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      Reproducible Neural Network Simulations: Statistical Methods for Model Validation on the Level of Network Activity Data

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          Abstract

          Computational neuroscience relies on simulations of neural network models to bridge the gap between the theory of neural networks and the experimentally observed activity dynamics in the brain. The rigorous validation of simulation results against reference data is thus an indispensable part of any simulation workflow. Moreover, the availability of different simulation environments and levels of model description require also validation of model implementations against each other to evaluate their equivalence. Despite rapid advances in the formalized description of models, data, and analysis workflows, there is no accepted consensus regarding the terminology and practical implementation of validation workflows in the context of neural simulations. This situation prevents the generic, unbiased comparison between published models, which is a key element of enhancing reproducibility of computational research in neuroscience. In this study, we argue for the establishment of standardized statistical test metrics that enable the quantitative validation of network models on the level of the population dynamics. Despite the importance of validating the elementary components of a simulation, such as single cell dynamics, building networks from validated building blocks does not entail the validity of the simulation on the network scale. Therefore, we introduce a corresponding set of validation tests and present an example workflow that practically demonstrates the iterative model validation of a spiking neural network model against its reproduction on the SpiNNaker neuromorphic hardware system. We formally implement the workflow using a generic Python library that we introduce for validation tests on neural network activity data. Together with the companion study (Trensch et al., 2018), the work presents a consistent definition, formalization, and implementation of the verification and validation process for neural network simulations.

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          Simple model of spiking neurons.

          A model is presented that reproduces spiking and bursting behavior of known types of cortical neurons. The model combines the biologically plausibility of Hodgkin-Huxley-type dynamics and the computational efficiency of integrate-and-fire neurons. Using this model, one can simulate tens of thousands of spiking cortical neurons in real time (1 ms resolution) using a desktop PC.
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            A methodology for performing global uncertainty and sensitivity analysis in systems biology.

            Accuracy of results from mathematical and computer models of biological systems is often complicated by the presence of uncertainties in experimental data that are used to estimate parameter values. Current mathematical modeling approaches typically use either single-parameter or local sensitivity analyses. However, these methods do not accurately assess uncertainty and sensitivity in the system as, by default, they hold all other parameters fixed at baseline values. Using techniques described within we demonstrate how a multi-dimensional parameter space can be studied globally so all uncertainties can be identified. Further, uncertainty and sensitivity analysis techniques can help to identify and ultimately control uncertainties. In this work we develop methods for applying existing analytical tools to perform analyses on a variety of mathematical and computer models. We compare two specific types of global sensitivity analysis indexes that have proven to be among the most robust and efficient. Through familiar and new examples of mathematical and computer models, we provide a complete methodology for performing these analyses, in both deterministic and stochastic settings, and propose novel techniques to handle problems encountered during these types of analyses.
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              Reconstruction and Simulation of Neocortical Microcircuitry.

              We present a first-draft digital reconstruction of the microcircuitry of somatosensory cortex of juvenile rat. The reconstruction uses cellular and synaptic organizing principles to algorithmically reconstruct detailed anatomy and physiology from sparse experimental data. An objective anatomical method defines a neocortical volume of 0.29 ± 0.01 mm(3) containing ~31,000 neurons, and patch-clamp studies identify 55 layer-specific morphological and 207 morpho-electrical neuron subtypes. When digitally reconstructed neurons are positioned in the volume and synapse formation is restricted to biological bouton densities and numbers of synapses per connection, their overlapping arbors form ~8 million connections with ~37 million synapses. Simulations reproduce an array of in vitro and in vivo experiments without parameter tuning. Additionally, we find a spectrum of network states with a sharp transition from synchronous to asynchronous activity, modulated by physiological mechanisms. The spectrum of network states, dynamically reconfigured around this transition, supports diverse information processing strategies.
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                Author and article information

                Contributors
                Journal
                Front Neuroinform
                Front Neuroinform
                Front. Neuroinform.
                Frontiers in Neuroinformatics
                Frontiers Media S.A.
                1662-5196
                19 December 2018
                2018
                : 12
                : 90
                Affiliations
                [1] 1Institute of Neuroscience and Medicine (INM-6) and Institute for Advanced Simulation (IAS-6) and JARA-Institut Brain Structure-Function Relationships (INM-10), Jülich Research Centre , Jülich, Germany
                [2] 2Theoretical Systems Neurobiology, RWTH Aachen University , Aachen, Germany
                [3] 3Simulation Lab Neuroscience, Jülich Supercomputing Centre, Institute for Advanced Simulation, JARA, Jülich Research Centre , Jülich, Germany
                Author notes

                Edited by: Robert Andrew McDougal, Yale University, United States

                Reviewed by: Richard C. Gerkin, Arizona State University, United States; Tadashi Yamazaki, University of Electro-Communications, Japan; Salvador Dura-Bernal, SUNY Downstate Medical Center, United States; Boris Marin, Universidade Federal do ABC, Brazil

                *Correspondence: Robin Gutzen r.gutzen@ 123456fz-juelich.de
                Article
                10.3389/fninf.2018.00090
                6305903
                30618696
                4484561f-8c64-4f13-a6a8-861e261ced01
                Copyright © 2018 Gutzen, von Papen, Trensch, Quaglio, Grün and Denker.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 18 June 2018
                : 14 November 2018
                Page count
                Figures: 9, Tables: 1, Equations: 11, References: 71, Pages: 19, Words: 14767
                Funding
                Funded by: Horizon 2020 10.13039/501100007601
                Award ID: 720270
                Award ID: 785907
                Funded by: Helmholtz Association 10.13039/501100009318
                Award ID: ZT-I-0003
                Categories
                Neuroscience
                Original Research

                Neurosciences
                spiking neural network,spinnaker,validation,reproducibility,statistical analysis,simulation

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