Model-free reconstruction of neuronal network connectivity from calcium imaging signals

A systematic assessment of global neural network connectivity through direct electrophysiological assays has remained technically unfeasible even in dissociated neuronal cultures. We introduce an improved algorithmic approach based on Transfer Entropy to reconstruct approximations to network structural connectivities from network activity monitored through calcium fluorescence imaging. Based on information theory, our method requires no prior assumptions on the statistics of neuronal firing and neuronal connections. The performance of our algorithm is benchmarked on surrogate time-series of calcium fluorescence generated by the simulated dynamics of a network with known ground-truth topology. We find that the effective network topology revealed by Transfer Entropy depends qualitatively on the time-dependent dynamic state of the network (e.g., bursting or non-bursting). We thus demonstrate how conditioning with respect to the global mean activity improves the performance of our method. [...] Compared to other reconstruction strategies such as cross-correlation or Granger Causality methods, our method based on improved Transfer Entropy is remarkably more accurate. In particular, it provides a good reconstruction of the network clustering coefficient, allowing to discriminate between weakly or strongly clustered topologies, whereas on the other hand an approach based on cross-correlations would invariantly detect artificially high levels of clustering. Finally, we present the applicability of our method to real recordings of in vitro cortical cultures. We demonstrate that these networks are characterized by an elevated level of clustering compared to a random graph (although not extreme) and by a markedly non-local connectivity.Comment: 54 pages, 8 figures (+9 supplementary figures), 1 table; submitted for publicatio

Topological exploration of artificial neuronal network dynamics

One of the paramount challenges in neuroscience is to understand the dynamics of individual neurons and how they give rise to network dynamics when interconnected. Historically, researchers have resorted to graph theory, statistics, and statistical mechanics to describe the spatiotemporal structure of such network dynamics. Our novel approach employs tools from algebraic topology to characterize the global properties of network structure and dynamics. We propose a method based on persistent homology to automatically classify network dynamics using topological features of spaces built from various spike-train distances. We investigate the efficacy of our method by simulating activity in three small artificial neural networks with different sets of parameters, giving rise to dynamics that can be classified into four regimes. We then compute three measures of spike train similarity and use persistent homology to extract topological features that are fundamentally different from those used in traditional methods. Our results show that a machine learning classifier trained on these features can accurately predict the regime of the network it was trained on and also generalize to other networks that were not presented during training. Moreover, we demonstrate that using features extracted from multiple spike-train distances systematically improves the performance of our method

Storage of phase-coded patterns via STDP in fully-connected and sparse network: a study of the network capacity

We study the storage and retrieval of phase-coded patterns as stable dynamical attractors in recurrent neural networks, for both an analog and a integrate-and-fire spiking model. The synaptic strength is determined by a learning rule based on spike-time-dependent plasticity, with an asymmetric time window depending on the relative timing between pre- and post-synaptic activity. We store multiple patterns and study the network capacity. For the analog model, we find that the network capacity scales linearly with the network size, and that both capacity and the oscillation frequency of the retrieval state depend on the asymmetry of the learning time window. In addition to fully-connected networks, we study sparse networks, where each neuron is connected only to a small number z << N of other neurons. Connections can be short range, between neighboring neurons placed on a regular lattice, or long range, between randomly chosen pairs of neurons. We find that a small fraction of long range connections is able to amplify the capacity of the network. This imply that a small-world-network topology is optimal, as a compromise between the cost of long range connections and the capacity increase. Also in the spiking integrate and fire model the crucial result of storing and retrieval of multiple phase-coded patterns is observed. The capacity of the fully-connected spiking network is investigated, together with the relation between oscillation frequency of retrieval state and window asymmetry

Modeling brain dynamics in brain tumor patients using the virtual brain

Presurgical planning for brain tumor resection aims at delineating eloquent tissue in the vicinity of the lesion to spare during surgery. To this end, noninvasive neuroimaging techniques such as functional MRI and diffusion-weighted imaging fiber tracking are currently employed. However, taking into account this information is often still insufficient, as the complex nonlinear dynamics of the brain impede straightforward prediction of functional outcome after surgical intervention. Large-scale brain network modeling carries the potential to bridge this gap by integrating neuroimaging data with biophysically based models to predict collective brain dynamics. As a first step in this direction, an appropriate computational model has to be selected, after which suitable model parameter values have to be determined. To this end, we simulated large-scale brain dynamics in 25 human brain tumor patients and 11 human control participants using The Virtual Brain, an open-source neuroinformatics platform. Local and global model parameters of the Reduced Wong-Wang model were individually optimized and compared between brain tumor patients and control subjects. In addition, the relationship between model parameters and structural network topology and cognitive performance was assessed. Results showed (1) significantly improved prediction accuracy of individual functional connectivity when using individually optimized model parameters; (2) local model parameters that can differentiate between regions directly affected by a tumor, regions distant from a tumor, and regions in a healthy brain; and (3) interesting associations between individually optimized model parameters and structural network topology and cognitive performance

Comparative evaluation of Ising couplings, kinetic Ising couplings,and partial correlations in inferring structural connectivity

The problem of inferring the structural connections from the functional connections obtained from the activity of the neuronal networks is one of the major challenges in neuroscience. Studies suggest that maximum entropy based Ising models can discount the effect of indirect interactions and provide good results in inferring the underlying structural connections in neuronal networks. Parameters of the kinetic formulation of the Ising models, kinetic Ising models, have been found to agree well with anatomical connectivity in in silico models of neuronal networks. Following this, Ising and kinetic Ising models have attracted attention in the area of connectivity studies. However, the performance of the Ising couplings and kinetic Ising couplings have not been evaluated in comparison with other functional con- nectivity metrics in the microscopic scale of neuronal networks for a varied set of network conditions and network structures. This thesis sets out to resolve this through a comparative evaluation of the ability of Ising cou- plings and kinetic Ising couplings to unravel the structural connections when compared to the widely used functional connectivity metrics of partial and cross-correlations in in silico networks. The thesis presents the finding that the network correlation level deter- mines the relative performance of the functional connectivity metrics in de- tecting the synaptic connections. At weak levels of network correlation, Ising couplings and kinetic Ising couplings yielded better performance when com- pared to partial and cross-correlations. Whereas at strong levels of network correlation, partial correlations detected more structural links when com- pared to other functional connectivity metrics in this study. This result was consistent across varying firing rates, network sizes, densities and topologies. Along with being directional and applicable in nonstationary cases, kinetic Ising couplings also displayed better performance when compared to Ising couplings. The findings of this thesis serve as a guide in selecting the right functional connectivity tool to reconstruct the structural connectivity

Feed-Forward Propagation of Temporal and Rate Information between Cortical Populations during Coherent Activation in Engineered In Vitro Networks.

Transient propagation of information across neuronal assembles is thought to underlie many cognitive processes. However, the nature of the neural code that is embedded within these transmissions remains uncertain. Much of our understanding of how information is transmitted among these assemblies has been derived from computational models. While these models have been instrumental in understanding these processes they often make simplifying assumptions about the biophysical properties of neurons that may influence the nature and properties expressed. To address this issue we created an in vitro analog of a feed-forward network composed of two small populations (also referred to as assemblies or layers) of living dissociated rat cortical neurons. The populations were separated by, and communicated through, a microelectromechanical systems (MEMS) device containing a strip of microscale tunnels. Delayed culturing of one population in the first layer followed by the second a few days later induced the unidirectional growth of axons through the microtunnels resulting in a primarily feed-forward communication between these two small neural populations. In this study we systematically manipulated the number of tunnels that connected each layer and hence, the number of axons providing communication between those populations. We then assess the effect of reducing the number of tunnels has upon the properties of between-layer communication capacity and fidelity of neural transmission among spike trains transmitted across and within layers. We show evidence based on Victor-Purpura's and van Rossum's spike train similarity metrics supporting the presence of both rate and temporal information embedded within these transmissions whose fidelity increased during communication both between and within layers when the number of tunnels are increased. We also provide evidence reinforcing the role of synchronized activity upon transmission fidelity during the spontaneous synchronized network burst events that propagated between layers and highlight the potential applications of these MEMs devices as a tool for further investigation of structure and functional dynamics among neural populations