Andreas Dabringhaus

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.

Human brain atlas : For high-resolution functional and anatomical mapping

We present the new computerized Human Brain Atlas (HBA) for anatomical and functional mapping studies of the human brain. The HBA is based on many high‐resolution magnetic resonance images of normal subjects and provides continuous updating of the mean shape and position of anatomical structures of the human brain. The structures are transformable by linear and nonlinear global and local transformations applied anywhere in 3‐D pictures to fit the anatomical structures of individual brains, which, by reformatting, are transformed into a high‐resolution standard anatomical format. The power of the HBA to reduce anatomical variations was evaluated on a randomized selection of anatomical landmarks in brains of 27 young normal male volunteers who were different from those on whom the standard brain was selected. The HBA, even when based only on standard brain surface and central structures, reduced interindividual anatomical variance to the level of the variance in structure position between the right and left hemisphere in individual brains.

Structural asymmetries in the human forebrain and the forebrain of non-human primates and rats

Possible asymmetries of the following structures were studied: volumes of total human hemispheres, cortex and white matter volumes in post-mortem- (unknown handedness) and living brains (male right-handers); volumes of the rat primary visual cortex, its mon- and binocular subfields, its layer iv and the density of myelinated fibres in layer iv; transmitter receptor densities (NMDA, AMPA, kainate and GABAA receptors) in sensorimotor regions of the rat cortex; volume of the motor cortex and the 3D-extent of the central sulcus in the post-mortem- (unknown handedness) and living human brain (male right-handers); petalia of the hemispheres in human (male right- and left-handers) and chimpanzee brains. Histological, MRI and receptor autoradiographic techniques were used. With the notable exceptions of the transmitter receptors and the total primary visual cortex in rats and the hemispheres in chimpanzees, which do not show any significant directional asymmetry, all other parameters studied are asymmetrically distributed between the right- and left hemispheres. The regional distribution pattern and the degree of asymmetry of frontal and occipital petalia in living human brains differ between right- and left-handers.

Hemispheric shape of European and Japanese brains: 3-D MRI analysis of intersubject variability, ethnical, and gender differences.

Hemispheric shape is studied using magnetic resonance imaging and 3-D reconstructions in right-handed, male and female, European and Japanese subjects. Japanese hemispheres are relatively shorter, but wider than European hemispheres. Regions of maximal intersubject variability in hemispheric shape are present in the occipital and temporal lobes in each sample. Deviations from this general pattern are found in the (i) right inferior parietal lobule (European hemispheres are more variable than Japanese), (ii) lower third of the pre- and postcentral gyri (female Japanese hemispheres are less variable than the other samples), (iii) right inferior frontal gyrus (male European hemispheres are more variable than the other samples), and (iv) polar part of the frontal lobe (female European hemispheres are less variable than the other samples). The distribution of intersubject variability between the hemispheres is less asymmetric in female than male brains. Male Japanese hemispheres are shorter but wider than female Japanese hemispheres, whereas European hemispheres show the inverse gender relations. These results demonstrate that hemispheric shape shows a considerable intersubject variability, which is not randomly distributed over the cortical surface but displays distinct regions of higher variability. Despite this intersubject variability significant interethnic- and gender-related differences in hemispheric shape are present, which may be relevant if individual brains have to be warped to a single or mean reference brain or realistic brain models are to be constructed.

Statistics of deformations in histology and application to improved alignment with MRI

An exact registration of magnetic resonance images (MRI) with histological sections is impeded by local deformations resulting from histological preparation procedures. Therefore, it is desirable to know the probability density function of spatial deformations in order to estimate optimal global least-square transformation parameters from suitable landmarks. For this reason, the statistics of deformations is investigated. It is shown analytically that the frequency of occurrence of the absolute geometrical differences (deformations) are Rayleigh-Bessel distributed for anisotropic histological preparation procedures and Rayleigh distributed in the case of isotropic procedures. The probabilistic analysis is given in conjunction with an iterative optimization technique in order to ensure that the probability density function is within a threshold required for the application to experimental data. The application of the analytical model is investigated with real data. It is shown with this data that the extent of deformations varies with the size of the histological section. An individual threshold can be selected on the basis of a Rayleigh-function restricting local corrections to small parts of the image. Thus, global misalignment in each section can be avoided, resulting in an improved 3-D reconstruction of the volume, i.e., the transitions from one section to the next are more continuous.

Mobilisation of hematopoietic CD34+ precursor cells in patients with acute stroke is safe--results of an open-labeled non randomized phase I/II trial.

Background Regenerative strategies in the treatment of acute stroke may have great potential. Hematopoietic growth factors mobilize hematopoietic stem cells and may convey neuroprotective effects. We examined the safety, potential functional and structural changes, and CD34+ cell–mobilization characteristics of G-CSF treatment in patients with acute ischemic stroke. Methods and Results Three cohorts of patients (8, 6, and 6 patients per cohort) were treated subcutaneously with 2.5, 5, or 10 µg/kg body weight rhG-CSF for 5 consecutive days within 12 hrs of onset of acute stroke. Standard treatment included IV thrombolysis. Safety monitoring consisted of obtaining standardized clinical assessment scores, monitoring of CD34+ stem cells, blood chemistry, serial neuroradiology, and neuropsychology. Voxel-guided morphometry (VGM) enabled an assessment of changes in the patients structural parenchyma. 20 patients (mean age 55 yrs) were enrolled in this study, 5 of whom received routine thrombolytic therapy with r-tPA. G-CSF treatment was discontinued in 4 patients because of unrelated adverse events. Mobilization of CD34+ cells was observed with no concomitant changes in blood chemistry, except for an increase in the leukocyte count up to 75,500/µl. Neuroradiological and neuropsychological follow-up studies did not disclose any specific G-CSF toxicity. VGM findings indicated substantial atrophy of related hemispheres, a substantial increase in the CSF space, and a localized increase in parenchyma within the ischemic area in 2 patients. Conclusions We demonstrate a good safety profile for daily administration of G-CSF when begun within 12 hours after onset of ischemic stroke and, in part in combination with routine IV thrombolysis. Additional analyses using VGM and a battery of neuropsychological tests indicated a positive functional and potentially structural effect of G-CSF treatment in some of our patients. Trial Registration German Clinical Trial Register DRKS 00000723

Extension of the Principle Axes Theory for the Determination of Affine Transformation

The classical principle axes theory (PAT) is generalized to affine transformations with a new parametrization approach. Based on this extended theory, a fast multi-scale technique is derived for the alignment of affine objects which is at least by one magnitude more accurate than the results of the classical PAT [1]–[8]. Compared to the algorithms of Cygansky & Orr [7] and Faber & Stokeley [8] the technique is not sensitive to noise [9] or to symmetries of the objects, since the transformation is derived from a second order moment tensor. In addition, it is shown with the extension of the theory, that the application of the PAT described in [1] by Bajcsi & Kovacic results in strong rotational and scaling misalignment (with rotational errors up to 45°), which can be completely suppressed by the generalized theory based on an appropriate parametrization and optimization of a similarity criterion.

Statistics of Nonlinear Spatial Distortions in Histological Images

Local spatial distortions in histological images hinder an exact global registration with corresponding magnetic resonance images (MRI) of the same object. In order to estimate appropriate reference points for an optimized least-square affine transformation matrix, the statistics of deformations is investigated. It is shown, that in the case of correlated and anisotropic histological procedures, local spatial distortions are Rayleigh-Bessel distributed according to the eigenvalues of matrix M describing variance and covariance of the distortions. For uncorrelated, anisotropic procedures, the probablity density function is given by a Rayleigh-Bessel function with corresponding variances and in the case of an uncorrelated and isotropic treatment the density can be described by a Rayleigh function. An advantage of this generalized theory is, that the information about the eigensystem of spatial deformations introduced by angle ϑ can be included in the Rayleigh-Bessel distribution which fits the experimental data more accurately over the entire histogram range and it is not necessary to rotate the images into the eigensystem of M. The application of the theory to histological and corresponding MR images demonstrates an improved registration quality.

Individual Assessment of Brain Tissue Changes in MS and the Effect of Focal Lesions on Short-Term Focal Atrophy Development in MS: A Voxel-Guided Morphometry Study

We performed voxel-guided morphometry (VGM) investigating the mechanisms of brain atrophy in multiple sclerosis (MS) related to focal lesions. VGM maps detect regional brain changes when comparing 2 time points on high resolution T1-weighted (T1w) magnetic resonace imaging (MRI). Two T1w MR datasets from 92 relapsing-remitting MS patients obtained 12 months apart were analysed with VGM. New lesions and volume changes of focal MS lesions as well as in the surrounding tissue were identified by visual inspection on colour coded VGM maps. Lesions were dichotomized in active and inactive lesions. Active lesions, defined by either new lesions (NL) (volume increase > 5% in VGM), chronic enlarging lesions (CEL) (pre-existent T1w lesions with volume increase > 5%), or chronic shrinking lesions (CSL) (pre-existent T1w lesions with volume reduction > 5%) in VGM, were accompanied by tissue shrinkage in surrounding and/or functionally related regions. Volume loss within the corpus callosum was highly correlated with the number of lesions in its close proximity. Volume loss in the lateral geniculate nucleus was correlated with lesions along the optic radiation. VGM analysis provides strong evidence that all active lesion types (NL, CEL, and CSL) contribute to brain volume reduction in the vicinity of lesions and/or in anatomically and functionally related areas of the brain.