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Biomedical subjects

Rolf Kötter

Publications and source records attributed to Rolf Kötter.

16 recordsLinked to original sources
PubMed2005

Q-ball imaging of macaque white matter architecture.

Diffusion-weighted magnetic resonance imaging holds substantial promise as a technique for non-invasive imaging of white matter (WM) axonal projections. For diffusion imaging to be capable of providing new insight into the connectional neuroanatomy of the human brain, it will be necessary to histologically validate the technique against established tracer methods such as horseradish peroxidase and biocytin histochemistry. The macaque monkey provides an ideal model for histological validation of the diffusion imaging method due to the phylogenetic proximity between humans and macaques, the gyrencephalic structure of the macaque cortex, the large body of knowledge on the neuroanatomic connectivity of the macaque brain and the ability to use comparable magnetic resonance acquisition protocols in both species. Recently, it has been shown that high angular resolution diffusion imaging (HARDI) can resolve multiple axon orientations within an individual imaging voxel in human WM. This capability promises to boost the accuracy of tract reconstructions from diffusion imaging. If the macaque is to serve as a model for histological validation of the diffusion tractography method, it will be necessary to show that HARDI can also resolve intravoxel architecture in macaque WM. The present study therefore sought to test whether the technique can resolve intravoxel structure in macaque WM. Using a HARDI method called q-ball imaging (QBI) it was possible to resolve composite intravoxel architecture in a number of anatomic regions. QBI resolved intravoxel structure in, for example, the dorsolateral convexity, the pontine decussation, the pulvinar and temporal subcortical WM. The paper concludes by reviewing remaining challenges for the diffusion tractography project.

Animals↗
PubMed2005

Mapping brains without coordinates.

Brain mapping has evolved considerably over the last century. While most emphasis has been placed on coordinate-based spatial atlases, coordinate-independent parcellation-based mapping is an important technique for accessing the multitude of structural and functional data that have been reported from invasive experiments, and provides for flexible and efficient representations of information. Here. we provide an introduction to motivations, concepts, techniques and implications of coordinate-independent mapping of microstructurally or functionally defined brain structures. In particular, we explain the problems of constructing mapping paths and finding adequate heuristics for their evaluation. We then introduce the three auxiliary concepts of acronym-based mapping (AM), of a generalized hierarchy (GM ontology), and of a topographically oriented regional map (RM) with adequate granularity for mapping between individual brains with different cortical folding and between humans and non-human primates. Examples from the CoCoMac database of primate brain connectivity demonstrate how these concepts enhance coordinate-independent mapping based on published relational statements. Finally, we discuss the strengths and weaknesses of spatial coordinate-based versus coordinate-independent microstructural brain mapping and show perspectives for a wider application of parcellation-based approaches in the integration of multi-model structural, functional, and clinical data.

Anatomy, Comparative↗
PubMed2005

Distributions of transmitter receptors in the macaque cingulate cortex.

The primate cingulate cortex is structurally and functionally complex. Although no studies have investigated the regional densities of multiple neurotransmitter receptor systems, such information would be useful for assessing its functions and disease vulnerabilities. We quantified nine different receptors in five transmitter systems by in vitro autoradiographic mapping of the cingulate cortex of macaque monkeys with the aim to link cytoarchitectonic regions and functional specialization. Receptor mapping substantiated the subdivision of the cingulate cortex into anterior versus posterior regions. In anterior cingulate cortex (ACC) AMPA glutamatergic receptors and GABA(A) inhibitory receptors were present in significantly higher concentrations than the modulatory alpha-adrenergic and muscarinic receptors. These differences were absent in the posterior cingulate cortex (PCC). By contrast, NMDA receptor densities were significantly higher than AMPA receptor densities in PCC, but not in ACC. The midcingulate area 24' shared more features with ACC than PCC. This area was characterized by the highest ratios of NMDA receptors to alpha-adrenergic, muscarinic and 5-HT2 receptors among all cingulate regions. Compared to rostrocaudal divisions, the differences between dorsoventral subdivisions a-c were small in all regions of cingulate cortex, and only muscarinic and alpha-adrenergic receptor densities followed the degree of cytoarchitectonic differentiation. We conclude that multiple receptor mapping reveals a highly differentiated classification of cingulate cortex with a characteristic predominance of fast ionotropic excitatory and inhibitory receptors in ACC, but a strong and varied complement of NMDA and metabotropic receptors in PCC.

Animals↗
PubMed2005

The human connectome: A structural description of the human brain.

The connection matrix of the human brain (the human "connectome") represents an indispensable foundation for basic and applied neurobiological research. However, the network of anatomical connections linking the neuronal elements of the human brain is still largely unknown. While some databases or collations of large-scale anatomical connection patterns exist for other mammalian species, there is currently no connection matrix of the human brain, nor is there a coordinated research effort to collect, archive, and disseminate this important information. We propose a research strategy to achieve this goal, and discuss its potential impact.

Animals↗
PubMed2004

Motifs in brain networks.

Complex brains have evolved a highly efficient network architecture whose structural connectivity is capable of generating a large repertoire of functional states. We detect characteristic network building blocks (structural and functional motifs) in neuroanatomical data sets and identify a small set of structural motifs that occur in significantly increased numbers. Our analysis suggests the hypothesis that brain networks maximize both the number and the diversity of functional motifs, while the repertoire of structural motifs remains small. Using functional motif number as a cost function in an optimization algorithm, we obtain network topologies that resemble real brain networks across a broad spectrum of structural measures, including small-world attributes. These results are consistent with the hypothesis that highly evolved neural architectures are organized to maximize functional repertoires and to support highly efficient integration of information.

Algorithms↗
PubMed2004

Functional diversity of layer IV spiny neurons in rat somatosensory cortex: quantitative morphology of electrophysiologically characterized and biocytin labeled cells.

Previous analyses of the spiny layer IV neurons have almost exclusively focused on spiny stellate cells. Here we provide detailed morphological data characterizing three subpopulations of spiny neurons in slices of adolescent rats: (i) spiny stellate cells (58%), (ii) star pyramidal cells (25%) and (iii) pyramidal cells (17%), which can be distinguished objectively by the preferential orientation of their dendritic stems. Spiny stellate cells lacked an apical dendrite and frequently confined their dendritic and axonal arbors to the respective column. Star pyramidal and pyramidal cells possessed an apical dendrite, which reached the supragranular layers. Their axonal arbors were similar, showing both a columnar component and transcolumnar branches with direct transbarrel projections. However, a small fraction of star pyramidal cells possessed few or even no transcolumnar branches. Electrophysiologically, all three types of neurons were either regular-spiking or intrinsically burst-spiking without a significant relation to the morphological subtypes. The basic synaptic properties of thalamic inputs were also independent of the type of target layer IV spiny neuron. All remained subthreshold and showed paired-pulse depression. In conclusion, the columnar axonal arborization of spiny stellate cells is supplemented by a significant oblique to horizontal projection pattern in pyramidal-like neurons. This offers a structural basis for either segregation or early context-dependent integration of tactile information, in a cell-type specific manner.

Action Potentials↗
PubMed2004

Orbitofrontal cortical dysfunction in akinetic catatonia: a functional magnetic resonance imaging study during negative emotional stimulation.

Catatonia is a psychomotor syndrome characterized by concurrent emotional, behavioral, and motor anomalies. Pathophysiological mechanisms of psychomotor disturbances may be related to abnormal emotional-motor processing in prefrontal cortical networks. We therefore investigated prefrontal cortical activation and connectivity patterns during emotional-motor stimulation using functional magnetic resonance imaging (FMRI). We investigated 10 akinetic catatonic patients in a postacute state and compared them with 10 noncatatonic postacute psychiatric controls (age-, sex-, diagnosis-, and medication-matched) and 10 healthy controls. Positive and negative pictures from the International Affective Picture System were used for emotional stimulation. FMRI measurements covered the whole frontal lobe, activation signals in various frontal cortical regions were obtained, and functional connectivity between the different prefrontal cortical regions was investigated using structural equation modeling. Catatonic patients showed alterations in the orbitofrontal cortical activation pattern and in functional connectivity to the premotor cortex in negative and positive emotions compared to psychiatric and healthy controls. Catatonic behavioral and affective symptoms correlated significantly with orbitofrontal activity, whereas catatonic motor symptoms were rather related to medial prefrontal activity. It is concluded that catatonic symptoms may be closely related to dysfunction in the orbitofrontal cortex and consequent alteration in the prefrontal cortical network during emotional processing. Because we investigated postacute patients, orbitofrontal cortical alterations may be interpreted as a trait marker predisposing for development of catatonic syndrome in schizophrenic or affective psychosis.

Acute Disease↗
PubMed2004

Online retrieval, processing, and visualization of primate connectivity data from the CoCoMac database.

Connectivity is the key to understanding distributed and cooperative brain functions. Detailed and comprehensive data on large-scale connectivity between primate brain areas have been collated systematically from published reports of experimental tracing studies. Although the majority of the data have been made easily available for online retrieval, the multiplicity of brain maps and the precise requirements of anatomical naming limit the intuitive access to the data. The quality of data retrieval can be improved by observing a small set of conventions in data representation. Standardized interfaces open up further opportunities for automated search and retrieval, for flexible visualization of data, and for interoperability with other databases. This article provides a discussion and examples in text and image of the capabilities of the online interface to the CoCoMac database of primate connectivity. These serve to point out sources of potential confusion and failure, and to demonstrate the automated interfacing with other neuroinformatics resources that facilitate selection and processing of connectivity data, for example, for computational modelling and interpretation of functional imaging studies.

Animals↗
PubMed2003

Cell type-specific circuits of cortical layer IV spiny neurons.

Sensory signal processing in cortical layer IV involves two major morphological classes of excitatory neurons: spiny stellate and pyramidal cells. It is essentially unknown how these two cell types are integrated into intracortical networks and whether they play different roles in cortical signal processing. We mapped their cell-specific intracortical afferents in rat somatosensory cortex through a combination of whole-cell patch-clamp recordings and caged glutamate photolysis. Spiny stellate cells received monosynaptic excitation and inhibition originating almost exclusively from neurons located within the same barrel. Pyramidal cells, by contrast, displayed additional excitatory inputs from nongranular layers and from neighboring barrels. Their inhibitory inputs originated, as for spiny stellate cells, mainly from neurons located in the same barrel. These results indicate that spiny stellate cells act predominantly as local signal processors within a single barrel, whereas pyramidal cells globally integrate horizontal and top-down information within a functional column and between neighboring barrels.

Afferent Pathways↗
PubMed2003

Network participation indices: characterizing component roles for information processing in neural networks.

We propose a set of indices that characterize-on the basis of connectivity data-how a network node participates in a larger network and what roles it may take given the specific sub-network of interest. These Network Participation Indices are derived from simple graph theoretic measures and have the interesting property of linking local features of individual network components to distributed properties that arise within the network as a whole. We use connectivity data on large-scale cortical networks to demonstrate the virtues of this approach and highlight some interesting features that had not been brought up in previously published material. Some implications of our approach for defining network characteristics relevant to functional segregation and functional integration, for example, from functional imaging studies are discussed.

Mental Processes↗
PubMed2002

GABA-ergic modulation of prefrontal spatio-temporal activation pattern during emotional processing: a combined fMRI/MEG study with placebo and lorazepam.

Various prefrontal cortical regions have been shown to be activated during emotional stimulation, whereas neurochemical mechanisms underlying emotional processing in the prefrontal cortex remain unclear. We therefore investigated the influence of the GABA-A potentiator lorazepam on prefrontal cortical emotional-motor spatio-temporal activation pattern in a combined functional magnetic resonance imaging/magnetoencephalography study. Lorazepam led to the reversal in orbito-frontal activation pattern, a shift of the early magnetic field dipole from the orbito-frontal to medial prefrontal cortex, and alterations in premotor/motor cortical function during negative and positive emotional stimulation. It is concluded that negative emotional processing in the orbito-frontal cortex may be modulated either directly or indirectly by GABA-A receptors. Such a modulation of orbito-frontal cortical emotional function by lorazepam has to be distinguished from its effects on cortical motor function as being independent from the kind of processing either emotional or nonemotional.

Adult↗
PubMed2002

Innervation of interneurons immunoreactive for VIP by intrinsically bursting pyramidal cells and fast-spiking interneurons in infragranular layers of juvenile rat neocortex.

Cortical columns contain specific neuronal populations with characteristic sets of connections. This wiring forms the structural basis of dynamic information processing. However, at the single-cell level little is known about specific connectivity patterns. We performed experiments in infragranular layers (V and VI) of rat somatosensory cortex, to clarify further the input patterns of inhibitory interneurons immunoreactive (ir) for vasoactive intestinal polypeptide (VIP). Neurons in acute slices were electrophysiologically characterized using whole-cell recordings and filled with biocytin. This allowed us to determine their firing pattern as regular-spiking, intrinsically bursting and fast-spiking, respectively. Biocytin was revealed histochemically and VIP immunohistochemically. Sections were examined for contacts between the axons of the filled neurons and the VIP-ir targets. Twenty pyramidal cells and five nonpyramidal (inter)neurons were recovered and sufficiently stained for further analysis. Regular-spiking pyramidal cells displayed no axonal boutons in contact with VIP-ir targets. In contrast, intrinsically bursting layer V pyramidal cells showed four putative single contacts with a proximal dendrite of VIP neurons. Fast-spiking interneurons formed contacts with two to six VIP neurons, preferentially at their somata. Single as well as multiple contacts on individual target cells were found. Electron microscopic examinations showed that light-microscopically determined contacts represent sites of synaptic interactions. Our results suggest that, within infragranular local cortical circuits, (i) fast-spiking interneurons are more likely to influence VIP cells than are pyramidal cells and (ii) pyramidal cell input probably needs to be highly convergent to fire VIP target cells.

Action Potentials↗
PubMedDate not supplied

Optical release of caged glutamate for stimulation of neurons in the in vitro slice preparation.

Optical stimulation techniques prove useful to map functional inputs in the in vitro brain slice preparation: Glutamate released by a focused beam of UV light induces action potentials, which can be detected in postsynaptic neurons. The direct activation effect is influenced by factors such as compound concentration, focus depth, light absorption in the tissue, and sensitivity of different neuronal domains. We analyze information derived from direct stimulation experiments in slices from rat barrel cortex and construct a computational model of a layer V pyramidal neuron that reproduces the experimental findings. The model predictions concerning the influence of focus depth on input maps and action potential generation are investigated further in subsequent experiments where the focus depth of a high-numerical-aperture lens is systematically varied. With our setup flashes from a xenon light source can activate neuronal compartments to a depth of 200 mum below the surface of the slice. The response amplitude is influenced both by tissue depth and focus plane. Specific somatodendritic structures can be targeted as the probability of action potential induction falls off exponentially with distance. Somata and primary apical dendrites are most sensitive to uncaged glutamate with locally increased sensitivity on proximal apical dendrites. We conclude that optical stimulation can be targeted with high precision.

Action Potentials↗