Harald Bornfleth

Universität Heidelberg, Heidelburg, Baden-Württemberg, Germany

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Publications (22)39.6 Total impact


  • No preview · Chapter · May 2007
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    ABSTRACT: Both the motor system and the frontal executive control system show a late maturation in humans which continues into school-age and even adolescence. We investigated the maturation of preparation processes towards a fast motor reaction in 74 healthy right-handed children aged 6 to 18 years and analyzed the topography of the late component of contingent negative variation (lCNV) in a 64-electrode high density sensor array. While adolescents from about 12 years on showed a bilaterally distributed centro-parietal maximum like adults do, younger children almost completely missed the negativity over the left central area contralaterally to the side of the anticipated movement. The reason, as revealed by current source density, was that only adolescents showed significant evoked activity of the left pre-/primary motor and supplementary/cingulate motor areas, while in contrast both age groups displayed significant current sinks over the right (ipsilateral) centro-temporal area and right posterior parietal cortex. Spatio-temporal source analysis confirmed that negativity over the right posterior parietal area could not be explained by a projection via volume conduction from frontal areas involved in motor preparation but represented an independent component with a different maturational course most likely related to sensory attention. Significant event-related desynchronization of alpha-power over the contralateral sensorimotor cortex was found in the younger age group, indicating that also 6- to 11-year-old children were engaged in motor preparation. Thus, the missing current sink over the contalateral sensorimotor cortex during late CNV in 6- to 11-year-old children might reflect the immaturity of a specific subcomponent of the motor preparation system which is related to evoked (late CNV) but not induced activity (alpha-ERD).
    No preview · Article · Nov 2005 · NeuroImage
  • M Scherg · T Bast · K Hoechstetter · N Ille · D Weckesser · H Bornfleth · P Berg
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    ABSTRACT: Using multiple regional source models, brain source montages can be defined to compute continuous, single trial or averaged brain source activity by applying a fixed or adaptive source transformation to the raw or averaged EEG or MEG data. Brain source montages can dissociate the activities of the different lobes, hemispheres and sublobar areas, e.g. the different surfaces of the right and left temporal lobes. Epileptiform spike and seizure activities in EEG and MEG can be made more conspicuous by using brain source montages as compared with conventional montages or raw surface signals. By using mirror sources in both hemispheres, lateralized focal activity can be immediately recognized from the on-going EEG and MEG data.
    No preview · Article · Aug 2004 · International Congress Series
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    ABSTRACT: This paper introduces source coherence, a new method for the analysis of cortical coherence using noninvasive EEG and MEG data. Brain electrical source analysis (BESA) is applied to create a discrete multiple source model. This model is used as a source montage to transform the recorded data from sensor level into brain source space. This provides source waveforms of the modeled brain regions as a direct measure for their activities on a single trial basis. The source waveforms are transformed into time-frequency space using complex demodulation. Magnitude-squared coherence between the brain sources reveals oscillatory coupling between sources. This procedure allows one to separate the time-frequency content of different brain regions even if their activities severely overlap at the surface. Thus, source coherence overcomes problems of localization and interpretation that are inherent to coherence analysis at sensor level. The principle of source coherence is illustrated using an EEG recording of an error-related negativity as an example. In this experiment the subject performed a visuo-motor task. Source coherence analysis revealed dynamical linking between posterior and central areas within the gamma-band around the time of button press at a post-stimulus latency of 200-300 ms.
    No preview · Article · Feb 2004 · Brain Topography
  • Michael Scherg · Nicole Ille · Harald Bornfleth · Patrick Berg
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    ABSTRACT: Digital EEG allows one to combine recorded EEG channels into new montages without the need to record new data. Using spherical splines, voltages can be estimated at any point on the head. This allows one to generate various montages with the recorded or virtual electrodes at standardized locations, to interpolate bad electrodes, and to generate topographic maps over the whole head. Simulations of EEG activity originating in various brain regions are used to illustrate the effects of known generators on various montages and on whole-head maps. Some properties of spatial filters are introduced, and it is shown how they can be used to develop source montages with signals that estimate the activity in specific brain regions. The usefulness and validity of a source montage designed to focus on temporal lobe activity is illustrated with simulations and examples of temporal lobe spikes and seizures. Additional tools such as cross-correlation among channels, fast Fourier transform, and phase maps are described. These tools are useful in estimating time lags between source channels and in interpreting propagating spike and seizure activity. In combination, these tools help to analyze and to enhance activities that may be hard to detect from the background scalp EEG in traditional montages.
    No preview · Article · May 2002 · Journal of Clinical Neurophysiology
  • Michael Scherg · Nicole Ille · Harald Bornfleth · Patrick Berg
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    ABSTRACT: Summary : Digital EEG allows one to combine recorded EEG channels into new montages without the need to record new data. Using spherical splines, voltages can be estimated at any point on the head. This allows one to generate various montages with the recorded or virtual electrodes at standardized locations, to interpolate bad electrodes, and to generate topographic maps over the whole head. Simulations of EEG activity originating in various brain regions are used to illustrate the effects of known generators on various montages and on whole-head maps. Some properties of spatial filters are introduced, and it is shown how they can be used to develop source montages with signals that estimate the activity in specific brain regions. The usefulness and validity of a source montage designed to focus on temporal lobe activity is illustrated with simulations and examples of temporal lobe spikes and seizures. Additional tools such as cross-correlation among channels, fast Fourier transform, and phase maps are described. These tools are useful in estimating time lags between source channels and in interpreting propagating spike and seizure activity. In combination, these tools help to analyze and to enhance activities that may be hard to detect from the background scalp EEG in traditional montages.
    No preview · Article · Mar 2002 · Journal of Clinical Neurophysiology
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    ABSTRACT: Chromosome territories formed by fluorescence-labeled sub-chromosomal foci were analyzed in time-lapse series of 3D confocal data sets of living HeLa and human neuroblastoma cells. The quantitative analysis of the chromosome territory morphology confirmed previous results obtained by visual observation [Zink et al., Hum. Genet. 102 (1998) 241–251] that chromosome territories persisted as stable entities over an observation time >4 h. The changes in morphology with time of single chromosome territories were found to be less pronounced than differences in morphology of different chromosome territories in fixed cells. The analysis of the individual motion of chromosome territories recently showed ‘Brownian’ diffusion-like motion at very slow rates [Bornfleth et al., Biophys. J. 77 (1999) 2871–2886]. Here, we show that the mutual motion of different chromosome territories was independent and also ‘Brownian’ diffusion-like.
    Full-text · Article · Aug 2001 · Biochimica et Biophysica Acta
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    ABSTRACT: We investigated whether attention to different stimulus attributes (location, intensity) has different effects on the activity of the secondary (SII) somatosensory cortex. Tactile stimuli were applied to the left index finger and somatosensory evoked fields (SEFs) were recorded using a whole-head magnetoencephalography (MEG) system. Two oddball paradigms with stimuli varying in location or intensity were performed in an ignore and an attend condition. Brain sources were estimated by magnetic source imaging. No attention effect was observed for the primary SI area. However, attention enhanced SII activity bilaterally from 55 to 130 ms by 52% in the spatial and 64% in the intensity discrimination task. SII attentional enhancement was very similar in both paradigms and occurred both for deviants and standards.
    No preview · Article · Sep 2000 · Neuroreport
  • J Tajbakhsh · H Luz · H Bornfleth · S Lampel · C Cremer · P Lichter
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    ABSTRACT: Previous topological analyses of DNA sequence organization in the interphase chromosome mainly focused on the spatial distribution of individual gene copies within chromosome territories. In order to achieve a more comprehensive view into the subchromosomal arrangement of DNA, we isolated the GC-richest/gene-richest fraction (H3 isochores) as well as AT-richest/gene-poorest fraction of human genomic DNA (L1+L2 isochores) and visualized the respective DNA within individual chromosome territories by means of dual-color FISH. Application of confocal laser scanning microscopy and dedicated 3D image analysis software, which differentiated territory subvolumes by peeling shells one voxel in width, revealed a significant difference in the intraterritorial distribution of these two DNA sequence classes. While the H3 isochores were found localized in all subvolumes of the territories at similar frequency, simultaneously detected L1+L2 isochores were observed more to the interior of the same chromosome territories. Thus the GC-rich sequences display a much higher variability in their intraterritorial localization than AT-rich DNA fragments.
    No preview · Article · Apr 2000 · Experimental Cell Research
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    ABSTRACT: A variety of experimental results indicates that the chromosomal 3D-structure and organization in cell nuclei is of great importance for the functioning of the genome. To study the spatial topology of intact, three dimensionally conserved cell nuclei, the technique of spectral precision distance microscopy is applied to DNA sequences specifically labelled by fluorochromes. This allows to analyze structures light-microscopically with a nearly molecular, resolution equivalent“. As examples, studies of the relative localization of the genes ANT2 and ANT3 in the X-chromosome territory and studies of the 3D-topology of the bcr-abl region in cell nuclei of a CML-patient are presented.
    No preview · Article · Dec 1999 · Zeitschrift für Medizinische Physik
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    ABSTRACT: The motion of subchromosomal foci and of whole chromosome territories in live human cell nuclei was investigated in four-dimensional space-time images. Visualization of subchromosomal foci was achieved by incorporating Cy3-dUTP into the nuclear DNA of two different cell types after microinjection. A subsequent segregation of the labeled cell nuclei led to the presence of only a few labeled chromosome territories on a background of nonlabeled chromatin (Zink et al.,1998. Hum. Genet. 102:241-251). This procedure yielded many distinct signals in a given cell nucleus. Motion analysis in four-dimensional space-time images was performed using single-particle tracking and a statistical approach to the detection of a possible directional motion of foci relative to the center of mass of a chromosome territory. The accuracy of the analysis was tested using simulated data sets that closely mirrored the experimental setup and using microparticles of known size. Application of the analysis tools to experimental data showed that mutual diffusion-like movements between foci located on different chromosomes were more pronounced than inside the territories. In the time range observed, movements of individual foci could best be described by a random diffusion process. The statistical test for joint directed motion of several foci inside chromosome territories revealed that foci occasionally switched from random to directional motion inside the territories.
    Full-text · Article · Dec 1999 · Biophysical Journal
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    ABSTRACT: It has been suggested that DNA organized into replication foci during S-phase remains stably aggregated in non-S-phase cells and that these stable aggregates provide fundamental units of nuclear or chromosome architecture [C. Meng and R. Berezney (1991)J. Cell Biol.115, 95a; E. Sparvoliet al.(1994)J. Cell Sci.107, 3097–3103; D. A. Jackson and A. Pombo (1998)J. Cell Biol.140, 1285–1295; D. Zinket al.(1998)Hum. Genet.112, 241–251]. To test this hypothesis, early and late replicating DNA of human diploid fibroblasts was labeled specifically by incorporating two different thymidine analogs [J. Aten (1992)Histochem. J.24, 251–259; A. E. Visser (1998)Exp. Cell Res.243, 398–407], during distinct time segments of S-phase. On mitotic chromosomes the amount and spatial distribution of early and late replicating DNA corresponded to R/G-banding patterns. After labeling cells were grown for several cell cycles. During this growth period individual replication labeled chromosomes were distributed into an environment of unlabeled chromosomes. The nuclear territories of chromosomes 13 and 15 were identified by additional chromosome painting. The distribution of early and late replicating DNA was analyzed for both chromosomes in quiescent (G0) cells or at G1. Early and late replicating DNA occupied distinct foci within chromosome territories, displaying a median overlap of only 5–10%. There was no difference in this regard between G1and G0cells. Chromosome 13 and 15 territories displayed a similar structural rearrangement in G1cells compared to G0cells resulting in the compaction of the territories. The findings demonstrate that early and late replicating foci are maintained during subsequent cell cycles as distinctly separated units of chromosome organization. These findings are compatible with the hypothesis that DNA organized into replicon clusters remains stably aggregated in non-S-phase cells.
    Full-text · Article · Mar 1999 · Experimental Cell Research
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    ABSTRACT: Confocal laser scanning fluorescence microscopy is presently being used widely in biomedical research. A severe limitation for its use is its often still insufficient resolution. In situ measurements in 3D conserved human cell nuclei showed that distance measurements between fluorescent targets located in the interior of such objects are limited a resolution regime of appr. greater than or equal to 0.3 micrometer in lateral and appr. greater than or equal to 0.7 micrometer in axial direction. A technique to overcome these restrictions is the recently developed Spectral Precision Distance Microscopy (SPM). This approach allows the determination of distances between targets which carry different spectral signatures with high precision. In situ measurements revealed that the SPM approach allows the determination of distances in 3D intact cell nuclei with a 'Resolution Equivalent' better than 50 nm. Here we present an improved chromatic shift calibration method for Spectral Precision Distance Microscopy. Furthermore, micro axial tomography allows the tilting of objects perpendicular to the optical axis; thus two objects can always be tilted in such a way that they can be recorded in the same focal plane. Therefore the error in distance determination is minimized. Here we present some preliminary data for the applicability of spectral precision distance microscopy (SPM) to micro axial microscopy.
    Full-text · Article · Jan 1999 · Proceedings of SPIE - The International Society for Optical Engineering
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    Full-text · Article · Jan 1999
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    ABSTRACT: The microscopic analysis of the 3D-nanostructure of chromatin in intact cell nuclei can contribute to a better understanding of the organization of breakpoint regions and thus of the formation of chromosome aberrations induced by ionizing radiation. Specific labelling of very small chromatin targets with dyes of different spectral signatures is feasible by fluorescence in situ hybridization. The use of DNA clones mapping breakpoint regions differently, allows precise measurements of the 3D-topology of these regions. However, 3D-fluorescence microscopy beyond the classical resolution limit is required. This can be fulfilled using a confocal laser scanning microscope in combination with principles of spectral precision distance microscopy. As an example, results obtained by digital image analysis are shown for the bcr-abl region involved in the formation of the Philadelphia chromosome [t(9;22)] of leukemia patients. These results support cytogenetic and molecular biology studies which have indicated that always one parental allele only may be involved in the rearrangement. For further studies with improved precision, spatially modulated excitation fluorescence microscopy can be applied, which is a promising technique to allow an almost molecular distance resolution equivalent in 3D-fluorescence light microscopy of intact cell nuclei.
    Full-text · Article · Jan 1999
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    ABSTRACT: Multicolor fluorescencein situhybridization with a whole chromosome composite probe for the X-chromosome and microdissection probes for the Xp and Xq arms, as well as for the Xp terminal, Xq terminal, and X centromer specific subregional probes, was applied to three-dimensional (3D) preserved human female amniotic fluid cell nuclei. Confocal laser scanning microscopy and three-dimensional image analysis demonstrated distinctly separated Xp arm and Xq arm domains. 3D distance measurements revealed a high variability of intrachromosomal distances between Xpter, Xcen, and Xqter specific probes within both X territories. A 3D distance measurement error of ±70 nm was found in control experiments using quartz glass microspheres labeled with different fluorochromes. Our data argue against the hypothesis of Walkeret al.(1991,Proc. Natl. Acad. Sci. USA88, 6191–6195) that a looped structure of the inactive X territory is formed by tight telomere–telomere associations.
    No preview · Article · Jun 1998 · Experimental Cell Research

  • No preview · Article · Oct 1997 · Cancer Genetics and Cytogenetics
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    ABSTRACT: In comparative genomic hybridization (CGH), quantitative measurement of fluorescence intensity ratios on metaphase chromosomes is the basic method for detecting copy number changes in the test DNA. The microscope images are usually acquired by high-resolution, highly sensitive, black and white (B&W) CCD cameras. This requires subsequent recording of the different color images using appropriate filter combinations for excitation and emission. We describe an alternative approach using the one-chip true-color CCD camera Kappa CF 15 MC and an Omega triple-bandpass filter for simultaneous registration of the three dyes Texas red, FITC, and DAPI. A detailed examination of the imaging properties of the system was performed. The camera response in the three color planes R, G, and B was evaluated, and calibration factors for image correction were calculated. An error estimate is given. A complete computer program for the image analysis of CGH experiments has been developed for an 80486 PC, using the commercially available software package Optimas as the basis for image recording. Examples that confirm the suitability of the system for ratio imaging in CGH are presented. The results were compared with others obtained from the same microscope slides using an established setup consisting of a B&W CCD camera (Photometrics) and a software program based on the TCL software package and run on a Macintosh Quadra 950. The results obtained using the two different systems were found to correspond closely.
    Full-text · Article · May 1996 · Cytometry

  • No preview · Conference Paper · Jan 1996
  • C Cremer · P Edelmann · H Bornfleth · H Luz · G Kreth · M Hausmann

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