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R Kötter

Publications and source records attributed to R Kötter.

At least 19 recordsLinked to original sources
PubMed2001

Neuroscience databases: tools for exploring brain structure-function relationships.

Faster than ever, neuroscience is generating vast amounts of data that await cross-referencing, comparison, integration and interpretation in the endeavour to unravel the mechanisms of the brain. The complex, diverse and distributed nature of these data requires the development of advanced neuroinformatics methodologies for databases and associated tools that are now beginning to emerge. This paper presents an overview of current issues in the representation, integration and analysis of neuroscience data from molecular to brain systems levels, including issues of implementation, standardization, management, quality control, copyright, confidentiality and acceptance. Particular emphasis is given to integrative neuroinformatics approaches for exploring structure-function relationships in the brain.

Animals↗
PubMed2001

Advanced database methodology for the Collation of Connectivity data on the Macaque brain (CoCoMac).

The need to integrate massively increasing amounts of data on the mammalian brain has driven several ambitious neuroscientific database projects that were started during the last decade. Databasing the brain's anatomical connectivity as delivered by tracing studies is of particular importance as these data characterize fundamental structural constraints of the complex and poorly understood functional interactions between the components of real neural systems. Previous connectivity databases have been crucial for analysing anatomical brain circuitry in various species and have opened exciting new ways to interpret functional data, both from electrophysiological and from functional imaging studies. The eventual impact and success of connectivity databases, however, will require the resolution of several methodological problems that currently limit their use. These problems comprise four main points: (i) objective representation of coordinate-free, parcellation-based data, (ii) assessment of the reliability and precision of individual data, especially in the presence of contradictory reports, (iii) data mining and integration of large sets of partially redundant and contradictory data, and (iv) automatic and reproducible transformation of data between incongruent brain maps. Here, we present the specific implementation of the 'collation of connectivity data on the macaque brain' (CoCoMac) database (http://www.cocomac.org). The design of this database addresses the methodological challenges listed above, and focuses on experimental and computational neuroscientists' needs to flexibly analyse and process the large amount of published experimental data from tracing studies. In this article, we explain step-by-step the conceptual rationale and methodology of CoCoMac and demonstrate its practical use by an analysis of connectivity in the prefrontal cortex.

Animals↗
PubMed2001

Simultaneity of responses in a hierarchical visual network.

The pattern of anatomical connections between areas of the primate visual system is organized hierarchically. However, onset latencies in parietal and occipital stations are often simultaneous, and this seems to contradict hierarchical organization in its simplest interpretation, as serial organization. To understand the reasons for this contradiction, we simulated the cortical network for which there is onset data, including the network's hierarchical structure. The network's dynamics reproduced the simultaneous onset latencies reported in several dorsal areas. These results show that a strictly hierarchical visual system is compatible with much more complex dynamics than serial processing, and that hodological and biophysical properties, are more closely related to onset dynamics than is hierarchical organisation.

Animals↗
PubMed2001

Layer-specific intracolumnar and transcolumnar functional connectivity of layer V pyramidal cells in rat barrel cortex.

Layer V pyramidal cells in rat barrel cortex are considered to play an important role in intracolumnar and transcolumnar signal processing. However, the precise circuitry mediating this processing is still incompletely understood. Here we obtained detailed maps of excitatory and inhibitory synaptic inputs onto the two major layer V pyramidal cell subtypes, intrinsically burst spiking (IB) and regular spiking (RS) cells, using a combination of caged glutamate photolysis, whole-cell patch-clamp recording, and three-dimensional reconstruction of biocytin-labeled cells. To excite presynaptic neurons with laminar specificity, the release of caged glutamate was calibrated and restricted to small areas of 50 x 50 microm in all cortical layers and in at least two neighboring barrel-related columns. IB cells received intracolumnar excitatory input from all layers, with the largest EPSP amplitudes originating from neurons in layers IV and VI. Prominent transcolumnar excitatory inputs were provided by presynaptic neurons also located in layers IV, V, and VI of neighboring columns. Inhibitory inputs were rare. In contrast, RS cells received distinct intracolumnar inhibitory inputs, especially from layers II/III and V. Intracolumnar excitatory inputs to RS cells were prominent from layers II-V, but relatively weak from layer VI. Conspicuous transcolumnar excitatory inputs could be evoked solely in layers IV and V. Our results show that layer V pyramidal cells are synaptically driven by presynaptic neurons located in every layer of the barrel cortex. RS cells seem to be preferentially involved in intracolumnar signal processing, whereas IB cells effectively integrate excitatory inputs across several columns.

Action Potentials↗
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↗
PubMed2000

Coordinate-independent mapping of structural and functional data by objective relational transformation (ORT).

Neuroscience has produced an enormous amount of structural and functional data. Powerful database systems are required to make these data accessible for computational approaches such as higher-order analyses and simulations. Available databases for key data such as anatomical and functional connectivity between cortical areas, however, are still hampered by methodological problems. These problems arise predominantly from the parcellation problem, the use of incongruent parcellation schemes by different authors. We here present a coordinate-independent mathematical method to overcome this problem: objective relational transformation (ORT). Based on new classifications for brain data and on methods from theoretical computer science, ORT represents a formally defined, transparent transformation method for reproducible, coordinate-independent mapping of brain data to freely chosen parcellation schemes. We describe the methodology of ORT and discuss its strengths and limitations. Using two practical examples, we show that ORT in conjunction with connectivity databases like CoCoMac (http://www.cocomac.org) is an important tool for analyses of cortical organization and structure-function relationships.

Animals↗
PubMed2000

Computational analysis of functional connectivity between areas of primate cerebral cortex.

Recent analyses of association fibre networks in the primate cerebral cortex have revealed a small number of densely intra-connected and hierarchically organized structural systems. Corresponding analyses of data on functional connectivity are required to establish the significance of these structural systems. We therefore built up a relational database by systematically collating published data on the spread of activity after strychnine-induced disinhibition in the macaque cerebral cortex in vivo. After mapping these data to two different parcellation schemes, we used three independent methods of analysis which demonstrate that the cortical network of functional interactions is not homogeneous, but shows a clear segregation into functional assemblies of mutually interacting areas. The assemblies suggest a principal division of the cortex into visual, somatomotor and orbito-temporo-insular systems, while motor and somatosensory areas are inseparably interrelated. These results are largely compatible with corresponding analyses of structural data of mammalian cerebral cortex, and deliver the first functional evidence for 'small-world' architecture of primate cerebral cortex.

Animals↗
PubMed2000

Global relationship between anatomical connectivity and activity propagation in the cerebral cortex.

Anatomical connectivity is a prerequisite for cooperative interactions between cortical areas, but it has yet to be demonstrated that association fibre networks determine the macroscopical flow of activity in the cerebral cortex. To test this notion, we constructed a large-scale model of cortical areas whose interconnections were based on published anatomical data from tracing studies. Using this model we simulated the propagation of activity in response to activation of individual cortical areas and compared the resulting topographic activation patterns to electrophysiological observations on the global spread of epileptic activity following intracortical stimulation. Here we show that a neural network with connectivity derived from experimental data reproduces cortical propagation of activity significantly better than networks with different types of neighbourhood-based connectivity or random connections. Our results indicate that association fibres and their relative connection strengths are useful predictors of global topographic activation patterns in the cerebral cortex. This global structure-function relationship may open a door to explicit interpretation of cortical activation data in terms of underlying anatomical connectivity.

Animals↗
PubMed2000

Laminar characteristics of functional connectivity in rat barrel cortex revealed by stimulation with caged-glutamate.

In rodent somatosensory (barrel) cortex input is processed by whisker-related columns before the integrated output is fed into behaviorally-relevant circuits. The layer-specific activation patterns of the rat barrel cortex were examined with a set-up for scanning functional connectivity in brain slices. Flash-induced release of caged-glutamate at a large number of stimulation sites was used in combination with simultaneous field potential recordings from layers II to VI with five electrodes. The field potentials revealed striking differences between the cortical layers. Glutamate-release in layer IV and lower layer III was most effective in evoking excitation in all other cortical layers, whereas field potentials recorded from layer IV itself were caused by stimulation of a very restricted columnar zone only. Field potentials in layers II and III were strongly driven by stimulation in layer IV and less consistently and much weaker by layer V. Layer V was the only lamina capable of responding to stimulation of all other cortical layers, thus displaying the largest input maps. Layer VI possessed functional connectivity intrinsically and with layer V. These data lead us to suggest that thalamic input may be boosted by its main target layer IV to start a sequence of excitation in layer IV, passing to the supragranular layers and finally reaching the infragranular layers. This sequence is likely to be backed-up by other simultaneous steps of transmission including a layer IV-to-V interaction. We proposed that the increasing size of the receptive fields when sampling granular, supragranular and infragranular layers in vivo, might have its functional basis in the laminar interactions described here in an in vitro preparation.

Animals↗
PubMed2000

Functional dissociation between medial and lateral prefrontal cortical spatiotemporal activation in negative and positive emotions: a combined fMRI/MEG study.

The orbitofrontal cortex has been cytoarchitectonically and connectionally subdivided into a medial and a lateral part which are assumed to subserve distinct functions in emotional processing. However the exact spatiotemporal mechanisms of negative and positive emotional processing in medial and lateral orbitofrontal cortex remain unclear. We therefore investigated spatiotemporal orbitofrontal and prefrontal cortical activation patterns during emotional stimulation in a combined fMRI/MEG study. We investigated 10 healthy subjects, 5 women and 5 men. Positive and negative pictures from the International Affective Picture system (IAPS) were used for emotional stimulation, whereas neutral and gray pictures were taken as control conditions. fMRI/MEG measurements covered the whole frontal lobe and a time window between -2000 and +200 ms around motor responses (right index finger extension) associated with each picture. Positively and negatively correlated activities were determined in various prefrontal/frontal cortical regions in fMRI. Isocontour maps and single dipoles in MEG were analyzed in 50 ms time windows ranging from -2000 to +200 ms. Dipoles and fMR images were mapped on three-dimensional anatomical MRI so that anatomical localization of single dipoles and regional fMRI activity could be compared. Both negative and positive emotional conditions differed from non-emotional control conditions by strong orbitofrontal and lateral prefrontal activation as well as by the presence of early magnetic fields (-1700 to +1100 ms). Negative emotional processing was characterized by strong medial orbitofrontal activation and earlier (-1700 ms), stronger and more medially oriented orbitofrontal dipoles. In contrast positive emotional processing showed a rather strong activation in lateral prefrontal cortex with later (-1500 ms), weaker and more laterally oriented orbito and prefrontal dipoles. Negative emotional processing can be characterized by strong and early medial orbitofrontal cortical activation, whereas positive emotional processing showed rather later and weaker activation in lateral orbitofrontal/prefrontal cortex. Such a functional dissociation between medial and lateral orbito-frontal/prefrontal cortex during negative and positive emotional processing lends further support to the assumption of a functional subdivision in the orbitofrontal cortex.

Adult↗
PubMed2000

Parameter precuing and motor preparation.

A movement task was used to investigate the effects of precued variables on reaction time. The task involved rapid rotation of a hand-held manipulandum to target locations and required either pronation or supination of the forearm through short or long extent. The effects on reaction time of precues signalling target direction, extent, or a combination of direction and extent, were measured. The longest reaction times occurred when no information about direction or extent was provided in the precue (all parameters uncertain). Complete prior specification of target position produced the shortest reaction times. Specification of direction when extent was uncertain produced a significantly larger reduction in reaction time than specification of extent when direction was uncertain. Prior specification of extent also produced a small but significant reduction in reaction time relative to the condition in which direction and extent were specified in a mutually conditional manner. The results are discussed in relation to parameter precuing and motor programming, in which the direction is programmed by the pre-selection of neurons representing the muscles to be used in the task while programming of extent is represented by their level of activity during task performance.

Acoustic Stimulation↗
PubMed2000

CT of the head by use of reduced current and kilovoltage: relationship between image quality and dose reduction.

BACKGROUND AND PURPOSE: CT is a frequent examination that is performed using ionizing radiation. We sought to assess image-quality changes on CT scans of the head when the radiation dose is reduced by changing tube current and kilovoltage. METHODS: A formalin-fixed cadaver was examined in conventional and helical mode by use of two CT-scanners. Surface dose was measured with standard scanning parameters, and after reduction of tube current and kilovoltage. Five experienced examiners independently evaluated subjective image quality. RESULTS: In the conventional mode, the highest surface dose was 83.2 mGy (scanner 1: helical mode, 55.6 mGy), and 66.0 mGy (scanner 2: helical mode, 55.9 mGy). By changing kVp and mAs, a dose reduction of up to 75% (scanner 1), and 60% (scanner 2) was achieved. No observable differences in image quality between scans obtained with doses from 100% to 60% of standard settings were noted. Ten of 20 images obtained with the highest dose and 13 of 20 images obtained with lowest dose (19-29.4 mGy) were reliably identified by subjective quality assessment. Scans produced with a surface dose of less than 30 mGy were judged uninterpretable. CONCLUSION: Standard parameters used in cranial CT are oriented toward best image quality. A dose reduction up to 40% may be possible without loss of diagnostic image quality.

Cadaver↗
PubMed1999

Motivation effects in a dichotic listening task as evident from functional magnetic resonance imaging in human subjects.

The present study addresses the effect of motivation on cerebral activity using functional magnetic resonance imaging. Five healthy volunteers performed a dichotic listening task in two sets of three trials during which high or low levels of achievement motivation were introduced. They were told that the first set would be used for calculation of intellectual capacity (high achievement motivation) and the second set for scanner calibration (neutral motivation). In three volunteers, high compared with neutral motivation produced activation in the right prefrontal cortex and the dorsal cingulate. We conclude that motivational effects may lead to significant activations and should be controlled in future cognitive imaging studies. We present preliminary evidence that right prefrontal and dorsal cingulate regions might be involved in motivational processes.

Adult↗
PubMed1999

Anti-proliferative activity of protein kinase C in apical compartments of human colonic crypts: evidence for a less activated protein kinase C in small adenomas.

The protein-kinase-C (PKC) family of iso-enzymes regulates mitogenic signal transduction in colorectal-cell lines. Its function in human colonic mucosal proliferation is controversial. Our study investigated the role of PKC with regard to proliferation and changes of PKC iso-enzyme expression in colonic biopsies compared with small adenomas. In short-term tissue-culture experiments of colonic mucosal biopsies, we found reduced S-phase labeling in the 2 apical compartments of longitudinally sectioned crypts when PKC was activated by 200 nM of the phorbol ester TPA (n = 8). Thus, PKC inhibited growth of differentiated colonocytes which may influence cell homeostasis in colonic crypts. Furthermore, we have determined the expression of PKC alpha, -beta1, -beta2, -delta and -epsilon in colonic adenomas smaller than 1 cm in diameter of 18 patients and found a significant increase of PKC alpha in the cytosolic fraction and decreased membrane levels of PKC beta2 in adenomas compared to normal, neighboring mucosa while protein levels of PKC beta1, -delta and -epsilon were not altered. Moreover PKC delta but not PKC alpha mRNA expression was significantly lowered in adenoma tissue in 7 patients, as determined by ribonuclease-protection analysis. Changes in the regulation patterns of PKC isoforms suggest a decreased activation state of PKC even in small adenomas. This is compatible with an anti-proliferative function of PKC serving to protect mucosa from expanding mutated cells.

Adenoma↗
PubMed1999

Connectivity in the somatosensory cortex of the adolescent rat: an in vitro biocytin study.

A promising way to elucidate neuronal information processing is to establish detailed structure-function relationships of identified single neurons or populations of nerve cells, especially their synaptic connectivity. This has been greatly improved by the development of acute brain slice preparations. The cellular physiology of the rodent primary somatosensory (barrel) cortex has been extensively studied. However, for a meaningful interpretation of physiological experiments the degree and pattern of connectivity has to be known for the particular preparation. Since such studies are not available for rat (P15-25) barrel cortex in vitro, we have traced the cortico-cortical and thalamo-cortical connections in 400-microm-thick slices with biocytin. In coronal slices, a wealth of axonal connections in retrograde and anterograde directions were heavily labeled, resembling the full pattern of cortico-cortical projections described in vivo. The most striking connections were vertical and horizontal connections within the primary somatosensory cortex, as well as a columnar projection to the secondary somatosensory cortex and beyond (mainly the parietal ventral area). Electron microscopic extensions of the study indicated that the full possible set of synaptic contacts with an adult-like appearance was already established in these connections. In thalamo-cortical slices, strong reciprocal connections with the ventrobasal (and to a much lesser extent also the posterior) thalamic nucleus were always observed, together with an intensive ramification of fibers in the reticular nucleus. A striatal terminal field was also consistently found. We conclude that all major intracortical and thalamo-cortical connection are richly preserved in the in vitro slice preparations of rats. Thus, these preparations are suitable for elucidation of the functional interaction of the most crucial brain structures involved in somatosensory information processing combining an in vivo-like anatomical structure with the controlled environment of an in vitro slice.

Animals↗
PubMed1999

Cellular morphology and physiology of the perinatal rat cerebral cortex.

The cellular morphology and electrophysiology of the rat neocortex between embryonic day (E) 18 and postnatal day (P) 3 was studied in vitro by extracellular biocytin injections and whole-cell recordings, respectively. Most neurons were characterized by a small number of short-range dendrites and a main axon that was directed towards the white matter. Biocytin injections into the marginal zone and the cortical plate labeled far-reaching connections extending up to 2 mm in horizontal direction, indicating the existence of a dense network of long-range intrinsic projections in the neonatal cortex. Action potentials could be elicited as early as E18 and repetitive firing could first be observed at P0. Electrical stimulation of the immature cortex at various positions elicited polyphasic and long-lasting (up to 1 s) excitatory postsynaptic potentials and currents, which were significantly reduced in amplitude by a selective N-methyl-D-aspartate receptor antagonist. Our data indicate that the perinatal cortex manifests the structural and functional conditions for powerful excitatory interactions, which increase the likelihood for the generation of epileptiform activity during this developmental period.

Animals↗