Revisiting the involvement of tau in complex neural network remodeling: analysis of the extracellular neuronal activity in organotypic brain slice co-cultures.

Objective.Tau ablation has a protective effect in epilepsy due to inhibition of the hyperexcitability/hypersynchrony. Protection may also occur in transgenic models of Alzheimer's disease by reducing the epileptic activity and normalizing the excitation/inhibition imbalance. However, it is difficult to determine the exact functions of tau, because tau knockout (tauKO) brain networks exhibit elusive phenotypes. In this study, we aimed to further explore the physiological role of tau using brain network remodeling.Approach.The effect of tau ablation was investigated in hippocampal-entorhinal slice co-cultures during network remodeling. We recorded the spontaneous extracellular neuronal activity over 2 weeks in single-slice cultures and co-cultures from control andtauKOmice. We compared the burst activity and applied concepts and analytical tools intended for the analysis of the network synchrony and connectivity.Main results.Comparison of the control andtauKOco-cultures revealed that tau ablation had an anti-synchrony effect on the hippocampal-entorhinal two-slice networks at late stages of culture, in line with the literature. Differences were also found between the single-slice and co-culture conditions, which indicated that tau ablation had differential effects at the sub-network scale. For instance, tau ablation was found to have an anti-synchrony effect on the co-cultured hippocampal slices throughout the culture, possibly due to a reduction in the excitation/inhibition ratio. Conversely, tau ablation led to increased synchrony in the entorhinal slices at early stages of the co-culture, possibly due to homogenization of the connectivity distribution.Significance.The new methodology presented here proved useful for investigating the role of tau in the remodeling of complex brain-derived neural networks. The results confirm previous findings and hypotheses concerning the effects of tau ablation on neural networks. Moreover, the results suggest, for the first time, that tau has multifaceted roles that vary in different brain sub-networks.

Modeling the effects of social distancing on the large-scale spreading of diseases.

To contain the propagation of emerging diseases that are transmissible from human to human, non-pharmaceutical interventions (NPIs) aimed at reducing the interactions between humans are usually implemented. One example of the latter kind of measures is social distancing, which can be either policy-driven or can arise endogenously in the population as a consequence of the fear of infection. However, if NPIs are lifted before the population reaches herd immunity, further re-introductions of the pathogen would lead to secondary infections. Here we study the effects of different social distancing schemes on the large scale spreading of diseases. Specifically, we generalize metapopulation models to include social distancing mechanisms at the subpopulation level and model short- and long-term strategies that are fed with local or global information about the epidemics. We show that different model ingredients might lead to very diverse outcomes in different subpopulations. Our results suggest that there is not a unique answer to the question of whether contention measures are more efficient if implemented and managed locally or globally and that model outcomes depends on how the full complexity of human interactions is taken into account.

Comparison of Different Spike Train Synchrony Measures Regarding Their Robustness to Erroneous Data From Bicuculline-Induced Epileptiform Activity.

As synchronized activity is associated with basic brain functions and pathological states, spike train synchrony has become an important measure to analyze experimental neuronal data. Many measures of spike train synchrony have been proposed, but there is no gold standard allowing for comparison of results from different experiments. This work aims to provide guidance on which synchrony measure is best suited to quantify the effect of epileptiform-inducing substances (e.g., bicuculline, BIC) in in vitro neuronal spike train data. Spike train data from recordings are likely to suffer from erroneous spike detection, such as missed spikes (false negative) or noise (false positive). Therefore, different timescale-dependent (cross-correlation, mutual information, spike time tiling coefficient) and timescale-independent (Spike-contrast, phase synchronization (PS), A-SPIKE-synchronization, A-ISI-distance, ARI-SPIKE-distance) synchrony measures were compared in terms of their robustness to erroneous spike trains. For this purpose, erroneous spike trains were generated by randomly adding (false positive) or deleting (false negative) spikes (in silico manipulated data) from experimental data. In addition, experimental data were analyzed using different spike detection threshold factors in order to confirm the robustness of the synchrony measures. All experimental data were recorded from cortical neuronal networks on microelectrode array chips, which show epileptiform activity induced by the substance BIC. As a result of the in silico manipulated data, Spike-contrast was the only measure that was robust to false-negative as well as false-positive spikes. Analyzing the experimental data set revealed that all measures were able to capture the effect of BIC in a statistically significant way, with Spike-contrast showing the highest statistical significance even at low spike detection thresholds. In summary, we suggest using Spike-contrast to complement established synchrony measures because it is timescale independent and robust to erroneous spike trains.

The nested structural organization of the worldwide trade multi-layer network.

Nestedness has traditionally been used to detect assembly patterns in meta-communities and networks of interacting species. Attempts have also been made to uncover nested structures in international trade, typically represented as bipartite networks in which connections can be established between countries (exporters or importers) and industries. A bipartite representation of trade, however, inevitably neglects transactions between industries. To fully capture the organization of the global value chain, we draw on the World Input-Output Database and construct a multi-layer network in which the nodes are the countries, the layers are the industries, and links can be established from sellers to buyers within and across industries. We define the buyers' and sellers' participation matrices in which the rows are the countries and the columns are all possible pairs of industries, and then compute nestedness based on buyers' and sellers' involvement in transactions between and within industries. Drawing on appropriate null models that preserve the countries' or layers' degree distributions in the original multi-layer network, we uncover variations of country- and transaction-based nestedness over time, and identify the countries and industries that most contributed to nestedness. We discuss the implications of our findings for the study of the international production network and other real-world systems.

A generalized approach to the modeling of the species-area relationship.

This paper proposes a statistical generalized species-area model (GSAM) to represent various patterns of species-area relationship (SAR), which is one of the fundamental patterns in ecology. The approach enables the generalization of many preliminary models, as power-curve model, which is commonly used to mathematically describe the SAR. The GSAM is applied to simulated data set of species diversity in areas of different sizes and a real-world data of insects of Hymenoptera order has been modeled. We show that the GSAM enables the identification of the best statistical model and estimates the number of species according to the area.

A systematic comparison of supervised classifiers.

Pattern recognition has been employed in a myriad of industrial, commercial and academic applications. Many techniques have been devised to tackle such a diversity of applications. Despite the long tradition of pattern recognition research, there is no technique that yields the best classification in all scenarios. Therefore, as many techniques as possible should be considered in high accuracy applications. Typical related works either focus on the performance of a given algorithm or compare various classification methods. In many occasions, however, researchers who are not experts in the field of machine learning have to deal with practical classification tasks without an in-depth knowledge about the underlying parameters. Actually, the adequate choice of classifiers and parameters in such practical circumstances constitutes a long-standing problem and is one of the subjects of the current paper. We carried out a performance study of nine well-known classifiers implemented in the Weka framework and compared the influence of the parameter configurations on the accuracy. The default configuration of parameters in Weka was found to provide near optimal performance for most cases, not including methods such as the support vector machine (SVM). In addition, the k-nearest neighbor method frequently allowed the best accuracy. In certain conditions, it was possible to improve the quality of SVM by more than 20% with respect to their default parameter configuration.

Multiple pathways analysis of brain functional networks from EEG signals: an application to real data.

In the present study, we propose a theoretical graph procedure to investigate multiple pathways in brain functional networks. By taking into account all the possible paths consisting of h links between the nodes pairs of the network, we measured the global network redundancy R(h) as the number of parallel paths and the global network permeability P(h) as the probability to get connected. We used this procedure to investigate the structural and dynamical changes in the cortical networks estimated from a dataset of high-resolution EEG signals in a group of spinal cord injured (SCI) patients during the attempt of foot movement. In the light of a statistical contrast with a healthy population, the permeability index P(h) of the SCI networks increased significantly (P < 0.01) in the Theta frequency band (3-6 Hz) for distances h ranging from 2 to 4. On the contrary, no significant differences were found between the two populations for the redundancy index R(h). The most significant changes in the brain functional network of SCI patients occurred mainly in the lower spectral contents. These changes were related to an improved propagation of communication between the closest cortical areas rather than to a different level of redundancy. This evidence strengthens the hypothesis of the need for a higher functional interaction among the closest ROIs as a mechanism to compensate the lack of feedback from the peripheral nerves to the sensomotor areas.

Generalized connectivity between any two nodes in a complex network.

This article focuses on the identification of the number of paths with different lengths between pairs of nodes in complex networks and how these paths can be used for characterization of topological properties of theoretical and real-world complex networks. This analysis revealed that the number of paths can provide a better discrimination of network models than traditional network measurements. In addition, the analysis of real-world networks suggests that the long-range connectivity tends to be limited in these networks and may be strongly related to network growth and organization.

Signal propagation in cortical networks: a digital signal processing approach.

This work reports a digital signal processing approach to representing and modeling transmission and combination of signals in cortical networks. The signal dynamics is modeled in terms of diffusion, which allows the information processing undergone between any pair of nodes to be fully characterized in terms of a finite impulse response (FIR) filter. Diffusion without and with time decay are investigated. All filters underlying the cat and macaque cortical organization are found to be of low-pass nature, allowing the cortical signal processing to be summarized in terms of the respective cutoff frequencies (a high cutoff frequency meaning little alteration of signals through their intermixing). Several findings are reported and discussed, including the fact that the incorporation of temporal activity decay tends to provide more diversified cutoff frequencies. Different filtering intensity is observed for each community in those networks. In addition, the brain regions involved in object recognition tend to present the highest cutoff frequencies for both the cat and macaque networks.