visual cortex. The most prominent regional differences were found for M2 receptors. In the SPL, rostrocaudally oriented changes of receptor densities were more pronounced than those in mediolateral direction. The receptor distribution in the rostral SPL was more similar to that of the somatosensory cortex, whereas caudal SPL resembled the receptor patterns of the dorsolateral extrastriate visual areas. These results suggest a segregation of the different SPL areas based on receptor distribution features typical for somatosensory or visual areas, which fits to the dual functional role of this cortical region, i.e., the involvement of the human SPL in visuomotor and somatosensory motor transformations.

Aged↗

PubMed2005

1alpha,25-dihydroxy-vitamin D3 in combination with 17beta-estradiol lowers the cortical expression of heat shock protein-27 following experimentally induced focal cortical ischemia in rats.

1alpha,25-(OH)(2)-vitamin-D(3) (1,25-D(3)) and 17beta-estradiol are both known to act neuroprotective in certain experimental in vitro and in vivo settings. We studied the effects of 1,25-D(3) or 17beta-estradiol or their combined application on heat shock protein-27 (HSP-27) distribution after focal cortical ischemia using the photothrombosis model. HSP-27 is a well-established marker of the cerebral oxidative stress response and a potent inhibitor of apoptosis. Lesioned rats were injected i.p. one hour after injury with either 1 microg 1,25-D(3)/kg or 7 microg 17beta-estradiol/kg or a combination of both steroids. Groups of non-lesioned steroid-treated rats and lesioned, solvent-treated rats served as controls. Treatment with both steroids did not affect the size of the lesion. In addition, 17beta-estradiol resulted in significant reduction of HSP-27 induction, whereas the combination of 1,25-D(3)+17beta-estradiol resulted in a highly significant reduction of HSP-27 within the infracted cerebral cortex, indicating that both steroids act synergistically in a protective manner.

Animals↗

PubMed2005

The human parietal operculum. I. Cytoarchitectonic mapping of subdivisions.

The human secondary somatosensory cortex (SII) is located on the parietal operculum, as shown by intraoperative stimulation and functional imaging studies. The position and extent of the anatomical correlates of this functionally defined region, however, are still unknown. We have therefore histologically mapped the putative anatomical correlates of the SII cortex in cell-body-stained histological sections of 10 human postmortem brains using quantitative cytoarchitectonic analysis. The gray level index (GLI), which is an indicator of the volume fraction of nerve cell bodies, was measured in the parietal operculum. GLI profiles as measures of the laminar pattern of the cortex were extracted perpendicular to cortical layers. Cytoarchitectonic borders were detected observer-independently by multivariate statistical analysis of the laminar profiles. Four cytoarchitectonic areas (termed OP 1-4) were identified. This cytoarchitectonic heterogeneity of the parietal operculum corresponds to results of functional imaging studies on the human SII cortex and data from non-human primates where multiple subregions within SII have been demonstrated by electrophysiological and connectivity studies.

Brain Mapping↗

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↗

PubMed2005

Subdivisions of human parietal area 5 revealed by quantitative receptor autoradiography: a parietal region between motor, somatosensory, and cingulate cortical areas.

Brodmann's area (BA) 5 of the human superior parietal cortex occupies a central anatomical position between the primary motor (BA 4), somatosensory (area 3b and BA 2), cingulate (area 23c), and superior parietal association cortex (BA 7). We studied the regional and laminar distributions of the binding sites of 12 different neurotransmitter receptors (glutamatergic: AMPA, kainate, NMDA; GABAergic: GABAA, GABAB; cholinergic: muscarinic M2, nicotinic; adrenergic: alpha1, alpha2; serotoninergic: 5-HT1A, 5-HT2; dopaminergic: D1) in human postmortem brains by means of quantitative receptor autoradiography, since the structural and functional aspects of human BA 5 are widely unknown, and previous observations have demonstrated characteristic differences in receptor distribution between motor and somatosensory areas. Binding site densities were measured in the cytoarchitectonically defined BA 5 and surrounding regions. Similarities and differences of receptor distribution between cortical areas were studied by cluster analysis of mean binding site densities averaged over all cortical layers, univariate and multivariate statistics, and by density profiles representing laminar receptor distribution patterns. Based on regional heterogeneities of binding site densities and of the cytoarchitecture within BA 5, we suggest a subdivision into three subareas: medial area 5M, lateral area 5L, and area 5Ci in the region around the cingulate sulcus. BA 5 is therefore a heterogeneous cortical region, comprising three subareas showing receptor expression patterns similar to the adjoining higher order somatosensory, multimodal parietal, or cingulate regions. These findings suggest that human BA 5 constitutes a higher order cortical area, clearly distinct from the primary somatosensory and motor cortex.

Aged↗

PubMed2005

Simplified quantification of cerebral A1 adenosine receptors using [18F]CPFPX and PET: analyses based on venous blood sampling.

[(18)F]CPFPX was proposed as a novel ligand for in vivo quantification of cerebral A(1) adenosine receptors (A(1)AR) using positron emission tomography (PET). The present study investigates the applicability of non-invasive non-compartment analyses to quantify the [(18)F]CPFPX total distribution volume (DV(') (t)) without arterial blood sampling. Five healthy volunteers underwent dynamic PET (90 min) with arterial and venous blood sampling after [(18)F]CPFPX bolus injection. Area under curve (AUC) analysis and Logan's graphical analysis (GA) were performed employing venous blood samples as non-invasive analyses. AUC analysis without data extrapolation (AUC(r)) and venous GA were also applied on voxel-level to generate parametric images. A conventional two-tissue compartment model (2TCM) using arterial blood samples served as reference method. Regional DV(') (t) estimates provided by venous AUC and GA analyses and 2TCM demonstrated very high agreement (venous AUC vs. 2TCM: r(2) = 0.968, linear regression slope = 0.943; venous GA vs. 2TCM: r(2) = 0.972, slope = 0.906). Although on voxel-level the venous AUC(r) and GA analyses were affected by a slight negative bias, they were still very highly correlated with the 2TCM (voxel-wise venous AUC(r) vs. 2TCM: r(2) = 0.969, slope = 0.858; voxel-wise venous GA vs. 2TCM: r(2) = 0.959, slope = 0.867). The proposed non-invasive analysis methods (particularly venous GA) allow reliable quantification of human [(18)F]CPFPX PET studies. In populations with altered metabolic/kinetic properties, the applicability of venous sampling has to be separately verified. The applicability of [(18)F]CPFPX PET in basic and clinical neurosciences will be considerably enhanced by the avoidance of arterial blood sampling.

Adult↗

PubMed2005

Yearning to yawn: the neural basis of contagious yawning.

Yawning is contagious: Watching another person yawn may trigger us to do the same. Here we studied brain activation with functional magnetic resonance imaging (fMRI) while subjects watched videotaped yawns. Significant increases in the blood oxygen level dependent (BOLD) signal, specific to yawn viewing as contrasted to viewing non-nameable mouth movements, were observed in the right posterior superior temporal sulcus (STS) and bilaterally in the anterior STS, in agreement with the high affinity of STS to social cues. However, no additional yawn-specific activation was observed in Broca's area, the core region of the human mirror-neuron system (MNS) that matches action observation and execution. Thus, activation associated with viewing another person yawn seems to circumvent the essential parts of the MNS, in line with the nature of contagious yawns as automatically released behavioural acts-rather than truly imitated motor patterns that would require detailed action understanding. The subjects' self-reported tendency to yawn covaried negatively with activation of the left periamygdalar region, suggesting a connection between yawn contagiousness and amygdalar activation.

Adolescent↗