arXiv subjects

Marcus Kaiser

Publications and source records attributed to Marcus Kaiser.

At least 37 records · Page 2Linked to original sources

arXiv2017

Acceleration of convergence to equilibrium in Markov chains by breaking detailed balance

We analyse and interpret the effects of breaking detailed balance on the convergence to equilibrium of conservative interacting particle systems and their hydrodynamic scaling limits. For finite systems of interacting particles, we review existing results showing that irreversible processes converge faster to their steady state than reversible ones. We show how this behaviour appears in the hydrodynamic limit of such processes, as described by macroscopic fluctuation theory, and we provide a quantitative expression for the acceleration of convergence in this setting. We give a geometrical interpretation of this acceleration, in terms of currents that are \emph{antisymmetric} under time-reversal and orthogonal to the free energy gradient, which act to drive the system away from states where (reversible) gradient-descent dynamics result in slow convergence to equilibrium.

cond-mat.stat-mech↗

arXiv2016

The BioDynaMo Project: Creating a Platform for Large-Scale Reproducible Biological Simulations

Computer simulations have become a very powerful tool for scientific research. In order to facilitate research in computational biology, the BioDynaMo project aims at a general platform for biological computer simulations, which should be executable on hybrid cloud computing systems. This paper describes challenges and lessons learnt during the early stages of the software development process, in the context of implementation issues and the international nature of the collaboration.

cs.DC↗

arXiv2016

The BioDynaMo Project

Computer simulations have become a very powerful tool for scientific research. Given the vast complexity that comes with many open scientific questions, a purely analytical or experimental approach is often not viable. For example, biological systems (such as the human brain) comprise an extremely complex organization and heterogeneous interactions across different spatial and temporal scales. In order to facilitate research on such problems, the BioDynaMo project (\url{https://biodynamo.web.cern.ch/}) aims at a general platform for computer simulations for biological research. Since the scientific investigations require extensive computer resources, this platform should be executable on hybrid cloud computing systems, allowing for the efficient use of state-of-the-art computing technology. This paper describes challenges during the early stages of the software development process. In particular, we describe issues regarding the implementation and the highly interdisciplinary as well as international nature of the collaboration. Moreover, we explain the methodologies, the approach, and the lessons learnt by the team during these first stages.

cs.NE↗

arXiv2015

A Computational Model Incorporating Neural Stem Cell Dynamics Reproduces Glioma Incidence across the Lifespan in the Human Population

Glioma is the most common form of primary brain tumor. Demographically, the risk of occurrence increases until old age. Here we present a novel computational model to reproduce the probability of glioma incidence across the lifespan. Previous mathematical models explaining glioma incidence are framed in a rather abstract way, and do not directly relate to empirical findings. To decrease this gap between theory and experimental observations, we incorporate recent data on cellular and molecular factors underlying gliomagenesis. Since evidence implicates the adult neural stem cell as the likely cell-of-origin of glioma, we have incorporated empirically-determined estimates of neural stem cell number, cell division rate, mutation rate and oncogenic potential into our model. We demonstrate that our model yields results which match actual demographic data in the human population. In particular, this model accounts for the observed peak incidence of glioma at approximately 80 years of age, without the need to assert differential susceptibility throughout the population. Overall, our model supports the hypothesis that glioma is caused by randomly-occurring oncogenic mutations within the neural stem cell population. Based on this model, we assess the influence of the (experimentally indicated) decrease in the number of neural stem cells and increase of cell division rate during aging. Our model provides multiple testable predictions, and suggests that different temporal sequences of oncogenic mutations can lead to tumorigenesis. Finally, we conclude that four or five oncogenic mutations are sufficient for the formation of glioma.

q-bio.CB↗

arXiv2015

Developmental time windows for axon growth influence neuronal network topology

Early brain connectivity development consists of multiple stages: birth of neurons, their migration and the subsequent growth of axons and dendrites. Each stage occurs within a certain period of time depending on types of neurons and cortical layers. Forming synapses between neurons either by growing axons starting at similar times for all neurons (much-overlapped time windows) or at different time points (less-overlapped) may affect the topological and spatial properties of neuronal networks. Here, we explore the extreme cases of axon formation especially concerning short-distance connectivity during early development, either starting at the same time for all neurons (parallel, i.e. maximally-overlapped time windows) or occurring for each neuron separately one neuron after another (serial, i.e. no overlaps in time windows). For both cases, the number of potential and established synapses remained comparable. Topological and spatial properties, however, differed: neurons that started axon growth early on in serial growth achieved higher out-degrees, higher local efficiency, and longer axon lengths while neurons demonstrated more homogeneous connectivity patterns for parallel growth. Second, connection probability decreased more rapidly with distance between neurons for parallel growth than for serial growth. Third, bidirectional connections were more numerous for parallel growth. Finally, we tested our predictions with C. elegans data. Together, this indicates that time windows for axon growth influence the topological and spatial properties of neuronal networks opening the possibility to a posteriori estimate developmental mechanisms based on network properties of a developed network.

q-bio.NC↗

arXiv2014

From Caenorhabditis elegans to the Human Connectome: A Specific Modular Organisation Increases Metabolic, Functional, and Developmental Efficiency

The connectome, or the entire connectivity of a neural system represented by network, ranges various scales from synaptic connections between individual neurons to fibre tract connections between brain regions. Although the modularity they commonly show has been extensively studied, it is unclear whether connection specificity of such networks can already be fully explained by the modularity alone. To answer this question, we study two networks, the neuronal network of C. elegans and the fibre tract network of human brains yielded through diffusion spectrum imaging (DSI). We compare them to their respective benchmark networks with varying modularities, which are generated by link swapping to have desired modularity values but otherwise maximally random. We find several network properties that are specific to the neural networks and cannot be fully explained by the modularity alone. First, the clustering coefficient and the characteristic path length of C. elegans and human connectomes are both higher than those of the benchmark networks with similar modularity. High clustering coefficient indicates efficient local information distribution and high characteristic path length suggests reduced global integration. Second, the total wiring length is smaller than for the alternative configurations with similar modularity. This is due to lower dispersion of connections, which means each neuron in C. elegans connectome or each region of interest (ROI) in human connectome reaches fewer ganglia or cortical areas, respectively. Third, both neural networks show lower algorithmic entropy compared to the alternative arrangements. This implies that fewer rules are needed to encode for the organisation of neural systems.

q-bio.NC↗

arXiv2014

Virtual Electrode Recording Tool for EXtracellular potentials (VERTEX): Comparing multi-electrode recordings from simulated and biological mammalian cortical tissue

Local field potentials (LFPs) sampled with extracellular electrodes are frequently used as a measure of population neuronal activity. However, relating such measurements to underlying neuronal behaviour and connectivity is non-trivial. To help study this link, we developed the Virtual Electrode Recording Tool for EXtracellular potentials (VERTEX). We first identified a reduced neuron model that retained the spatial and frequency filtering characteristics of extracellular potentials from neocortical neurons. We then developed VERTEX as an easy-to-use Matlab tool for simulating LFPs from large populations (>100 000 neurons). A VERTEX-based simulation successfully reproduced features of the LFPs from an in vitro multi-electrode array recording of macaque neocortical tissue. Our model, with virtual electrodes placed anywhere in 3D, allows direct comparisons with the in vitro recording setup. We envisage that VERTEX will stimulate experimentalists, clinicians, and computational neuroscientists to use models to understand the mechanisms underlying measured brain dynamics in health and disease.

q-bio.NC↗

arXiv2014

Perspective: network-guided pattern formation of neural dynamics

The understanding of neural activity patterns is fundamentally linked to an understanding of how the brain's network architecture shapes dynamical processes. Established approaches rely mostly on deviations of a given network from certain classes of random graphs. Hypotheses about the supposed role of prominent topological features (for instance, the roles of modularity, network motifs, or hierarchical network organization) are derived from these deviations. An alternative strategy could be to study deviations of network architectures from regular graphs (rings, lattices) and consider the implications of such deviations for self-organized dynamic patterns on the network. Following this strategy, we draw on the theory of spatiotemporal pattern formation and propose a novel perspective for analyzing dynamics on networks, by evaluating how the self-organized dynamics are confined by network architecture to a small set of permissible collective states. In particular, we discuss the role of prominent topological features of brain connectivity, such as hubs, modules and hierarchy, in shaping activity patterns. We illustrate the notion of network-guided pattern formation with numerical simulations and outline how it can facilitate the understanding of neural dynamics.

q-bio.NC↗

arXiv2014

Predicting age of human subjects based on structural connectivity from diffusion tensor imaging

Predicting brain maturity using noninvasive magnetic resonance images (MRI) can distinguish different age groups and help to assess neurodevelopmental disorders. However, group-wise differences are often less informative for assessing features of individuals. Here, we propose a simple method to predict the age of an individual subject solely based on structural connectivity data from diffusion tensor imaging (DTI). Our simple predictor computed a weighted sum of the strength of all connections of an individual. The weight consists of the fiber strength, given by the number of streamlines following tract tracing, multiplied by the importance of that connection for an observed feature--age in this case. We tested this approach using DTI data from 121 healthy subjects aged 4 to 85 years. After determining importance in a training dataset, our predicted ages in the test dataset showed a strong correlation (rho = 0.77) with real age deviating by, on average, only 10 years.

q-bio.NC↗

arXiv2014

Mapping neuron positions to curved cortical surfaces

Real cortical tissue curves and folds according to experimental data. However, our current simulations only use unfolded cortical layers. This project extends the cortical slice model in order to be able to specify arbitrary curvatures to the cortical layers and investigate the effect of curvature and folding on neuron density and layer morphology.

q-bio.NC↗

arXiv2014

Common Connectome Constraints: From C. elegans and Drosophila to Homo sapiens

Neural systems show a modular and typically also a hierarchical organisation across different levels and across different species. Topology relates to function, but it is also influences dynamics as earlier studies showed its effect on synchrony, oscillation, and activity propagation. Understanding the link between the hierarchical organisation and processing (e.g. does consciousness structurally correlate with the top level of the hierarchy and where is the 'top' in a network?) remains one of the main challenges of the field. In addition, although neuron nodes are often treated as uniform entities, they can differ in terms of function (e.g. inhibitory vs. excitatory), morphology, or gene expression pattern.

q-bio.NC↗

arXiv2014

A hierarchical network organization helps to retain comparable oscillation patterns in rats and human-sized brains

Activity in coupled systems is often oscillatory, for example, the firing pattern of neuronal populations. Whereas these oscillations have been studied predominantly in local circuits, here we show how the topology of large-scale networks, leading to large feedback loops, influences oscillations in the resting state. We find that the hierarchical modular organization of neuronal networks supports distinct spectral patterns of neural rhythms similar to those observed experimentally in different species such as rat and human. For individual neurons, multiple peak frequencies with non-integer ratios between subsequent peaks occurred. These ratios occurred both for models with the spatial size of the rat as well as for the human brain. We argue that the potential influence of longer connections, and thus longer delays, are balanced by a reduced number of long-distance connections in larger brain networks. In conclusion, we show that a hierarchical neuronal network provides a scalable backbone for multiple brain rhythms. This structural backbone could complement well-studied regional and cellular mechanisms for the generation or prevention of rhythms.

q-bio.NC↗

arXiv2014

Graphic Processing Unit Simulation of Axon Growth and Guidance through Cue Diffusion on Massively Parallel Processors

Neural development represents not only an exciting and complex field of study, with ongoing progress, but it also became the epicentre of neuroscience and developmental biology, as it strives to describe the underlying cellular and molecular mechanisms by which the central nervous system emerges during the various levels of embryonic development phases. The nervous system is a dynamic entity, where the genetic information plays an important role in shaping the intra- and extracellular environments, which in turn offer a reliable foundation for the stem cell precursors to divide and form neurons. Throughout the embryonic development stages, the neurons undergo different processes: migration at an immature level from the initial place in the embryo to a predefined final position, axonal differentiation and guidance of the motile growth cone towards a postsynaptic target, synaptic formation between axons and target, and lastly long-term synaptic changes which underlie learning and memory. In order to gain a better understanding of how the nervous system develops, mathematical and computational models have been created and expanded in order to bridge the gap between system-level dynamics and lower level cellular and molecular processes. This research paper aims to illustrate the potential of theoretical mathematical and computational models for analysing one important stage of neural development - axonal growth and guidance mechanisms in the presence of diffusion cues, through a visual simulation which is optimized via the graphic processing unit and parallel programming techniques.

q-bio.NC↗

arXiv2014

Preferential Detachment During Human Brain Development: Age- and Sex-Specific Structural Connectivity in Diffusion Tensor Imaging (DTI) Data

Human brain maturation is characterized by the prolonged development of structural and functional properties of large-scale networks that extends into adulthood. However, it is not clearly understood which features change and which remain stable over time. Here, we examined structural connectivity based on diffusion tensor imaging (DTI) in 121 participants between 4 and 40 years of age. DTI data were analyzed for small-world parameters, modularity, and the number of fiber tracts at the level of streamlines. First, our findings showed that the number of fiber tracts, small-world topology, and modular organization remained largely stable despite a substantial overall decrease in the number of streamlines with age. Second, this decrease mainly affected fiber tracts that had a large number of streamlines, were short, within modules and within hemispheres; such connections were affected significantly more often than would be expected given their number of occurrences in the network. Third, streamline loss occurred earlier in females than in males. In summary, our findings suggest that core properties of structural brain connectivity, such as the small-world and modular organization, remain stable during brain maturation by focusing streamline loss to specific types of fiber tracts.

q-bio.NC↗

arXiv2013

The Potential of the Human Connectome as a Biomarker of Brain Disease

The human connectome at the level of fiber tracts between brain regions has been shown to differ in patients with brain disorders compared to healthy control groups. Nonetheless, there is a potentially large number of different network organizations for individual patients that could lead to cognitive deficits prohibiting correct diagnosis. Therefore changes that can distinguish groups might not be sufficient to diagnose the disease that an individual patient suffers from and to indicate the best treatment option for that patient. We describe the challenges introduced by the large variability of connectomes within healthy subjects and patients and outline three common strategies to use connectomes as biomarkers of brain diseases. Finally, we propose a fourth option in using models of simulated brain activity (the dynamic connectome) based on structural connectivity rather than the structure (connectome) itself as a biomarker of disease. Dynamic connectomes, in addition to currently used structural, functional, or effective connectivity, could be an important future biomarker for clinical applications.

q-bio.NC↗

arXiv2013

Spreading dynamics on spatially constrained complex brain networks

The study of dynamical systems defined on complex networks provides a natural framework with which to investigate myriad features of neural dynamics, and has been widely undertaken. Typically, however, networks employed in theoretical studies bear little relation to the spatial embedding or connectivity of the neural networks that they attempt to replicate. Here, we employ detailed neuroimaging data to define a network whose spatial embedding represents accurately the folded structure of the cortical surface of a rat and investigate the propagation of activity over this network under simple spreading and connectivity rules. By comparison with standard network models with the same coarse statistics, we show that the cortical geometry influences profoundly the speed propagation of activation through the network. Our conclusions are of high relevance to the theoretical modelling of epileptic seizure events, and indicate that such studies which omit physiological network structure risk simplifying the dynamics in a potentially significant way.

q-bio.NC↗

arXiv2013

Resting-State Functional Connectivity in Late-Life Depression: Higher Global Connectivity and More Long Distance Connections

Functional magnetic resonance imaging recordings in the resting-state (RS) from the human brain are characterized by spontaneous low-frequency fluctuations in the blood oxygenation level dependent signal that reveal functional connectivity (FC) via their spatial synchronicity. This RS study applied network analysis to compare FC between late-life depression (LLD) patients and control subjects. Raw cross-correlation matrices (CM) for LLD were characterized by higher FC. We analyzed the small-world (SW) and modular organization of these networks consisting of 110 nodes each as well as the connectivity patterns of individual nodes of the basal ganglia. Topological network measures showed no significant differences between groups. The composition of top hubs was similar between LLD and control subjects, however in the LLD group posterior medial-parietal regions were more highly connected compared to controls. In LLD, a number of brain regions showed connections with more distant neighbors leading to an increase of the average Euclidean distance between connected regions compared to controls. In addition, right caudate nucleus connectivity was more diffuse in LLD. In summary, LLD was associated with overall increased FC strength and changes in the average distance between connected nodes, but did not lead to global changes in SW or modular organization.

q-bio.NC↗

arXiv2012

Critical paths in a metapopulation model of H1N1: Efficiently delaying influenza spreading through flight cancellation

Disease spreading through human travel networks has been a topic of great interest in recent years, as witnessed during outbreaks of influenza A (H1N1) or SARS pandemics. One way to stop spreading over the airline network are travel restrictions for major airports or network hubs based on the total number of passengers of an airport. Here, we test alternative strategies using edge removal, cancelling targeted flight connections rather than restricting traffic for network hubs, for controlling spreading over the airline network. We employ a SEIR metapopulation model that takes into account the population of cities, simulates infection within cities and across the network of the top 500 airports, and tests different flight cancellation methods for limiting the course of infection. The time required to spread an infection globally, as simulated by a stochastic global spreading model was used to rank the candidate control strategies. The model includes both local spreading dynamics at the level of populations and long-range connectivity obtained from real global airline travel data. Simulated spreading in this network showed that spreading infected 37% less individuals after cancelling a quarter of flight connections between cities, as selected by betweenness centrality. The alternative strategy of closing down whole airports causing the same number of cancelled connections only reduced infections by 18%. In conclusion, selecting highly ranked single connections between cities for cancellation was more effective, resulting in fewer individuals infected with influenza, compared to shutting down whole airports. It is also a more efficient strategy, affecting fewer passengers while producing the same reduction in infections. The network of connections between the top 500 airports is available under the resources link on our website http://www.biological-networks.org.

physics.soc-ph↗