Computational Concepts for Reconstructing and Simulating Brain Tissue.

It has previously been shown that it is possible to derive a new class of biophysically detailed brain tissue models when one computationally analyzes and exploits the interdependencies or the multi-modal and multi-scale organization of the brain. These reconstructions, sometimes referred to as digital twins, enable a spectrum of scientific investigations. Building such models has become possible because of increase in quantitative data but also advances in computational capabilities, algorithmic and methodological innovations. This chapter presents the computational science concepts that provide the foundation to the data-driven approach to reconstructing and simulating brain tissue as developed by the EPFL Blue Brain Project, which was originally applied to neocortical microcircuitry and extended to other brain regions. Accordingly, the chapter covers aspects such as a knowledge graph-based data organization and the importance of the concept of a dataset release. We illustrate algorithmic advances in finding suitable parameters for electrical models of neurons or how spatial constraints can be exploited for predicting synaptic connections. Furthermore, we explain how in silico experimentation with such models necessitates specific addressing schemes or requires strategies for an efficient simulation. The entire data-driven approach relies on the systematic validation of the model. We conclude by discussing complementary strategies that not only enable judging the fidelity of the model but also form the basis for its systematic refinements.

An all-round AI-Chemist with a scientific mind.

The realization of automated chemical experiments by robots unveiled the prelude to an artificial intelligence (AI) laboratory. Several AI-based systems or robots with specific chemical skills have been demonstrated, but conducting all-round scientific research remains challenging. Here, we present an all-round AI-Chemist equipped with scientific data intelligence that is capable of performing basic tasks generally required in chemical research. Based on a service platform, the AI-Chemist is able to automatically read the literatures from a cloud database and propose experimental plans accordingly. It can control a mobile robot in-house or online to automatically execute the complete experimental process on 14 workstations, including synthesis, characterization and performance tests. The experimental data can be simultaneously analysed by the computational brain of the AI-Chemist through machine learning and Bayesian optimization, allowing a new hypothesis for the next iteration to be proposed. The competence of the AI-Chemist has been scrutinized by three different chemical tasks. In the future, the more advanced all-round AI-Chemists equipped with scientific data intelligence may cause changes to the landscape of the chemical laboratory.

A Spiking Neural Network Builder for Systematic Data-to-Model Workflow.

In building biological neural network models, it is crucial to efficiently convert diverse anatomical and physiological data into parameters of neurons and synapses and to systematically estimate unknown parameters in reference to experimental observations. Web-based tools for systematic model building can improve the transparency and reproducibility of computational models and can facilitate collaborative model building, validation, and evolution. Here, we present a framework to support collaborative data-driven development of spiking neural network (SNN) models based on the Entity-Relationship (ER) data description commonly used in large-scale business software development. We organize all data attributes, including species, brain regions, neuron types, projections, neuron models, and references as tables and relations within a database management system (DBMS) and provide GUI interfaces for data registration and visualization. This allows a robust "business-oriented" data representation that supports collaborative model building and traceability of source information for every detail of a model. We tested this data-to-model framework in cortical and striatal network models by successfully combining data from papers with existing neuron and synapse models and by generating NEST simulation codes for various network sizes. Our framework also helps to check data integrity and consistency and data comparisons across species. The framework enables the modeling of any region of the brain and is being deployed to support the integration of anatomical and physiological datasets from the brain/MINDS project for systematic SNN modeling of the marmoset brain.

Toward a Comprehensive Delineation of White Matter Tract-Related Deformation.

Finite element (FE) models of the human head are valuable instruments to explore the mechanobiological pathway from external loading, localized brain response, and resultant injury risks. The injury predictability of these models depends on the use of effective criteria as injury predictors. The FE-derived normal deformation along white matter (WM) fiber tracts (i.e., tract-oriented strain) recently has been suggested as an appropriate predictor for axonal injury. However, the tract-oriented strain only represents a partial depiction of the WM fiber tract deformation. A comprehensive delineation of tract-related deformation may improve the injury predictability of the FE head model by delivering new tract-related criteria as injury predictors. Thus, the present study performed a theoretical strain analysis to comprehensively characterize the WM fiber tract deformation by relating the strain tensor of the WM element to its embedded fiber tract. Three new tract-related strains with exact analytical solutions were proposed, measuring the normal deformation perpendicular to the fiber tracts (i.e., tract-perpendicular strain), and shear deformation along and perpendicular to the fiber tracts (i.e., axial-shear strain and lateral-shear strain, respectively). The injury predictability of these three newly proposed strain peaks along with the previously used tract-oriented strain peak and maximum principal strain (MPS) were evaluated by simulating 151 impacts with known outcome (concussion or non-concussion). The results preliminarily showed that four tract-related strain peaks exhibited superior performance than MPS in discriminating concussion and non-concussion cases. This study presents a comprehensive quantification of WM tract-related deformation and advocates the use of orientation-dependent strains as criteria for injury prediction, which may ultimately contribute to an advanced mechanobiological understanding and enhanced computational predictability of brain injury.