Neuroscience education is challenged by rapidly evolving technology and the development of interdisciplinary approaches for brain research. The Human Brain Project (HBP) Education Programme aimed to address the need for interdisciplinary expertise in brain research by equipping a new generation of researchers with skills across neuroscience, medicine, and information technology. Over its ten year duration, the programme engaged over 1,300 experts and attracted more than 5,500 participants from various scientific disciplines in its blended learning curriculum, specialised schools and workshops, and events fostering dialogue among early-career researchers. Key principles of the programme’s approach included fostering interdisciplinarity, adaptability to the evolving research landscape and infrastructure, and a collaborative environment with a focus on empowering early-career researchers. Following the programme’s conclusion, we provide here an analysis and in-depth view across a diverse range of educational formats and events. Our results show that the Education Programme achieved success in its wide geographic reach, the diversity of participants, and the establishment of transversal collaborations. Building on these experiences and achievements, we describe how leveraging digital tools and platforms provides accessible and highly specialised training, which can enhance existing education programmes for the next generation of brain researchers working in decentralised European collaborative spaces. Finally, we present the lessons learnt so that similar initiatives may improve upon our experience and incorporate our suggestions into their own programme.

In recent years, brain research has indisputably entered a new epoch, driven by substantial methodological advances and digitally enabled data integration and modelling at multiple scales—from molecules to the whole brain. Major advances are emerging at the intersection of neuroscience with technology and computing. This new science of the brain combines high-quality research, data integration across multiple scales, a new culture of multidisciplinary large-scale collaboration, and translation into applications. As pioneered in Europe’s Human Brain Project (HBP), a systematic approach will be essential for meeting the coming decade’s pressing medical and technological challenges. The aims of this paper are to: develop a concept for the coming decade of digital brain research, discuss this new concept with the research community at large, identify points of convergence, and derive therefrom scientific common goals; provide a scientific framework for the current and future development of EBRAINS, a research infrastructure resulting from the HBP’s work; inform and engage stakeholders, funding organisations and research institutions regarding future digital brain research; identify and address the transformational potential of comprehensive brain models for artificial intelligence, including machine learning and deep learning; outline a collaborative approach that integrates reflection, dialogues, and societal engagement on ethical and societal opportunities and challenges as part of future neuroscience research.

Integration of information across heterogeneous sources creates added scientific value. Interoperability of data, tools and models is, however, difficult to accomplish across spatial and temporal scales. Here we introduce the toolbox Parallel Co-Simulation, which enables the interoperation of simulators operating at different scales. We provide a software science co-design pattern and illustrate its functioning along a neuroscience example, in which individual regions of interest are simulated on the cellular level allowing us to study detailed mechanisms, while the remaining network is efficiently simulated on the population level. A workflow is illustrated for the use case of The Virtual Brain and NEST, in which the CA1 region of the cellular-level hippocampus of the mouse is embedded into a full brain network involving micro and macro electrode recordings. This new tool allows integrating knowledge across scales in the same simulation framework and validating them against multiscale experiments, thereby largely widening the explanatory power of computational models.

An open challenge on the road to unraveling the brain's multilevel organization is establishing techniques to research connectivity and dynamics at different scales in time and space, as well as the links between them. This work focuses on the design of a framework that facilitates the generation of multiscale connectivity in large neural networks using a symbolic visual language capable of representing the model at different structural levels—ConGen. This symbolic language allows researchers to create and visually analyze the generated networks independently of the simulator to be used, since the visual model is translated into a simulator-independent language. The simplicity of the front end visual representation, together with the simulator independence provided by the back end translation, combine into a framework to enhance collaboration among scientists with expertise at different scales of abstraction and from different fields. On the basis of two use cases, we introduce the features and possibilities of our proposed visual language and associated workflow. We demonstrate that ConGen enables the creation, editing, and visualization of multiscale biological neural networks and provides a whole workflow to produce simulation scripts from the visual representation of the model.

Neuroscience models commonly have a high number of degrees of freedom and only specific regions within the parameter space are able to produce dynamics of interest. This makes the development of tools and strategies to efficiently find these regions of high importance to advance brain research. Exploring the high dimensional parameter space using numerical simulations has been a frequently used technique in the last years in many areas of computational neuroscience. Today, high performance computing (HPC) can provide a powerful infrastructure to speed up explorations and increase our general understanding of the behavior of the model in reasonable times. Learning to learn (L2L) is a well-known concept in machine learning (ML) and a specific method for acquiring constraints to improve learning performance. This concept can be decomposed into a two loop optimization process where the target of optimization can consist of any program such as an artificial neural network, a spiking network, a single cell model, or a whole brain simulation. In this work, we present L2L as an easy to use and flexible framework to perform parameter and hyper-parameter space exploration of neuroscience models on HPC infrastructure. Learning to learn is an implementation of the L2L concept written in Python. This open-source software allows several instances of an optimization target to be executed with different parameters in an embarrassingly parallel fashion on HPC. L2L provides a set of built-in optimizer algorithms, which make adaptive and efficient exploration of parameter spaces possible. Different from other optimization toolboxes, L2L provides maximum flexibility for the way the optimization target can be executed. In this paper, we show a variety of examples of neuroscience models being optimized within the L2L framework to execute different types of tasks. The tasks used to illustrate the concept go from reproducing empirical data to learning how to solve a problem in a dynamic environment. We particularly focus on simulations with models ranging from the single cell to the whole brain and using a variety of simulation engines like NEST, Arbor, TVB, OpenAIGym, and NetLogo.

The Virtual Brain (TVB) is now available as open-source services on the cloud research platform EBRAINS (ebrains.eu). It offers software for constructing, simulating and analysing brain network models including the TVB simulator; magnetic resonance imaging (MRI) processing pipelines to extract structural and functional brain networks; combined simulation of large-scale brain networks with small-scale spiking networks; automatic conversion of user-specified model equations into fast simulation code; simulation-ready brain models of patients and healthy volunteers; Bayesian parameter optimization in epilepsy patient models; data and software for mouse brain simulation; and extensive educational material. TVB cloud services facilitate reproducible online collaboration and discovery of data assets, models, and software embedded in scalable and secure workflows, a precondition for research on large cohort data sets, better generalizability, and clinical translation.

Simulating the brain-body-environment trinity in closed loop is an attractive proposal to investigate how perception, motor activity and interactions with the environment shape brain activity, and vice versa. The relevance of this embodied approach, however, hinges entirely on the modeled complexity of the various simulated phenomena. In this article, we introduce a software framework that is capable of simulating large-scale, biologically realistic networks of spiking neurons embodied in a biomechanically accurate musculoskeletal system that interacts with a physically realistic virtual environment. We deploy this framework on the high performance computing resources of the EBRAINS research infrastructure and we investigate the scaling performance by distributing computation across an increasing number of interconnected compute nodes. Our architecture is based on requested compute nodes as well as persistent virtual machines; this provides a high-performance simulation environment that is accessible to multi-domain users without expert knowledge, with a view to enable users to instantiate and control simulations at custom scale via a web-based graphical user interface. Our simulation environment, entirely open source, is based on the Neurorobotics Platform developed in the context of the Human Brain Project, and the NEST simulator. We characterize the capabilities of our parallelized architecture for large-scale embodied brain simulations through two benchmark experiments, by investigating the effects of scaling compute resources on performance defined in terms of experiment runtime, brain instantiation and simulation time. The first benchmark is based on a large-scale balanced network, while the second one is a multi-region embodied brain simulation consisting of more than a million neurons and a billion synapses. Both benchmarks clearly show how scaling compute resources improves the aforementioned performance metrics in a near-linear fashion. The second benchmark in particular is indicative of both the potential and limitations of a highly distributed simulation in terms of a trade-off between computation speed and resource cost. Our simulation architecture is being prepared to be accessible for everyone as an EBRAINS service, thereby offering a community-wide tool with a unique workflow that should provide momentum to the investigation of closed-loop embodiment within the computational neuroscience community.

Integration of information across heterogeneous sources creates added scientific value. It is, however, a challenge to progress, often a barrier, to interoperate data, tools and models across spatial and temporal scales. Here we present a design template for coupling simulators operating at different scales and enabling co-simulation. We illustrate its functioning along a neuroscience example, in which individual regions of interest are simulated on the cellular level to address mechanistic questions, while the remaining network is efficiently simulated on the population level. A workflow is illustrated for the use case of The Virtual Brain and NEST, in which the cellular-level hippocampus of the mouse is embedded into a full brain network involving micro and macro electrode recordings. This new tool allows integrating knowledge across scales in the same simulation framework and validate them against multiscale experiments, thereby largely widening the explanatory power of computational models.

The Human Brain Project (HBP) ( https://humanbrainproject.eu/ ) is a large-scale flagship project funded by the European Commission with the goal of establishing a research infrastructure for brain science. This research infrastructure is currently being realised and will be called EBRAINS ( https://ebrains.eu/ ). The wide ranging EBRAINS services for the brain research communities require diverse access, processing and storage capabilities. As a result, it will strongly rely on e-infrastructure services. The HBP led to the creation of Fenix ( https://fenix-ri.eu/ ), a collaboration of five European supercomputing centres, who are providing a set of federated e-infrastructure services to EBRAINS. The Fenix architecture has been designed to uniquely address the need for a wide spectrum of services, from high performance computing (HPC) to on-demand cloud technologies to identity and access federation, for facilitating ease of access and usage of distributed e-infrastructure resources. In this article we describe the underlying concepts for an audience of computational science end-users and developers of domain-specific applications, workflows and platforms services. To exemplify the use of Fenix, we will discuss selected use cases demonstrating how brain researchers can use the offered infrastructure services and describe how access to these resources can be obtained.

Large-scale in silico experimentation depends on the generation of connectomes beyond available anatomical structure. We suggest that linking research across the fields of experimental connectomics, theoretical neuroscience, and high-performance computing can enable a new generation of models bridging the gap between biophysical detail and global function. This Focus Feature on "Linking Experimental and Computational Connectomics" aims to bring together some examples from these domains as a step toward the development of more comprehensive generative models of multiscale connectomes.

Five European supercomputing centres, namely BSC (Spain), CEA (France), CINECA (Italy), CSCS (Switzerland), and JSC (Germany), agreed to align their high-end computing and storage services to facilitate the creation of the Fenix Research Infrastructure. In addition to the traditional extreme-scale computing and data services, Fenix provides a set of Cloud-type services as well as services needed for federation. In this paper, we describe the architecture of the Fenix infrastructure and how it can be used for representative workflows from the Human Brain Project (HBP). The concept of the Active Data Repository (ACD) is chosen to highlight demarcation between HPC and Cloud access models.

Researchers within the Human Brain Project and related projects have in the last couple of years expanded their needs for high-performance computing infrastructures. The needs arise from a diverse set of science challenges that range from large-scale simulations of brain models to processing of extreme-scale experimental data sets. The ICEI project, which is in the process of creating a distributed infrastructure optimised for brain research, started to build-up a set of benchmarks that reflect the diversity of applications in this field. In this paper we analyse the performance of some selected benchmarks on IBM POWER8 and Intel Skylake based systems with and without GPUs.

We introduce Arbor, a performance portable library for simulation of large networks of multi-compartment neurons on HPC systems. Arbor is open source software, developed under the auspices of the HBP. The performance portability is by virtue of back-end specific optimizations for x86 multicore, Intel KNL, and NVIDIA GPUs. When coupled with low memory overheads, these optimizations make Arbor an order of magnitude faster than the most widely used comparable simulation software. The single-node performance can be scaled out to run very large models at extreme scale with efficient weak scaling.

Running scientific workflows on a supercomputer can be a daunting task for a scientific domain specialist. Workflow management solutions (WMS) are a standard method for reducing the complexity of application deployment on high performance computing (HPC) infrastructure. We introduce the design for a middleware system that extends and combines the functionality from existing solutions in order to create a high-level, staged user-centric operation/deployment model. This design addresses the requirements of several use cases in the life sciences, with a focus on neuroscience. In this manuscript we focus on two use cases: 1) three coupled neuronal simulators (for three different space/time scales) with in-transit visualization and 2) a closed-loop workflow optimized by machine learning, coupling a robot with a neural network simulation. We provide a detailed overview of the application-integrated monitoring in relationship with the HPC job. We present here a novel usage model for large scale interactive multi-application workflows running on HPC systems which aims at reducing the complexity of deployment and execution, thus enabling new science.