Biomedical subjects

Claus C Hilgetag

Publications and source records attributed to Claus C Hilgetag.

14 recordsLinked to original sources

PubMed2006

Nonoptimal component placement, but short processing paths, due to long-distance projections in neural systems.

It has been suggested that neural systems across several scales of organization show optimal component placement, in which any spatial rearrangement of the components would lead to an increase of total wiring. Using extensive connectivity datasets for diverse neural networks combined with spatial coordinates for network nodes, we applied an optimization algorithm to the network layouts, in order to search for wire-saving component rearrangements. We found that optimized component rearrangements could substantially reduce total wiring length in all tested neural networks. Specifically, total wiring among 95 primate (Macaque) cortical areas could be decreased by 32%, and wiring of neuronal networks in the nematode Caenorhabditis elegans could be reduced by 48% on the global level, and by 49% for neurons within frontal ganglia. Wiring length reductions were possible due to the existence of long-distance projections in neural networks. We explored the role of these projections by comparing the original networks with minimally rewired networks of the same size, which possessed only the shortest possible connections. In the minimally rewired networks, the number of processing steps along the shortest paths between components was significantly increased compared to the original networks. Additional benchmark comparisons also indicated that neural networks are more similar to network layouts that minimize the length of processing paths, rather than wiring length. These findings suggest that neural systems are not exclusively optimized for minimal global wiring, but for a variety of factors including the minimization of processing steps.

Animals↗

PubMed2006

Functional circuitry underlying visual neglect.

Visuospatial neglect is a common neurological syndrome caused by unilateral brain damage to the posterior and inferior parietal cerebral cortex, and is characterized by an inability to respond or orient to stimuli presented in the contralesional hemifield. Neglect has been elicited in experimental models of the rat, cat and monkey, and is thought to result in part from a pathological state of inhibition exerted on the damaged hemisphere by the hyperexcited intact hemisphere. We sought to test this theory by assessing neural activity levels in multiple brain structures during neglect using 2-deoxyglucose (2DG) as a metabolic marker of neural activity. Neglect was induced in two ways: (i) by cooling deactivation of posterior parietal cortex or (ii) in conjunction with broader cortical blindness produced by unilateral lesion of all contiguous visual cortical areas spanning occipital, parietal and temporal regions. The direction and magnitude of changes in 2DG uptake were measured in cerebral cortex and midbrain structures. Finally, the 2DG uptake was assessed in a group of cats in which the lesion-induced neglect component of blindness was cancelled by cooling of either the contralateral posterior parietal cortex or the contralateral superior colliculus (SC). Overall, we found that (i) both lesion- and cooling-induced neglect are associated with decreases in 2DG uptake in specific ipsilateral cortical and midbrain regions; (ii) levels of 2DG uptake in the intermediate and deep layers of the SC contralateral to both cooling and lesion deactivations are increased; (iii) changes in 2DG uptake were not identified in the contralateral cortex; and (iv) reversal of the lesion-induced neglect component of blindness is associated with a reduction of contralesional 2DG uptake to normal or subnormal levels. These data are in accord with theories of neglect that include mutually suppressive mechanisms between the two hemispheres, and we show that these mechanisms operate at the level of the SC, but are not apparent at the level of cortex. These results suggest that the most effective therapies for visual neglect will be those that act to decrease neural activity in the intermediate layers of the SC contralateral to the brain damage.

Animals↗

PubMed2006

Role of mechanical factors in the morphology of the primate cerebral cortex.

The convoluted cortex of primates is instantly recognizable in its principal morphologic features, yet puzzling in its complex finer structure. Various hypotheses have been proposed about the mechanisms of its formation. Based on the analysis of databases of quantitative architectonic and connection data for primate prefrontal cortices, we offer support for the hypothesis that tension exerted by corticocortical connections is a significant factor in shaping the cerebral cortical landscape. Moreover, forces generated by cortical folding influence laminar morphology, and appear to have a previously unsuspected impact on cellular migration during cortical development. The evidence for a significant role of mechanical factors in cortical morphology opens the possibility of constructing computational models of cortical development based on physical principles. Such models are particularly relevant for understanding the relationship of cortical morphology to the connectivity of normal brains, and structurally altered brains in diseases of developmental origin, such as schizophrenia and autism.

Algorithms↗

PubMed2006

Axiomatic scalable neurocontroller analysis via the Shapley value.

One of the major challenges in the field of neurally driven evolved autonomous agents is deciphering the neural mechanisms underlying their behavior. Aiming at this goal, we have developed the multi-perturbation Shapley value analysis (MSA)--the first axiomatic and rigorous method for deducing causal function localization from multiple-perturbation data, substantially improving on earlier approaches. Based on fundamental concepts from game theory, the MSA provides a formal way of defining and quantifying the contributions of network elements, as well as the functional interactions between them. The previously presented versions of the MSA require full knowledge (or at least an approximation) of the network's performance under all possible multiple perturbations, limiting their applicability to systems with a small number of elements. This article focuses on presenting new scalable MSA variants, allowing for the analysis of large complex networks in an efficient manner, including large-scale neurocontrollers. The successful operation of the MSA along with the new variants is demonstrated in the analysis of several neurocontrollers solving a food foraging task, consisting of up to 100 neural elements.

Models, Statistical↗

PubMed2005

Parallel organization of contralateral and ipsilateral prefrontal cortical projections in the rhesus monkey.

BACKGROUND: The neocortical commissures have a fundamental role in functional integration across the cerebral hemispheres. We investigated whether commissural projections in prefrontal cortices are organized according to the same or different rules as those within the same hemisphere, by quantitatively comparing density, topography, and laminar origin of contralateral and ipsilateral projections, labeled after unilateral injection of retrograde tracers in prefrontal areas. RESULTS: Commissural projection neurons constituted less than one third of the ipsilateral. Nevertheless, projections from the two hemispheres were strongly correlated in topography and relative density. We investigated to what extent the distribution of contralateral projections depended on: (a) geographic proximity of projection areas to the area homotopic to the injection site; (b) the structural type of the linked areas, based on the number and neuronal density of their layers. Although both measures were good predictors, structural type was a comparatively stronger determinant of the relative distribution and density of projections. Ipsilateral projection neurons were distributed in the superficial (II-III) and deep (V-VI) layers, in proportions that varied across areas. In contrast, contralateral projection neurons were found mostly in the superficial layers, but still showed a gradient in their distribution within cortical layers that correlated significantly with cortical type, but not with geographic proximity to the homotopic area. CONCLUSION: The organization of ipsilateral and contralateral prefrontal projections is similar in topography and relative density, differing only by higher overall density and more widespread laminar origin of ipsilateral than contralateral projections. The projections on both sides are highly correlated with the structural architecture of the linked areas, and their remarkable organization is likely established by punctuated development of distinct cortical types. The preponderance of contralateral projections from layer III may be traced to the late development of the callosal system, whose function may be compromised in diseases that have their root late in ontogeny.

Animals↗

PubMed2005

Developmental mechanics of the primate cerebral cortex.

The idea that the brain is shaped through the interplay of predetermined ontogenetic factors and mechanisms of self-organization has a long tradition in biology, going back to the late-nineteenth century. Here we illustrate the substantial impact of mechanical forces on the development, morphology, and functioning of the primate cerebral cortex. Based on the analysis of quantitative structural data for prefrontal cortices of the adult rhesus monkey, we demonstrate that (1) the characteristic shape of cortical convolutions can be explained by the global minimization of axonal tension in corticocortical projections; (2) mechanical forces resulting from cortical folding have a significant impact on the relative and absolute thickness of cortical layers in gyri and sulci; (3) folding forces may affect the cellular migration during cortical development, resulting in a significantly larger number of neurons in gyral compared to non-gyral regions; and (4) mechanically induced variations of morphology at the cellular level may result in different modes of neuronal functioning in gyri and sulci. These results underscore the significant contribution of mechanical forces during the self-organization of the primate cerebral cortex. Taking such factors into account within a framework of developmental mechanics can lead to a better understanding of how genetic specification, the layout of connections, brain shape as well as brain function are linked in normal and pathologically transformed brains.

Animals↗

PubMed2005

Graded classes of cortical connections: quantitative analyses of laminar projections to motion areas of cat extrastriate cortex.

Current hierarchical models of the cerebral cortex are mainly based on qualitative connection studies. From wheatgerm-agglutinin-horseradish peroxidase injections, we examined the laminar patterns of projections to and between the three major subdivisions of the motion-processing lateral suprasylvian (LS) complex [areas posteromedial lateral suprasylvian area (PMLS), anteromedial lateral suprasylvian (AMLS), posterolateral lateral suprasylvian area (PLLS)] of cat extrastriate cortex and of an adjoining form-processing area, 21a. We counted approximately 145,000 labelled projection cells in 20 cortical areas in 11 cats, and applied various analyses to the data, expressed as the percent supragranular layer (%SG) origin of each connection. We report two main results. (i) A wide range of %SG values was obtained, both from each individual cat and across the 163 projections examined. Nonetheless, both hierarchical and non-parametric cluster analyses of the pooled connection origins suggested the presence of three distinct laminar projection classes, constrained by graded %SG values of 0-33%, 39-69% and 76-97%. These conformed, respectively, to feedback, lateral and feedforward laminar patterns seen qualitatively in our material. (ii) Hierarchical connectivity analyses suggested that PMLS, AMLS and PLLS are ordered in a hierarchical sequence. Macaque motion areas V5/MT, MST and FST are arranged in a similar sequence, and areas at equivalent levels of the two motion hierarchies have some analogous functional specializations. Our findings provide the first objective support for the three laminar projection classes that underpin existing theoretical models of hierarchical cortical organization, and they suggest that the implementation of higher-order motion processing evolved along similar lines in the cat and monkey visual cortex.

Animals↗

PubMed2004

Edge vulnerability in neural and metabolic networks.

Biological networks, such as cellular metabolic pathways or networks of corticocortical connections in the brain, are intricately organized, yet remarkably robust toward structural damage. Whereas many studies have investigated specific aspects of robustness, such as molecular mechanisms of repair, this article focuses more generally on how local structural features in networks may give rise to their global stability. In many networks the failure of single connections may be more likely than the extinction of entire nodes, yet no analysis of edge importance (edge vulnerability) has been provided so far for biological networks. We tested several measures for identifying vulnerable edges and compared their prediction performance in biological and artificial networks. Among the tested measures, edge frequency in all shortest paths of a network yielded a particularly high correlation with vulnerability and identified intercluster connections in biological but not in random and scale-free benchmark networks. We discuss different local and global network patterns and the edge vulnerability resulting from them.

Animals↗

PubMed2004

Spatial growth of real-world networks.

Many real-world networks have properties of small-world networks, with clustered local neighborhoods and low average-shortest path. They may also show a scale-free degree distribution, which can be generated by growth and preferential attachment to highly connected nodes, or hubs. However, many real-world networks consist of multiple, interconnected clusters not normally seen in systems grown by preferential attachment, and there also exist real-world networks with a scale-free degree distribution that do not contain highly connected hubs. We describe spatial-growth mechanisms, not using preferential attachment, that address both aspects.

Journal Article↗

PubMed2004

Organization, development and function of complex brain networks.

Recent research has revealed general principles in the structural and functional organization of complex networks which are shared by various natural, social and technological systems. This review examines these principles as applied to the organization, development and function of complex brain networks. Specifically, we examine the structural properties of large-scale anatomical and functional brain networks and discuss how they might arise in the course of network growth and rewiring. Moreover, we examine the relationship between the structural substrate of neuroanatomy and more dynamic functional and effective connectivity patterns that underlie human cognition. We suggest that network analysis offers new fundamental insights into global and integrative aspects of brain function, including the origin of flexible and coherent cognitive states within the neural architecture.

Brain↗

PubMed2004

Fair attribution of functional contribution in artificial and biological networks.

This letter presents the multi-perturbation Shapley value analysis (MSA), an axiomatic, scalable, and rigorous method for deducing causal function localization from multiple perturbations data. The MSA, based on fundamental concepts from game theory, accurately quantifies the contributions of network elements and their interactions, overcoming several shortcomings of previous function localization approaches. Its successful operation is demonstrated in both the analysis of a neurophysiological model and of reversible deactivation data. The MSA has a wide range of potential applications, including the analysis of reversible deactivation experiments, neuronal laser ablations, and transcranial magnetic stimulation "virtual lesions," as well as in providing insight into the inner workings of computational models of neurophysiological systems.

Algorithms↗

PubMed2004

Fair localization of function via multi-lesion analysis.

Acknowledging that causal localization of function in a processing network requires a multi-lesion analysis, this paper presents a rigorous and efficient method for defining and calculating the functional contributions of network elements as well as their interactions. The method's applicability to biological networks is demonstrated in the investigation of spatial attention in cats via lesion and reversible deactivation experiments.

Acoustic Stimulation↗

PubMed2004

Clustered organization of cortical connectivity.

Long-range corticocortical connectivity in mammalian brains possesses an intricate, nonrandom organization. Specifically, projections are arranged in "small-world" networks, forming clusters of cortical areas, which are closely linked among each other, but less frequently with areas in other clusters. In order to delineate the structure of cortical clusters and identify their members, we developed a computational approach based on evolutionary optimization. In different compilations of connectivity data for the cat and macaque monkey brain, the algorithm identified a small number of clusters that broadly agreed with functional cortical subdivisions. We propose a simple spatial growth model for evolving clustered connectivity, and discuss structural and functional implications of the clustered, small-world organization of cortical networks.

Animals↗

PubMed2001

Restoration of visual orienting into a cortically blind hemifield by reversible deactivation of posterior parietal cortex or the superior colliculus.

A contralateral hemineglect of the visual field can be induced by unilateral cooling deactivation of posterior middle suprasylvian (pMS) sulcal cortex of the posterior parietal region, and this neglect can be reversed by additional cooling deactivation of pMS cortex in the opposite hemisphere. The purpose of the present study was to test whether an enduring hemianopia induced by removal of all contiguous visual cortical areas of one hemisphere could be reversed by local cooling of pMS cortex in the opposite hemisphere. Two cats sustained large unilateral ablations of the contiguous visual areas, and cooling loops were placed in the pMS sulcus, and in contact with adjacent area 7 or posterior ectosylvian (PE) cortex of the opposite hemisphere. In both instances cooling of pMS cortex, but neither area 7 nor PE, restored a virtually normal level of orienting performance to stimuli presented anywhere in the previously hemianopic field. The reversal was highly sensitive to the extent of cooling deactivation. In a third cat, cooling deactivation of the superficial layers of the contralateral superior colliculus also restored orienting performance to a cortical ablation-induced hemianopia. This reversal was graded from center-to-periphery in a temperature-dependent manner. Neither the cortical ablation nor any of the cooling deactivations had any impact on an auditory detection and orienting task. The deactivations were localized and confirmed by reduced uptake of radiolabeled 2-deoxyglucose to be limited to the immediate vicinity of each cooling loop. The results are discussed in terms of excitation and disinhibition of visual circuits.

Animals↗